bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP373: Tracts Enfolded by Small Hematomas Remain Intact in Acute Intracerebral Hemorrhage
Authors: McCourt Rebecca , Guinand Taurian , Gioia Laura , Kate Mahesh , Treit Sarah , Beaulieu Christian , Butcher Ken
Published: July 2021

Background:
Mortality can be predicted by intracerebral hemorrhage (ICH) volume, but motor recovery in survivors is variable. Motor impairment is likely related to the spatial relationship between the hematoma and corticospinal tract (CST). Diffusion Tensor Imaging (DTI) tractography can be used to visualize white matter tracts in three dimensions. We hypothesized that the interaction between the hematoma and CST would predict motor impairment in ICH patients.

Methods:
ICH patients with small-moderate hematomas were prospectively imaged with CT and DTI within 14 days of onset. Hematoma volume was assessed on CT using planimetric techniques. Three-dimensional recreations of the ipsilateral CST and the hematoma were made for each patient. The CST was categorized by interaction with the ICH as CST: Unaffected, Displaced, Partially Severed, Completely Severed, and Splitting the ICH. Motor function was classified as 'good' (NIHSS motor subscale 0-2) or 'poor' (3-8).

Results:
Thirty patients (mean age 68±13) underwent CT at a median (IQR) of 2.3 (3.5)h and DTI at 2.0 (3.6, range 0.6-13) days. Median hematoma volume was 8.2 (23) ml.

Lesion distribution was: lobar 11 (37%), basal ganglia 18 (60%), brainstem 1 (3%). CSTs were primarily Displaced (n=9) or Unaffected (8), with the remainder being Partially Severed (4), Completely Severed (5), and Splitting the ICH (4). The latter 4 (13%) patients had small (<6ml, median 2.5 [3.0] ml) basal ganglia bleeds which enfolded the intact CST.

Motor score at Day 7 was good in 50% of patients. Good outcome was seen in 8 (100%) Unaffected, 4 (44%) Displaced, 1 (25%) Partially Severed, 0 (0%) Severed and 2 (50%) Splitting the ICH patients. Logistic regression indicated that good motor score was predicted by CST category (r=2.3, p=0.016).

Conclusion:
CST integrity can be maintained when enfolded by small basal ganglia bleeds. Diffusion tractography patterns may be useful for predicting motor scores in small to moderate-sized hematomas.
Abstract TP379: Excessive Daytime Sleepiness in Stroke Survivors: Evidence From an Integrative Literature Review
Authors: Ding Qinglan , Whittemore, Robin , Redeker Nancy
Published: July 2021

Background and Purpose:
Excessive daytime sleepiness (EDS) is a prevalent symptom among stroke survivors. An understanding and accurate diagnosis of EDS is important, not only because EDS has been identified as an independent risk factor for stroke, but also because EDS may reduce stroke survivors’ quality of life, cognitive functioning and daytime functional performance. The lack of a universally accepted definition of EDS makes it difficult to measure and synthesize research. The purpose of this integrative review is to describe post-stroke EDS; to ascertain conceptual and operational definitions of EDS; to identify factors that contribute to EDS in stroke survivors; and to explore consequences of EDS in stroke survivors.

Methods:
Guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, an integrative review of the literature was conducted. We searched the following databases: PubMed, MEDLINE (OvidSP 1946 - April, Week 2, 2015), Embase (OvidSP 1974 - March, Week 1, 2015) and PsycINFO (OvidSP 1967 - April, Week 2, 2015), which yielded 340 articles and 27 articles met inclusion criteria.

Results:
The evidence suggests EDS is a multidimensional construct that is operationalized with subjective and objective measures. Choosing measures that can quantify both the objective and subjective components is useful to gain a comprehensive understanding of EDS. The antecedents of EDS are sub-types of stroke, sleep disordered breathing, Reversed Robin Hood Syndrome and depression. Consequences of EDS in stroke are serious and negative. A potential framework of post-stroke EDS is proposed and may be of use in clinical practice and in research to identify valid quantifying methods for EDS as well as to prevent harmful outcomes in stroke survivors.

Conclusion:
EDS is frequently experienced after stroke and may not always be caused by SDB. Healthcare providers and sleep specialists can seek to influence stroke survivors’ functional, neurological, and health-related outcomes through interventions that avoid EDS, depressive symptoms or SDB. Whenever SDB is suspected in stroke survivors, choosing both a subjective and objective evaluation of sleep may be indicated.
Abstract TP402: Stroke Nurse Coordinators: Role in Transient Ischemic Attack (TIA) Care in the National Veterans Health Administration
Authors: Damush Teresa M , Miech Edward J , Phipps Michael , Sico Jason , Arling Greg , Myers Laura , Austin Curt , Ferguson Jared , Williams Linda S , Bravata Dawn M
Published: July 2021

Background:
With the purpose of identifying gaps as well as best practices in guideline-concordant TIA/minor stroke care in the Veterans Health Administration (VHA) system, we sought to elucidate the perceived challenges and facilitators of TIA care across clinical specialties and across settings of care.

Methods:
We conducted a prospective, formative evaluation in 14 VHA hospitals across the US. We conducted 70 semi-structured interviews with front-line clinicians, leadership and quality managers. Interviews were audiorecorded, transcribed, and double coded in Nvivo 10 software using an emergent codebook. We analyzed the reported challenges and facilitators of TIA guideline care.

