bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP449: Short Term (1 month) Daily Remote Ischemic Conditioning (RIC) Induces Vascular Remodeling and Improves Long Term Outcomes (6 month) in a Mouse Model of Vascular Cognitive Impairment (VCI)
Authors: Khan Mohammad B , Hafez Sherif , Wagner Jesse D , Hoda M N , Hess David C
Published: June 2021

Background and Purpose:
There is presently no specific therapy for the treatment of VCI. The bilateral carotid artery stenosis (BCAS) model is regarded as a valid model for VCI and vascular dementia. We reported that daily RIC is effective by improving cerebral blood flow (CBF), reducing white matter (WM) damage and improving cognition. The purpose of this study was to determine if 1MO RIC is as effective as 4MO RIC and if the treatment effects are durable out to 6MO.

Methods:
Microcoil induced BCAS model was used to induce chronic hypoperfusion. Adult C57BL/6J male mice (10-weeks) were randomly assigned to 4-different groups (N=10), and subjected to Sham-BCAS, BCAS-(+sham RIC), BCAS+RIC-1MO and BCAS+RIC-4MO. RIC was started 7d post-surgery daily for 1MO or 4MOs. Behavioral test and CBF was performed at 1, 4 and 6MO after BCAS surgery. Functional outcomes were assessed using novel object recognition (NOR) test for non-spatial working memory, and hanging wire test for motor impairment. Histopathology as well as immunohistochemistry for CD31 and myelin basic protein (MBP) were also performed on the of the brain tissue collected after the neurobehavioral tests. Statistical significance was determined at p <0.05.

Results:
RIC-therapy for 1MO or 4MO significantly improved CBF in the BCAS+RIC groups. The RIC-1MO treatment was effective as the RIC-4MO treatment at improving CBF at 6MO. Mice from the BCAS group showed significant loss in the discrimination index as determined by the NOR test, and poor motor function in hanging wire test. RIC-therapy in BCAS+RIC (1MO & 4MO) groups significantly improved functional outcomes as compared to the BCAS group whereas there was no difference between the RIC groups. Histopathological studies showed prevention of WM degeneration by RIC. Immunohistochemical analysis at 6 MOs showed increased CD31 staining (angiogenesis) and increased MBP staining (myelination) in the RIC groups compared to sham RIC.

Conclusions:
Both 1MO and 4MO RIC-therapy improve long term CBF and angiogenesis at 6 MO and reduce WM damage and improve functional outcomes. One month of daily RIC is as effective as 4MO of daily RIC at improving CBF and long term functional outcomes (6MO) in the BCAS model. This suggests that 1MO of RIC induces durable vascular remodeling.
Abstract WP45: Regional Contribution of Salvaged Brain Tissue on Outcome in Endovascular Stroke Therapy
Authors: Sheth Sunil A , McElhinney Priscilla , Weng Julius , Ichwan Daniel , Quachtran Ben , Liang Conrad W , Saver Jeffrey L , Duckwiler Gary , Liebeskind David S , Scalzo Fabien
Published: June 2021

Introduction:
Endovascular stroke treatments (ET) require an understanding of the relative eloquence of brain regions, particularly when treating distal occlusions. However, prior studies of regional eloquence have focused on the effect of infarcted territories on outcome. Here, we evaluate the relative importance of salvaging different brain regions.

Methods:
From our prospectively maintained institutional registry, we identified patients treated with ET from 2010-2015 with presentation and day 5-7 MRI scans. Brain regions were defined as follows: initial infarct from presentation ADC (manually identified), penumbra from initial perfusion MRI TMax > 6 seconds, and final infarcts from hyperintense day 5-7 FLAIR regions (manually identified). Salvaged brain tissue (SBT) was computed by co-registering day 5-7 FLAIR with presentation perfusion MRI against the SRI24 Brain Atlas, and calculating the difference between penumbra and final infarct. SBT maps of all patients were combined and weighted against 90-day modified Rankin scale (mRS) to create an outcomes-weighted SBT map.

Results:
Among 338 patients treated with ET, mean age was 66, 54% were female, and median NIHSS score was 14 [IQR 8-19]. Mean initial infarct was 19 mL (SD 28), final infarct 48 mL (SD 67), and penumbra 414 mL (SD 241). Average SBT was 366 mL (SD 241). SBT volume correlated positively with 90-day mRS (p<0.05). Eloquence maps of SBT brain regions demonstrated differential weighting for the right and left hemisphere (Figure). For both hemispheres, salvaging the Rolandic territory was associated with good outcome, and for the left hemisphere only, salvaging the perisylvian regions (likely representing language areas) was also important.

Conclusions:
The volume and location of brain tissue salvaged by ET is an important determinant of clinical outcome. The results of our outcomes-weighted salvaged brain tissue maps support targeting eloquent regions when considering a patient for ET.
Abstract WP450: Cognitive Impairment and Asymptomatic Intracranial Atherosclerotic Stenosis in General Population
Authors: Suri M.Fareed K. , Zhou Jincheng , Qiao Ye , Chu Haitao , Qureshi Adnan I , Mosley Tom , Gottesman Rebecca F. , Wruck Lisa , Sharrett A. Richey , Alonso Alvaro , Wasserman Bruce A.
Published: June 2021

Background:
There is growing evidence suggesting that intracranial atherosclerosis is associated with cognitive impairment. We investigated the association between asymptomatic intracranial atherosclerosis and cognitive impairment in the bi-racial Atherosclerosis Risk in Communities (ARIC) cohort.

Methods:
ARIC participants who underwent high-resolution 3T magnetic resonance angiography, and a neuropsychology battery and neurological examination adjudicated by an expert panel, to detect mild cognitive impairment (MCI) and dementia. We adjusted for demographic and vascular risk factors in weighted logistic regression analysis, accounting for stratified sampling design and attrition, to determine the association of intracranial atherosclerotic stenosis (ICAS) with cognitive impairment.

