bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP39: Increasing the Amount of Upper Extremity Rehabilitation in the First Four Weeks Following Stroke: A Feasibility Study
Authors: McDonnell Michelle N , Serrada Ines , Hillier Susan L
Published: June 2021

Background and purpose:
Recovery of early voluntary finger extension is an important predictor of recovery of upper extremity (UE) function, but the intensity of UE rehab is reported to be low during the acute stage post stroke. This may be the period of greatest neuroplasticity, where intensive rehabilitation may have greater gains. The aim of this study was to examine the feasibility of implementing an intensive evidence-based UE rehabilitation program in the first four weeks post stroke.

Methods:
Twenty participants were recruited to the study 5 ± 4 days after a first-ever stroke. All participants received usual physical and occupational therapy. Those randomly allocated to the intervention group received a supplementary program based on an evidence-based algorithm, which was monitored and progressed weekly by an experienced physiotherapist. Participants were asked to perform this for 60 mins/day for four weeks, supervised and assisted as necessary by a carer or therapy assistant. Accelerometers were used to measure changes in real-world use of the affected UE, in addition to the Action Research Arm Test and Motor Activity Log to record arm activity. Interviews were conducted to explore acceptability for participants and their carers.

Results:
Two patients were withdrawn due to medical issues, but there were no adverse events from the intervention. All measures improved significantly over time, with no between-group difference. Accelerometry measures correlated strongly with the ARAT, at baseline and post-intervention (e.g. use ratio and ARAT post-intervention, Pearson’s r = 0.86, P < 0.001).

Conclusion:
Additional evidence-based therapy was feasible and acceptable in the acute setting, but there was no superior effect in this pilot group. This study confirms the strong relationship between objective measures of acceleration and self-reported and clinical measures of UE activity in the acute setting post-stroke.
Abstract TMP42: Safety and Efficacy of High-dose OnabotulinumtoxinA for Post-stroke Upper Limb Spasticity: Results of a Double-blind, Placebo-controlled Trial
Authors: Patel Atul T , Geis Carolyn , Alter Katharine , Pan Grace , Thorpe Adele , James Lynn , Dimitrova Rozalina
Published: June 2021

Introduction:
OnabotulinumtoxinA (onabotA) is approved for treatment of post-stroke upper limb spasticity (PSULS) at a maximum dose of 400U across elbow, wrist, and finger sites. Safety and efficacy of a higher dose for PSULS were evaluated in elbow and shoulder sites not previously assessed.

Methods:
A multicenter, double-blind, randomized, placebo-controlled study evaluated a single treatment of onabotA 300U (150U: elbow flexors; 150U: shoulder adductors) or 500U (250U; 250U) vs placebo in adults with PSULS (Modified Ashworth Scale [MAS] score ≥3). Safety and efficacy were assessed at weeks 2, 4, 6, 8, and 12. The study was terminated early for administrative reasons.

Results:
All 53 enrolled patients completed the study. Baseline characteristics were similar between groups, except the onabotA 500U group had more men. Most patients were Caucasian and had a cerebral ischemic stroke of moderate severity (mean=101.7 months before enrollment). Mean change from baseline in elbow MAS for onabotA 500U was significantly greater than placebo at all time points (300U at wks 2 and 4,
Figure 1)
. Significant tone reductions were also observed in the shoulder adductors with 500U (wks 2 and 4). The proportion of treatment responders (≥1-grade reduction in elbow MAS) was numerically greater for onabotA 500U and 300U than placebo at all time points (300U significant [
P
<0.05] at wks 2, 4, and 8). CGI generally improved more with onabotA than placebo (not significant). AEs were typically mild/moderate, not related to treatment, and occurred in a similar proportion of both onabotA dose groups and a greater proportion of the placebo group (300U, 27.8%; 500U, 29.4%; placebo, 50%).

Conclusions:
Preliminary results from this randomized trial investigating the safety and efficacy of higher-dose onabotA for elbow and shoulder spasticity indicate a dose-related benefit. At the higher dose of 500U onabotA, no new safety signals were observed; AEs did not appear to be dose-related.
Funding:
Allergan
Abstract TMP69: Incidence of Intracranial Hemorrhage After Intravenous Thrombolysis in Telestroke
Authors: Herial Nabeel A , Fitchett Evan M , DePrince Maureen , Labella Giuliana , Bekelis Kimon , Reynolds Matthew , Jabbour Pascal M , Rosenwasser Robert H , Tjoumakaris Stavropoula I
Published: June 2021

Background:
Promoting intravenous tissue plasminogen activator (IV tPA) in treating eligible patients with acute ischemic stroke (AIS) is critical in reducing overall stroke burden. Effective telestroke networks are proven to facilitate higher rates of IV tPA use. Increasing data on stroke outcomes continues to emerge with expansion of telestroke services nationwide.

Objective:
To estimate the incidence of intracranial hemorrhage (ICH) in AIS patients treated with IV tPA via telestroke evaluation.

Methods:
In this study, data from a large telestroke network comprising 36 hospitals from 3 States and associated with a university-based health system and comprehensive stroke center was utilized. Data included total of 3198 acute telestroke evaluations performed within the network between January 2014 and June 2016. Distance of spoke hospitals from the hub ranged between 2.5 and 125 miles. All telestroke consultations were done using the remote presence robotic technology. 15% of all telestroke evaluations and 51% of post-IV tPA patients were transferred to the hub. CT imaging was used for identification and ICH as defined mainly in the NINDS trial was used for comparison.

