bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP91: Open-cell Stent Design for Coil Embolization of Side Branching Vessel Internal Carotid Artery Aneurysms: Clinical and Angiographic Results
Authors: Hou Samuel Y , Kuhn Anna Luisa , Gounis Matthew J , Wakhloo Ajay K
Published: March 2022

Background and Purpose:
Treatment of side branch internal carotid artery (ICA) cerebral aneurysms, i.e. ophthalmic and anterior choroidal artery aneurysms, pose unique treatment difficulties. Visual loss or anterior choroidal artery territory infarcts have been reported as clinical sequelae for both surgical and endovascular treatment approaches for these aneurysms. Here we evaluate the safety and efficacy of endovascular treatment by use of open cell design for stent assisted coil embolization of side branch ICA aneurysms.

Materials and Methods:
Between 2007 and 2012, 60 consecutive patients treated with open cell stent assisted coil embolization for a cerebral aneurysm were reviewed. Inclusion criteria were wide neck aneurysms incorporating an ICA branching vessel at the neck of the aneurysm. Aneurysm occlusion was assessed on cerebral angiograms by using the Raymond Score immediately after endovascular treatment and at 6 months follow-up. Clinical outcomes were assessed by the modified Rankin Scale (mRS) at baseline, discharge and 6 months follow-up.

Results:
Of the 60 consecutive patients treated with open cell stent assisted coil embolization, 6 patients were identified as having side branching ICA cerebral aneurysms. In each of these 6 cases, the side branching ICA vessel originated from the neck of the aneurysm. Flat panel CTA obtained post open cell stent deployment showed preferential outward herniation of open cell stent struts towards the neck of the aneurysm, thus protecting the side branching vessel. On immediate post treatment angiograms, a Raymond Score of 1 was assessed on each of these 6 aneurysms with patency of the side branching vessel. A mRS of 0 or 1 was assessed at baseline and at discharge on all 6 patients. A Raymond Score of 1 was also identified on 3 of the 6 aneurysms on the 6 months follow-up exam. 3 additional patients are still awaiting their 6 months follow-up. Of the 3 patients that have received 6 months follow-up, all 3 patients have a stable mRS of 0 or 1.

Conclusions:
Our short to mid-term results for open cell stent assisted coil embolization of side branch ICA aneurysms is safe and effective. The independent open cell stent strut’s outward radial force protects side branching vessels that originate from the neck of these aneurysms.
Abstract 103: Mobile Telestroke During Ambulance Transport is Feasible in a Rural EMS setting - pilot data from the
Improving Treatment with Rapid Evaluation of Acute stroke via mobile Telemedicine (iTREAT)
study
Authors: Lippman Jason M , Chapman Sherita N , Gunnell Brian , McMurry Timothy L , Mehndiratta Prachi , Burns Donna M , Perina Debra G , Solenski Nina J , Worrall Bradford B , Southerland Andrew M
Published: March 2022

Introduction:
The American Heart Association-American Stroke Association (AHA-ASA)
Target:Stroke
iniative calls for innovative approaches to prehospital stroke care. We hypothesize that mobile telestroke from a hospital-based neurologist to an ambulance-based provider, using tablet devices and commercially available broadband, will facilitate earlier stroke diagnosis and more accurate prenotification to reduce stroke onset-to-treatment times.

Methods:
We assessed the technical feasibility of mobile teleconferencing along the six common rural emergency medical service (EMS) routes into the University of Virginia Medical Center, allowing a minimum travel time of 15 minutes and continuous connectivity of 5 minutes. Our mobile telestroke platform included Apple iPad with retina display, high-speed 4G LTE modem, Cisco Jabber secure video conferencing application, and magnetic-mount external antennae. Continuous mobile connectivity was facilitated through the commercial Verizon Wireless network. Continuous transmission audiovisual (AV) quality along each route was rated by independent raters from both hospital and vehicle using a standardized six-point scale (≥4 indicating technical feasibility).

Results:
Of 31 test runs, two had extraneous technical issues and one failed to meet the minimum duration for continuous connectivity. The mean transmission video quality rating was 4.51 (4.54 vehicle; 4.48 hospital) and overall audio quality 5.00 (5.13 vehicle; 4.87 hospital). Both raters deemed AV quality as "good" or "excellent" (rating ≥4) for 78.5% of test runs. Five out of six EMS routes consistently demonstrated feasible connectivity, with 87.5% of runs achieving "good" or "excellent" bidirectional AV quality for these five routes.

Conclusion:
Our pilot data suggest technical feasibility for mobile teleconferencing between transporting ambulance and hospital-based provider using low-cost, off-the-shelf technology and commercial networks. These results support our hypothesis that mobile telestroke in a rural EMS setting can be implemented. Further troubleshooting along routes with limited connectivity, and prospective testing of the impact on stroke diagnosis and time-to-treatment is planned.
Abstract 107: Infectious Burden and Cognitive Performance: the Northern Manhattan Study
Authors: Wright Clinton B , Gardener Hannah , Dong Chuanhui , Marquez Chensy , DeRosa Janet T , Cheung Kenneth , Sacco Ralph L , Stern Yaakov , Elkind Mitchell S
Published: March 2022

Background:
Serological evidence of the burden of common infections (IB=infectious burden) has been associated with stroke, carotid atherosclerosis, and global cognitive function in the race/ethnically diverse community-based Northern Manhattan Study (NOMAS) cohort. We hypothesized that IB is associated with worse performance and decline on a battery of neuropsychological tests.

Methods:
A subsample of stroke-free NOMAS participants underwent a neuropsychological battery, and a subsample of these had repeated testing a mean of six (SD=2) years later. Using factor analysis-derived domain-specific Z scores for memory, language, executive function, and processing speed, we examined associations between a quantitative IB index previously associated with stroke risk and based on five common infections (Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex viruses 1 and 2) and cognitive performance in each domain. We used multivariable linear regression and adjusted for age, sex, education, race/ethnicity, insurance status, diabetes, hypertension, hypercholesterolemia, BMI, moderate alcohol, moderate-heavy physical activity, and smoking.