Results:
In 1705 participants (mean age 76 ± 5.3, 41% men, 71% Whites and 29% African-Americans) with adequate imaging quality and no previous history of stroke, MCI was identified in 578 (34%) and dementia in 79 (4.6%). In white participants, after adjustment for demographic and vascular risk factors, ICAS ≥50% (vs no ICAS) was strongly associated with dementia (odds ratio [OR] 4.1, 95% confidence interval [CI] 1.7-10) and with any-cognitive impairment (OR 1.7, 95% CI 1.06 - 2.8). In contrast, no association was found between ICAS ≥50% and MCI or dementia in African-Americans, though sample size was limited and estimates were imprecise.

Conclusion:
Our results suggest asymptomatic ICAS is independently associated with cognitive impairment and dementia in Whites
Abstract WP52: White Matter Hyperintensity, Cerebral Microbleeds and Risk of Hemorrhagic Transformation with Intravenous rt-PA
Authors: Tasneem Nudrat , Dandapat Sudeepta , Shaban Amir , Ahmed Uzair , Policeni Bruno , Olalde Heena , Samaniego Edgar , Pieper Connie , Leira Enrique C , Ortega-Gutierrez Santiago , Adams Harold P , Nagaraja Nandakumar
Published: June 2021

Background and Purpose:
Intravenous rt-PA is associated with risk of hemorrhagic transformation. We sought to determine if the degree of white matter hyperintensity on Fluid Attenuated Inversion Recovery (FLAIR) and the presence of cerebral microbleeds (MB) on Gradient Recalled Echo (GRE) sequences on MRI was associated with increased risk of hemorrhagic transformation following intravenous rt-PA.

Methods:
Acute ischemic stroke patients admitted to University of Iowa Hospitals and Clinics between 1/1/2009 and 12/31/2013 were included in the study if - i) received intravenous rt-PA ii) had MRI brain with Diffusion Weighted Imaging (DWI), GRE and FLAIR sequence within the first 48 hours of stroke onset, and iii) had CT head or MRI at 20-36hr post rt-PA to evaluate for hemorrhagic transformation. White matter hyperintensity on FLAIR was evaluated based on Fazekas scale from 0-4. A score of 0 and 1 on Fazekas scale was combined to form group 1 and a score 3 and 4 was combined to form group 2 for analysis. MB were evaluated on GRE. Presence of MB was categorized as group 1 (1-5 MB) and 2 (6 or more MB). CT or MRI head performed at 20-36 hours after rt-PA was evaluated for hemorrhagic transformation. If present it was classified as group 1 (HI 1 and 2) and 2 (PH 1 and 2).

Results:
A total of 402 patients met the study criteria among 607 patients. Mean age was 67±14 years. Among them 45% were women and 88% whites. FLAIR deep white matter hyperintensity was graded on Fazekas as 0 - 26%, 1-51%, 2-12% and 3-11%. FLAIR periventricular white matter hyperintensity was graded as 0 - 10%, 1-49%, 2-25% and 3- 16%. MB were present in 26% of the study population with only 3 patients in group 2. Hemorrhagic transformation was seen in 24% of the patients with 66% of these having petechial hemorrhage. Deep white matter (p=0.47) and periventricular (p=0.73) white matter hyperintensity was not significantly associated with hemorrhagic transformation. However, presence of MB was significantly associated with hemorrhagic transformation (p=0.006, OR = 2.03, CI 1.215-3.392).

Conclusion:
Microbleeds increases the risk of hemorrhagic transformation following administration of intravenous rt-PA. However, white matter hyperintensity did not result in increased risk of hemorrhagic transformation after rt-PA.
Abstract WP55: Through Thick and Thin: Improved Aspects Grading and Dense Vessel Detection Using Simple Ncct Post-processing
Authors: Evans James W , Dey Sadanand , Eesa Muneer , Eswaradass Prasanna , Lun Ronda , Horn MacKenzie , Neweduk Anneliese , Mcdougall Brooklyn , Pordeli Pooneh , Jayaraman Mahesh V , McTaggart Ryan A , Najm Mohamed , Goyal Mayank , Demchuk Andrew M , Menon Bijoy K
Published: June 2021

Introduction:
Assessing Alberta Stroke Program Early CT Score (ASPECTS) and identifying hyperdense arteries on non-contrast CT (NCCT) are important components of decision-making in acute stroke. Conventional practice uses 5mm averaged slice thickness NCCT for interpretation of these features. We have systematically evaluated several post processing techniques on NCCT to determine if there is improved reliability in identification of ASPECTS and hyperdense artery.

Methodology:
We assessed four post-processing techniques on NCCT namely (1) 5mm averaged thickness (2) Minimum Intensity Projection (mIP) - 5mm thickness (3) thin slices (0.625mm) and (4) Maximum Intensity Projection (MIP) - 5mm thickness (Figure 1). Three raters (student, fellow and expert) independently assessed 100 NCCT scans from the PRoveIT database. All scans were read at four different times 10-14 days apart. At each time-point the post processing modality was changed and the patient order randomized. Information on side of suspected infarction was provided. Raters were asked to score ASPECTS and identify presence of hyperdense artery at each reading. Inter-rater reliability was assessed using Intra-cluster correlation (ICC) for ASPECTS and weighted kappa (wKap) for hyperdense artery.

Results:
The highest inter-rater reliability was found with the MIP technique (ICC 0.42; p<0.001), followed by 5 mm average, mIP and thin slice respectively (ICC 0.33, 0.32, 0.20; all p<0.01). Highest agreement for hyperdense vessel detection was noted with thin slice (wKap 0.30; p<0.001) followed by Average, MIPs and mIPs respectively (wKap 0.25, 0.18, 0.13; all p <0.05).