Results:
Mean age of patients was 67 years (sd=16) and majority were women (n=1759, 55%). Average NIHSS score at presentation was 7. IV tPA was administered to 18% of all telestroke patients. Post IV tPA, any ICH (symptomatic or not) was noted in 8.7% of patients. Petechial hemorrhage was most frequently reported finding. Rate of any ICH in our telestroke population was relatively lower compared to the ECASS II (39%, p<0.001), ECASS III (27%, p<0.001), SITS-MOST (9.6%, p=0.63), ATLANTIS (11.4%, p=0.30), and higher than the NINDS (6.4%, p=0.29).

Conclusions:
Higher rate of IV tPA use and lower rate of hemorrhagic complication observed in this large study further supports and strengthens the role of telestroke technology and expertise in treatment of AIS.
Abstract TP418: Red Blood Cell Transfusion Increases Cerebral Oxygen Delivery After Subarachnoid Hemorrhage Regardless of Hemoglobin Level
Authors: Dhar Rajat , Zazulia Allyson , Videen Tom , Derdeyn Colin P , Diringer Michael
Published: June 2021

Introduction:
Impaired oxygen delivery (DO
2
), as a result of reduced cerebral blood flow (CBF), is the hallmark of delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). Anemia further contributes to reductions in DO
2
and places the brain at risk for infarction. Transfusion, by raising hemoglobin (Hgb) and oxygen content of arterial blood, may be able to reduce the risk of ischemia. However, it is unknown whether an Hgb threshold exists above which CBF will fall sufficient to negate any benefit of transfusion on DO
2
. In this physiologic proof-of-principle study we evaluated whether transfusion improves DO
2
and reduces brain vulnerable to ischemia across a broad range of Hgb values.

Methods:
47 SAH patients with/at-risk for DCI with Hgb 7-13 g/dl were transfused 1 unit of red blood cells (RBCs).
15
O-PET imaging was used to measure CBF, DO
2
, and oxygen extraction fraction (OEF) before and after transfusion. Vulnerable brain regions were defined as those with baseline DO
2
< 4.5 ml/100g/min (equivalent to CBF of 25 ml/100g/min at low-normal Hgb).

Results:
Baseline Hgb was 9.7 g/dl (range 6.9-12.5) and CBF was 43±11 ml/100g/min. After transfusion, Hgb rose by 12% and global DO
2
by 10% (from 5.0 to 5.5 ml/100g/min, p=0.001), with CBF only marginally lower; response to transfusion was not dependent on Hgb level. Transfusion resulted in a greater (16%) rise in DO
2
, associated with a larger reduction in OEF, in vulnerable brain regions (p=0.005 for low vs. normal regions), even after adjusting for Hgb. Number of vulnerable regions was reduced from median 9 to 4 per patient (p=0.005).

Conclusions:
Transfusion of RBCs to patients at-risk for DCI improves cerebral oxygen delivery, preferentially to vulnerable regions and reduces brain at-risk for ischemia. This physiologic benefit does not appear limited to those with severe anemia but persists to Hgb as high as 13 g/dl. Our findings suggest that restrictive transfusion practices may not be appropriate in this population. Prospective trials are needed to determine if these physiologic benefits outweigh risks of transfusion and translate into clinical prevention of DCI.
Abstract TP421: Admission Neutrophil-Lymphocyte Ratio Predicts Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage
Authors: Dodson Vincent , Wasjwol Ethan , Al-Mufti Fawaz , Amuluru Krishna , Elghanem Mohammad , Thabet Ahmad , Nuoman Rolla , Singh Paul , Prestigiacomo Charles , Gandhi Chirag
Published: June 2021

Introduction:
Immune dysregulation has long been implicated in the development of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). The neutrophil-lymphocyte ratio (NLR) is an established prognostic marker in patients with cancer, cardiac disease, or sepsis. This study sought to determine whether there is a relationship between NLR and DCI in SAH patients.

Methods:
We evaluated 340 aneurysmal SAH patients between 2002 and 2015 enrolled into a single center, retrospective, observational cohort study. Admission NLR was analyzed using a ≥10 cutoff. DCI from cerebral vasospasm was defined as (1) clinical deterioration (i.e., a new focal deficit, decrease in level of consciousness, or both), and/or (2) a new infarct on CT that was not visible on the admission or immediate postoperative scan, when the cause was thought by the research team to be vasospasm. Logistic regression models were generated.

Results:
We found that 132 (39%) patients had an admission NLR ≥ 10. Admission NLR predicted development of DCI (OR: 1.7; 95% CI: 1.1- 2.5, p=0.008) after controlling known predictors including age and incidence of rebleed.

Conclusions:
This study shows that the admission NLR provides further evidence to the association between inflammation and DCI. Admission NLR is a readily available biomarker that may be a clinically useful tool for prognostication when evaluating SAH.
Abstract TP422: Platelet Transfusion In Patients Presenting With Aneurysmal Subarachnoid Hemorrhage Does Not Improve Outcome
Authors: Sultan-Qurraie Ali , de Havenon Adam , Lynch John , Tirschwell David , Lazzaro Marc , Fred-Fitzsimmons Brian
Published: June 2021

Introduction:
The effect of platelet transfusion (PT) has been studied in patients with intracerebral hemorrhage, but has not been reported for aneurysmal subarachnoid hemorrhage (aSAH). We investigated the effect of PT on the outcome of patients with aSAH.

Methods:
We retrospectively evaluated 84 patients admitted with aSAH to a Comprehensive Stroke Center in the United States between 2011 and 2015. Charts were reviewed for variables including length of hospitalization, 3-month modified Rankin Scale (mRS), and complications related to endovascular treatment of cerebral aneurysm. Intergroup differences were evaluated with the Chi-squared and Student’s t-test. mRS was evaluated using multivariate ordinal logistic regression. Variables with a univariate p-value <0.2 association with 3 month mRS were included in the ordinal logistic regression model.