Results:
There were 588 NOMAS participants with IB index and cognitive data (mean age=71, 62%women, 14% white, 16% black, 70% Hispanic) and 287 with repeat cognitive testing. After adjusting for demographic variables, IB index was inversely associated with all cognitive domains, although not all associations were significant (executive function, beta=-0.11, p=0.002; language, beta=-0.07, p=0.04; memory, beta=-0.06, p=0.11; processing speed, beta=-0.07, p=0.07). These effects attenuated only slightly after adjusting for vascular risk factors. The IB index associated with cognitive decline across domains, but a trend toward significance existed only for memory, after adjusting for baseline performance, demographic and vascular risk factors (beta=-0.09, p=0.07).

Conclusions:
A quantitative measure of IB associated with stroke risk was inversely associated with executive function and language, and decline in memory performance. Past exposure to common infections may contribute to vascular cognitive impairment and warrant further study.
Abstract 111: Outpatients Referred for Carotid Doppler Evaluation Who Have Elevated Coated-Platelets Demonstrate Early Cognitive Impairment
Authors: Kirkpatrick Angelia , Vincent Andrea , Dale George , Prodan Calin
Published: March 2022

Background:
Coated-platelets, a subset of procoagulant platelets observed upon dual agonist stimulation with collagen and thrombin, support a robust prothrombinase activity and provide a unique measure of platelet thrombotic potential. Our recently published data show that coated-platelet levels are increased in large artery stroke compared to controls, and higher levels are associated with early stroke recurrence. Because carotid occlusive disease and recurrent strokes are known risk factors for cognitive decline, we investigated the impact of coated-platelets on cognitive function among patients referred for carotid Doppler evaluation.

Methods:
Sixty consecutive patients without known dementia or stroke referred for carotid Doppler evaluation were screened for evidence of cognitive impairment using the Montreal Cognitive Assessment (MoCA). Coated-platelets were determined at baseline and are reported as percent of cells converted to coated-platelets. Differences in mean coated-platelet levels between groups were assessed using the independent t-test and ANCOVA.

Results:
Fifty-seven percent (34/60) had evidence of cognitive impairment (MoCA<26, range 17-25). Mean coated-platelets for patients with cognitive impairment were significantly higher compared to patients with normal cognitive function (42.7 ± 11.5% vs. 34.1 ± 12.3%; mean ± SD; p=0.008), which remained significant after adjusting for age, remote history of stroke, carotid stenosis, and statin use (p=0.013).

Conclusions:
Coated-platelets are elevated in patients at risk for cerebrovascular disease who have cognitive impairment compared to those with normal cognition. The increased prevalence of vascular risk factors and range of abnormal MoCA scores (17-25) suggest that the cognitively impaired individuals are in the early stages of vascular cognitive impairment. The key finding in this study is the existence of a link between coated-platelets, cerebrovascular disease risk, and early vascular cognitive impairment, which is in keeping with the chronic disease model of vascular dementia etiology.
Abstract 112: Long-term Cognitive Changes after Stroke: The Regards Study
Authors: Levine Deborah A , Galecki Andrzej T , Langa Kenneth M , Unverzagt Frederick W , Kabeto Mohammed U , Giordani Bruno J , Wadley Virginia G
Published: March 2022

Objective:
Although stroke’s short-term cognitive effects are known, less is known about long-term cognitive changes after stroke. We determined changes in cognitive function among survivors of incident stroke, controlling for prestroke cognition.

Methods:
REasons for Geographic And Racial Differences in Stroke participants aged 45-84 years were recruited from 2003-2007 and followed through March 2013. Cognitive function was assessed every 18-24 months with the Consortium to Establish a Registry for Alzheimer’s Disease Word List Delayed Recall (WLD), a verbal memory test, and the Animal Fluency Test (AFT) of executive function. Adults with cognitive impairment (Six Item Screener <5) or incident stroke before their first WLD or AFT test were excluded. We examined changes in cognitive function over time, adjusting for time-varying incident stroke and initial values of cognitive scores, socio-demographics, vascular risk factors, and clinical factors using linear mixed effects models.

Results:
There were 10,665 adults with ≥1 follow-up WLD measure, of whom 190 had incident stroke, and 11,909 with ≥1 follow-up AFT measure, of whom 213 had incident stroke. Participants with incident stroke had acute decreases in WLD scores (adjusted decrease for incident stroke vs. no stroke, 1.58 points; 95% CI, 0.90-2.27 points) and AFT scores (adjusted decrease, 0.78 points; 95% CI, 0.23-1.33 points)(Figure). Following stroke, WLD scores improved over time (adjusted improvement, 0.24 points per year; 95% CI, 0.07-0.40; P for stroke*time interaction=0.005) but AFT scores did not change significantly (P for stroke*time interaction=0.91) compared with pre-stroke slopes.

Conclusion:
In this prospective population-based cohort, incident stroke was associated with significant new deficits in verbal memory and executive function and a new slope for verbal memory. These findings suggest that verbal memory recovers years after stroke, but executive function deficits persist.
Abstract 113: Dodecafluoropentane Emulsion Delays and Reduces MRI Markers of Infarction in a Rat Stroke Model
Authors: Fitzgerald Ryan T , Nix J. S , Brown Aliza T , Arthur Melinda C , Ou Xiawei , Skinner Robert D , Borrelli Michael J , Culp William C
Published: March 2022

Introduction:
Dodecafluoropentane emulsion (DDFPe), a perfluorocarbon suspension, transports oxygen to ischemic regions of the brain, making it an ideal neuroprotectant for patients with acute stroke. Although DDFPe has been shown through analysis of excised tissue to reduce infarct volume, relatively little is known about the mechanism of DDFPe in vivo. We assess the effect of intravenous (IV) DDFPe on MRI findings in stroke evolution in the early hours after vascular occlusion in a rat stroke model.