Conclusion:
The use of MIP images for ASPECTS grading and thin images for hyperdense vessel detection improves reliability on NCCT. These simple processing steps are easily available on any modern scanner and may help improve patient care.
Abstract WP56: Impact of Perfusion and Diffusion Lesion Load in the Corticospinal Tract on Response to Reperfusion
Authors: Zhou Ying , Zhang Ruiting , Zhang Sheng , Yan Shenqiang , Wang Ze , Campbell Bruce C , Liebeskind David S , Lou Min
Published: June 2021

Objective:
To examine the impact of corticospinal tract (CST) involvement in acute ischemic stroke patients on functional outcome and the interaction with reperfusion.

Methods:
We retrospectively examined clinical and imaging data in consecutive anterior circulation ischemic stroke patients undergoing thrombolysis. MRI perfusion (time to maximum of tissue residue function, Tmax) and apparent diffusion coefficient (ADC) images were transformed into standard space and the volumes of CST involvement by Tmax > 6s (CST-Tmax) and ADC < 600х10
-6
mm
2
/s (CST-ADC) lesions were calculated. Good outcome was defined as modified Rankin Scale ≤ 2 at 3 months. Reperfusion was defined as a reduction in Tmax > 6s lesion volume of ≥ 70% between baseline and 24 hours.

Results:
A total of 82 patients were included. Binary logistic regression revealed that both CST-Tmax volume (odds ratio, 1.4,
p
= 0.008) and CST-ADC volume (odds ratio, 4.9,
p
= 0.002) at baseline were significantly associated with poor outcome. The 24-hour CST-ADC volume was correlated with baseline CST-ADC volume in patients with reperfusion (r = 0.79,
p
< 0.001) and with baseline CST-Tmax volume in patients without reperfusion (r = 0.67,
p
< 0.001). In patients with CST-Tmax volume > 0 mL and CST-ADC volume < 3 mL, the rate of good outcome was higher in patients with reperfusion than those without (70.4% vs 38.1%,
p
=0.04).

Interpretation:
The use of CST-Tmax in combination with CST-ADC provides prognostic information beyond that provided by mismatch volumes in patients considered for reperfusion therapies.
Abstract WP64: City-wide Stroke Team in the U.S. Delivers the Highest Intravenous Thrombolysis Treatment Rate
Authors: Alexandrov Andrei V , Tsivgoulis Georgios , Nearing Katherine , Malkoff Marc , Kargiotis Odysseas , Metter E Jeffrey , Wahba Mervat , Alexandrov Anne W , Elijovich Lucas ,   for the Univ Clinical Health Stroke Team
Published: June 2021

Background:
An increasing shortage of vascular neurologists forced an academic provider to find a city-wide solution to offer 24x7 access to intravenous thrombolysis (IVT) across independent and competing health care systems in the area. We sought to prospectively evaluate the annual IVT treatment delivery in our population and compare it to leading stroke centers worldwide.

Methods:
The largest single ER system and 3 other independent hospital providers in the area agreed to work with a single practice plan vascular neurology team (catchment area of 1,344,127 individuals). All acute ischemic stroke patients that were treated with IVT across all primary or tertiary care centers in our area were prospectively documented over a 12-month period (January-December 2015). A literature search was performed using narrative review methodology to document similar population-based treatment rates across leading stroke centers in North America, Europe and Australasia.

Results:
A total of 552 patients received IVT with tissue plasminogen activator (tPA) in 2015. Single ER system delivered 433 IV tPA treatments and 119 more patients were treated in the remaining hospitals. The annual tPA treatment rate was 41 per 100.000 individuals (95%CI: 38-44) favorably comparable to published annual treatment rates from leading international stroke centers (Table, 1998 thru 2015).

Conclusions:
A city-wide vascular neurology team can attend to patient populations across competing health care systems in the U.S. and deliver IVT at volumes and rates above those reported by leading treatment centers worldwide. Communities with competing systems can improve tPA delivery by sharing vascular neurology resources.
Abstract WP67: Ultra-early Institution of Statin Treatment is Associated With Improved Outcomes Among Acute Ischemic Stroke Patients Receiving Thrombolytic Treatment
Authors: Qureshi Adnan I , Saleem Muhammad A
Published: June 2021

Background:
There is preliminary evidence that early statin use may improve the outcomes of acute ischemic stroke patients following endovascular treatment.

Methods:
We analyzed data from subjects treated with intravenous (IV) recombinant tissue plasminogen activator (rt-PA) alone or in combination with endovascular treatment the Interventional Management of Stroke III trial. We compared the rates of functional independence (defined by modified Rankin scale of 0-2) and minimal impairment of activities of daily living (Barthel index at 90 days 95-100)at 3 and 12 months among subjects with ultra-early institution of statin treatment (on Day 0) with those in whom statin treatment was not initiated and in those in whom statins were initiated between Day 1-discharge (delayed institution)after adjusting for age and baseline National Institutes of Health Stroke Scale score strata, history of hyperlipidemia; and statin use at baseline

Results:
Of the 656 subjects who were recruited in the trial, ultra-early institution of statin treatment and delayed institution occurred in 51 and 387 subjects, respectively. At 3 months post randomization, the adjusted rates of independent functional outcome (odds ratio [OR] 2.3; 95 % confidence interval [CI] 1.2-4.5;
P
= 0.015) and minimal impairment of activities of daily living (OR 2.2; 95 % CI 1.1-4.3;
P
= 0.022) were higher among subjects with ultra-early institution of statin treatment compared with those without any statin treatment. The adjusted rates of functional independence (OR 2.7; 95 % CI 1.4-5.2;
P
= 0.004) continued to higher among subjects with ultra-early institution of statin treatment at 12 months post randomization. The adjusted rates of functional independence and minimal impairment of activities of daily living were higher among subjects with ultra-early institution of statin treatment compared with those without any statin treatment in subjects randomized to endovascular treatment.

