bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 24: Implementing Target Stroke Best Practice Time Sensite Guidelines Improves Door To Needle Time (DTN).
Authors: Zimmermann Susan , Camp Deborah , Barker Jessica , Perez Amy , Rogers-Lege Jaimee , Lugtu James , Bryant Katja , Anda Kim , Hormes Joseph T , Mills Jeremy , Burkhalter Misty , Valadi Nojan , Johnson Corrina
Published: March 2022

Implementing:
Target Stroke Best Practice Time Sensitive Guidelines Improves Door to Needle Time (DTN)

Background:
Target Stroke Honor Roll (TSHR) facilities have demonstrated compliance meeting Get With the Guidelines (GWTG) standards for care of the acute stroke patient. TSHR leaders collaborated and recognized there are similar barriers resulting in not achieving the DTN goal.

Objective:
To review IV-TPA data of patients from TSHR facilities that did not meet the DTN time of less than 60 minutes and specify which of the three categories had the greatest delay. • Internal Process • Patient dynamics • Hemodynamic instability

Methods:
A six month retrospective review of IV t-PA administrations from 9 Georgia TSHR facilities was performed. The review included those administrations that did not meet the DTN Goal of < 60 minutes. Meaningful intervals in treatment were calculated using uniformly abstracted data, and analyzed as proportions of the total DTN time (expressed as a decimal) with the cause(s) for the delay in t-PA administration in each case being placed in one of the three categories.

Results:
There were 171 cases of which 48 (28%) did not meet the DTN goal time of 60 minutes or less. The data indicates that the most significant barrier to a DTN of < 60 minutes is the delay between resulted labs/ CT and the delivery of TPA. The intervals were the time from CT and labs resulted to TPA delivery (.52), patient arrival to MD arriving at the bedside (.13), the time from labs being drawn to labs being resulted (.32), the time from a CT being performed to the CT being resulted (.29), the time from when a CT was resulted to when TPA was ordered (.22), and the time from when TPA was ordered to when it was delivered (.27). Once the total data set was collated, a single factor ANOVA was performed. The results indicated a significant pattern in the data, and meaningful differences between variables (p-value = 1.43E-18). Category results: Internal Process; 28 (58%), Hemodynamic ; 9 (19%), Patient/family ; 11 (23%)

Conclusion:
The data indicated the primary delay was related to Internal Process 58% (28/48). This concludes that continued vigilance on Target Stroke time sensitive Guidelines can impact the success rate of DTN < 60 minutes.
Abstract 27: Caregiver Task Difficulty and Life Changes among Stroke Family Caregivers: Comparing Caregivers with no Depressive Symptoms to those with Mild or Greater Depressive Symptoms
Authors: McLennon Susan M , Bakas Tamilyn , Jessup Nenette M , Weaver Michael T
Published: March 2022

Background/Purpose:
Identifying caregivers at risk for negative outcomes is an important part of the discharge process for stroke survivors. Screening caregivers for depressive symptoms may be one method to assess caregivers at risk for difficulty with tasks and negative life changes. The purpose of this study was to test for differences in task difficulty and life changes in caregivers with no depressive symptoms versus those with mild or greater depressive symptoms, screened with the PHQ-9 within 8 weeks after discharge.

Methods:
Telephone interviews were conducted with 176 stroke caregivers enrolled in an ongoing caregiver intervention study. Baseline data were analyzed to determine differences in Task Difficulty (OCBS) and Life Changes (BCOS) based on PHQ-9 cutoff scores (PHQ-9 < 5 no depressive symptoms, n = 90; PHQ-9 > 5 mild or greater depressive symptoms, n = 86). Differences in total OCBS and BCOS scores were analyzed using ANOVA. Response differences for individual OCBS and BCOS items were tested using exact-likelihood ratio Chi-square (Bonferroni adjusted for significance at p = .003).

Results:
There were significant differences in task difficulty (OCBS) [F(1,174) = 24.46, p < .001] and life changes (BCOS) [F(1,174) = 31.47; p < .001) in caregivers with no depressive symptoms versus those with mild or greater depressive symptoms. One half of the task difficulty and life changes items demonstrated different response patterns between groups. In the caregivers with mild or greater depressive symptoms, the most difficult tasks were performing household tasks (60%) and managing survivor behavior problems (51%). The most negative life changes were financial well-being (61%), level of energy (60%), and emotional well-being (57%).

Conclusions:
Findings support the need for assessment and treatment of stroke caregiver depressive symptoms during the early discharge period. The PHQ-9 is a useful screening tool to identify at risk caregivers. For those who score in the mild or greater depressive symptom range, assistance with the behavior problems of the survivor and helping the caregiver to manage household tasks, energy levels, emotions, and finances may be priority areas for further intervention.
Abstract 29: A New Biomarker for Diagnosis of Ischemic Stroke: Plasma Glycogen Phosphorylase-BB
Authors: Avery Ross , Caceres Juan A , Park Kwang Yeol , Lorenzano Svetlana , Pontes Neto Octavio , Siket Matthew , Ay Ilknur , Buonanno Ferdinando S , Bhat Ram , Kapetanovic Ernest , Yastas Samir , Furie Karen L , Ay Hakan
Published: March 2022

Background:
Glycogen phosphorylase-BB (GPBB) is the key enzyme that breaks down glycogen to yield glucose-1-phosphate in order to meet the emergent ATP need during cerebral ischemia. GPBB is one of the most sensitive and specific plasma markers for early detection of acute myocardial ischemia. GPBB concentration is about 100 times higher in brain than in heart. We hypothesized that plasma levels of GPBB might elevate following cerebral ischemia.

Methods:
We measured plasma GPBB levels in 172 patients with imaging-confirmed brain infarction at two time points (within 9 hours of symptom onset and at 48 hours). The control group consisted of 97 age-matched subjects without stroke. GPBB levels were determined blind to case/control assignment using a commercially available ELISA kit (Diagenics, Germany).