Hypothesis:
We hypothesize that DDFPe will delay the development of MRI markers of acute ischemic stroke and/or reduce infarct volume compared to controls.

Methods:
With IACUC approval rats were assigned to control (n=4) and treatment (n=10) groups. All rats underwent permanent, unilateral surgical occlusion of the middle cerebral and common carotid arteries. The treatment group received 1 IV dose of 2% w/v DDFPe at 0.6 mL/kg at 1 hour post-occlusion while the control group received none. Diffusion Weighted (DWI) and Inversion Recovery (IR) MRI sequences were obtained over 4 hours after occlusion. Scans were reviewed and scored by consensus of two board certified and blinded radiologists, and the number of abnormal MRI slices per sequence was tallied for each group and time point. Student’s T-test was applied.

Results:
The mean ±SE numbers of abnormal slices were decreased in the DDFPe group vs. control over total time points for IR at 5.43 ±0.40 vs. 7.38 SE ±0.58 (P=0.01) and DWI at 9.14 ±1.11 vs. 13.88 ±1.79 (P=0.03). Development of abnormal DWI and IR signal was delayed by DDFPe (see Graph) with significance for IR at 2 hours at 5.5 ±0.97 vs. 8.25 ±0.63 (P=0.04) and 3 hours at 5.14 ±0.83 vs. 7.75 ±0.48 (P=0.02).

Conclusions:
DDFPe delays and reduces MRI markers of acute ischemic stroke in the early hours following vascular occlusion in a rat stroke model. Further study is warranted.
Abstract 114: Interim Recanalization in Acute Ischemic Stroke Patients Selected for Endovascular Treatment by CT Angiography
Authors: Qureshi Mushtaq H , Siddiq Farhan , Kaint Daraspreet , Qureshi Adnan I
Published: March 2022

Background:
In the Interventional Management of Stroke III trial, there was a 35% incidence of improvement or resolution of occlusion in IV alteplase treated patients selected by computed tomographic (CT) angiogram for endovascular treatment.

Objective:
To determine the frequency of resolution or change in occlusion site in patients with CT angiogram demonstrated occlusion in IV alteplase treated or untreated patients.

Methods:
All acute ischemic stroke patients who underwent a computed tomographic (CT) angiogram and subsequently underwent endovascular treatment were included. The CT angiogram images were reviewed by an independent reviewer to determine presence and location of arterial occlusion and severity of occlusion was classified by a previously described grading scheme. The cerebral angiographic images were reviewed for similar endpoints. Clinical outcome at discharge was determined using modified Rankin scale (mRS).

Results:
CT angiogram was performed in 151 patients (mean age ± SD of 64±16 years) prior to endovascular treatment. The mean interval (±SD) between CT angiogram and cerebral angiogram was 190±10 (min) and 66 of 151 patients (43.7%) received IV alteplase prior to cerebral angiography. The rate of any recanalization prior to cerebral angiography was 28 of 151 (18.5%) and no change in occlusion was found in 92 (60.9%) patients whereas 31 (20.5%) patients showed worsening in occlusion based on the grading scheme. The rate of interim recanalization was similar in IV alteplase treated patients versus untreated patients (19.6% vs % 17.6, p= 0.7) The frequency of Angiographic recanalization following endovascular treatment was similar in both groups (67.8% versus 71.2%, p=0.7), After adjusting for age and initial NIHSS score strata, interim recanalization was not associated with higher rate of mRS 0-2 at discharge (OR 1.9, 95% CI 0.7-5.2).

Conclusions:
A relatively high proportion of patients have interim recanalization between CT angiogram and cerebral angiogram in acute ischemic stroke patients selected for endovascular treatment.
Abstract 121: Effects of Modifiable Risk Factors on the Age of Collagen in Intracranial Aneurysms
Authors: Etminan Nima , Dreier Rita , Buchholz Bruce A , Beseoglu Kerim , Bruckner Peter , Torner James C , Steiger Hans J , Hänggi Daniel , Macdonald Loch
Published: March 2022

Introduction:
The time required for intracranial aneurysms (IAs) to develop until their diagnosis is unknown. We used a novel method of vascular radiocarbon birth dating of collagen extracted from aneurysms of patients undergoing surgical repair of ruptured and unruptured IAs to estimate their ages.

Methods:
Between 03/2009 and 04/2013, 46 aneurysm samples from 43 patients were obtained. Collagen was extracted and purified after pepsin digestion of IA tissue. and accelerator mass spectrometry was used to measure
14
C levels in the collagen samples. The age of the aneurysm collagen was estimated and then correlated with patient age, incidence of modifiable risk factors for aneurysm progression, IA rupture status and morphological measurements.

Findings:
Nearly all collagen in cerebral aneurysms was five or less years old, irrespective of patient age, aneurysm size, morphology, or rupture status. However, IAs from patients with a history of risk factors for aneurysm formation (smoking and hypertension) contained significantly younger collagen, as compared to patients with no risk factors (mean 1·6 ± 1·2 years vs. 3·9 ± 3·3 years, respectively, p= 0·012).