Results:
Six of the fourteen sites reported the existence of a Stroke Nurse Coordinator to track the quality of stroke care and to minimize the gaps in services across inpatient and outpatient settings. Of the six, only one site had a defined algorithm for TIA care services specifically for and separate from their stroke protocols. A lack of care coordination for TIA patients across services and across the inpatient and outpatient settings were major reported challenges. Sites without a stroke coordinator often reported a lack of staff to reduce this service gap. Some provided outpatient follow-up as well as risk factor management at the inpatient bedside for all admitted TIA patients and this appeared to facilitate TIA care. Educating facility staff for stroke care was a common responsibility, but few stated they provided TIA-specific staff education. Stroke/TIA quality data collection was often performed by the Stroke Nurse Coordinator; however the data feedback process varied widely across facilities from none to a stroke team, and by schedule from weekly or, quarterly to occasionally. It is unclear how the Stroke Nurse Coordinator interacted with the neurology service from these data, but the six sites with a Stroke Nurse Coordinator had much lower rates of consulting the Neurology service.

Conclusions:
Extending the role of the local Stroke Coordinator to include specifying a TIA protocol, assisting care coordination for patients with TIA, tracking and feeding quality data back to local providers may improve the quality of TIA care. SDP # 12-178.
Abstract TP432: Ventriculostomy Placement Improves Outcome in Hunt and Hess Grade 3-5 Subarachnoid Hemorrhage Patients Irrespective of Hydrocephalus
Authors: Janjua Nazli , Panichpisal Kessarin , Tse-Chang Karen , Jones Kimberly , Keasler Debbie , Desai Bhupat
Published: July 2021

Background:
Cerebrospinal fluid diversion may be necessary in the acute period after subarachnoid hemorrhage (SAH) if patients develop hydrocephalus. Though there is an opinion that certain ‘severe grade’ patients, e.g. Hunt and Hess (HH) grades 3-5, should have external ventricular drain (EVD) placement, regardless of hydrocephalus, there is no firm data, leaving the decision up to the judgement of the evaluating clinical team.

Objective:
We sought to measure changes in HH grades among grade 3-5 patients based on whether or not they had EVD placement.

Methods:
We prospectively collect demographic, clinical, and radiographic data on our SAH patients since January 2014. We selected HH grades 3-5 patients and compared admission and discharge HH grades among groups of patients who underwent EVD placement or surgical decompression within the first 24 hours and those who did not, using chi square test.

Results:
Among 54 total patients, there were 37 grades 3-5 patients (HH 3, n=26, 70.3%; HH 4, n=5, 13.5%; HH 5, n=6, 16.2%) in two groups: no EVD, n=22 (59.5%) and EVD, n=14 (37.8%, data unavailable for 1 patient). At discharge HH grades were: HH 1, n=10 (27%); HH 2, n=1 (2.7%); HH 3, n=10 (27%); HH 4, n=3 (8.1%); HH 5, n=1 (2.7%); dead, n=11 (29.7%); missing data, n=1. Mean age of 37 HH 3-5 patients was 58 years with no significant difference between the 2 groups. Hydrocephalus was seen in 11 of the 22 no EVD group and 13 of the 14 EVD group, p=0.007. Improvement in HH score between admission and discharge was seen in 10/14 EVD group, compared with 5/22 of the no EVD group, p=0.010. Worsening of HH score was found in 8/17 no EVD group (5 HH grade 5 patients excluded from this analysis), and 1 HH 4 patient (out of 14) in the EVD group, p=.014. Mortality occurred in 11/22 of the no EVD group (HH 3=5; HH 4-5=6) and 1/14 of the EVD group (HH 4, p=0.007).

Conclusion:
While the presence of hydrocephalus could potentially be a determinant in the decision to place EVDs among HH grades 3-5 patients, clinical change in patients who did not have an EVD placed occurred independently of hydrocephalus. Improvement of HH grade was more frequent, while its worsening was less common, among patients who underwent EVD or surgery within the first 24 hours. Mortality of HH grade 3 patients may also be impacted with EVD placement.
Abstract TP44: Low Cerebral Blood Flow (CBF) at Baseline Best Predicts Parenchymal Hematoma (PH) Post Revascularization Therapy
Authors: Batchelor Connor , McDougall Connor , Wee Patrick , Boesen Mari , Qazi Emmad , Najm Mohamed , Fainardi Enrico , Sajobi Tolu , d'Esterre Christopher D , Lee Ting Y , Aviv Richard I , Demchuk Andrew M , Goyal Mayank , Menon Bijoy K
Published: July 2021

Introduction:
In patients with acute ischemic stroke (AIS), parenchymal hematoma (PH) after revascularization therapy can lead to clinical deterioration and is often unpredictable. We sought to examine the association between admission CT perfusion (CTP) parameters (cerebral blood volume (CBV), cerebral blood flow (CBF), and Tmax) and PH in a case-controlled sample of patients receiving intravenous tPA ± endovascular treatment when using an industry standard CTP algorithm.

Hypothesis:
We hypothesize that CTP derived parameters (CBV, CBF, and Tmax) can predict PH in AIS.

Methods:
PH was classified according to ECASS II criteria. Two-phase (150s) and single-phase (66s) CTP acquisitions were performed within 12hrs of ictus. CTP 4D(GE Healthcare) delay-insensitive software was used to calculate CBF, CBV, and Tmax maps. Ipsilateral hemisphere gray and white matter (GM, WM) were flooded to determine volumes (mm3) for 3 lesion types: 1) patient-specific very low CBV (vlCBV) thresholds derived from the lower 10th, 5th and 2.5th percentiles of the contralateral hemisphere, 2) very low CBF threshold of ≤7ml/(min·100g), and 3) very high Tmax threshold of ≥16s. To correct for varying scan coverage, ratio of threshold output volume by ipsilateral hemisphere volume within slices that contained lesions was obtained. Receiver operating characteristic (ROC) analysis was used to compare models to determine which CTP parameter best predicted PH.

Results:
34 AIS patients (18 PH, 16 no hemorrhage) were included. Very low CBF threshold of ≤7ml/(min·100g) best predicted the occurrence of PH post revascularization therapy (p < 0.001; comparison of c-statistic). CBV and Tmax parameters were not discriminative of PH. (See Figure 1 for comparison of c- statistics).