Results:
Patient demographics and clinical variables are seen in Table 1. 30% of patients received PT. PT was associated with male gender, Hunt-Hess score, Fisher Score, external ventricular drain placement, and longer hospital length of stay. After multivariate ordinal regression, PT was associated with higher mRS and there was a trend for association with Hunt-Hess score (Table 2).

Conclusion:
Our findings suggest that platelet transfusion is common in patients presenting with aSAH. Platelet transfusion in these patients is associated with longer hospital stay and a significantly lower rate of good clinical outcome, with a nearly 4- to 6-fold higher odds of a one-point increase in mRS at 3 months. The association of platelet transfusion to worse outcome in patients with aSAH warrants further study.
Abstract TP424: Re-bleed in Nontraumatic Convexity Subarachnoid Hemorrhage
Authors: Harris Jennifer , Forman Rachel , Conners James , Garg Rajeev , John Sayona , Lee Vivien
Published: June 2021

Introduction:
Re-bleeding can have significant adverse consequences, but has not been well described in isolated nontraumatic convexity subarachnoid hemorrhage (cSAH), and therefore we sought to report the clinical spectrum of re-bleed in this population.

Methods:
With IRB approval, we retrospectively reviewed consecutive nontraumatic cSAH admitted to our institution from August 1, 2006 to June 1, 2016. cSAH was defined as radiographic hemorrhage isolated to the convexities, without cisternal component. Trauma was excluded. Data was abstracted on demographics, medical history, neuroimaging, etiology, and clinical presentation. Good clinical outcome was defined as modified rankin score of 0-2 at 3 months.

Results:
Among 93 cSAH patients, re-bleed occurred in 9 (10%) patients. The mean age of patients with re-bleed was 55.6 years (range, 24-68) and 8 (89%) were women. The majority 6 (67%) were Hispanic. Most patients 8 (89%) presented with severe headache. The etiology of cSAH was reversible cerebral vasoconstriction syndrome (RCVS) in 6 (67%), amyloid angiopathy in 1 (11%), cerebral venous thrombosis (CVT) in 1 (11%), and post-procedural related in 1 (11%). Initial re-bleeding was new remote subarachnoid hemorrhage in 1 (11%) and new intracerebral hemorrhage in 8 (89%). Clinical symptoms of initial re-bleeding included isolated worsening headache in 2 (22%), focal neurological deficits in 4 (44%), and no clinical change in 3 (33%). Time from initial neuroimaging documenting cSAH to CT documenting re-bleed was 40 hours (range, 5 - 74), and re-bleed occurred within 60 hrs in most patients (89%). Two patients had subsequent re-bleeding (due to CVT and RCVS) documented at 1.9 and 11.8 hours after the initial re-bleed CT. Good clinical outcome was seen in 7 (78%) .

Conclusion:
Re-bleeding was seen in 10% of cSAH patients and in the majority of patients occurred early, within 2.5 days. Clinicians should be aware of this potential complication of cSAH.
Abstract TP427: National Estimates of Recurrent Intracranial Hemorrhage Among Patients with Ruptured Intracranial Aneurysms: Effect of Treatment Modality
Authors: Chaudhry Saqib A , Afzal Mohammad R , Chaudhry Burhan , Rehman Haseeb , Riaz Ahmed , Saeed Ali , Safdar Adnan , Kassab Mounzer , Qureshi Adnan
Published: June 2021

Background:
The estimates of recurrent intracranial hemorrhage in post hospitalization period among patients treated for ruptured intracranial aneurysms are not available outside clinical trials.

Objective:
To determine the rates of recurrent intracranial hemorrhage related hospitalization within 1 year post hospitalization for treatment of ruptured intracranial aneurysm in a nationwide cohort of patients admitted for subarachnoid hemorrhage (SAH).

Methods:
We identified all readmissions related to new SAH or intracerebral hemorrhage in the nationally representative data for all patients hospitalized for SAH using the Nationwide Readmissions Database (NRD) 2013 who had undergone endovascular or surgical treatment.. Cox proportional hazards analysis was used to assess the relative risk (RR) of recurrent intracranial hemorrhage for patients in treatment cohorts after adjusting for potential confounders. The 1-year survival was estimated for both treatment groups by using Kaplan-Meier survival method.

Results:
A total of 5,844 patients with SAH were treated with either endovascular (n = 2,843, 48.6%) or surgical treatment (n = 3000, 51.4%).The rate of all-cause in-hospital mortality (10.2% vs 12.1%, P = 0.1895) was similar among patients treated with surgical or endovascular treatment. The estimated 1-year recurrent intracranial hemorrhage survival was 99.5% and 97.4% in patients who underwent surgical and endovascular treatments, respectively (p= <.0001). After adjusting for age, and All Patient Refined DRGs (APDRG) severity score, the RRs of recurrent any intracranial hemorrhage was higher with endovascular treatment (RR, 6.0; 95% confidence interval (CI), 2.3 -15.7 p= 0.0002). The rates of SAH (RR, 6.1; 95% CI, 2.1 -17.9 p= <.0001) was significantly higher and a trend was observed for higher rate ofintracerebral hemorrhage (RR, 6.2; 95% confidence interval, 0.7 -52.5 p=0.0940) among patients treated with endovascular modality. .

Conclusion:
Although the rates of recurrent intracranial hemorrhage related hospitalization were low among patients with ruptured intracranial aneurysms, there was a higher rate among patients treated with endovascular treatment.
Abstract TP449: Clinical and Angiographic Outcomes From Combined Direct and Indirect Bypass in Adult Patients with Moyamoya Disease: A Retrospective Study of 76 Procedures
Authors: Zhao Jinbing , Liu Hongyi , Zou Yuanjie , He Shengxue
Published: June 2021

Objective:
Surgical revascularization is the mainstay of treatment for moyamoya patients. This study was to evaluate the progonosis of combined direct and indirect procedure for moyamoya disease patients.