Interpretation:
We show that chronological development of IAs can be consistently estimated, that they are relatively young when detected, and/or that there is constant collagen remodelling within them. In either case, the results suggest there are no cerebral aneurysms that are stable and old. Furthermore, aneurysm age or collagen turnover is significantly more rapid in patients with modifiable risk factors for aneurysm progression and rupture. These results have important implications for the understanding of the biology of cerebral aneurysms as well as for recommendations for follow-up of patients with unruptured cerebral aneurysms.
Abstract 123: The Unruptured Intracranial Aneurysm Treatment Score (UAITS) - Proposal of a Multidisciplinary Research Group
Authors: Etminan Nima , Beseoglu Kerim , Macdonald Loch ,   UIATS panel members
Published: March 2022

Objective:
Unruptured intracranial aneurysms (UIAs) are being identified with increasing frequency. Their natural history is being defined but their appropriate treatment remains controversial. We convened a panel of experts with the aim being the development of a treatment score (UIATS) that could guide decision making for treatment of UIAs.

Method:
An international, multidisciplinary (Neurology, Clinical Epidemiology, Neurosurgery and Neuroradiology) panel of experts on research and treatment of cerebral aneurysms was formed. Panel members were chosen to be geographically and professionally dispersed, to increase the validity of the score. A 5-round, Delphi consensus process was initiated to identify and rate all features, relevant to assess UIAs and their treatment based on current evidence and practice. Rating scales and risk percentages were repeatedly used to determine statistical weight for each factor and to exclude significant discrepancies between rounds. Medians from all rounds were then transformed into corresponding scores for every item to create the scoring system. Representative cases of patients with UIAs were used to test decision-making and the level of acceptance as well to validate the score.

Results:
A minimum of 85% of 39 experts, from 12 different countries participated in the first 4 rounds. More than 60 relevant features were initially listed by the panel. These items were subsequently rated repeatedly, until the least relevant items were omitted. The UIATS system was then created based on 13 highly relevant items. Despite some heterogeneity for individual ratings, there were no significant inconsistencies throughout the rounds. The system comprises different features of 3 main categories (patient-, aneurysm - and treatment-related factors), which all add up to one specific ratio. This ratio reflects the sum of factors supporting treatment or conservative management for UIAs, based on individual medical constellations.

Conclusion:
Following internal and external validation, this scoring system, derived from a consensus among a large, international and multidisciplinary group of experts, may aid clinicians to decide about the expected natural history and treatment risk of an UIA.
Abstract 13: Novel Humanized Recombinant T Cell Receptor Ligand Protects Brain in Females after Experimental Stroke
Authors: Pan Jie , Palmateer Julie , Schallert Tim , Offner Halina , Hurn Patricia
Published: March 2022

Background:
Recent evidence emphasizes the importance of T lymphocytes of differing subtypes in ischemic cell death mechanisms. RTL, composed of partial major histocompatibility complex (MHC) ClassIImolecules covalently bound to myelin peptides, is currently under clinical study for multiple sclerosis. We have shown that RTL is effective in male mice treated with middle cerebral artery occlusion (MCAO) by inhibiting early accumulation of inflammatory cells. We now show for the first time that post-treatment improves functional outcomes and that efficacy is present in females.

Methods:
HLA-DR2 transgenic female mice (17-20g) were subjected to 60 min MCAO (isoflurane). Cortical laser-Doppler flowmetry (LDF) was continuously monitored and only animals with LDF of below 40% of baseline during MCAO were included in study. Mice were treated with RTL1000 RTL 1000 (HLA-DR2 moiety linked to human MOG-35-55 peptide) (0.1mL, 1mg/mL sq) (RTL) or vehicle (VEH) at 3h, 24h, 48h, 72h after reperfusion. Mice were recovered for 96h or 2 weeks post-injury for measurement of histology (TTC staining) or behavioral testing respectively. Sham operated females received either vehicle or RTL and identical testing paradigms.

Results:
All sham mice showed no evidence of infarction or behavioral deficit. Mortality rate and general health score were similar between MCAO groups. RTL mice sustained smaller infarcts as compared to VEH group (% of contralateral structure): Total hemisphere: 13.9 ±4.1 % RTL (n=15) vs. 28.3 ±3.0% (p < 0.05) in VEH (n=15); cortex: 19.9 ±6.3 % in RTL vs. 44.2 ±5.0% (p < 0.05) in VEH; striatum 24.2 ±6.8% in RTL vs. 52.4 ± 4.7% (p < 0.05) in VEH. Histological protection was profound; 6 out of 15 in MCAO-RTL group showed no measurable infarction at 96 hours. Using a standard cylinder test repeated at 3, 7 and 14 days post MCAO, we observed that RTL strongly improved functional recovery as compared to MCAO-VEH group (RTL vs. VEH: day 3, p=0.02, day 7 p=0.00 and day 14 p=0.00). By 7days, animal performance in the RTL group was not different from shams. In contrast, recovery in the VEH group remained poor at all time points.

Conclusion:
RTL1000 offers strong protection after ischemic injury in females, including prolonged improvement of functional outcomes.
Abstract 131: Prostaglandin D2 DP1 Receptor Ameliorates Stroke Outcomes Through Cerebral Blood Flow and Hemostasis
Authors: Ahmad Abdullah S , Narumiya Shuh , Dore Sylvain
Published: March 2022

Background and Purpose:
The association of PGD2 with vasculature and blood makes it a prime candidate to be investigated in stroke. Here, we tested whether selective DP1 receptor agonist BW245C treatment after stroke improves the outcomes by regulating cerebral blood flow (CBF) and hemostasis.

Methods:
First, the effect of BW245C on basal CBF was determined by giving a single i.p. injection of vehicle or 0.02, 0.2, 2.0mg/kg BW245C in WT and DP1-/- mice. Mice were given an i.p. injection of the vehicle or 0.2mg/kg BW245C and excised tail tip was placed in PBS to record bleeding time. To test the effect of BW245C on ex-vivo coagulation, mouse blood was mixed with vehicle or BW245C and the un-coagulated content was quantified. Next, to determine whether BW245C can prevent brain damage after MCAO, WT and DP1-/- mice were subjected to MCAO. Immediately at reperfusion mice were given a single i.p. injection of vehicle or 0.02, 0.2, 2.0mg/kg BW245C, and the functional and anatomical outcomes were tested at 96h. Further, to determine if BW245C can improve CBF during or after stroke, BW245C was given during occlusion and changes in CBF in peri-infarct and core were continuously recorded. Finally, the effect of BW245C on stroke outcomes was also tested in DP1-/- mice.