Conclusion:
When using a delay insensitive industry standard CTP paradigm, very low CBF≤7ml/(min·100g) has the ability in predicting PH post revascularization therapy.
Abstract TP446: Independent Measures of Cerebral Blood Flow in Asymptomatic Carotid Artery Disease.
Authors: Marshall Randolph S , Pavol MaryKay , Cheung Ken , Strom Isabelle , Slane Kevin , Asllani Iris , Lazar Ronald M
Published: July 2021

Background:
Cerebral blood flow (CBF) regulation is a critical element in cerebrovascular pathophysiology, particularly in large vessel disease. Different methods to assess hemodynamics may represent different aspects of blood flow regulation, however, uniquely affecting outcomes and management. We examined 4 different blood-flow related measures in patients with high-grade unilateral carotid disease, assessing asymmetry between the occluded vs non-occluded side, and the correlations among the measures.

Methods:
Thirty-three patients (age 50-93, 19M) with unilateral 80-100% ICA occlusion but no stroke underwent: 1) quantitative resting CBF using continuous arterial spin labeling (CASL) MRI, 2) mean flow velocity (MFV) in both middle cerebral arteries (MCAs) by transcranial Doppler, 3). Vasomotor reactivity (VMR) in response to 2 minutes of 5% CO2 inhalation, and 4) Dynamic cerebral autoregulation (DCA) using continuous insonation of both MCAs for 10 minutes at depth 56mm with a standard head frame. Phase shift (PS) between spontaneous oscillations in blood pressure (measured with finger photoplethysmography) and MCA MFV at frequencies .06-.12 Hz was calculated for each hemisphere using transfer function analysis. Lower PS indicated worse autoregulation. Paired T-tests and Pearson correlations were used to look for side-to-side differences within each measure, and correlations between measures (SPSS v.22).

Results:
CASL CBF (p=.001), MFV (p<.001), VMR (p=.008), and DCA (p=.047) all showed significantly lower values on the occluded side. The 4 measures were independent of each other on correlation analysis, even when controlling for age and anterior circle of Willis collateral (correlation coefficients all <0.40, p-values >0.09).

Conclusions:
These 4 measures showed high sensitivity to the occluded carotid artery, but appear to represent independent aspects of cerebral blood flow (CASL: resting gray matter CBF; MFV: whole-hemisphere CBF; VMR: cerebrovascular reserve, and DCA: homeostatic blood flow regulation) suggesting that any given measure only partially characterizes hemodynamic state. Further investigation will use these 4 measures to predict outcomes including vascular cognitive impairment.
Abstract TP448: High Residual Platelet Reactivity (hrpr) for Adenosine Diphosphate (adp) Stimuli is a Determinant Factor for Long-term Outcomes in Acute Ischemic Stroke With Anti-platelet Agents
Authors: Cha Jae-Kwan , Kim Eun-Kyu
Published: July 2021

Background and Purpose:
High residual platelet activation (HRPA) after ADP stimuli has associated with recurrent vascular events in acute atherothrombosis with the use of antiplatelet agents (APAs). However, there has been little evidence supporting this association in acute ischemic stroke (AIS). In this study, we evaluated the influences of HRPR after ADP stimuli on the 1-year incidence of recurrent cardiovascular events and mortality in AIS with APAs.

Methods:
We conducted an observational, referral center cohort study on 968 AIS patients with APAs from January 2010 to December 2013 who were evaluated using optical platelet aggregometry (OPA). All patients received the dual APA combination of aspirin and clopidogrel or aspirin alone. We evaluated their platelet function 5 days after hospital admission using OPA. HRPR after ADP stimuli was defined as platelet aggregation of 70% or greater according to OPA after 10 μM ADP stimuli.

Results:
The primary endpoint was a composite of all causes of death, myocardial infarction, and stroke at the 1-year follow-up. The secondary endpoints were each component of the primary endpoint. The event rate of primary endpoint was 11.3% (109/968). Its rate was significantly higher in the patients with HRPR (16.7%) than in those without (9.7%). HPRP was independently associated with the primary endpoint (OR=1.97, CI 1.22 to 3.18, p<0.01). According to the AIS subtype, the presence of HRPR was independently significant for the occurrence of the primary endpoint in the large artery atherosclerosis (LAA) subtype only (OR=2.26, CI 1.15 to 4.45, P=0.02).

Conclusions:
In this study, the presence of HRPR after ADP stimuli is associated with a poor long-term outcome after acute ischemic stroke. In particular, the influence of this factor might be more prominent in LAA compared with other types of AIS.
Abstract TP451: Age-associated Changes in the Structure and Biomechanical Properties of Parenchymal Arterioles
Authors: Diaz-Otero Janice M , Jackson William F , Dorrance Anne M
Published: July 2021