Methods:
76 cerebral hemispheres from 64 adult moyamoya patients undergoing combined superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-myo-synangiosis (EDMS) were reviewed retrospectively. The mean follow-up period was 23±14m (6m-70m). CT or MR perfusion and Digital subtraction angiography (DSA) were performed for preoperative diagnosis and postoperative evaluation of cerebral perfusion and revascularization. mRS score, angiographic collateralization score, vessel diameter were recorded to measure neurological dysfunction, revascularization area and vascular compensatory effect respectively.

Results:
Among the 64 MMD patients, 69 hemispheres received combined direct and indirect operations; 7 hemispheres only received indirect operations. During our follow-up periods, neurological deficits of 57/64 patients (89.1%) were partially alleviated. mRS was significantly decreased after operations not only in all patients, but also in stroke subgroup or hemorrhage subgroup. Generally, good revascularization was established in most of the patients by combined bypass. 92.1% (70/74) sides was scored 2 and 77.6% (59/74) sides was scored 3 determined by angiographic collateralization score. Compared to the preoperative situations (2.60±0.65mm), the calibers of STA main trunk increased profoundly in at postoperative 10 days (3.32±1.05mm, p<0.05
versus
pre-operation), and shrinked back to preoperative status at 6 months (2.24±1.00mm, p>0.05
versus
pre-operation) and 12 months (2.36±0.73mm, p>0.05
versus
pre-operation).

Conclusion:
Our findings strongly suggested that combined STA-MCA bypass and EDMS provided efficient revascularization and excellent results in preventing strokes and hemorrhage in adult patients. The direct STA-MCA bypass provided early augmentation of cerebral perfusion, whereas the indirect EDMS provided a more durable long-term revascularization, indicating a complementary relationship between the two revascularization methods.
Abstract TP6: Factors Influencing Infarct Progression During Ischemic Stroke Patients Transfer: Collaterals Lost is Brain Lost
Authors: Boulouis Gregoire , Lauer Arne , Siddiqui Ahmer Khawdja , Charidimou Andreas , Regenhardt Robert , Viswanathan Anand , Rost Natalia S , Leslie-Mazwi Thabele M , Schwamm Lee H
Published: June 2021

Introduction:
When transferred from a referring hospital (RH) to a thrombectomy capable stroke center (TCSC), patients with initially favorable imaging profile (ASPECT score ≥6) often demonstrate infarct progression significant enough to make them ineligible at arrival. We sought to determine the clinical and imaging factors associated with this phenomenon in transferred ischemic stroke patients.

Methods:
We identified adult stroke patients transferred from one of 30 RH between 2010 and 2016 for which (1) a RH computed tomography (CT) and (2) a CT Angiography (CTA) at arrival were available for review. ASPECT scores were evaluated by 2 raters. The adequacy of leptomeningeal collateral flow was rated as none/poor, decreased, adequate or augmented per the Maas et al (Stroke 2009), modified scale. ASPECTS decay was defined as an ASPECT initial score ≥6 worsening between RH and TCSC CTs to a score <6.

Results:
A total of 330 patients were included in the analysis (mean age 70.2 ± 14.2, 43.3% females). Univariable subgroup analyses showed that patients with ASPECTs decay were more likely to be females (55% vs 40%, p=0.02), not on anticoagulants (4% vs 15%, p=0.01), and with higher initial NIHSS (Median [IQR] 19 [15.3-22] vs 11 [6-17], p<0.001), hyperdense vessel sign on initial CT (71% vs 26%, p<0.001) and poor collaterals on CTA (72% vs 19%, p<0.001). In multivariable models, higher NIHSS, lower baseline ASPECTs, CTA evidence of a proximal occlusion, and none/poor collaterals were strong predictors of ASPECTs decay, with collateral status demonstrating the highest odds ratio (aOR 10.3, 95%CI: [4.1-29], p<0.001). Similar results were found after stratification by vessel occlusion level.

Conclusion:
In ischemic stroke patients transferred for thrombectomy, poor collateral flow, stroke severity and proximal vascular occlusion, but not time interval, are the main determinants of ASPECTs decay.
Abstract TP70: Incidence of Serious Adverse Events Following Acute Stroke: Data From the Efficacy of Nitric Oxide in Stroke (ENOS) Trial
Authors: Stodolak Szymon , Woodhouse Lisa J , Sprigg Nikola , Bereczki Daniel , Bath Philip M
Published: June 2021

Background:
Reporting of serious adverse events (SAEs) is an essential safety procedure in randomised controlled trials. Risk factors for SAEs post-stroke and the relationship of SAEs with outcome were studied in the ENOS trial.

Methods:
ENOS assessed glyceryl trinitrate (GTN, 5 mg) vs no GTN for 7 days in 4,011 patients with acute stroke and high blood pressure. Information on SAEs was collected up to day 90. SAEs were adjudicated centrally with blinding to treatment assignment.

Results:
SAEs were reported in 1022 (25.5%) patients, 43.8% of whom died. Patients who suffered SAEs were more likely to be older (mean age 74.2 vs. 69.0 years, p<0.001) and have a history of atrial fibrillation (AF) (relative risk [RR] 1.80, p<0.001). Patients with non-oral feeding at baseline were more vulnerable to SAEs (RR 2.14, p<0.001) and fatal SAEs (RR 3.77, p<0.001) as compared with those with oral feeding. Males were at less risk than females to suffer an SAE (RR 0.83, p<0.001), as were smokers (RR 0.73, p<0.001). Smokers also suffered fewer fatal SAEs (RR 0.55, p<0.001). GTN did not increase the incidence of SAEs. The most common type of SAE was pneumonia (6% incidence) with a high risk of death (RR 9.29, p<0.001).