Results:
Baseline mean (±SD) GPBB level was 46.3 ng/ml (± 38.6 ng/ml) in cases and 4.8 ng/ml (±8.0 ng/ml) in controls (p < 0.001, Figure). GPBB levels slightly decreased from baseline to 48 hours in patients with stroke (38.7 ± 36.5 ng/ml, p = 0.02). The discriminative ability of GPBB between cases and controls as measured by the area under the Receiver Operating Characteristic (ROC) curve was high (0.95, 95% CI 0.93-0.98). GPBB level corresponding to optimal operating point on the ROC curve was 6 ng/ml. Based on the 6 ng/dl cut-off, baseline plasma GPBB showed 94% sensitivity and 90% specificity for diagnosis of ischemic stroke.

Conclusion:
Plasma GPBB appears to be a sensitive and specific marker for early diagnosis of brain ischemia. Its high proportional rise with respect to the discriminator value suggests that GPBB may find utility particularly in the diagnosis of mild ischemic syndromes associated with trace amounts of brain injury.
Abstract 3: Predictors of In-hospital Death in Patients with Acute Ischemic Stroke Treated with Thrombolytic Therapy: Paul Coverdell Acute Stroke Registry 2008-2011
Authors: Tong Xin , Yang Quanhe , George Mary G
Published: March 2022

Background:
Limited studies exist on the outcome of thrombolytic therapy of acute ischemic stroke patients, especially outside of clinical trials. This study assessed the association between in-hospital death and possible risk factors among patients who received intravenous thrombolytic therapy (IV tPA) in Paul Coverdell Acute Stroke Registry (PCNASR) between January 2008 and December 2011.

Methods:
A total of 5,766 patients with a clinical diagnosis of acute ischemic stroke and National Institutes of Health Stroke Scale (NIHSS), were treated with IV tPA within 4.5 hours after last well known time (LKW). Generalized estimating equations (GEE) modeling was used to assess the association between in-hospital death and age, gender, race, NIHSS, medical history of hypertension, myocardial infarction (MI) or coronary artery disease (CAD), heart failure (HF), diabetes, atrial fibrillation (AF), smoking and prior stroke.

Results:
Among 5,766 patients treated with IV tPA, 432 (7.5%) died. Factors associated with in-hospital death were older age (for each 1-year increment, adjusted odds ratio [AOR], 1.03; 95% CI, 1.02-1.04, p<0.0001), NIH scale score (For each 1-unit increment, AOR, 1.11; 95% CI, 1.09-1.13, p<0.001), and history of MI/CAD (AOR, 1.28, 95% CI, 1.02-1.60, p=0.03). Symptomatic intracranial hemorrhage was observed in 4.7% and life threatening/serious systemic hemorrhage in 0.8% of patients receiving IV tPA. Eighty-three percent of patients received IV tPA within 3 hours of LKW and the rates of in-hospital death and bleeding complications were not different for patients treated within 3 hours and from >3-4.5 hours.

Conclusion:
In this study of acute ischemic stroke patients, older age, NIHSS and history of MI/CAD were associated with increased in-hospital death among patients receiving IV tPA.
Abstract 36: Elevated Expression of Dual Oxidases (Duox) Under Ischemic Conditions Contributes to Oxidative Stress and Decreased Cell Viability.
Authors: Wesley Umadevi V , Ashokan Karthik , Vemuganti Raghu , Ondoma Solomon , Dempsey Robert J
Published: March 2022

Introduction:
Redox imbalance during ischemia/reperfusion Injury in the brain following focal ischemic stroke is associated with impaired neurological functions. Following ischemia/reperfusion, there is a burst of oxidative stress/reactive oxygen species (ROS). ROS physiologically serve as signaling molecules but excessive amounts of ROS contribute to destruction of endothelial integrity, blood brain barrier disruption, and neuronal cell death. NADPH oxidases (NOX) are important sources of ROS during ischemic stroke. Dual oxidases (Duox) are new members of NOX family and are known for directly generating hydrogen peroxide/ROS. Role of Duox following brain ischemic injury has been little investigated.

Methods:
Ischemia was induced by middle cerebral artery occlusion (MCAO) and reperfusion. In vitro ischemia was generated by oxygen-glucose deprivation (OGD). Expression was analysed by western blot analysis, RT-PCR, Immunofluorescence staining. ROS was measured by dichloro-dihydrofluorescein staining.

Results:
Our preliminary studies for the first time have identified that expression of Duox are spatially and temporally regulated in ipsilateral hemisphere of spontaneously hyertensive rat brains following MCAO and reperfusion. Expression of Duox 1 was up-regulated about 2 folds after 3 days, and16 folds after 7 days of reperfusion. Its expression was further increased to about 30 folds at day 21 after reperfusion. The expression of Duox 1 was specifically up-regulated in activated astrocytes and VWF and CD31 positive endothelial cells indicating its presence in blood vessels. In support of these in vivo observations, Duox1 expression was significantly increased in astrocytes and endothelial cell cultures exposed to either ATP or OGD. Duox1 expression was associated with increased ROS production and decreased cell viability. However, pre-treatment with Duox1 specific siRNA decreased the ROS production and increased the cell viability by about 30 percent.

Summary:
Up-regulation of Duox under ischemic/reperfusion conditions suggests that this enzyme potentially contributes to excessive ROS production. Further studies targeting these novel oxidases may open up a promising approach to reduce brain injury after stroke.
Abstract 44: Do the Addition of Non-Label Inclusion and Exclusion Criteria for tPA Impact U.S. Treatment Rates?
Authors: Cudlip Fern , Swatzell Victoria , Alexandrov Andrei V , Alexandrov Anne W
Published: March 2022

Background:
U.S. IV tPA treatment rates are lower than many countries, despite more than 800 certified Stroke Centers. We sought to understand if Stroke Centers utilized expanded inclusion/exclusion criteria beyond the Activase® label, and how use of these impacts treatment rates.