Arterial aging, a phenomenon that we do not fully understand, results in dysfunctional arteries. Age-associated changes in physiological and vascular functions increase the risk of cardiovascular disease. Aging results in peripheral artery remodeling, described as a change in artery size and wall structure. Age-related cerebral artery remodeling could increase the risk of stroke and vascular dementia particularly in situations where comorbidities, such as hypertension, are present. The effects of aging on the biomechanical properties of parenchymal arterioles (PAs) have not been characterized. PAs regulate perfusion of the cerebral microcirculation and are important in determining cerebrovascular resistance. We hypothesized that aging would decrease the lumen diameter, and increase the wall thickness and collagen deposition in PAs from C57Bl/6 mice. PAs were collected from 3-5 month (young; n=8) and 22-24 month (old; n=8) old male mice for assessment of structure by pressure myography. Data collected at 60mmHg are presented as mean ± SEM, young vs. old. Advanced age was associated with increased systolic blood pressure (126 ± 1 vs 145 ± 2mmHg). Aging did not significantly affect the outer (49 ± 5 vs 53 ± 3μm) or lumen (41 ± 5 vs 41 ± 2μm) diameter of the PAs (p > 0.05 for all comparisons). However, the PAs from older mice had increased wall thickness (4 ± 1 vs 6 ± 1μm), wall area (591 ± 96 vs 853 ± 101μm2), and wall-to-lumen ratio (0.10 ± 0.01 vs 0.13 ± 0.01) (p < 0.05 for all comparisons). Wall stress (302 ± 27 vs 220 ± 11 dynes/cm2) was reduced with age. Changes in artery wall structure have been associated with modifications in the components of the extracellular matrix such as collagen and calcium. The PAs from older mice had increased collagen deposition in the wall (427 ± 172 vs 2699 ± 442μm2; p < 0.05) but the number of arteries with calcium deposits was similar between groups (2 ± 1 vs 3 ± 1 positive vessels/area; p > 0.05). Our studies of geriatric mice with high blood pressure suggest that aging is associated with hypertrophic remodeling of the PAs that is accompanied by alterations in the extracellular matrix of the artery wall; these changes could increase the risk of cerebrovascular diseases.
Abstract TP459: Higher Coated-Platelet Levels in Patients with Acute Stroke are Associated with Lower Cognitive Performance at 3 Months
Authors: Kirkpatrick Angelia C , Stoner Julie A , Mathews Eleanor , Dale George L , Prodan Calin I
Published: July 2021

Introduction:
Coated-platelets, a subset of procoagulant platelets observed upon dual agonist stimulation with collagen and thrombin, support a robust prothrombinase activity and provide a unique measure of platelet thrombotic potential. Coated-platelet levels are increased in non-lacunar stroke compared to healthy controls, and higher levels are associated with stroke recurrence. In prior studies, we have shown that coated-platelet levels in patients with carotid atherosclerosis and cognitive impairment are elevated as compared to those with normal cognition.

Hypothesis:
To examine whether coated-platelet levels measured at the time of the stroke correlate with cognitive performance at 3 months following the brain infarction.

Methods:
Consecutive patients with a diagnosis of non-lacunar stroke were enrolled in this pilot study over 12 months. Coated-platelets were determined at the time of the stroke and reported as percent of platelets converted to coated-platelets. Cognitive screening was performed using the Mini-Mental State Examination (MMSE) during a stroke clinic visit 3 months after hospital discharge. Patients with prior dementia or significant aphasia were excluded. The linear correlation between initial coated-platelet levels and MMSE scores at 3 months was examined using the Pearson correlation coefficient.

Results:
We enrolled 66 patients, 97% male, with a mean age of 66.7 years (range 49-88) and mean NIHSS score of 4.4 points (range 0-11). Mean MMSE was 26.3 points (range 18-30) and mean coated-platelet levels were 41.4% (range 15.4-76.2). 34 patients (52%) had MMSE scores of ≤26, suggestive of a degree of cognitive impairment. An inverse relationship was found between coated-platelet levels and MMSE score, with higher levels seen in patients with lower MMSE scores (r=-0.45, R
2
=0.21, p=0.0001). This association remained despite adjustment for presence of large-artery disease and stroke severity.

Conclusions:
Higher initial coated-platelet levels are associated with lower cognitive performance at 3 months post stroke. These findings support a link between increased platelet procoagulant potential and development of vascular cognitive impairment following cerebral infarction.
Abstract TP53: Imaging Insight on Therapeutic Hypothermia with Thrombolysis: ICTUS 2
Authors: Liebeskind David S , Ernstrom Karin , Rapp Karen , Agarwal Sachin , Concha Mauricio , Hussain Syed , Dugan Guy M , Rzesiewicz Teresa , Grotta James C , Hemmen Thomas M , Raman Rema , Lyden Patrick D ,   for the ICTUS 2 Investigators
Published: July 2021

Background:
Therapeutic hypothermia for acute ischemic stroke is most likely to benefit patients with large vessel occlusion that require reperfusion. Until the recent success of endovascular trials with advanced imaging selection, noncontrast CT prior to intravenous (IV) thrombolysis has been the mainstay. We analyzed the ICTUS 2 trial CT findings before and after thrombolysis to disclose the impact of large vessel occlusion and subsequent edema formation.

Methods:
Noncontrast CT findings at baseline and 36 hours after enrollment were analyzed by imaging variables linked with large vessel occlusion. Presence of hyperdensity artery sign (HAS) and ischemic changes were analyzed in hypothermia and normothermia arms of the randomized safety and efficacy trial. Data were presented using descriptive statistics and Fisher’s exact test for comparisons between treatment arms.

Results:
120 patients (median age 69±IQR 15 years; 51 (43%) women; median NIHSS 14±8 IQR) with acute stroke treated with IV thrombolysis were enrolled in ICTUS 2, including 63 randomized to hypothermia (H) and 57 to normothermia (N). CT abnormalities were balanced (68% H vs. 61% N, p=NS) across treatment arms, including hyperdense arteries (HAS) (33% H vs. 37% N, p=NS). At 36 hours, the vast majority of patients had CT abnormalities (92% H vs. 84% N, p=NS), including edema (52% H vs. 44% N, p=NS), hemorrhagic transformation (13% H vs. 19% N, p=NS) and HAS (22% H vs. 15% N, p=NS). Topography of ischemic changes at 36 hours was similar between arms, involving the insular cortex in 60%, frontal lobe 65%, parietal lobe 59% and temporal lobe 52%. Large vessel atherosclerosis was identified as cause of stroke in 29% of hypothermia and 19% normothermia subjects, p=NS. Serial CT changes from baseline to 36 hours based on topography were similar between arms. No interactions could be discerned between imaging findings, treatment allocation and 90-day mRS clinical outcomes.