Results:
BW245C treatment significantly increased the basal CBF only in WT. Interestingly, the tail bleeding time was significantly higher in BW245C group (29.0±14.7%; p<0.01) as compared with the vehicle group, and similarly the un-coagulated content was also higher in BW245C group (14.9±5.9%; p<0.005). The infarction volume was significantly reduced to 38.7±8.1% in 0.2mg/kg BW245C group as compared with the control (51.2±7.1%) and vehicle (52.7±8.6%) groups. Moreover, a strong correlation was observed between the decrease in infarction and CBF improvement in peri-infarct immediately at reperfusion and at 60min after reperfusion. The infarction in DP1-/- was significantly higher (66.3±11.4%) than the WT control mice and it was unaffected by BW245C treatment.

Conclusions:
Overall the data suggests that activation of the DP1 receptor after stroke improves CBF, and minimizes brain damage and functional deficits partially through CBF and hemostasis regulation. [Supported by AHA SDG (ASA) and NIH R01 (SD) funds]
Abstract 132: Roles of Angiotensin (1-7) And Angiotensin II Type 2 Receptor on Intracranial Aneurysmal Rupture
Authors: Shimada Kenji , Wada Kosuke , Tada Yoshiteru , Kuwabara Atsushi , Shikata Fumiaki , Wei Yuan , Kitazato Keiko T , Nagahiro Shinji , Hashimoto Tomoki
Published: March 2022

Background and Purpose:
Angiotensin (Ang) 1-7 is emerging as a new key player of the vascular renin-angiotensin system. Ang (1-7) generated from either Ang I or Ang II, acts to oppose the vasoconstrictor and proinflammatory actions of Ang II. However, which receptor Ang (1-7) activates still remains unclear. It has been suggested that Ang (1-7) mediates its effect via Mas receptor (MasR), although some suggest that it may also act at Ang II type 2 receptor (AT2R). Therefore, we hypothesized that Ang (1-7) has protective effect against aneurysmal rupture via MasR or AT2R. We tested this hypothesis by using our own established mouse model of intracranial aneurysm.

Methods:
Intracranial aneurysms were induced in male mice using a combination of a single injection of elastase into the cerebrospinal fluid and the deoxycorticosterone acetate (DOCA) salt hypertension (Figure 1). Six days after aneurysm induction, we started 2-week treatment with vehicle or Ang (1-7). MasR antagonist (A779) or AT2R antagonist (PD123319) was added to Ang (1-7) treatment. We induced aneurysms to AT2R knockout mice and treated them with vehicle or Ang (1-7) with the same protocol mentioned above. Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysms with subarachnoid hemorrhage.

Results:
Ang (1-7) reduced the incidence of ruptured aneurysms and rupture rate. AT2R antagonist but not MasR antagonist reversed the reduced rupture rate by Ang (1-7) (Figure 2, 3). To confirm whether the effect of Ang (1-7) is through the AT2R, we administered Ang (1-7) to AT2R knockout mice. Although there was no significant difference between wild type and AT2R knockout mice, Ang (1-7) was not effective against aneurysmal rupture in AT2R knockout mice (Figure 4, 5).

Conclusion:
Our results indicate that Ang (1-7) is protective against intracranial aneurysmal rupture and that its protective effect is exerted via AT2R rather than MasR.
Abstract 133: Inhibition of TRPV4 is Protective of the Brain and Cerebral Circulation During Ischemic Stroke
Authors: Cipolla Marilyn J , Sweet Julie G , Chan Siu-Lung , Nelson Mark T
Published: March 2022

Background:
Transient receptor potential vanilloid 4 (TRPV4) channels are highly calcium permeable channels expressed in brain and cerebral endothelium and are regulated by a diverse array of stimuli including shear stress, cell swelling and second messengers. We hypothesized that inhibition of TRPV4 during postischemic reperfusion would be protective of the brain and cerebral endothelium.

Methods:
Transient MCAO was used for all experiments. Infarction (by TTC) was measured in TRPV4 knockout mice (n=3) or C57B mice treated upon reperfusion with the TRPV4 inhibitor HC067047 (1mg/kg; n=7) or vehicle (n=8) after 90 minutes of ischemia with 24 hours of reperfusion. To determine the effect of TRPV4 inhibition on BBB permeability, hyperglycemic male Wistar rats (3 days by STZ) were treated with HC067047 (1mg/kg; n=6) or vehicle (n=6) upon reperfusion after 2 hours of ischemia and edema measured at 2 hours by wet:dry weights. Lastly, basal tone of MCAs isolated from male Wistar rats after 2 hours of ischemia with 2 hours of reperfusion (MCAO, n=7) or sham controls (Sham, n=6) was measured before and after addition of HC067047 (1μM) at 75 mmHg.

Results:
Infarct volume was significantly reduced in TRPV4 knockout mice and with HC067047 treatment vs. vehicle (17.8 ± 2.8% for KO, 22.9 ± 2.7% for HC067047 vs. 39.8 ± 3.3% for vehicle; p<0.05). Hyperglycemic stroke caused considerable edema formation the ipsilateral vs. contralateral brain in vehicle-treated rats (81.38 ± 0.21% vs. 78.64 ± 0.12%; p<0.01) that was prevented by treatment with HC067047 (78.58 ± 0.22% vs. 78.24 ± 0.11%;p>0.05). MCAO diminished basal tone of MCAs vs. sham (16.3 ± 3.3 vs. 26.4 ± 2.8%; p<0.05) that was restored by HC067047 (25.9 ± 3.0%; p<0.05). The constriction to HC067047 did not occur in MCA that were denuded of endothelium or from sham animals.