Conclusions:
SAEs are associated with a range of risk factors that should be taken into account in clinical practice. AF and non-oral feeding status were associated with increased, and smoking with reduced, risk of of SAEs. Incidence of pneumonia was a common and life threatening issue amongst patients.
Abstract TP73: Evaluation of Intervention Aimed at Reducing Alteplase Returns without Compromising Clinical Care in Acute Ischemic Stroke
Authors: Swearingen Natalie , Myers Jillian T , Lesko Alexandra
Published: June 2021

Introduction:
In 2010, the AHA/ASA’s Target Stroke best practice recommendations to reduce door to needle times (DTN) included early pre-mix of intravenous alteplase, which ultimately leads to unused vials. However, hospitals have largely recouped the cost of unused, premixed vials through returns to the drug manufacturer, although this practice is unlikely to continue. As a result, we evaluated an intervention to reduce the number of returned vials and the impact on clinical care at our certified primary stroke center (PSC).

Methods:
A 6-month pre-intervention period (January 2015-June 2015) was compared to two 6-month post-intervention periods, July 2015-December 2015 and January 2016-May 2016. Acute ischemic stroke patients presenting at our PSC and considered for alteplase treatment were included. Inpatient strokes or those with diagnoses unrelated to stroke or uncertain treatment eligibility were excluded. Primary outcomes were as follows: 1. Percent of alteplase vials returned out of the total number mixed and the associated costs 2. Average DTN time 3. Pharmacy alteplase mix time to needle time. Average minutes (min) with associated p-values and 95% confidence intervals (95%CI) were reported. Price for replacement vials ranged from $6,400 to $8,400 per 100 mg vial.

Results:
Data from 95 AIS patients were included. The percentage of alteplase returns for the evaluation period were as follows: 40.6% (13/32) for the pre-intervention, 11.4% (4/35) for the first post-intervention and 6.1% (2/33) for the second post-intervention period. Total cost savings was between $128,000 and $168,000 comparing pre and post-intervention periods. Among those treated, DTN times were not significantly different between pre-intervention (55.5 min, n=19), post-1 (59.7 min, n=27) and post-2 (49.9 min, n=30) (p=.13, 95%CI: 50.6,59.1). Similarly, the pharmacy alteplase mix times to needle times were also not significantly different (16.6 min vs 14.8 min vs 11.8 min) across the three time periods (p=.14, 95%CI:12.2,15.9).

Conclusion:
The percentage of vials returned reduced by over 6-fold after the intervention resulting in considerable cost savings. PSCs can reduce overall waste of alteplase and decrease costs without negatively effecting clinical care.
Abstract TP75: Creatinine on Admission Interacts with Intravenous Thrombolysis and Thrombectomy Procedures in Predicting Post-stroke Outcomes
Authors: El Husseini Nada , Redmond Cintasha , Lee Seung-Jae , D’Agostino Ralph B , Bushnell Cheryl
Published: June 2021

Background:
Renal impairment may be associated with reduced efficacy of thrombolysis, increased hemorrhagic complications and risk of contrast-induced nephropathy associated with catheter angiogram used in thrombectomies. It is unclear if creatinine interacts with IV-tpa and thrombectomy in predicting post stroke outcomes.

Methods:
This is a retrospective analysis of consecutive patients admitted with acute ischemic stroke to a single tertiary care center between October 2012 and July 2015. Logistic regression analysis was used to evaluate whether there was a differential impact of the association of IV-tpa and/or thrombectomy with discharge disposition (discharge home vs. other) and 3 months functional outcome (modified Rankin Score mRS<3 vs. mRS≥3) based on the admission creatinine (Cr) level (<1.5 and ≥1.5) after adjusting for sex, age, race, NIHSS on admission, history of atrial fibrillation and history of stroke/TIA.

Results:
A total of 570 subjects were included (48.6% male, 69.4% white, mean age 67years, mean NIHSS 7.1, mean Cr. 1.17 , 13.1% with Cr≥1.5). A total of 18.4% (N=105) received IV-tpa and an additional 6.5%(N=37) received thrombectomy in addition to IV-tpa. About 57% were discharged home and 46% had mRS<3 at 3 months. The mean NIHSS on admission was not significantly different based on creatinine level (7.0 vs.8.1, p=0.271 in subjects with Cr<1.5 and Cr≥1.5 respectively). After adjusting for other relevant variables, the interaction of creatinine with IV-tpa with/without thombectomy was significant in predicting both discharge home (p= 0.0009) and 3 months mRS (p=0.0063). In those with creatinine <1.5, IV-tpa with/without thrombectomy was associated with increased odds of being discharged home (OR=2.81, 95%CI 1.55-5.08), p=0.0006) and a good functional outcome (mRS<3 at 3 months) (OR= 2.91, 1.66-5.10), P=0.0002. In contrast, in those with Cr ≥1.5, IV tpa with/without thrombolysis was associated with lower odds of being discharged home (OR= 0.11; 95% CI 0.01-0.74), p=0.023 and lower odds of having a favorable 3 months functional outcome (mRS<3) (OR= 0.06; 95% CI 0.006-0.80), p=0.033.