Conclusions:
ICTUS 2 selection criteria based on NIHSS yielded a substantial proportion of large vessel strokes. The relatively high rate of persistent hyperdense arteries and extensive ischemic changes suggest more effective reperfusion strategies than IV thrombolysis may be warranted and enhanced by advanced imaging surveillance.
Abstract TP55: Rate of Infarct Growth in Acute Ischemic Stroke is Independent of Apparent Diffusion Coefficient Threshold
Authors: Gupta Sah Rani , Khan Saad , Mahajan Ajay , Forkert Nils D , Hafeez Moiz , Tsang Adrian , d'Esterre Christopher D , Barber Phillip A
Published: July 2021

Background:
For acute stroke assessment, apparent diffusion coefficient (ADC) obtained from diffusion-weighted imaging (DWI) provides sensitive detection of infarct volume. Identification of infarct growth in patients with acute ischemic stroke (AIS) is important for determining the efficacy of stroke therapy. Reported ADC thresholds for detecting AIS vary from 550 to 650 x10^-6mm^2/s. Therefore, the measurement of infarct growth is not standardized.

Hypothesis:
Measurement of the rate of infarct growth after stroke is independent of the ADC threshold used.

Methods:
38 AIS patients (age; 71.5±17.0) were imaged acutely (within 4h) after stroke symptoms (Time1-Baseline) and repeated at 24h (Time2) on a 3T MR scanner. DTI data with 15 directions was acquired and used for ADC map calculations. Lesion volumes were calculated with ADC thresholds of 550, 600, 630 and 650 x10^-6mm^2/s using ANTONIA software. Rate (r) of infarct growth was calculated by r=Δvolume(ADC2-ADC1)/Δtime(time2-time1).

Results:
ADC volume and rate of infarct growth is reported in table 1. No significant difference was found in the rate of infarct growth between the two time points (one way ANOVA).

Conclusion:
Quantification of infarct evolution is critical for determining the efficacy of stroke therapy. Although absolute lesion volumes vary considerably, the rate of infarct growth is independent of the ADC threshold and should be the preferred measure of acute infarct growth.
Abstract TP61: Automated Labeling of Cerebral Vasculature on MR Angiography Using Nonparametric Bayesian Inference
Authors: Quachtran Benjamin , Sheth Sunil , Saver Jeffrey , Liebeskind David , Scalzo Fabien
Published: July 2021

Background:
An automated, unbiased method to accurately label cerebrovascular territories would greatly advance our ability to assess individual stroke patients as well as study large databases. Previous attempts have failed due to the wide variation in normal vascular topography. We test the hypothesis that a nonparametric probabilistic model that learns the configurational characteristics of vascular territories will better annotate the cerebrovasculature.

Methods:
In the George Mason Brain Vasculature database, we identified patients with MRA reconstructions segmented into seven major regions (left and right MCA, PCA, and ACA and Circle of Willis). We then augment these labels by manually segmenting the MCA territory into an additional eight regions. We then divide the database into training and validation cohorts to assess the algorithm.

Results:
Among 54 patients that met the inclusion criteria, 39 reconstructions were used as training input to the model among the 61 digital reconstructions of human brain arterial structures available. The model was then validated on an independent cohort of 15 patients. The algorithm was found to be 94+-5.2% accurate in annotating the vascular segments.

Conclusions:
Kernel density estimation, used in conjunction with a Bayesian inference-based algorithm, can accurately label cerebral vascular territories using spatial and radial features. This process can provide a framework for further vascular segmentation and analysis of artery occlusion in stroke patients.
Abstract TP69: Administration of Tissue Plasminogen Activator: to Wait or not to Wait for Screening Coagulation Tests? Impact on Door to Needle Time and Symptomatic Intracerebral Hemorrhage
Authors: Dahlberg Katie W , Selph James , Thakker Parth , Dennis Lauren C , Cotter Amanda , Sen Souvik
Published: July 2021

Introduction and Hypothesis:
Administration of intravenous tissue plasminogen activator (IV tPA) is currently the only FDA approved medical treatment for acute ischemic stroke. To improve outcomes the goal is to have reduced door to needle time (DTN) to IV tPA. Guidelines recommend obtaining coagulation tests prior to IV tPA, but new prescribing information suggest physicians may not need to wait for coagulation test results in patients not on anticoagulation therapy. We assessed the hypothesis if not waiting for these tests prior to IV tPA reduced the DTN time, without affecting the rate of symptomatic intracerebral hemorrhage (SICH).

Methods:
The study is a retrospective analysis of prospectively collected data on acute ischemic stroke patients treated at a Joint Commission Certified Stroke Center. Based on differing physician practices, patients received IV tPA prior to results of screening coagulation tests or they received IV tPA after tests returned. Measures obtained from chart review included initial NIH stroke scale (NIHSS), DTN time, lab return time, abnormal lab results, and development of post IV tPA SICH (defined as ICH associated with an NIHSS increase ≥4).

Results:
From January 2013 to May 2015, 136 patients received IV tPA. (Mean age ± SD = 65 ± 15 years, 53% male, 46% African American, 51% Caucasian, and 2% other, median NIHSS = 10, mean DTN ± SD = 65 ± 35 min). Group one, 102 patients, received IV tPA after test results were available (Mean age ± SD = 66 ± 15 years, 51% male, 50% African American, 48% Caucasian, and 2% other, median NIHSS = 10, mean DTN ± SD = 71 ± 34 min). Group two, 34 patients, received IV tPA prior to test results being available (Mean age ± SD = 64 ± 15 years, 59% male, 35% African American, 62% Caucasian, and 3% other, median NIHSS = 12, mean DTN ± SD = 46 ± 31 min). Group two had a significantly reduced DTN time (t test p<0.0002). No abnormal screening coagulation tests were found upon final review. There was no difference between in the rates of SICH (group one 4%, group two 6%, Fisher's exact test p>0.99).