Conclusion:
These results suggest that postischemic reperfusion activates TRPV4 in cerebral endothelium to cause dilation and BBB permeability. The decreased infarct size after TRPV4 inhibition suggests that activation of TRPV4 during ischemia contributes to neuronal cell death. Thus, inhibition of TRPV4 may be an effective treatment for acute ischemic stroke.
Abstract 141: Door-to-Puncture: A Practical Metric for Capturing and Enhancing System Processes Associated With Endovascular Stroke Care, Preliminary Results From the Rapid Reperfusion Registry
Authors: Sun Chung-Huan J , Ribo Marc , Goyal Mayank , Yoo Albert , Jovin Tudor , Cronin Carolyn , Zaidat Osama , Nogueira Raul , Nguyen Thanh , Hussain Shazam , Menon Bijoy , Mehta Brijesh , Jindal Gaurav , Horev Anat , Norbash Alex , Leslie-Mazwi Thabele , Gupta Rishi
Published: March 2022

Background/Purpose:
In 2011, the Brain Attack Coalition proposed an “Arrival-to-Treatment” of two hours as a benchmark for ischemic stroke patients undergoing intra-arterial therapy (IAT). We designed the Rapid Reperfusion Registry to capture the percentage of stroke patients being treated within the targeted time frame, and to assess the clinical impact of the metric on patient outcomes.

Methods:
This is a retrospective analysis of consecutive anterior circulation patients treated with IAT within 9 hours of symptom onset from nine institutions. Data was collected from December 31, 2011 to Dec 31, 2012 at two centers and from July 1, 2012 to December 31, 2012 at seven centers. Short “Door to Puncture” (D2P) time was hypothesized to be associated with good patient outcomes (90 day modified Rankin Scale score of 0-2), which was confirmed on logistic regression modeling.

Results:
A total of 478 patients were analyzed, with a mean age of 68±14 years and median NIHSS of 18 (IQR 14-21). The median times for IAT delivery were 234 minutes (IQR 164-304) from ‘last known normal to puncture’ (LKN-to-GP) and 111 minutes (IQR 65-173) from D2P. The overall good outcome rate was 39.7% for the entire cohort. In a multivariable model adjusting for age, NIHSS, hypertension, diabetes, reperfusion status, and symptomatic hemorrhage, both short LKN-to-GP (OR 0.996; 95%CI [0.994-0.998]; p<0.001) and short D2P times (OR 0.993, 95%CI [0.990-0.996]; p<0.001) were associated with good outcomes. Only 52% of all patients in the registry achieved the targeted D2P time of two hours.

Conclusions:
The pre-treatment time interval of D2P presents a clinically relevant time frame by which system processes can be targeted on a national level to streamline the delivery of IAT care. At present, there is much opportunity to reduce delays within this narrow time window, thus, providing an opportunity to enhance patient outcomes.
Abstract 142: ASPECTS Decay During Inter-Facility Transfer Predicts Patient Outcomes in Endovascular Reperfusion for Ischemic Stroke: A Unique Assessment of Dynamic Physiologic Change Over Time
Authors: Sun Chung-Huan J , Nogueira Raul , Connelly Kerrin , Glenn Brenda , Zimmermann Susan , Anda Kim , Camp Deborah , Gaunt Susan , Eckenroth Michele , Frankel Michael , Belagaje Samir , Anderson Aaron , Nahab Fadi , Yepes Manuel , Gupta Rishi
Published: March 2022

Background:
In acute ischemic stroke, delays in reperfusion lead to a reduced probability of good clinical outcomes. Pre-treatment Alberta Stroke Program Early CT Scores (ASPECTS) are also associated with clinical outcomes, but the rate of change between subsequent CT images in transferred patients may be more predictive as it incorporates time. We hypothesized that patients with significant change in ASPECT scores would have worse clinical outcomes despite having a favorable pre-treatment baseline ASPECTS.

Methods:
A cohort of patients transferred from seven Primary Stroke Centers and treated with endovascular reperfusion (December 15, 2010 to March 15, 2013) were retrospectively studied. All patients were analyzed with respect to radiographic, demographic, and time-related variables. Absolute ASPECTS decay was defined as [(ASPECTS First CT - ASPECTS Second CT)/time elapsed between CTs in hours]. A binary logistic regression model was performed to determine if the rate of ASPECTS decay was predictive of good 90 day outcomes (mRS 0-2).

Results:
A total of 106 patients with a mean age of 66±14 years and median NIHSS of 19 [IQR 15-23] were analyzed. The median time between initial imaging at the outside hospital to repeat imaging at our treatment facility was 2.7 hours (IQR 2.0-3.6). Patients with good outcomes had lower rates of absolute ASPECTS decay compared to those who did not (0.14±0.23 score/hr vs. 0.49±0.39 score/hr; p<0.001). In multivariable modeling, the absolute rate of ASPECTS decay (OR 0.043; 95%CI 0.004-0.457; p=0.01) was a stronger predictor of good patient outcome than the static pre-treatment ASPECTS obtained immediately before intervention (OR 0.653; 95%CI 0.39-1.05; p=0.076). Practically, patients with a decay of two ASPECTS points per hour compared to those who decay at one point per hour had a 23 fold lower probability of a good outcome.