Conclusions:
Creatinine on admission modified the effect of IV-tpa and thrombectomy. Reasons for this interaction warrant further investigation.
Abstract TP86: The Ischemic Blood-brain Barrier In A Dish: Use Of Patient-derived Stem Cells To Model The Response Of The Neurovascular Unit To Oxygen-glucose Deprivation Stress
Authors: Page Shyanne , Patel Ronak , Alahmad Abraham
Published: June 2021

The blood-brain barrier (BBB) constitutes a component of the neurovascular unit formed by specialized brain microvascular endothelial cells (BMECs) surrounded by astrocytes, pericytes and neurons. During ischemic stroke injury, the BBB constitutes the first responding element resulting in the opening of the BBB and eventually neural cell death by excitotoxicity. A better understanding of the cellular mechanisms underlying the opening of the BBB during ischemic stroke is essential to identify targets to restore such barrier function after injury. Current
in vitro
models of the human BBB, based on primary or immortalized BMECs monocultures, display poor barrier properties but also lack one or two cellular components of the neurovascular unit.In this study, we designed an integrative in vitro model of the BBB by generating BMECs, astrocytes and neurons using patient-derived BMECs from two iPSC lines (IMR90-c4 and CTR66M). We were able to obtain all three cell types from these two cell lines. iPSC-derived BMECs showed barrier properties similar or better barrier function than hCMEC/D3 monolayer (an immortalized adult somatic BMEC). Furthermore, iPSC—derived astrocytes were capable to induce barrier properties in BMECs upon co-cultures. whereas iPSC-derived neurons were capable to form extensive and branched neurites. Upon OGD stress, iPSC-derived BMECs showed a disruption of their barrier function as early as 6 hours of OGD stress and showed a complete disruption by 24 hours. Such disruption was reversed by reoxygenation. Interestingly such barrier disruption occurs through a VEGF-independent mechanism. In the other hand, iPSC-derived neurons showed a significant decrease in cell metabolic activity preceding neurites pruning. Finally, astrocytes showed the most robust phenotype, as we noted no cell death by 24 hours OGD.In this study, we demonstrated the ability to differentiate three cell types from the same patient in two iPSC lines. We also demonstrated the ability of these cells to respond to OGD/reoxygenation stress in agreement with the current literature. We are currently investigating the molecular mechanisms by which OGD/reoxygenation drive the cellular response in these cell types.
Abstract TP97: Korean Red Ginseng Ameliorates Cerebral Hypoxic-Ischemic Damage Through the Activation of the Nrf2 Pathway by Preferentially Altering Reactive Astrogliosis
Authors: Liu Lei , Vollmer Mary K. , Carson Morgan W. , Sahagian Todd J. , Kim Hocheol , Dore Sylvain
Published: June 2021

Introduction:
Endogenous defense mechanisms by which the brain protects itself against noxious stimuli and recovers from ischemic damage are key targets of stroke research that may ultimately facilitate functional recovery. Multiple evidences indicate that the transcriptional factor Nrf2 plays a vital role in cellular defense against oxidative stress and inflammation, and consequently, targeting Nrf2 has emerged as a promising therapeutic strategy for disease prevention. Korean Red Ginseng (Ginseng), one of the most widely used herbal medicines in the world, has been suggested as one of the most potent Nrf2 activators, thereby making it efficacious against various acute neurological disorders, including stroke.

Hypothesis:
To evaluate whether Ginseng could exert protective effects against hypoxic-ischemic brain damage and whether Nrf2 activation is pivotal to the various neuroprotective effects of Ginseng.

Methods:
C57BL/6 WT and Nrf2 knockout mice (10-18 weeks old, n=12-16) were orally administered Ginseng (100mg/kg/d) or vehicle 7d prior to cerebral hypoxic-ischemic damage. At 6 and 24h after stroke, mice were neurologically scored. Brain lesion size and edema formation were measured at 24h. Using immunostaining, we examined which cells appeared to be most preferentially activated in a spatiotemporal pattern by this Nrf2 pathway, in particular, in the early stage of ischemic injury. Based on the results, we are further evaluating the efficacy of inducing the Nrf2 pathway and assess the extended neuroprotective effects of Ginseng at 7d after stroke.

Results:
Ginseng treatment significantly reduced cerebral infarct size, neuronal death, edema formation and the resultant functional neurological deficits at 24h after stroke (P<0.001); whereas, Nrf2 ablation remarkably attenuated all benefits. Notably, the above protective effects of Ginseng were significantly attenuated in Nrf2 knockouts (P<0.05). In addition, Ginseng treated mice also exhibited reduced neuronal death and delayed severe reactive astrogliosis at 6 and 12h (P<0.05).

Conclusion:
Our findings indicate a neuroprotective effect of Ginseng against hypoxic-ischemic brain damage, and that Nrf2-dependent cytoprotective responses appear to be more prominent in astrocytes.
Abstract WMP1: Cost Effectiveness Analysis of Mechanical Thrombectomy: the THRACE Randomized Trial
Authors: Achit Hamza , guillemin Francis , Soudant Marc , Hosseini Kossar , Bannay Aurelie , Bracard Serge
Published: June 2021

Background and purpose:
The benefit of mechanical thrombectomy added to intravenous thrombolysis in patients with acute ischemic stroke has been largely demonstrated. However, evidence on economic incentive of this strategy is still limited, especially in the context of randomized trial. The purpose of this study is to analyze whether the combination of mechanical thrombectomy with intravenous thrombolysis is more cost-effective than implementing intravenous thrombolysis alone.

Patients and methods:
Individual-level cost and outcome data were collected in the THRACE randomized clinical trial, including patients with acute ischaemic stroke and proximal cerebral artery occlusion. Patients were assigned to either intravenous thrombolysis (IVT; n = 208) or intravenous thrombolysis plus intra-arterial thrombectomy (IVMT; n=204). The primary outcomes were both modified Rankin scale of functional independence at 90 days (score 0-2) and the EuroQol-5D score of quality of life. This study considered the perspective of the National Health Security System in France.