Conclusions:
Selection of appropriate patients to receive IV tPA without waiting for screening coagulation tests to be returned, significantly improved DTN time. There was no significant difference between the rates of SICH in the two groups.
Abstract TP97: Experimental Stroke During Aging: Docosahexaenoic Acid Therapy Provides Robust Neuroprotection
Authors: Belayev Ludmila , Khoutorova Larissa , Obenaus Andre , Bazan Nicolas G
Published: July 2021

Introduction:
Recently we have shown that docosahexaenoic acid (DHA) is neuroprotective after experimental stroke in young rats. The purpose of this study was to determine whether treatment with DHA would be protective in aged rats after focal cerebral ischemia.

Methods:
Isoflurane/nitrous oxide-anesthetized normothermic (brain temperature 36-36.5
o
C) male Sprague-Dawley aged rats (16-months old) received 2h middle cerebral artery occlusion (MCAo) by poly-L-lysine-coated intraluminal suture. The behavioral function was evaluated during occlusion (60 min), and on days 1, 3 and 7 after MCAo; a grading scale of 0-12 was employed (0=normal and 12=maximal deficit). The agent (DHA, 5 mg/kg; n=6) or vehicle (saline; n=7) was administered i.v. at 3h after MCAo onset. The composite neuroscore comprises two different neurological tests, the postural reflex test and the forelimb placing test, to measure visual, tactile and proprioceptive stimuli, which were evaluated on days 1, 2, 3 and 7. High resolution
ex vivo
MRI using an 11.7T Bruker was performed on day 7. The core and penumbra were automatically identified using the Hierarchical Region Splitting method for penumbra identification. Histopathology and immunostaining were conducted after completion of MRI on day 7.

Results:
DHA treatment improved neurological scores on days 1 (by 18%), 2 (by 25%), 3 (by 22%) and 7 (by 36%). Total, cortical and subcortical lesion volumes computed from T2WI were significantly reduced by DHA treatment (by 62-75%). DHA treatment also reduced cortical, subcortical and total brain infarction (by 65- 80%). In addition, DHA therapy decreased ED-1 positive microglia/microphages (by 62%), GFAP-positive astrocytes (by 21%), and NeuN-positive neurons (by34%), and it increased SMI-71-positive vessels (by 46%) in the ischemic penumbra.

Conclusion:
DHA therapy is highly neuroprotective in aged rats following focal cerebral ischemia and has potential for the effective treatment of ischemic stroke in aged individuals.
Abstract WMP111: Stroke and Alzheimer’s Disease: Shared Mechanisms of Vascular Disruption
Authors: Lucke-Wold Brandon , Logsdon Aric , Mohammad Afroz , Adkins Chris , Ren Xuefang , Huber Jason , Rosen Charles , Simpkins James , Lockman Paul
Published: July 2021

Recent evidence suggests that Alzheimer’s disease is a vascular disorder that can be accelerated by ischemic stroke. We propose that the underlying pathophysiology accelerating degenerative changes is due to blood brain barrier disruption following ischemia. A transient middle cerebral artery occlusion suture model was used in triple-transgenic AD mice and C57/Bl6 wild type controls. A separate triple-transgenic AD mice group was used for sham control. The middle cerebral artery was occluded for 1 hour followed by reperfusion. Mice were evaluated for sickness behavior and received a modified neurologic score. 5 hours after reperfusion, blood brain barrier tracers (Texas red, IcG, and AIB1) were injected i.v. into the femoral vein and allowed to circulate for 10 minutes. H&E, Cresyl Violet, and Thioflavin were used to stain sections of the brain for areas of degeneration. Images were obtained by quantitative fluorescent and bright-field microscopy. One-way ANOVA with Tukey’s post-hoc comparison was used to compare between groups. P<0.05 was considered statistically significant. A statistically significant difference between groups was seen for blood brain barrier permeability following ischemia and reperfusion. Triple-transgenic AD mice had a 2-fold increase in Texas red and a 4-fold increase in AIB1 at 5 hours after reperfusion. No significant differences were seen in the control groups. H&E staining revealed nuclear fragmentation, chromatolysis, and vacuolization in the ipsilateral cortex of the triple-transgenic AD mice exposed to stroke. Limited areas of necrosis were seen in the C57/Bl6 controls. A significant increase in thioflavin staining was seen post-stroke in the triple-transgenic AD mice. The amyloid distribution was perivascular and significantly increased compared to the triple-transgenic AD sham mice. Triple-transgenic AD mice had a worse sickness score (avg. 13) compared to C57/Bl6 controls (avg. 17). Stroke and Alzheimer’s disease share similar vascular mechanisms related to blood brain barrier disruption. We show that blood brain barrier disruption post-stroke accelerates degenerative changes. Targeting blood brain barrier disruption as a treatment approach may prove promising and warrants continued investigation.
Abstract WMP116: Multi-center Assessment of Morbidity After Cerebral Arteriovenous Malformation Rupture
Authors: Fukuda Keiko A , Majumdar Monica , Masoud Hesham , Nguyen Thanh , Honarmand Amir R , Ansari Sameer A , Tan Lee A , Chen Michael
Published: July 2021

Background:
Previously published single center studies suggest the morbidity associated with brain arteriovenous malformations (AVM) hemorrhage to be lower than assumed. Given the recent controversy over the appropriate management of unruptured brain AVMs, we performed a multi-center critical assessment of the morbidity associated with ruptured brain AVMs.

Methods:
A retrospective chart review from tertiary care, urban, academic medical centers was performed. Inclusion criteria consisted of patients admitted for intracranial hemorrhage caused by a previously untreated AVM. Thirty-seven variables were analyzed, including patient demographics, imaging findings, clinical course and clinical exams.

Results:
101 patients from three medical centers dating from 2008-2014 met the inclusion criteria. Admission NIHSS scores of 0, 1-9 and ≥10 were 26%, 29% and 45% respectively. Hematoma location was parenchymal in 32%, intraventricular in 11%, subarachnoid in 5%, and combined in 52%. Deep venous drainage was present in 43% of cases, and associated aneurysms were present in 44%. Thirty-seven percent underwent emergent hematoma evacuation while 8 patients expired during their admission. At discharge, of those that survived, 69% had a NIHSS ≥ 1, and 23% had a NIHSS ≥ 10. At 90 day follow-up, 27% had a mRS ≥ 3. Patients with admission NIHSS ≥ 10 had significantly higher rates of midline shift, surgical hematoma evacuation, and follow-up mRS ≥ 3(
p
< 0.05).