Methods:
U.S. Stroke Centers were invited to participate in a survey consisting of a checklist of tPA inclusions/exclusions derived from the Activase® label and stroke center websites. Data were entered and analyzed in SPSS using descriptives, Student t-test, Pearson’s correlation, and binary logistic regression.

Results:
229 responses were received from 43 states and the District of Columbia; 31% were academic medical centers, 69% were community hospitals, 92% were PSC certified. Annual ischemic strokes averaged 374+261 (median 300), with 31+41 (median 20) IV tPA cases, for an overall tPA treatment rate of 8.7% + 6.4 (median 7%). Academic hospital tPA treatment rate was significantly higher (10.8 + 7.7; median 8%; t=2.3; mean difference 2.75; p=.026, 95% CI .33-5.2) than community hospitals (8+5.9; median 6%); 24% limited treatment to 3 hours. Additional criteria beyond the Activase® label (Table 1) were reported by 81%, the most common additional inclusions were “total NIHSS > 4 points” and “occlusion on CTA;” the most common additional exclusion was “rapid improvement despite remaining disabling deficit.” As the number of non-standard inclusions/exclusions increased, the tPA treatment rate decreased (r = -.153; p=.038). Using binary logistic regression, utilization of non-standard inclusions/exclusions was predicted by hospital type, admission volume, and use of the 3 hour window (p<.0001).

Conclusions:
Custom inclusion/exclusion criteria are common and likely contribute to national treatment rates. Certifying bodies should consider requiring adherence to Activase®-label defined criteria as a method to improve tPA treatment rates.
Abstract 53: Cerebral Hemodynamic Changes in Patients with Wartime Traumatic Brain Unjury
Authors: Razumovsky Alexander , Tigno Teodore , Kouperberg Efim , Bell Randy , Severson Meryl V , Hochheimer Sven M , Marshall Scott A , Aden James , Oppenheimer Stephen M , Ecker Robert , Armonda Rocco A
Published: March 2022

Cerebral vasospasm (VSP) is a frequent complication after aneurysmal and traumatic subarachnoid hemorrhage (SAH) and carries significant morbidity and mortality. Traumatic brain injury (TBI) is associated with the severest casualties from Operation Iraqi Freedom and Operation Enduring Freedom. From Oct. 1, 2008 the US Army Medical Department initiated a transcranial Doppler (TCD) ultrasound service for TBI; included patients were retrospectively evaluated for TCD-determined incidence of posttraumatic cerebral vasospasm and intracranial hypertension after wartime TBI.

Patients were identified using a computerized registry and a prospective TCD database maintained in the Sentient NeuroCare Services. TCD recordings of mean cerebral blood flow velocities (CBFV) and Pulsatility Indices of the anterior and posterior circulation vessels were recorded using a 2-MHz transducer (Doppler Box, DWL/Compumedics, USA, Germany/Australia). Comprehensive TCD protocol was applied in all cases: if mean CBFV equaled or exceeded 100 cm/sec., 140 cm.sec and 200 cm/sec the TCD signs of mild vasospasm, moderate vasospasm and severe vasospasm respectively were considered present. 122 patients were investigated with daily TCD studies and comprehensive TCD protocol and published diagnostic criteria for VSP and raised intracranial pressure (ICP) were applied. TCD signs of mild, moderate and severe VSP involving anterior circulation vessels were observed in 71%, 42% and 16% of patients, respectively. TCD signs of mild, moderate and severe VSP involving posterior circulation vessels were observed in 57%, 32% and 14% of patients, respectively. TCD signs of intracranial hypertension were recorded in 43%, eight patients (7%) underwent transluminal angioplasty for post-traumatic symptomatic vasospasm treatment. These findings demonstrate that cerebral arterial VSP and intracranial hypertension are frequent and significant complications of combat TBI, therefore daily TCD monitoring is recommended for their recognition and subsequent management.

Acknowledgements.
The opinions and views expressed herein belong solely to those of the authors. They are not nor should they be implied as being endorsed by the Uniformed Services University of the Health Sciences, Department of the Army, Department of the Navy, Department of Defense or any other branch of the Federal government of the United States. This paper supported in part, by the US Army Medical Research and Material Command’s Telemedicine and Advanced Technology Research Center (Fort Detrick, MD, USA).
Abstract 55: Prediction of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage Using Variations of Dynamic Cerebral Autoregulation
Authors: Calviere Lionel , Nasr Nathalie , Guidolin Brigitte , Czosnyka Marek , Viguier Alain , Sol Jean-Christophe , Lagarrigue Jacques , Larrue Vincent
Published: March 2022

The risk of delayed cerebral ischemia (DCI) after cerebral aneurysm rupture is increased in patients with large cerebral artery vasospasm (VS). The predictive value of VS is, however, far to be optimal. Assessment of cerebral microcirculation impairment using dynamic cerebral autoregulation (DCA) measurement might improve our ability to predict DCI in these patients.

Methods.
We included consecutive patients with low-grade aneurysmal subarachnoid hemorrhage (SAH) (WFNS 1 to 3) within 4 days of aneurysm rupture. DCA was evaluated using the moving correlation coefficient Mx calculated from spontaneous fluctuations of cerebral blood flow velocities and arterial blood pressure. Impairment of DCA was defined as Mx ≥ 0.3. Transcranial colour-coded sonography was performed every 48 hours to look for VS. Diagnosis of VS was based on a Lindegaard ratio >3 (MCA), or mean flow velocities > 130 cm/s (ACA). DCI was defined as neurologic deterioration caused by brain ischemia confirmed by brain imaging.