Results:
Bridging therapy increased by 10.9% the rate of functional independence compared to IVT (53% vs 42,1%) at an increased cost of 1909 є, with no significant difference in mortality (12% vs 13%) or symptomatic intracranial haemorrhage (2% vs 2%). Cost per one averted case of disability was consequently estimated at 17,480 є. The incremental cost per quality-adjusted life year gained was 13,423 є. Sensitivity analysis showed that combined approach had 84.1% probability of being cost-effective regarding cases of averted disability and 92.2% probability regarding quality-adjusted life year outcome. The national implementation of this new strategy would result in additional cost of 12.9 million є and avoid about 737 cases of death or disability.

Conclusions:
Based on randomized trial, this study demonstrates that intravenous thrombolysis plus mechanical intra-arterial thrombectomy for treating acute ischemic stroke is more cost-effective than intravenous thrombolysis alone.
Abstract WMP117: Patterns of All Bleeding Complications Associated with r-tPA Use-experience of an Acadamic Center in China
Authors: Chang Hong , Wang Xiaojuan , Qiao Yuchen , Zhao Jie , Song Haiqing
Published: June 2021

Background and objective:
Rapid administration of intravenous recombinant tissue-type plasminogen activator (rt-PA) is the standard treatment for patients with acute ischemic stroke (AIS). While hemorrhage represents as an important and unpredictable complication of thrombolytic treatment, few studies have specifically assessed the prevalence and predictors of bleeding complications among AIS patients in Asia. We assessed characteristics of hemorrhagic complications after intravenous thrombolysis in Chinese AIS patients.

Methods:
This single-academic-center study retrospectively evaluated 351 acute ischemic stroke patients who received rt-PA intravenously from April 2011 to April 2016. The occurrence and characteristics of any hemorrhagic complications, as well as their associated risk factors were recorded and summarized. Multivariate logistic regression was conducted to analyze significant predictors of bleeding.

Results:
134 (38.1%) patients experienced one hemorrhagic event in one or more locations The top seven common sites were gingiva (49.3%), skin (18.3%), urinary system (10.4%), digestive tract (7.5%), intra-cranial cavity (7.5%), mouth (4.4%) and nasal cavity (2.2%). All the gingival bleeding occurred during 1 to 24 hours after thrombolysis and was the first sign of bleeding. Intracranial hemorrhage (both symptomatic and asymptomatic) occurred in 16 patients, of whom 4 presented first with gingival bleeding. Multivariate analysis showed that high systolic blood pressure (SBP) and National Institutes of Health Stroke Scale (NIHSS) score were independent risk factors for hemorrhage post thrombolysis (P<0.05).

Conclusions:
One out of three AIS patients in this study had a bleeding complication. The most common site of initial hemorrhage after intravenous thrombolysis was gingival, which frequently occurred as the initial bleeding site within 24 hours after thrombolysis. Consistent with literature, elevated SBP and higher NIHSS were the two key predictors of bleeding risk.
Abstract WMP15: A Simple Tool to Predict Target Mismatch in Ischemic Stroke Patients with Anterior Circulation Occlusion
Authors: de Havenon Adam , O’Donnell Steve , Linn Alex , McNally Scott , Dunleavy Bailey , Majersik Jennifer
Published: June 2021

Introduction:
The efficacy of endovascular thrombectomy in an extended time window for acute ischemic stroke patients with Target Mismatch (TM) on perfusion imaging was shown in a recent study and the ongoing DEFUSE-3 trial is studying thrombectomy in a 6-16 hour window for TM patients. A limitation of TM is that perfusion imaging is not widely available. We sought to identify a tool to predict TM based on clinical factors and CT angiogram (CTA) imaging, which is available at most hospitals.

Methods:
We reviewed acute ischemic stroke patients from 2010-2014 with proximal middle cerebral artery occlusion, CTA and CT perfusion (CTP) at hospital admission. TM was identified on CTP using the Olea Sphere volumetric analysis software with Bayesian deconvolution. TM was defined by the DEFUSE-3 criteria. ASPECTS was derived from the non-contrast CT head and the CTA source images (CTA-ASPECTS). Two collateral scores were derived from CTA source images.

Results:
61 patients met inclusion criteria. The mean±SD age was 61±18 years and 61% were male. Mean NIH Stroke Scale (NIHSS) was 14.1±8.0 and median (IQR) follow-up modified Rankin Scale was 3 (1,6). TM was present in 35/61 (57%), who had lower mRS at follow-up (z=3.5, p<0.001). The predictor variables are shown in Table 1. The best combination of predictors was CTA-ASPECTS >4 and NIHSS <16, which had a sensitivity of 80% and specificity of 85% for TM (Figure 1).

Discussion:
We report a reliable, accessible, and clinically useful tool for predicting TM. This score warrants further study as a tool to guide transfer decisions from primary or secondary stroke centers to tertiary centers where endovascular intervention would be possible for selected patients.
Abstract WMP21: The Delayed Vessel Sign in Multiphase CT Angiography: Facilitating the Rapid On-table Confirmation of Acute Ischaemic Stroke
Authors: Byrne Danielle , Sugrue Gavin , Stanley Emma , Murphy Sean , Kavanagh Eoin , MacMahon Peter
Published: June 2021

Objective:
The “delayed vessel sign” refers to the presence of relative unilateral delayed enhancement of a vessel or vessels in the anterior circulation on delayed phases of a multiphase CTA (MPCTA) distal to the point of vessel occlusion. We aimed to determine if educating radiologists on the “delayed vessel sign” would improve sensitivity, confidence and speed in the detection of distal anterior circulation vessel occlusions in the suspected stroke patient.