Conclusion:
This multicenter critical assessment of the morbidity associated with brain AVM rupture suggests poorer clinical outcomes than previously assumed and reported. Rupture morbidity should be considered alongside rupture risk and procedural risk when considering preventative anatomic treatment of unruptured brain AVMs.
Abstract WMP22: Reduced White Matter Integrity in Acute Stroke Patients With Language Deficits: a Tract-based Spatial Statistics Study
Authors: Mossahebi Pouria , Nair Veena A , La Christian , Sattin Justin A , Prabhakaran Vivek
Published: July 2021

Introduction:
We examined white matter integrity in acute stroke Patients with Language Deficits.

Hypothesis:
Microstructural abnormality in specific white matter tracts would show significant reduction in stroke patients with language deficits.

Methods:
Stroke patients with language deficits (N = 10, mean age = 56.3 years, within 7 days from stroke onset, normed verbal fluency score of less than -1.5), and age- and gender-matched healthy controls without language deficits (N = 10, mean age = 55.6 years, normal verbal fluency score) were scanned on GE750 3T MRI scanners. 3D T1-weighted whole brain BRAVO and DTI data (56 directions, b value = 1000 s/mm2) were collected. Verbal fluency test was administered to all subjects. Fractional anisotropy (FA) maps were generated from a tensor-model fit of eddy current corrected DTI data using FSL software. The skeletonized and fully non-linearly registered FA data were obtained using Tract-Based Spatial Statistics (TBSS) implemented in FSL, and then they were used for voxel-wise statistical analysis across subjects. Corona radiata (CR) (anterior, superior, posterior), cingulum, superior longitudinal fasciculus (SLF), and uncinate fasciculus of both right and left hemisphere from Johns Hopkins University (JHU)-ICBM-DTI-81 white matter labels atlas were used to identify significantly affected white matter tracts revealed by TBSS. Student t-tests were used to compare group means for normally distributed data and Mann-Whitney U tests to compare group means for non-normal data. Statistical analysis was performed using StatPlus package. Significance was set at p <.05.

Results:
There was a significant reduction of FA in the left SLF, left superior CR, and both right and left posterior CR of stroke patients with language deficits compared to healthy controls. A slight trend toward significant reduction of FA was also seen in right superior CR (p = 0.089) of stroke patients with language deficits. No significant group differences in FA value were seen in uncinate fasciculus and cingulum.

Conclusions:
Stroke patients with language deficits showed significant reduction in FA values in functionally relevant white matter tracts such as the left SLF, left superior CR, and both right and left posterior CR.
Abstract WMP40: Intra-arterial Mesenchymal Stem Cells in a Large Animal Endovascular Canine Stroke Model: Findings on Serial Diffusion Tensor Imaging
Authors: Guada Luis , Pradip Pattany , Ramdas Kevin , Pafford Ryan , Saigal Gaurav , Dileep Yavagal
Published: July 2021

Background:
Cell therapy is promising in rodent pre-clinical studies. Confirmation of efficacy of this novel approach in large animals is recommended. Diffusion Tensor Imaging (DTI) assesses white matter microstructure in the CNS using Fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Diffusion Tensor Tractography (DTT) DTT produces a 3D representation of the white matter tracts (WMT) in which data are displayed on a colored map that helps to identify the integrity of the tracts selected under the region of Interest (ROI). The purpose of this study was to use DTI-DTT analysis, and correlate it with the neuro-assessment of dogs over one month after ipsilateral intra-arterial (IA) Mesenchymal Stem Cell (MSCs) 48 hours after a brain-stroke was reversible middle cerebral artery occlusion (rMCAo)

Methods:
Mongrel Hounds (n=5), aged 12-36 months, were included in this pilot study. rMCAo was induced via endovascular approach using a detachable helical ultra-coil over 35-80 min. MSCs (1-20 millions) were infused intra-arterially 48hrs post stroke in the ipsilesional cervical internal carotid. DTI-T images were obtained at 48h post rMCAo pre-IA cell delivery, 15 & 30 days. DTT was also generated. FA-ADC values of the right & left hemisphere and CST were determined. Weekly neuro-evaluations were performed using our canine neuro-scale

Results:
Our data suggest a correlation between the neurological recovery and improvement in the FA-ADC values (see figure). An increase in the caliber of corticospinal tracts ipsilateral to the stroke by day 30 compared to pre-injection was observed on the DTT reconstruction for two canines that showed neurological improvement ( see figure)

Conclusions:
Serial DTI-DTT imaging after IA cell therapy shows improvement in white matter tracts correlating with neurologic recovery. This supports further development of DTI-DTT biomarkers to measure neurologic recovery in experimental models as well as early clinical trials.
Abstract WMP84: Worse Functional Outcome in Stroke Patients With Elevated Urine Specific Gravity
Authors: Bahouth Mona N , Hillis Argye E , Gottesman Rebecca F
Published: July 2021

Introduction:
An estimated 44-70% of stroke patients present to the hospital in a dehydrated state. Prior studies suggest that volume contraction contributes to worsened neglect syndromes and reduced chance of early recovery. Thus we hypothesized that patients who were clinically dehydrated at the time of stroke carried a higher probability of worse functional outcome at three months.

Methods:
We enrolled a consecutive series of ischemic stroke patients who presented to the hospital within 12 hours from stroke symptom onset. Patients were excluded if they had baseline kidney disease, presented with signs of active infection, or were unable to complete MRI. Clinical function was measured via daily NIHSS and 3 month modified Rankin scale (mRS). A priori, we defined a volume contracted state as BUN/creatinine ratio > 15 or urine specific gravity (SG) > 1.010.