Conclusions:
Ultra-early institution of statin treatment in acute ischemic stroke patients treated with IV rt-PA with or without endovascular treatment was associated with improved outcome at both 3 and 12 months
Abstract WP68: Impact on ER Arrival & IV TPA Treatment Times Following Hospital Bypass Protocol Implementation: Northwest Ohio Experience
Authors: Sahwver Julie , Popa Theodore , Panjwani Sharjeel , Abdelaziz Rami , Tietjen Gretchen , Jumaa Mouhammad , Zaidi Syed
Published: June 2021

Background:
There is concern regarding hospital bypass stroke protocols potentially compromising IVtPA treatment due to transit time delay. We compared our IV thrombolysis time efficiencies before and after Rapid Arterial oCclusion Evaluation Alert (RACE) bypass protocol (RA) implementation in Lucas County (LC) Ohio.

Methods:
RA protocol whereby RACE score ≥5 patients are transferred directly to comprehensive stroke center (CSC) for potential mechanical thrombectomy (MT) was implemented in Jul 2015. All stroke alerts (SA) that required MT from July 2013 through June 2015 were compared to MT cases performed following RA protocol implementation. Transfers from other counties, private transport and in-hospital cases were excluded and only patients brought via LC-EMS were included in the analysis. Basic demographics, risk factors, 911 activation to treatment time, and outcomes were compared.

Results:
Between Jul 2015-Jun 2016, 37 RA patients underwent MT of which 21 (56.8%) were given IV tPA at the CSC. Whereas in the preceding 2 years from Jul 2013-Jun 2015, 56 SA patients underwent MT, of which 22 (39%) received IVtPA. Of these SA cases, 11 (50%) were drip and transfer from other LC ERs and the remaining 11 (50%) presented directly to CSC. The 911 activation to 1
st
ER arrival remained unchanged (34 vs. 32 mins, p 0.4), whereas tPA administration was significantly faster (64 vs. 88 mins, p <0.05) in the RA cohort (see graphic).

Conclusions:
Within LC, the RA bypass protocol did not result in a significant delay to ER arrival and it significantly expedited IV tPA delivery to patients undergoing MT. Further prospective studies are warranted.
Abstract WP87: Related Factors to Growth of Intracranial Aneurysm: Time Course Analysis
Authors: Yokota Hajime , Chien Aichi , Morimoto Emiko , Abe Takashi , Villablanca Pablo , Salamon Noriko
Published: June 2021

Introduction:
Intracranial aneurysms, especially small and asymptomatic ones, are often monitored with imaging studies. However, the prognosis of aneurysms varies according to many factors, which is reflected in variation in growth.

Hypothesis:
A time course analysis with a long follow up period can reveal characteristics of aneurysm growth and factors related to growth.

Methods:
All patients who underwent two CTA, including one in 2015, were reviewed. Intracranial saccular aneurysms were selected and fusiform, dissecting and mycotic aneurysms were excluded. Aneurysm characteristics, patient information, and medical history were recorded. Growth was defined as more than a 0.5 mm size increase compared with the first study. Log-rank and Cox regression tests were applied to identify factors related growth.

Results:
This study included 119 aneurysms of 91 patients that underwent a total of 474 CTA, with initial size 0.0-17.0 mm and follow-up duration of 42.9 ± 44.8 months. Eighteen aneurysms increased in size. Follow-up period to growth was 25.4 ± 20.8 months. Growth rate was highly variable (0.74 ± 3.23 mm/year). On univariate log-rank or Cox regression test, only history of transient ischemic attack (TIA) (P = 0.016) showed significance for aneurysm growth. On multivariate Cox regression test, history of TIA (P = 0.010, hazard ratio = 7.939), the maximum diameter at the first CTA (P = 0.026, hazard ratio = 1.216) and history of cancer (P = 0.028, hazard ratio = 4.499). Cancers existed in breast, thyroid, and lung.

Conclusions:
Aneurysm growth rate can vary even in the same patient. Aneurysm growth frequency varied according to size and risk factors. History of cancer has not previously been associated with aneurysm growth and may benefit from further study.
Abstract WP92: Risk Factors for Thrombotic Events in the Endovascular Treatment of Ruptured Cerebral Aneurysms
Authors: Sultan-Qurraie Ali , de Havenon Adam , Lynch John , Tirschwell David , Lazzaro Marc , Fred-Fitzsimmons Brian
Published: June 2021

Introduction:
Aneurysmal subarachnoid hemorrhage (aSAH) carries a high risk of morbidity and mortality. Endovascular coiling is an effective treatment option for ruptured aneurysms and offers certain advantages over microsurgical clipping. Thromboembolism is a known complication of endovascular therapy, but little has been reported regarding its causes. We hypothesized that platelet transfusion (PT) is a risk factor for thrombotic events (TE) during endovascular therapy.

Methods:
We retrospectively evaluated 84 patients presenting with aSAH to a Comprehensive Stroke Center in the United States between 2011 and 2015 who underwent endovascular treatment. In addition to TE related to endovascular aneurysm repair, charts were reviewed for variables including length of hospitalization, 3-month modified Rankin Scale (mRS), and smoking. Intergroup differences were evaluated with a Chi-squared and Student’s t-test. Logistic regression models were also fitted to the outcome of TE.

Results:
Patient demographics and clinical variables are seen in Table 1. 23% of patients incurred TE. Platelet transfusion was more common in patients with TE, but this association was not statistically significant in the logistic regression models (Table 2). In the adjusted model, active smoking and procedure length remained significantly associated with TE.

Conclusion:
To our knowledge, risk factors for thrombotic events in the setting of endovascular cerebral aneurysm treatment have not been previously reported. Procedure length and active smoking are associated with TE, and PT has a trend towards significance. After adjusting for potential confounders, active smoking remains the best predictor of TE (p=0.004), conferring an 11-fold risk.
Abstract WP94: Emphysema: A Potential Risk Factor for Ruptured Cerebral and Aortic Aneurysms
Authors: Mahta Ali , Merkler Alexander E , Reznik Michael E , Kamel Hooman
Published: June 2021

Background:
Whether emphysema is associated with the development and rupture of cerebral and abdominal aortic aneurysms is unclear.