Methods:
Non-contrast CT (NCCT) and MPCTA studies of 53 individual patients, who presented with signs/symptoms of acute anterior circulation stroke, were retrospectively selected by an independent radiologist. 15 cases without a vessel occlusion, 15 cases with a M1 occlusion and 23 cases with a distal anterior circulation (A2/M2/M3) occlusion were included. Initially, NCCT and single phase CTA (SPCTA) studies were independently interpreted by four observers (two neuroradiologists, two radiology trainees) and observers’ confidence (scale 1-5), speed and sensitivity of detection were recorded. Observers were then educated on the “delayed vessel sign” and each study was re-examined after an interval of at least 14 days.

Results:
There was a significant improvement in the sensitivity of detection of distal anterior circulation vessel occlusions on MPCTA compared to SPCTA (p=0.0003) and this was also true for M1 occlusions (p=0.045). Overall confidence was 4.0 for SPCTA and 4.88 with MPCTA (p<0.0001). Average time taken to interpret each case on SPCTA was 85.5s and decreased to 40.1s with MPCTA (p<0.0001).

Conclusion:
The “delayed vessel sign” is a reliable indicator of ipsilateral vessel occlusion, and is particularly useful in cases involving distal MCA branches where the occlusion is not easily identified on the initial angiographic phase. We have found this sign facilitates the rapid on-table confirmation of acute ischemic stroke, even when small vessels are involved and the clinical diagnosis is uncertain.
Abstract WMP30: Circulating MicroRNAs as Potential Novel Diagnostic Biomarkers for Ruptured Intracranial Aneurysm
Authors: Xin Zhang , Ping Liu L
Published: June 2021

Background and Objective:
MicroRNAs have been shown to regulate in several pathological process of intracranial aneurysms. The study aimed to estimate whether miRNAs have the potential to become novel biomarkers for intracranial aneurysm rupture.

Materials and methods
Forty-five ruptured intracranial aneurysm patients were enrolled according to the inclusion criteria, meanwhile thirty-five healthy individuals were recruited in this study. Differentially expressed plasma miRNA profiles were screened in five pairs of patients and controls in microarray study. Then validation was performed in the rest of the objects using quantitative real-time PCR assays.

Results:
Fourteen significantly changed miRNAs were screened out from patients with aneurysms compared with healthy controls. More than three thousand target genes related to these disregulated miRNAs were found and bioinformatic analysis revealed that these miRNA were involved in intracranial aneurysm development and rupture. Ultimately four miRNAs from screening profile and one supplementary miRNA were demonstrated to be significantly altered.

Conclusion:
We demonstrated that several miRNAs were differentially expressed among ruptured aneurysm patients and healthy participants, and plasma miRNAs may be novel diagnostic biomarkers in intracranial aneurysm rupture.
Abstract WMP48: Cerebral Endothelial Derived Exosomes Abolish Cognitive Impairment Induced by Ablation of Dicer in Adult Neural Progenitor Cells
Authors: Zhang Rui Lan , Pan Wanlong , Zhang Xiaoming , Liu Xianshuang , Landschoot-Ward Julie , Li Chao , Fan Baoyan , Wang Xinli , Chopp Michael , Zhang Zheng Gang
Published: June 2021

Introduction:
Dicer processes precursor miRNAs into mature miRNAs. We have demonstrated that conditional knockout of Dicer (Dicer/Cko) in adult neural progenitor cells (NPCs) impairs neurogenesis and cognitive function. The present study tested the hypothesis that cerebral endothelial-derived exosomes carrying mature miRNAs promote neurogenesis and improve cognitive function by communication with NPCs in Dicer/Cko mice.

Methods and Results:
Exosomes harvested from cultured cerebral endothelial cells (CEC-Ex, 1x10
9
exosomes) were intranasally administered twice a week for two consecutive weeks into mice (n=10) with conditional ablation of Dicer (Dicer/Cko) in NPCs (

Ascl1-
CreER
:Dicer
flox/flox

). Dicer/Cko mice treated with saline (n=12) were used as control. Cognitive tests were performed, including Morris Water Maze (MWM) for hippocampal related learning and memory, odor-based novelty recognition for olfactory memory, and social interaction for memory of interactions with novel conspecifics. Compared to wild-type mice, Dicer/Cko mice treated with saline exhibited substantial cognitive impairment. The CEC-Ex treatment diminished cognitive deficits and these mice exhibited an increase of 40% more time spent in the correct quadrant (p<0.05) of the MWM, and increased time exploring new odor objects (71±9% vs 41 ±10% saline, p<0.05) and increased time in contact with a strange mouse during the sociability test. Using a Cre/flox reporter approach, we found that the exosomes carrying Cre mRNA entered NPCs in the subventricular zone (SVZ) and dentate gyrus (DG). The CEC-Ex treatment significantly (p<0.05) increased BrdU
+
NPCs (20 ± 1% vs 14 ± 2%, SVZ, 16±1% vs 12±3%, DG ) and DCX+ neuroblasts (27 ± 2% vs 22 ± 3%, SVZ, 33 ± 2% vs 25 ± 3%, DG), and reduced apoptotic cells by more than 50% in these two areas. RT-PCR analysis showed that Dicer/Cko mice exhibited substantial reduction of mature miRNAs that regulate neurogenesis including miR-124, -146a and -17-92 cluster in NPCs, whereas the CEC-Ex treatment increased these mature miRNAs in Dicer/Cko NPCs.

Conclusion:
The CEC-Ex can reverse impaired neurogenesis and cognitive function induced by ablation of Dicer, which is likely attributed to the delivery of mature miRNAs into NPCs by CEC-Ex.