Conclusions:
Our analysis demonstrates that patients with faster rates of ASPECTS decay are associated with worse clinical outcomes, reflecting the rate of physiological infarct expansion. This metric may be valuable in selecting patients for IAT, as patients with rapid ASPECTS decay are less likely to derive treatment benefit, particularly with delays in inter-facility transfers and procedure times.
Abstract 147: Time to Angiographic Reperfusion Predicts Good Clinical Outcome in the Penumbra Studies
Authors: Khatri Pooja , Yoo Albert , Frei Don , Buell Hope , Bose Arani , Sit Siu Po ,   On behalf of the Penumbra Pivotal, POST, PICS, START and RetroSTART Trialists
Published: March 2022

BACKGROUND:
Faster time to reperfusion (TTR) is associated with better clinical outcome in the IMS trials and other cohorts. We tested this association in the Penumbra-sponsored studies of exclusively mechanical embolectomy cases.

METHODS:
We pooled prospective (125 Pivotal, 289 PICS, 146 START) and retrospective/registry (157 POST, 225 RetroSTART) Penumbra cases. All were IV tPA-ineligible/refractory with treatment at <8 hours. Penumbral imaging selection was based on local practice. Pivotal and PICS revascularization results were core lab-adjudicated. Outcome assessments were not necessarily blinded. For this analysis, we included the subcohort achieving TICI 2-3 reperfusion of either ICA, M1, or M2 occlusions. We tested the association of TTR (based on time of procedure completion) and good clinical outcome (mRS 0-2 at 90 days) in both unadjusted and adjusted analyses. Tested covariates [age (per 10 years), gender, NIHSS strata (10-19 vs 20+), glucose, target vessel (MCA vs ICA), ASPECTS (0-4 vs 5-10)] with p<0.20 were considered in the multivariable model.

RESULTS:
Among 942 subjects, 75 were excluded due to occlusion site and 186 due to missing key data (141 mRS, 75 TICI, 38 TTP). Reperfusion was achieved in 563 (83%) of 681 cases. Among these 563 cases, TTR was associated with mRS 0-2 (OR 0.95; 95% CI 0.91-1.00; p=0.045); see graph. In the final model with complete covariate data (n=347; 69 Pivotal, 0 POST, 133 PICS, 88 START, 57 Retro), TTR remained associated with mRS 0-2 (OR 0.92; 95% CI 0.86-0.98; p=0.01). Missing data did not appear to influence the results.

CONCLUSION:
In this pooled cohort of Penumbra cases, TTR significantly predicted good clinical outcome. This is despite the possibility that registry data and local multimodal imaging selection methods could have favored inclusion of cases with better outcomes. Our findings suggest that rapid treatment should be emphasized regardless of the reperfusion and selection modality chosen.
Abstract 148: Cortical Connectivity is a Powerful Predictor of Motor Recovery in Chronic Stroke
Authors: Wu Jennifer , Kathuria Nikhita , Burke Erin , Dodakian Lucy , See Jill , McKenzie Alison , Srinivasan Ramesh , Cramer Steven C
Published: March 2022

Introduction:
Refinement of biomarkers and predictors of treatment response could greatly benefit restorative stroke therapeutics. The current study examined the performance of established biomarker/predictor measures in patients undergoing 4 weeks of therapy, and also examined performance of dense array EEG (d-EEG) measures of cortical connectivity.

Methods:
Twelve adults (mean age=54.0 ± 16.6 years) with chronic stroke and hemiparesis (Fugl-Meyer (FM) score=39 ± 12, range 23-56, max 66) underwent a baseline 3 minute resting dEEG recording (256 leads) as well as a 3T MRI scan, then received 4 weeks of telerehabilitation therapy. For dEEG measurement of cortical connectivity, mean coherence was derived for the high beta (20-30 Hz) frequency band, then partial least squares (PLS) regression was used to relate resting-state mean beta coherence to: (1) baseline impairment (FM score), and (2) improvement (change in FM across 4 weeks of therapy). Infarct volume and % corticospinal tract (CST) injury, measured on MRI scans, were also analyzed.

Results:
Arm motor status improved across the 4 weeks of therapy (FM change=4.5 ± 2.6, p=0.0001). Regarding biomarkers, CST injury correlated with baseline FM (R2=0.52, p=0.008), but infarct volume and age did not (p>0.05). Resting-state dEEG beta coherence correlated with baseline FM (R2=0.95); adding infarct volume and CST injury to the dEEG findings did not improve predictive strength. Regarding predictors, infarct volume, CST injury, age, and baseline FM each did not predict change in FM across the 4 wk of therapy (p>0.05). However, resting-state beta coherence, using a leave-one-out and predict validation procedure on the pre-therapy dEEG, predicted change in FM score with R2=0.74; adding infarct volume, CST injury, and baseline FM to the dEEG findings again did not improve prediction.

Conclusions:
The dEEG measures of cortical connectivity were strong correlates of baseline status and excellent predictors of behavioral improvement across 4 weeks of therapy. These dEEG measures compared favorably with established behavioral, demographic, and radiological measures. Resting state dEEG is a rapid, simple, safe method for studying brain function that performs excellently as a biomarker and as a predictor.
Abstract 150: Dalfampridine in Patients With Chronic Post-Ischemic Stroke Deficits: Results From a Phase 2 Study
Authors: Simpson David M , Reding Michael , Nash Marshall , Kasner Scott , Suarez Gustavo , Zhao Ping , Henney Herbert R , Rabinowicz Adrian L , Carrazana Enrique
Published: March 2022

Objective:
To evaluate the safety and tolerability of dalfampridine extended release tablets (D-ER; prolonged-release fampridine in Europe) 10 mg twice daily administered to patients with chronic post-ischemic stroke deficits, and to perform an exploratory assessment on sensorimotor function.

Background:
Ischemic stroke is a major cause of sensorimotor deficits that may lead to persistent disability, such as walking impairment.