Methods and Materials:
We performed a retrospective cohort study using outpatient and impatient claims data from a nationally representative 5% sample of Medicare beneficiaries > 66 years of age. Our predictor variable was emphysema and our outcome was a hospitalization for aneurysmal subarachnoid hemorrhage (SAH) or ruptured aortic aneurysm. All predictors and outcomes were defined using previously reported

International Classification of Diseases, 9
th
Revision, Clinical Modification

(
ICD-9-CM
) diagnosis code algorithms. Survival statistics were used to calculate incidence rates and Cox regression was used to measure the association between emphysema and outcomes while adjusting for demographics and previously reported risk factors for aneurysm rupture: hypertension, diabetes, and tobacco and alcohol use.

Results:
We identified 133,337 patients with emphysema and 1,484,760 patients without emphysema. Over a mean follow-up period of 4.3 (+/-1.9) years, we identified 5,396 cases of aneurysm rupture, 477 of which occurred in patients with emphysema. The annual incidence of aneurysm rupture was 159 (95% confidence interval [CI], 146-174) per 100,000 in patients with emphysema and 74 (95% CI, 72-76) per 100,000 in patients without emphysema. After adjusting for demographics and other risk factors, emphysema was independently associated with aneurysm rupture (hazard ratio [HR], 1.6; 95% CI, 1.4-1.8). In secondary analyses, emphysema was associated with both aneurysmal SAH (HR, 1.4; 95% CI, 1.2-1.6) and ruptured aortic aneurysm (HR, 2.1; 95% CI, 1.7-2.5).

Conclusion:
Patients with emphysema faced an increased risk of developing SAH and aortic aneurysm rupture. This finding is consistent with the hypothesis that protease/anti-protease imbalance, which is seen in emphysema, may play a role in vessel wall weakening and the development and rupture of aneurysms.
Abstract WP98: Role of Hydrogen Peroxide in Preconditioning of Microglia to Achieve Improved Hematoma Cleanup After ICH
Authors: Zhao Xiurong , Sun Guanghua , Ting Shun-Ming , Aronowski Jaroslaw
Published: June 2021

Background:
Red blood cells (
RBC
) and other blood components deposited in brain parenchyma during intracerebral hemorrhage (
ICH
) are the source of secondary brain injury, inflammation, and oxidative stress. Therefore, a fast and efficient removal of the blood from the brain is essential for ameliorating secondary injury and for recovery and repair process. Microglia/macrophages (
MΦ
)-mediated phagocytosis is a key component of hematoma clearance after ICH. However, the high levels of pro-oxidative molecules (including

H
2
O
2

) generated by MΦ during phagocytosis could be highly cytotoxic not only to brain cells, but also to MΦ themselves. Thus, an efficient coupling between MΦ-mediated phagocytosis and anti-oxidative processes is essential for the safe and efficient hematoma cleanup.

Methods and Results:
H
2
O
2
at higher concentrations is known to be neurotoxic. In this study, we established that H
2
O
2
at submicromolar, biologically relevant concentrations, acts as a pro-survival factor for MΦ. By activating transcription factor nuclear factor-erythroid 2 p45-related factor 2 (
Nrf2
), a master regulator of anti-oxidative regulation, H
2
O
2
stimulates the expression of many antioxidant proteins, which protects MΦ from oxidative injury and damaging components of inflammation. We established that Nrf2-deficient MΦ are more susceptible to H
2
O
2
-mediated or toxic blood components-mediated damage (“ICH-like” injury). Nrf2-KO mice subjected to ICH experienced more severe brain edema and delayed hematoma resolution. In addition, the phagocytosis of RBCs (in vitro model of hematoma clearance) was significantly diminished in MΦ treated with Nrf2 decoy or in MΦ that were harvested from Nrf2-KO mice. On the other hand, pharmacologic activation of Nrf2 or administration of low dosages of H
2
O
2
improved phagocytic capacity of MΦ toward RBC. Furthermore, low levels of H
2
O
2
protected MΦ from ICH-like injury, suggesting that improved phagocytic function could involve preservation of MΦ’ integrity by activating Nrf2.

Conclusion:
H
2
O
2
at low doses could protect MΦ for oxidative injury and facilitate their phagocytic function, which could benefit hematoma clearance, inflammation resolution, and improve neurological recovery after ICH.
Abstract 1: Optical Coherence Tomography Imaging in Acute Ischemic Stroke: Preliminary Animal and Human Results
Authors: Pasarikovski Christopher , Keith Julia , daCosta Leodante , Ramjist Joel , Dobashi Yuta , Black Sandra E , Yang Victor
Published: June 2021

Background:
Studies evaluating endothelial injury after EVT have been done by means of retrieved human thrombus, MR vessel-wall imaging, and animal histopathologic studies. These techniques have limitations, as MR imaging has insufficient spatial resolution to directly visualize endothelium, and histopathologic examinations are ex-vivo and unable to provide real-time patterns of injury.

Objective:
Endovascular imaging after EVT using optical coherence tomography (OCT) to examine for vessel injury in real-time.

Methodology:
Three swine weighing 35-40kg were selected for the animal model. Autologous venous whole-blood was used to create thrombus. A second-generation stent retriever was used for EVT. Next, three consecutive patients with basilar artery occlusion underwent EVT and endovascular OCT imaging.

Results:
In the animal model, revascularization and OCT imaging was successful for all 9 vessels. Endothelial injury was observed in 4/9 (44%) of vessels, and residual thrombus was observed in 4/9 (44%) of vessels despite complete angiographic revascularization. All vessels undergoing EVT after 6 hours had evidence of endothelial injury, and 2/3 (66%) had residual thrombus. Two basilar stroke patients (2/3) 66% had significant residual thrombus despite complete angiographic revascularization. The residual thrombus was also not visible on CT angiography or MR imaging done within 24 hours of EVT.