Results:
One hundred and four patients were eligible for inclusion after 1 year of recruitment, of whom 83 (80%) had urinalysis measured and were thus included in this analysis. 62/83 patients (75%) had elevated urine SG consistent with a clinically dehydrated state. Independent of age, sex, and baseline NIHSS score, patients with elevated urine SG > 1.010 had a 3.6 increased odds (95% CI; 1.31-9.93) of being in a higher (worse) modified mRS category (Figure). A combined model defining volume contraction using both elevated BUN/creatinine ratio and urine SG did not demonstrate a statistically meaningful difference in outcomes.

Conclusions:
Elevated urine specific gravity at the time of ischemic stroke is associated with worse 3 month outcome. This objective marker may represent a readily available, standardized way to measure clinical dehydration syndromes as we attempt to define structured rehydration strategies for this population of patients.
Abstract WMP97: Regional Cerebral Oxygen Extraction is Elevated in Tissue at High Risk of Stroke in Pediatric Sickle Cell Disease
Authors: Ford Andria L , Guilliams Kristin P , Fields Melanie , Ragan Dustin K , Eldeniz Cihat , Binkley Michael , Rhodes Trey , McKinstry Robert , Shimony Joshua , Vo Katie D , Wang Danny J , Hulbert Monica , An Hongyu , Lee Jin-Moo
Published: July 2021

Introduction:
Children with sickle cell disease (SCD) are at high risk of stroke. Hemispheric oxygen extraction fraction (OEF) is a predictor of stroke in adults with carotid occlusion, but OEF has not been evaluated as a predictor of stroke in children with SCD.

Hypothesis:
OEF is elevated in SCD children compared to controls within a region at high risk of stroke as defined by an infarct heat-map created from a separate retrospective SCD cohort.

Methods:
A prospective MRI study enrolled 37 children aged 5-21: 17 with SCD and no stroke, 12 with SCD and silent infarcts (median infarct volume=0.3ml), and 8 sibling controls. None were on transfusions or had overt stroke history. Voxel-wise OEF was measured using an asymmetric spin echo sequence. In a separate retrospective cohort of 67 SCD children with overt and silent stroke, infarct regions on FLAIR were manually outlined and coregistered to an average T1 map to create an infarct heat-map (Fig A) which was used to define a “high risk” ROI (defined by >3% infarct density). This ROI was aligned to individual OEF maps from the prospective cohort (Fig B, average OEF map). OEF within the “high risk” ROI was compared between SCD children and controls; and between SCD children with and without infarction using Mann Whitney U tests.

Results:
The infarct heat-map from the retrospective cohort (Fig A) and the average OEF map from the prospective SCD cohort (Fig B) demonstrate striking co-localization of infarct density and elevated OEF. Within the “high risk” ROI, OEF was higher in SCD children compared to controls (39% [36, 46] vs. 23% [22, 27], p<0.0001 (Fig C). OEF within this “high risk” ROI did not differ between SCD children with and without infarcts (40% [38, 47] vs. 38% [35, 46], p=0.6).

Conclusion:
OEF in SCD children is elevated in the internal borderzone, a region with high stroke risk in SCD. Regional OEF may be a marker of cerebral metabolic stress that could be exploited to stratify stroke risk in this vulnerable population.
Abstract WP102: Cerebrolysin Improves Neurological Outcome in Rats After Acute Stroke: a Prospective, Randomized, Blinded, Placebo-controlled Study
Authors: Zhang Li , Chopp Michael , Lu Mei , Zhang Talan , Pabla Pardeep , Winter Stefan , Doppler Edith , Meier Dieter , Zhang Zheng Gang
Published: July 2021

Background and Purpose:
Cerebrolysin is a mixture of neuropeptides and free amino acids that exert potent neuroprotective and neurorestorative properties in experimental models of stroke. We conducted a prospective, randomized, double-blind and placebo controlled dose-response study of Cerebrolysin in both male and female rats after embolic stroke.

Methods:
Randomization schemas were generated using nQuery3.0. Male and female Wistar rats (3-4 months) were subjected to embolic middle cerebral artery occlusion (MCAO). After confirming successful stroke with a 5 point neurological scale (Longa scale) at 3h after MCAO, ischemic rats were treated with Cerebrolysin at doses of (0.8, 2.5, 5.0, 7.5ml/kg) and saline based on the randomization schema 4h after MCAO and continued daily for a total of 10 consecutive days. The primary outcome was neurologic outcome measured by adhesive removal test, foot-fault test, and modified neurological severity score at day 28, lesion volume and mortality were secondary and safety outcomes, respectively.

Results:
There was a significant dose effect of Cerebrolysin on neurological functional improvement 28 day after MCAO. Cerebrolysin at a dose of ≥ 2.5ml/kg significantly (P<0.001) improved neurological outcome (Mean Estimate with 95%CL): 0.8ml/kg: 6.2 (-6.0/18.4), 2.5ml/kg: -28.9 (-41.6/-16.2), 5.0ml/kg: -33.4 (-45.0/-21.7), 7.5ml/kg: -36.3 (-48.2/-24.4). Higher doses (≥2.5ml/kg) resulted in better recovery; however, differences between effective doses were not significant. Treatment with 5ml/kg reduced lesion volume (19.5±8.9%) compared with saline treated rats (27.7±11.9%, P=0.016). No treatment gender interactions were found and there were no differences on mortality rate.

Conclusion:
Cerebrolysin in a dose-dependent manner significantly improved neurological outcomes in ischemic rats. Cerebrolysin at a dose of 5ml/kg reduced infarct volume. Our data on Cerebrolysin efficacy demonstrate the feasibility of a preclinical study setup following a randomized, placebo controlled, and blinded design with a clinical relevant treatment scheme.