Results.
Thirty patients (19 women; mean age ± SD: 44.7 ± 12.1 years) were included. Twenty (66.7%) patients had VS. DCI occurred in six (20%) patients after a median delay of 10 days (range 8 to 13 days). Mx (mean ± SD) was heightened at baseline (0.43 ± 0.2) and at day 7 (0.46 ± 0.2), then decreased at day 14 (0.37 ± 0.18 (p = 0.034). Isolated measures of VS and Mx were not associated with DCI. However, the elevation of Mx between baseline and day 7 in patients with VS was predictive of subsequent DCI (positive likelihood ratio=5.01; negative likelihood ratio=0.19; P=0.005).

Conclusion.
Findings suggest that DCA assessment may help to predict better the risk of DCI after cerebral aneurysm rupture than the simple recordings of mean flow velocities.
Abstract 72: Evolution Of Cerebral Diaschisis In Childhood Arterial Ischemic Stroke
Authors: Kirton Adam , Williams Elizabeth , Dowling Michael , Ichord Rebecca ,   PedNIHSS Investigators
Published: March 2022

Objectives:
Early diffusion MRI (DWI) demonstrates acute restriction in corticospinal pathways after arterial ischemic stroke (AIS) that correlate with outcome. DWI may also detect changes in other remote but connected brain structures in neonatal AIS. We have termed this diaschisis and hypothesized here that the same process can be measured in childhood AIS and evolves over time.

Methods:
This substudy of the Validation of the Pediatric NIH Stroke Scale study prospectively enrolled 112 children with acute AIS and both acute and early follow-up (5-14 days) DWI. Inclusion criteria here were: (1) unilateral AIS (MCA), (2) acute and subacute DWI (b=1000/1500), and (3) 12 month neurological follow-up (Pediatric Stroke Outcome Measure). A validated method using Image J software quantified DWI diaschisis in anatomically connected structures. Diaschisis measures were corrected for infarct volume, and compared to imaging timing and outcome (Chi-square/Fisher, Mann-Whitney).

Results:
Fifteen children were evaluated (60% male, median 9.3 years). Median times to MRI were 17 and 168 hours respectively. Diaschisis was common and evolved over time; observed in 1(7%) on the 1st MR but 5(33%) by the 2nd MR. Thalamic and callosal diaschisis were most common (4, 27%). Children with diaschisis tended to be younger (7.02±5.4vs11.82±4.3years, p=0.08). Estimates of perilesional diaschisis varied (54±18% of infarct volume). Most children with poor outcome had diaschisis (3/5) while most with good outcome did not (8/10,p=0.12). Corticospinal tract DWI changes correlated with motor outcome (p=0.005). Method reliability was excellent (ρ=0.99).

Conclusions:
DWI diaschisis occurs in childhood AIS. Mistaking diaschisis for new areas of infarction carries important clinical implications. Improved recognition and study are required to establish clinical relevance.
Abstract 75: Gliosis After Perinatal Stroke: Quantification And Outcomes
Authors: Kirton Adam , Shinde Siddharth , Wei Xing-Chang
Published: March 2022

Background:
Perinatal stroke diseases cause most hemiparetic cerebral palsy: Neonatal Arterial Ischemic Stroke (NAIS), arterial presumed perinatal stroke (APPIS), and periventricular venous infarctions (PVI). Gliosis, a brain reaction to injury, may be both a marker of lesion timing and a potential barrier to cell-based therapies. We hypothesized that gliosis is measureable, comparable between NAIS and APPIS, and associated with poor outcome.

Methods:
Children from the Alberta Perinatal Stroke Project were included with: (1) unilateral NAIS, APPIS, or PVI, (2) axial FLAIR MRI >24mos of age, and (3) >24mos follow-up (Pediatric Stroke Outcome Measure). Novel ImageJ software protocols quantifying gliosis were developed (Figure). Gliosis scores (GS) corrected for infarct and brain volume were compared across stroke types, and outcomes (motor, overall).

Results:
Of 149 APSP children, 39 were studied (median 10 years, 51% male). GS ranged from 19-1191 (mean 369±361) and did not correlate with age at imaging. GS were comparable between NAIS (438±171) and APPIS (444±380, p=0.97). Arterial GS tended to be higher than PVI lesions (443±337 vs 266±378, p=0.15). Arterial GS correlated with good motor outcome (705±338 vs 312±259, p=0.008) but not overall outcome (p=0.53). PVI GS were not associated with overall or motor outcome. Method reliability was excellent (ρ=0.99).

Conclusion:
MRI quantification of gliosis is feasible in children with perinatal stroke. Comparable gliosis in NAIS and APPIS provide further indirect evidence of similar perinatal timing. The association of gliosis with good motor outcome warrants further study.
Abstract 80: Amino-terminal Pro-B-type Natriuretic Peptide (NT-Pro-BNP) And Risk Of Stroke: The Reasons For Geographic And Racial Differences In Stroke (REGARDS) Cohort
Authors: Cushman Mary , Judd Suzanne E , Howard Virginia J , Thacker Evan L , Ahmed Ali , Jenny Nancy S , Kissela Brett , Zakai Neil A
Published: March 2022

Background:
Higher NT-Pro-BNP is a biomarker of cardiac dysfunction associated with risk of future heart failure and atrial fibrillation, and as such may be a marker of stroke risk.

Methods:
REGARDS enrolled 30,239 US participants in 2003-07 (41% black, 59% white, 55% living in the southeastern stroke belt). With 5.4 years follow-up, baseline NT-Pro-BNP was measured in 610 subjects with first-time stroke and a 1017 person cohort random sample free from prebaseline stroke. Cox proportional hazards models were used to calculate hazard ratios (HR) of stroke by quartiles of NT-Pro-BNP. Net reclassification improvement (NRI) was calculated using the category free NRI statistic.