Conclusions:
Endothelial injury and residual thrombus despite complete revascularization is present after EVT and can be observed in real-time using OCT. It is possible that the longer occlusive thrombus is present, the more endothelial injury will occur during EVT.
Abstract 10: Outcomes of Drip-and-Stay Telestroke Patients at Spoke Sites With Rehabilitation Units
Authors: Nahhas Michael I , Almallouhi Eyad , Baki Linda M , Grant Cheryl , Al Kasab Sami , Holmstedt Christine A
Published: June 2021

Background and Purpose:
In spite of the increase of thrombolysis treatment rates at remote hospitals (spoke) due to implementation of telestroke systems, only 25% of telestroke patients who received tissue plasminogen activator (tPA) are transferred to a Comprehensive Stroke Center (CSC) in the United States. This leaves 3 out of 4 treated patients to receive their post-stroke care at telestroke spoke sites. As post-stroke rehabilitation is a pivotal component of recovery, we aimed to report outcomes of acute ischemic stroke (AIS) patients who received thrombolytic therapy, yet remained at a spoke hospital with a rehabilitation unit (RU).

Methods:
This was a retrospective review of the telestroke registry at our institution from January 2016 through July 2019. We included patients who received intravenous tPA at spoke sites and were not candidates to be transported to a CSC for mechanical thrombectomy (Drip-and-Stay paradigm). We compared baseline characteristics, discharge disposition, and excellent outcome [defined as a 90-day Modified Rankin Scale (mRS) of 0-1] of patients who remained at spoke sites with a RU to patients at spoke sites without a RU. A logistic regression model was used to assess the effect of RU on the possibility of having excellent outcomes controlling for confounding factors.

Results:
Of the 740 eligible AIS patients during the study period, 40% (n=294) received post-stroke care at a spoke with a RU. There were no significant differences in patient age, sex, admission NIHSS, door to needle times, or length of stay between patients in both groups. More patients in the spoke with rehabilitation units were discharged home (62% vs. 52%, P=0.001). Excellent long-term functional outcome was reported in 66% (n=193) of patients remaining at spoke sites with RU versus 58% (n=285) at those without RU (P=0.033). On multivariate analysis, RU was an independent predictor of having excellent outcomes (OR 2.02, 95% CI 1.42-2.87, P<0.001).

Conclusions:
Our study indicates a higher likelihood of both favorable discharge outcome and excellent long-term functional outcome in drip-and-stay patients who receive their post-stroke care at spoke sites with RU.
Abstract 101: Predictors of Early Neurological Deterioration in Minor Strokes With Large Vessel Occlusion Treated With Intravenous Thrombolysis. A French Multicentric Observational Study (MINOR-STROKE)
Authors: Seners Pierre , Perrin Claire , Turc Guillaume
Published: June 2021

Introduction:
Whether thrombectomy added on intravenous thrombolysis (IVT), as compared to IVT alone, is beneficial in minor strokes with large vessel occlusion (LVO) is unknown. To identify predictors of early neurological deterioration (END) following IVT alone may help to select the best candidates for additional thrombectomy.

Methods:
MINOR-STROKE was a multicentric retrospective registry collecting data of IVT-treated minor strokes (NIHSS≤5) with LVO (internal carotid artery [ICA], M1, M2 or basilar artery; with central reading) treated with or without additional thrombectomy in 45 French stroke units. The patients initially intended for IVT alone, including those who eventually received thrombectomy due to END, were included in the present analysis. END was defined as a ≥4 points on NIHSS within 24hrs following admission. Thrombus length was measured centrally either on T2*-MRI, CT (hyperdense middle cerebral artery) or CT-angiography.

Results:
Overall, 799 patients were included: mean age 69 years, median NIHSS 3, occlusion located in ICA±M1/M2, proximal M1, distal M1, M2, or basilar artery in 20%, 7%, 19%, 50% and 4% of patients, respectively. Thrombus was visible in 78% of patients (median length 9mm, IQR 6-12mm). END occurred in 15% of patients and was associated with poor 3-month functional outcome (mRS>2: 55%
vs.
12% of patients with and without END, respectively). Only 15% of ENDs were due to intracranial haemorrhage. In multivariable analysis, a more proximal occlusion site (M2 [reference], distal M1: OR 2.1 [IC95% 1.1-4.1], proximal M1: OR 3.8 [1.6-9.1], ICA±M1/M2: OR 5.0 [2.6-9.6], basilar artery: OR 4.9 [1.1-4.1];
P
<0.001) and a longer thrombus (<6mm [reference], [6-9mm[: OR 1.3 [IC95% 0.6-2.9], [9-12mm[: OR 1.8 [0.8-3.9] and ≥12mm: OR 2.7 [1.3-5.6];
P
=0.036) were independently associated with END. END occurred in 33%, 19%, 14%, 7% and 27% of patients with ICA±M1/M2, M1 proximal, M1 distal, M2 and basilar artery, respectively, and in 8%, 10%, 14% et 23% of patients with thrombus length of <6, [6-9[, [9-12[ and ≥12mm, respectively.

Conclusion:
Our study suggests that thrombus location and length are strong predictors of END in minor strokes with LVO. This may help to select the best candidates for additional endovascular therapy.
Abstract 108: Sex Differences in Stroke-induced Lymphocyte Responses in the Gut Epithelia
Authors: Lee Juneyoung , Quaicoe Victoria , Holmes Aleah , Ganesh Bhanu P , McCullough Louise D , Venna Venugopal R
Published: June 2021

Introduction:
Stroke is a sexually dimorphic disease. Notably, emerging evidence suggests that stroke leads to gut dysbiosis and pathological shifts in the gut microbiota. However, little is known about how the gut epithelial surface maintains homeostasis after stroke. In this study, we isolated intraepithelial lymphocytes (IELs), which are mainly CD8
+
T cells and do not need priming against antigens, as well as intestinal epithelial cells (IECs). We examined their responses to stroke-induced gut epithelial damage.