Methods:
The study design included 2-wk screening, 2-wk treatment, 1-wk placebo (PBO) washout and crossover, 2-wk treatment, and 1-wk follow-up. Patients with a history of ischemic stroke ≥6 months prior to enrollment, with stable sensorimotor deficits and Fugl-Meyer Assessment lower extremity motor score ≤28, and who were able to complete the Timed 25-foot walk (T25FW) were eligible. Patients were randomized into 2 sequences: A (PBO/D-ER) or B (D-ER/PBO). Safety was the primary endpoint. Walking speed assessed by T25FW was the prespecified key efficacy exploratory outcome. Potential changes in community ambulation categories were based on walking speed.

Results:
Patient (N=83) demographics were comparable except for age, which varied significantly between sequences (mean [SE]: A=57.5 [1.31]; B=63.5 [1.68];
P
=0.008). Seventy subjects (84.3%) completed the study with 6 withdrawals for adverse events (AEs). Treatment emergent AE rates were 55% for D-ER and 37% for PBO; most common were dizziness, nausea, and fatigue. Four subjects (2/treatment) had serious AEs including 3 seizures; 1 PBO and 2 D-ER one of which was secondary to an intentional overdose. The overall change in T25FW speed from baseline was greater with D-ER relative to PBO (0.21 vs 0.10 ft/sec; N=78;
P
=0.027). Based on walking speed, there was a near 2-fold increase in those who shifted from household to limited community ambulation and from limited to full community ambulation in the D-ER versus PBO groups (15.3% vs 7.7%, respectively).

Conclusions:
Results suggest that D-ER is well tolerated and may improve walking in patients with chronic post-ischemic stroke deficits. These data provide a foundation for larger efficacy and safety studies in this population.
Abstract 152: The Contrastim Stroke Study: Improving Hand and Arm Function After Stroke With Combined Non-Invasive Brain Stimulation and Task-Oriented Therapy - A Pilot Study
Authors: Harvey Richard L , Roth Heidi R , Tappan Rachel S , Kermen Rachel , Laine Jarmo , Stinear James , Rogers Lynn M
Published: March 2022

Objective:
To determine whether neuro-navigated 1hz rTMS targeted to the non-lesioned hemisphere (NLH) combined with task-oriented occupational therapy (OT) can improve motor function of arm and hand in patients with subacute stroke.

Methods:
30 patients (3-9 months post-stroke) were randomly assigned to sham (n=10) or active 1hz rTMS (n=20) targeted to the wrist extensor representation in the NLH. Patients completed 3 visits per week for 6 weeks that included: 20min pre-functional OT, neuro-navigated 1hz rTMS or sham, and 60 min upper-limb task-oriented OT. Patients returned for 1 week, 1 month, and 6 month follow-up visits. Groups were well matched at baseline but there was a trend toward more severe impairment in the active treatment group on the Upper Extremity Fugl Meyer (UEFM) (23.8±10.2, active; 31.5±15.3, sham: p=0.11).

Results:
Patients receiving active rTMS prior to OT made significantly greater gains on the UEFM by 6 months post-intervention than patients receiving sham stimulation (change in UEFM 14.4 ± 10.0 vs. 4.1 ± 5.5; p=0.013). On ANOVA differences were significant for group, time and group x time (F=5.73, df=2, p=0.006). Individuals receiving active rTMS were significantly more likely to exceed the published minimal clinical important difference (MCID) on the UEFM at 6 months post (88% vs. 38%, p = 0.002). Similar trends at 1 week and 1 month post were not statistically significant. Ceiling effects were unlikely.

Conclusion:
These findings suggest neuro-navigated 1hz rTMS paired with task-oriented OT is more likely to promote clinically important improvements than OT alone. Of note is the finding that significant improvements in impairment were seen 6 months following therapy, suggesting non-invasive brain stimulation as an adjuvant to therapy promotes lasting motor improvement.
Abstract 16: Regional Variation in the Physician Case Volume for Carotid Artery Stenting (CAS) vs. Carotid Endarterectomy (CEA)
Authors: Kumamaru Hiraku , Jalbert Jessica J , Nguyen Louis L , Setoguchi Soko
Published: March 2022

Background:
Inverse relationship between outcome and physician volume has been reported for carotid endarterectomy (CEA) and carotid artery stenting (CAS). After the 2005 National Coverage Determination which reimburses CAS for Medicare beneficiaries, CAS procedures are now performed throughout the US. We hypothesized that CAS are more likely to be performed by low case volume physicians compared to CEA in some areas, causing regional variation in the clinical outcomes.

Methods:
We identified inpatient CEA and CAS procedures and performing surgeons in the Medicare claims files 2007/2008. We calculated surgeon volume as the number of CAS or CEA performed in the past 365 days and classified physicians with <9 cases as low volume. We calculated the proportion of CEA and CAS procedures performed by low volume physicians in each hospital referral regions (HRRs), an empirically defined local health care markets, and categorized the HRRs into 5 levels based on the proportion of low volume physician procedures (0-20, 20-40, 40-60, 60-80, 80-100%).

Results:
We identified 94838 and 13430 Medicare beneficiaries in 306 and 280 HRRs undergoing CEA and CAS. HRRs with larger number of low volume physicians were more prevalent for CAS than for CEA (median proportion: 0.8 (IQR:0.5-1.0) vs. 0.2 (IQR:0.1-0.3). Decreasing trend of 30-day post procedural death was observed as the proportion of low volume physician procedures decreased for CAS (from 2.6% in 80-100% group to 1.3% in 0-20% group), but not for CEA. This trend persisted after adjustment for patient demographics and baseline comorbidities.

Conclusion:
Procedure volume of physicians performing CAS remains low in many regions throughout the US compared to CEA. HRRs with higher proportions of CAS performed by low volume physicians had increased risk of peri-procedural mortality. Dissemination of newly introduced procedures such as CAS may benefit from careful planning of physician selection and regionalization.