Results:
Baseline NT-Pro-BNP was higher with older age, in whites, women, and with diabetes, impaired kidney function, atrial fibrillation, prebaseline heart disease, lower body-mass index and left ventricular hypertrophy by ECG. Levels were higher in those who developed incident stroke. Adjusting for age, race and sex there was an increased HR of stroke with increasing quartiles of NT-Pro-BNP (Model 1 in table); subjects in the 4
th
versus 1
st
quartile had a 3.7-fold increased stroke risk. Adjustment for income, education and traditional stroke risk factors attenuated this HR to 3.0. There was minimal impact of added adjustment for kidney function, BMI and heart failure. Associations did not differ by age, sex, race or kidney disease status. Based on NRI, predicted stroke risk was more accurate in 27% of participants if NT-Pro-BNP was measured with traditional stroke risk factors (p<0.001).

Discussion:
NT-Pro-BNP was a major risk marker for stroke and improved risk classification. By comparison, in this cohort the HRs of stroke were 1.5 for atrial fibrillation and 1.8 for hypertension. More work is needed to confirm that measuring NT-Pro-BNP improves clinical prediction scores for stroke.
Abstract 83: Long-Term Blood Pressure Trajectories and Stroke Risk
Authors: Allen Norrina B , Ning Hongyan , Lloyd-Jones Donald
Published: March 2022

Background—
Previous studies have used blood pressure (BP) measurements at a single point in time to predict future CVD outcomes. We hypothesize that long-term BP trajectories are associated with stroke risk.

Methods—
Data from 4 diverse cohorts were pooled. Each had 3+ exams where BP was ascertained and adjudicated stroke events. BP was classified into 5 categories: [1] ideal BP (<120/<80, no meds); [2] elevated BP (120-139/80-89, no meds); [3] controlled hypertension (<140/<90, treated); [4] uncontrolled hypertension (≥140/≥90, treated); and [5] untreated hypertension (≥140/≥90, no meds). BP trajectories were identified using group-based trajectory modeling. A cox proportional hazards model was used to assess BP trajectories as predictors of stroke occurrence adjusted for sex, race and cohort.

Results—
This study included 13,028 participants (52% female, 93% White, avg baseline age 53.5 yrs). Six unique BP trajectories were identified (see figure). The ideal BP trajectory (group 1) included 19.4% of the population, 18.4% experienced modest age-related increases in BP (group 2), 36.7% developed hypertension but it remained under control (group 3), 14.2% experienced an early period of uncontrolled hypertension but later maintained control (group 4), 5.9% developed hypertension early in middle-age which remained untreated until later in life (group 5), and 5.3% developed hypertension later in life but it remained untreated (group 6 ). BP trajectory was significantly associated with risk for stroke even after adjustment for demographic characteristics. As compared to the ideal BP trajectory, groups 3, 4, 5 and 6 had elevated risk for stroke, HR (95% CI) 1.55 (1.33-1.81), 3.00 (2.45-3.69), 2.99 (2.39-3.75) and 2.18 (1.76-2.71), respectively.

Discussion—
Long-term trends in BP are associated with the risk for stroke. Risk prediction algorithms should take long-term BP trajectories into account in order to identify individuals at high risk for stroke.
Abstract 89:
Bdnf val66met
polymorphism is Associated with Enhanced Motor Recovery Following Stroke
Authors: Qin Luye , Jing Deqiang , Parauda Sarah , Ratan Rajiv , Lee Francis S , Cho Sunghee
Published: March 2022

Background and Purpose:
Genetics is one of several key factors that influence stroke recovery. A single nucleotide polymorphism (SNP) of the
bdnf
gene (Val66Met) is common in humans, ranging from 20-30% in Caucasians up to 70% in the Asian population. Previous studies show several disadvantages to carrying this allele in humans. However, the high rate of SNP occurrence raises the intriguing possibility of a selective advantage to carrying the Met allele, such as motor function. The current study investigates the impact of
bdnf val66met
SNP on long term recovery after stroke.

Methods:
Mice with a genetic knock-in of the human BDNF variant (val66met) were generated. Adult male BDNF
+/+
(WT) and BDNF
Met/Met
(M/M) mice were subjected to the proximal middle cerebral artery occlusion. Motor and gait functions were assessed by rotarod and Catwalk analysis at acute phase and recovery phase. Anatomical volume analysis was evaluated by cresyl violet and Golgi staining at 6 months after stroke.

Results:
As previously reported (Qin et al., 2011), there was greater acute impairment in motor behavioral outcomes in M/M mice after stroke, compared to WT mice. However, M/M mice displayed significantly enhanced rotarod performance at 2 weeks and the enhancement was sustained up to 6 months post-stroke. Similarly, Catwalk gait analyses in swing speed and stride length showed that M/M mice exhibited enhanced gaits (i.e. faster and longer stride) than WT mice during long-term recovery phases, especially in the ipsilesional right hind limb. Since ipsilesional limbs are controlled by the contralesional hemisphere, sub-regional volumes in this hemisphere were assessed. M/M mice showed specifically increased striatal volume at 6 months post-ischemia. The increased striatal volume was also associated with higher dendritic complexity of medium spiny neurons in this region, which indicated that the contralesional anatomical plasticity may account for enhanced motor recovery in MM mice.

Conclusions:
The findings suggest that BDNF SNP may have selective advantage in enhancing motor/gait function through the contralesional hemisphere during stroke recovery. The study has clinical importance by providing a means to predict the course of stroke recovery based on an individual’s SNP.
Abstract 9: Perfusion-based Selection Leads To Improved Outcomes Compared With Time-based Selection For Endovascular Reperfusion Therapy In Acute Ischemic Stroke
Authors: Prabhakaran Shyam , Soltanolkotabi Maryam , Bernstein Richard A , Alberts Mark J , Curran Yvonne , Bergman Deborah , Lee Vivien H , Conners James J , Shaibani Ali , Hurley Michael C , Ansari Sameer
Published: March 2022

Background:
Controversy exists on the role of perfusion imaging-based selection of patients with acute ischemic stroke (AIS) for endovascular reperfusion therapy (ERT). We hypothesized that perfusion imaging based selection would improve functional outcomes at 3 months compared to time based selection alone.

Methods:
We reviewed consecutive patients with anterior circulation strokes, baseline NIHSS score > 8, and treated with ERT at 4 centers between 2006 and 2011. Data were collected on demographics, initial NIHSS score, intravenous tissue plasminogen activator (IV tPA), use of perfusion imaging (CT or MRI), time from onset to groin puncture, reperfusion grade using the modified TICI scale, symptomatic hemorrhage, and functional outcome using the modified Rankin Scale (mRS) at 3 months. Using univariable statistics and multivariable logistic regression, we assessed whether patients who underwent perfusion imaging had better outcomes than those selected based on time alone.

Results:
One-hundred eighty-five patients (mean age 66.7 years; median NIHSS score 19; MCA occlusion 73% and ICA occlusion 27%) were included. TICI 2b or 3 reperfusion grade was achieved in 49.7% while symptomatic hemorrhage (PH1, PH2, or perforation) occurred in 10.8%. Perfusion imaging was used in 69 (37.3%) patients (45 CT and 24 MRI) and was associated with increased onset-to-groin puncture time (359 vs. 298 minutes, P=0.019). Patients who underwent perfusion imaging were also older (73 vs. 63 years, P<0.001). Overall, good outcome (mRS 0-2) at 3 months was seen in 41.7% of patients. Those who underwent perfusion imaging were more likely to have good outcomes (53.6 vs. 34.5%, P=0.011). In multivariable analysis, perfusion imaging remained a predictor of good outcome (adj. OR 2.35, 95% CI 1.17-4.72), independent of initial NIHSS score, TICI 2b or 3 reperfusion, and IV tPA use.

Conclusions:
In this multi-center observational study, patients with AIS who underwent perfusion imaging were over 2-fold more likely to have good outcomes following ERT despite a delay in time to treatment and advanced age compared to time-based selected patients. Further studies should continue to address the optimal perfusion imaging criteria for patient selection for ERT.
Abstract 92: Understanding The Impact Of Anesthetics On Ischemic Cortical Damage By Inducing Stroke In Awake, Freely Moving Mice
Authors: Brown Craig E , Swan Ian , Delaney Kerry
Published: March 2022

Anesthetics such as isoflurane are commonly used to sedate experimental animals during the induction of stroke. However, there is an abundance of data showing that anesthetics modulate brain excitability, blood flow and vascular tone. Given these diverse effects, it begs the question of to what extent do anesthetics modulate ischemic damage and functional outcome? To better understand the effect of isoflurane on stroke outcome, we developed a protocol for inducing photothrombotic cerebral ischemia in an awake, unanesthetized mouse. This protocol involves temporary attachment of a 1mm diameter plastic fiber optic cable to a previously implanted Luer lock headmount for delivery of photoactivating green laser light (532nm, 1100 mW/cm
2
) for 15 minutes to the forelimb somatosensory cortex. Evidence for compromised forelimb use is observed within 2 minutes of illumination onset. Histological assessment of ischemic damage and behavioural tests of functional outcome are being examined at different times following stroke induction in awake versus 1.5% isoflurane anesthetized mice. Our preliminary results suggest that infarct volume at 1 and 7 days post-stroke is significantly increased in awake relative to anesthetized mice (
1 day
= 3.4mm
3
± 0.6 vs. 2.03mm
3
±0.39;
7 days
= 2.97mm
3
+/-0.36 vs. 1.97mm
3
+/-0.19, respectively). Consistent with larger infarct volume, mice that were awake during stroke induction show greater and more persistent deficits in sensory function of the affected forepaw. These experiments will enhance our understanding of whether anesthetics modulate ischemic damage. Further, our simple method for inducing stroke in awake, freely moving animals might be useful for future neuroprotective studies that wish to avoid the potentially confounding effects of anesthetics or examine state-dependent modulation of ischemic damage (e.g. sleep, exercise).
Abstract NS10: Development of a Comprehensive Stroke Center Electronic Medical Records Navigator: Experience in one Academic Stroke Center
Authors: Bell-Stephens Teresa E , Baumann JJ , Kerr Alison , Taylor Connie , Fleck Nanci , Heldenbrant Laura , Marcellus Mary , Gidwani Risha , Choudhri Omar , Casal Stephanie , Vavao Joli A
Published: March 2022

Electronic medical records (EMR) have become the standard of care for documentation in today’s health care settings. The EMR system allows for standardization of care and widespread access to information with ability to subsequently evaluate that care. Additionally, trends are more easily documented and monitored. Development of a stroke specific EMR system for a comprehensive stroke center (CSC) was the goal from the initiation of our multidisciplinary steering committee. Our center enlisted the stroke nursing and physician teams, administration, health services researcher, quality and clinical informatics teams to develop an EMR navigator tool based on guidelines from the American Heart/Stroke Association (AHA/ASA) in anticipation of being an early CSC. It was designed to be used for all patients with a diagnosis of stroke during hospitalization. The informatics team developed a method to capture proposed CSC metrics and quality indicators. Progress notes were developed to auto populate necessary data using a specific template. Order sets were standardized according to AHA/ASA guidelines. Discrete fields were built into the EMR to ensure data could be automatically aggregated to evaluate quality-of-care for all stroke patients without requiring chart review. Efforts were made to ensure ease of use and efficiency while preventing errors. The navigators were designed to allow for reports required by Joint Commission to be more readily run on a regular and ongoing basis. Clinical informatics worked with representatives from EPIC to develop custom code for unique situations such as “door to needle time,” as required by Joint Commission. Smart phrases were identified when able, but minimized to prevent duplicity and erroneous assessment and documentation. Stroke patients often require complex interdisciplinary team care. Having a stroke navigator EMR in place enables all health care providers to have consistent access to information at hand to improve our ability to provide comprehensive care. Cues for care can be provided, improving safety and preventing errors. It also enables standardization of data extraction with ability to track progress between notes and trend data in spread sheet format.
Abstract NS15: Behavioral Outcomes in Pediatric Stroke: Emotional Changes and Depression in the Pediatric NIH Stroke Scale Cohort
Authors: Plumb Patricia , Dowling Michael M , Stavinoha Peter , Robertson Brian , Hynan Linda S , Bastian Rachel , Abraham Lisa , Askalan Rand , Benedict Susan , Bernard Timothy , Beslow Lauren , deVeber Gabrielle , Friedman Neil , Fullerton Heather , Jordan Lori , Kan Li , Kirton Adam , Amlie-Lefond Catherine , Licht Daniel , Lo Warren , McClure Chalmer , Pavlakis Steve , Smith Sabrina E , Tan Marilyn , Kasner Scott , Jawad Abbas F , Ichord Rebecca N
Published: March 2022

Background and Purpose:
Stroke affects 2-13/100,000 children annually and ranks among the top ten causes of childhood death with long-term deficits in 40-60% of survivors. Parents report behavioral changes, such as short temper, irritability, or symptoms of depression. Using data collected in the multicenter study to validate the Pediatric NIH Stroke Scale, we report the prevalence and factors associated with emotional changes and depression following childhood stroke.

Methods:
Children 2-18 years old with arterial ischemic stroke were prospectively enrolled over 34 months at 15 sites with daily PedNIH Stroke Scale examination. Outcomes were assessed by Pediatric Stroke Outcome Measure (PSOM) at 3 and 12 months. Parents reported the presence or absence of emotional changes or depression. Hemispheric localization and vascular distribution was determined by MRI. Associations were evaluated by logistic regression.

Results:
105 children were enrolled (mean age 10.4y, 63% male). Emotional changes were reported in 39/93 (42%) at 3m and 28/78 (36%) at 12m. Depressive symptoms were reported in 13/93 (14%) and 11/80 (14%) at 3 and 12m, respectively. Among those with data at both timepoints, emotional changes present at 3m resolved at 12m for 9/30 (30%) and 6/41 (15%) of those initially without changes at 3m, developed emotional changes at 12m. Symptoms of depression resolved at 12m in 7/12 (58%) with symptoms at 3m, while 5/60 (8.3%) of those without symptoms at 3m reported depressive symptoms at 12m. In multivariate analyses, only PSOM, and not gender, hemispheric lateralization, vascular distribution, or PedNIHSS were predictive of emotional changes or depressive symptoms.

Conclusions:
Behavioral changes affect a large proportion of children after stroke. In multivariate analysis, parent-reported emotional changes and depression correlated with physician scored severity (PSOM). Behavioral assessment of pediatric stroke survivors and parental education is needed as children encounter emotional struggles in recovery. These potentially treatable behavioral changes could impede therapy and inhibit maximal recovery.
Abstract NS16: The Discriminant Validity of the AD8 in Detecting Post-stroke Vascular Cognitive Impairment
Authors: Dong Yanhong , Pang Wan Shin , Chan Bernard P , Sharma Vijay K , Venketasubramanian Narayanaswamy , Chen Christopher
Published: March 2022

Background:
The AD8 is an informant-based brief cognitive screening instrument, which can be administered to the patient in the absence of an informant in detecting patients with dementia at the memory clinic or in the community. However, its discriminant validity in detecting post-stroke Vascular Cognitive Impairment (VCI) has not been reported.

Purpose:
Our aims were to examine the discriminant validity of the AD8 for the detection of VCI by comparing the AD8 (both informant-rated and patient-rated) to the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE).

Method:
Patients with ischemic stroke and TIA were recruited from the stroke neurology service of the National University Health System in Singapore. Their consensus diagnoses of VCI and no cognitive impairment (NCI) were established by clinical assessment including formal neuropsychological evaluation and neuroimaging according to the internationally accepted criteria. Patients received the AD8, MMSE and MoCA whilst their informants received AD8. Area under the receiver operating characteristic curve (ROC) analysis was employed to examine the discriminant validity of the informant AD8 in detecting VCI.

Results:
Sixty patient-informant dyads were recruited (34 VCI and 26 NCI). There were no significant differences in age between patients with VCI and NCI (69.5 ±9.4 vs 66.8±6.8, p>.05). Informant AD8 had shown a trend of superior discriminant validity compared to patient AD8 in detecting VCI (Area Under the Curve (95% Confident Interval): .81 (.70- .93), .67 (.54- .81), p=.06). At the respective optimal cutoff points, the informant AD8 (≥1) had acceptable sensitivity and specificity whilst the patient AD8 (≥3) had poor sensitivity and good specificity (sensitivity: .79 vs .32; specificity: .73 vs .96, correctly classified 76.7% vs 60.0%). In addition, the informant AD8 was equivalent to the MMSE and inferior to the MoCA in detecting VCI.

Conclusions:
The informant AD8 has demonstrated a trend of superior discriminant validity compares to the patient AD8 in detecting post-stroke VCI. Stroke nurses may adopt this brief instrument for targeted cognitive screening of older patients with stroke/TIA.
Abstract NS18: The Impact of Subtle but Significant Executive Function Deficits in Persons with Very Mild Ischemic Stroke
Authors: Morrison M. T , Giles Gordon M , Baum M. C , Ryan Jennifer R , Polatajko Helene , Dromerick Alexander W , Edwards Dorothy F
Published: March 2022

Background:
Executive functions (EF) are essential for independence and engagement in complex activities. Neuropsychological and functional evaluations of stroke outcome may be insensitive to subtle EF deficits present in mild stroke (mCVA) despite low NIHSS scores and excellent outcome based on the Barthel Index (BI>95) and Modified Rankin Scale (MRS< 1). We evaluated EF deficits in 25 individuals with first mCVA (admission NIHSS < 5) and 21 matched controls on the Multiple Errands Test-Revised (MET-R).

Methods:
Inclusion criteria: age > 18 years, first clinical stroke, functional independence (pre-stroke BI >95 and MRS < 1) and community residence at admission and 6 month follow-up. Demographic and clinical information were obtained at acute admission to acute neurology stroke service. Stroke was confirmed by a neurologist and acute imaging reviewed to score stroke lesions and location and white matter disease. Six month follow-up included a neuropsychological test battery, self-reported outcomes by the Stroke Impact Scale (SIS) and Reintegration to Normal Living Scale (RNLI) and the MET-R, a performance test previously used with TBI. The MET-R is a timed test which requires following standard instructions and rules while performing multiple tasks in a real-world environment.

Results:
Sample mean age was 60 ± 10.8 years; 65% female and 30 % Black, with no significant demographic differences between groups. The mCVA group reported SIS Global Recovery Scores of 68 ± 21.6, Participation Scores of 73.8 ±24.1 and Memory Scores of 77.2 ± 17.5. Differences between controls and the mCVA group were significant for MET-R sub-scores including: Tasks Completed (p<0.0001), Rules Broken (p<0.001), and Performance Efficiency (p <0.002). Poor performance on the MET-R was associated with lower SIS scores and lower life satisfaction and measured by the RNLI.

Conclusion:
Persons with Persons with mCVA lacking obvious cognitive or motor impairments may be discharged home without rehabilitation or support because currently available measures are inadequate to identify the presence of EF deficits. Subjective complaints of difficulty with cognitively demand activities at follow-up should be evaluated. Rehabilitation can effectively address these deficits.
Abstract NS9: Symptom Onset to ED Arrival Time Decreases with a Simple Public Education Campaign
Authors: Constable Mark , Gentry Candace , Zhao Yanfang , Goldstein Larry , Prvu-Bettger Janet
Published: March 2022

Background:
Most patients with acute ischemic stroke arrive at an Emergency Department (ED) too late to be eligible for treatment with IV t-PA. Educational programs have had variable success in improving public knowledge of stroke symptoms and the need to call 9-1-1 for expedited hospital transport. Duke University Hospital (DUH) implemented a 3-month long campaign of stroke-related educational signs on city buses and full page news print advertisements in Durham County, NC between May 1 and July 31, 2010. Education was focused on stroke symptoms and 9-1-1 activation. This study determined if there was a change in symptom onset to ED arrival time associated with the educational intervention.

Methods:
Patients with acute stroke/TIA arriving at Durham’s tertiary care hospital (DUH) were identified based on ED ICD-9 CM codes (430-436). We measured symptom onset to arrival delay during the 6-months before and after the educational campaign for Durham residents (based on residence zip codes) compared to controls (non-residents who were transported from adjacent counties).

Results:
The study sample included 270 patients with an ED encounter for ischemic stroke/TIA (112 Durham County residents and 158 non-residents). The mean symptom onset to ED arrival time decreased from 278.3(+ 464.4) min before to 229.6 (+314.8) min after the campaign for Durham County residents, whereas the delay increased from 329.5 (+346.5) min to 410.4 (+472.2) min for non-residents over the same period.

Conclusion:
These data suggest that a simple public educational campaign can have a meaningful impact on reducing delays between symptom onset and ED arrival, potentially increasing the numbers of stroke patients eligible for treatment with IV-tPA.
Abstract TMP10: A 4D Patient-specific Metamorphosis-based Method to Model Ischemic Stroke Lesion Evolution from Acute Diffusion-weighted to Final T2-defined Outcome
Authors: Rekik Islem , Allassonnière Stéphanie , Carpenter Trevor K , Wardlaw Joanna M
Published: March 2022

There is considerable interest in how well acute DWI can predict the infarct on final T2-w imaging at >1month after stroke. We estimated the 4D dynamic change, from the acute DWI to the final T2-w lesion, to assess DWI predictive ability. Our model dynamically simulates the evolution of uni- or multi-component lesions.

We applied a 4D metamorphosis, modeling the morphogenesis of the acute (<6hr) DWI lesion boundary into that of the final (90 day) T2-w in 10 representative patients, dividing the 90 days into 10 equal intervals. We estimated the mean contraction and expansion deformation velocities that drive change in the acute DWI to the final T2-w boundary, focusing on areas where the DWI volume differed from the final T2-w volume (DWI\T2).

In DWI\T2, over the 10 patients, time-evolving contraction velocity values show a rapid decrease from 0.206+/-0.0091 (mean over time, mm/9days +/- sd) to 0.00097+/-0.001 with time, indicating that contracting DWI\T2 areas were very dynamic acutely and rapidly slowed. Expansion areas displayed a rapid and quasi-monotonic fall from 0.025+/-0.01 to 0.00075+/-0.00028 showing that some parts of DWI tissue had an early high expansion velocity which slowed with time, leading to appearance of newly infarcted areas not present in the acute DWI. A high correlation index (r=0.72, p<0.001) between contraction (also expansion) velocity curves of all patients shows that the 4D evolution patterns of DWI\T2 were similar between patients.

Our imaging derived 4D model of acute DWI-final T2-W lesion evolution shows a consistent pattern, with both ‘recovery’ and ‘new’ infarct happening rapidly at early time points. This confirms that a) acute DWI lesion includes salvageable tissue and is not all statically dead, b) acute DWI lesion does not include all final T2-w dead tissue and c) the method can accurately assess and quantify early treatment response, eg in clinical trials.