Methods:
C57BL/6 (2-3 months) mice of both sexes were subjected to either 60-minute middle cerebral artery occlusion or sham surgery. At day 7 after stroke, IECs and IELs, which are intercalated between IECs, were isolated from mouse colonic tissues using Percoll density gradients. RNA was isolated from the cells and amplified to quantitate expression levels of cell-specific genes for antibacterial proteins and chemotactic cytokines. Tissues were then used for histological analysis by hematoxylin and eosin staining and bacterial fluorescence in situ hybridization (FISH).

Results:
Stroke caused significant colonic damage in male mice, compared to female mice. Bacterial FISH demonstrated microbial encroachment into the host gut epithelium in males after stroke; whereas female mice maintained spatial segregation between the host gut and bacteria. Stroke increased expression levels of pro-inflammatory cytokine genes in male IELs including IL-1β (28.3 fold increase,
P
<0.05), KC or CXCL1 (5.8 fold increase,
P
<0.05) and MIP2α or CXCL2 (9.9 fold increase,
P
<0.05) after stroke compared with sham mice. Additionally, both IELs and IECs of male stroke mice exhibited an up-regulation of antimicrobial protein gene, regenerating islet-derived protein 3 (Reg3γ,
P
<0.05). This pattern of up-regulation, however, was not present in female mice.

Conclusions:
This is the first study that demonstrates robust sex differences in lymphocyte responses at the gut mucosal surface between males and females following stroke. The closer proximity of the gut microbiota with the host may direct gene expression related to microbial responses in the injured epithelium after brain injury. Our study provides novel insight into host-microbial homeostasis in stroke.
Abstract 11: Assessing the True ImpACT-24B: Magnitude of Benefit of Sphenopalatine Ganglion Stimulation for Acute Ischemic Stroke with Confirmed Cortical Involvement
Authors: Ordonez Fausto E , Liebeskind David , Bahr Mersedeh , Shuaib Ashfaq Shuaib , Bornstein Natan , Hill Michael , Molina Carlos , Saver Jeffrey
Published: June 2021

Background:
Sphenopalatine ganglion (SPG) stimulation enhances collateral flow, stabilizes blood-brain barrier, and showed evidence of benefit in patients with confirmed cortical involvement (CCI) when started 8-24h after onset in the ImpACT-24B randomized trial. To characterize SPG stimulation benefit magnitude, we derived number needed to treat (NNT) values based on shifts over all levels of 3 month global disability.

Methods:
From the distribution of the 7-level modified Rankin Scale (mRS) at 3m in SPG- and sham-stimulation CCI patients, NNT to benefit (NNTB) and NNT to harm (NNTH) values were derived by automated (algorithmic min-max) and expert generation of joint outcome distribution tables. For dichotomized mRS outcomes, net NNT values were derived directly from absolute risk differences.

Results:
Among 520 patients with confirmed cortical infarction ineligible for thrombolysis, 244 were treated with SPG and 276 with sham stimulation. NNT values for dichotomized and shift mRS outcomes are shown in the Table. Of the 6 possible binary cutpoints on the mRS, 4 showed more favorable outcome with SPG stimulation. The dichotomized endpoint with the greatest group difference was ambulatory and capable of bodily self-care (mRS 0-3), 62.3% vs 51.1%, NNTB 8.9. Across all 6 individual possible dichotomizations of the mRS, the NNTB ranged from 8.9 to -166.7. For shifts by 1 or more levels across all 6 transitions of the mRS, the biologically most plausible NNTB was 5.7 (IQR 5.6-6.5), NNTH 34.5 (IQR 30.3-40.0), and net NNTB 6.8 (IQR 6.5-7.7), These values correlated closely with the automatically derived net NNTB of 5.9.

Conclusions:
The findings of this pivotal trial indicate that, out of every 1000 CCI patients treated with SPG stimulation, 146 patients will have a less disabled 3-month outcome, including 76 more who will be functionally independent. SPG stimulation can substantially improve the outcome of thrombolysis-ineligible acute ischemic stroke patients.
Abstract 113: Regulatory T Cells Contribute to Sexual Dimorphic Outcomes After Acute Ischemic Brain Injury
Authors: Sun Zeyu , Su Wei , Shi Ligen , Chen Jie , Hu Xiaoming
Published: June 2021

Introduction:
The contribution of CD4
+
Foxp3
+
regulatory T cells (Treg) to acute stroke outcomes has been controversially reported in young male murine models of stroke, their effects in female stroke mice, however, are not characterized. This study explored the sexual dimorphisms in Treg and its contribution to acute stroke outcomes.

Methods:
Cerebral ischemia was induced by 60 min tMCAO in male or female (Young: 10-week, aged: 15-month) wild type (WT) mice and DTR mice expressing the diphtheria toxin (DT) receptor under the control of Foxp3 promoter. Tregs depletion was achieved by DT injection in DTR mice for 3 days prior to tMCAO. Infarct volume, sensorimotor functions and peripheral immune cell populations were assessed up to 5d after stroke. For RNA sequencing analysis, Tregs were sorted from blood of male or female DTR mice at 5d after sham or tMCAO surgery.

Results:
Young Treg competent (WT mice or DTR mice without DT) female mice exhibited significantly reduced infarct volume, as assessed by MRI T2 scanning and MAP2 staining, and greatly improved sensorimotor functions (rotarod test and adhesive removal test) compared to age- and genotype-matched male mice (n=8/group) 5d after tMCAO. Treg depletion deprived the neuroprotection in young female, while showed no significant effect on young male or aged female mice (n=8/group). RNA-seq analysis showed that IFN-γ signaling was downregulated in female Treg while upregulated in male Treg, suggesting a sexual difference in Treg-mediated immune response after stroke. Flow cytometry revealed ameliorated immune cell activation in blood and brain in female vs male mice 5d after stroke. Furthermore, Treg were isolated from young female, young male, aged female or female mice subjected to ovariectomy, and adoptively transferred (1 million cell/animal, iv) to young male mice 1 hour after tMCAO. Only young female Treg significantly reduced the infarct volume and improved sensorimotor functions compared to other treatment groups (n=7-8/group).

Conclusion:
Treg contribute to the neuroprotection in young female vs male in an age- and hormone-dependent manner. Transcriptomic analysis uncovered sexual differences in an IFN-γ centered regulatory pathways in Tregs, which keep post-stroke immune responses in check.
Abstract 120: Systolic Blood Pressure Trajectories 72 Hours After Mechanical Thrombectomy Are Associated With Poor Functional Outcome: A Multicenter Analysis of Individual Patient Blood Pressure Data
Authors: Kodali Sreeja , Meng Can , Strander Sumita , Nguyen Cindy Khanh , Silverman Andrew , Kimmel Alexandra , Peshwe Krithika Umesh , Wang Anson , Anadani Mohammad , Spiotta Alejandro M , de Havenon Adam , Wong Ka-Ho , Holcombe Andrea , Ortega-Gutiérrez Santiago , Zevallos Cynthia , Mistry Eva A , Fakhri Hiba , Mistry Akshitkumar , Tarasaria Karan , Nouh Amre , Maier Ilko L , Psychogios Marios-Nikos , Liman Jan , Goyal Nitin , Arthur Adam S , Pandhi Abhi , Wolfe Stacey Q , Nascimento Fábio A , Kan Peter , Riou-Comte Nolwenn , Gory Benjamin , Kim Joon-Tae , Sheth Kevin N , Petersen Nils
Published: June 2021

Introduction:
Blood pressure (BP) is an important modifiable parameter after endovascular thrombectomy (EVT). Observational studies have found associations between elevated BP after EVT with hemorrhagic transformation and poor functional outcome. However, blood pressure course after EVT has not been well characterized and optimal hemodynamic management in the immediate post-stroke period remains unresolved. We utilized blood pressure data up to 72 hours after EVT to identify distinct systolic BP (SBP) trajectories and studied their associations with functional outcome.

Methods:
We retrospectively studied a multicenter cohort of 1060 patients with large-vessel occlusion stroke who underwent EVT. BP was recorded non-invasively recorded at least hourly for the first 72 hours. Functional outcome was assessed using the modified Rankin scale (mRS). Favorable functional outcome was defined as mRS <. Latent variable mixture modeling was applied to identify patient subgroups that have comparable SBP trajectories. All analyses were adjusted for age, admission NIHSS, and recanalization status.

Results:
One thousand sixty patients (mean age 70±15, mean NIHSS 16) were included in the analysis. Five distinct SBP trajectories were identified: (1) low (17%), (2) moderate (38%), (3) moderate-to-high (21%), (4) high-to-moderate (17%), and (5) high (7%) (Figure 1A). SBP trajectory group was an independent predictor of functional outcome at discharge (p=0.001) and 90 days (p=0.010, Figure 1B). Patients with high and high-to-moderate SBP trajectories had a significantly higher odds of an unfavorable outcome at 90 days (adjusted OR 2.3, 95%CI 1.2 - 4.3, p=0.01 and adjusted OR 4, 95% CI 1.5-10.7, p=0.06, respectively)

Conclusions:
During the first 72 hours after EVT, acute ischemic stroke patients show distinct SBP trajectories, which differ in relation to functional outcome. The findings may help recognize potential candidates for future blood pressure control trials.
Abstract 130: Outcomes of Rescue Endovascular Treatment of Acute Ischemic Stroke in Patients With Underlying Intracranial Atherosclerosis- Insights From the STAR Registry
Authors: Al Kasab Sami , Almallouhi Eyad , Casey Michael A , Alawieh Ali , Chalhoub Reda M , Psychogios Marios , Arthur Adam , Kim Joon-Tae , De Leacy Reade , Rai Ansaar , Keyrouz Salah , Fargen Kyle M , Dumont Travis , Kan Pater , Starke Robert M , Spiotta Alejandro M
Published: June 2021

Introduction:
Mechanical Thrombectomy (MT) is currently the standard of care for patients presenting with emergent large vessel occlusion (ELVO) with salvageable tissue. A subgroup of patients with ELVO are found to have refractory occlusion due to underlying intracranial atherosclerosis (ICAS), often requiring angioplasty with or without stenting. Whether this treatment is safe or effective in this group of patients remains to be established. The purpose of this study is to investigate the safety, efficacy and long-term outcome of MT with rescue therapy in patients with ICAS.

Methods:
STAR registry combined prospectively maintained databases of 11 thrombectomy-capable centers in the US, Europe and Asia. In this analysis, we included patients who underwent rescue balloon angioplasty and/or stenting in the setting of ELVO. A matched sample was produced by matching on the variables of age, admission NIHSS, and location of occlusion.

Results:
Out of 2827 thrombectomy patients included in STAR registry, 190 patients received MT and required rescue angioplasty and/or stenting. Balloon angioplasty was performed on 116 patients, and 84 patients had intracranial stenting. Compared to the 161 ICAS patients matched to similar number of controls. There was no difference in age, race, sex, rate of IV tPA administration, ASPECTS score, or onset to groin time. Successful first attempt was higher in patients with embolic LVO (22 vs 52, p=0.001), procedural time was longer in patients with ICAS (47 min Vs 31 min, p=<0.001). There was no difference in symptomatic intracranial hemorrhage, or long term functional outcome.

Conclusion:
In patients with ELVO with underlying ICAS requiring rescue angioplasty and/or stenting; despite longer procedural time and lower rate of first pass revascularization, rescue therapy appears to be safe with similar complication rates and long-term functional outcomes compared to patients with large vessel occlusion from embolic source.

Table 1: