bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP444: Older Age, Hypertension and Diabetes Influence the Proportion of Salvageable Ischemic Tissue Following Stroke
Authors: Mohamed Wazim , Jowkar Abbas , Bhattacharya Pratik
Published: March 2022

Objective:
Increasing age, hypertension (HTN), diabetes (DM), hyperlipidemia, smoking and chronic kidney disease are implicated in endothelial dysfunction. Our hypothesis was that endothelial dysfunction would decrease the amount of salvageable ischemic tissue (penumbra) in patients with acute ischemic stroke.

Methods:
Patients with ischemic stroke that underwent perfusion computed tomography (PCT) at admission from August 2011 to March 2012 were reviewed. Demographics and risk factors were abstracted. PCT protocol included 4 supratentorial slices, 8 mm thick. Areas of increased mean transit time were traced and marked as ischemic area. Corresponding area of preserved cerebral blood volume was labeled as penumbra area. The ischemic and penumbra areas in four slices were added and multiplied by the slice thickness (0.8 cm) to give ischemic volume (IV) and penumbra volume (PV) respectively. The proportion of penumbra (penumbra/ischemia volume) was calculated and compared across the different risk factors.

Results:
Of the 47 patients that underwent PCT, 43 (22 males; mean age 61.6 ±12.6 years) had perfusion abnormalities. Subjects younger than 45 years had significantly higher median IV (118.8 cm
3
vs. 58.4 cm
3
; p=0.01) and median PV (97.9 cm
3
vs. 38.7 cm
3
; p<0.01). The median proportion of penumbra, was significantly lower in subjects older than 45 years (72.2% vs. 82.0%; p=0.04). Other factors that demonstrated trends toward a decrease in proportion of penumbra, but did not reach statistical significance due to small numbers: HTN (72.8% vs. 80.0% ; p=0.20) and DM (67.5% vs. 75.7%; p=0.56). In our subset, smoking, hyperlipidemia and kidney disease did not affect the penumbra proportion.

Conclusion:
Older patients and those with HTN or DM are less likely to have a large proportion of salvageable penumbra. While endothelial dysfunction may be a common denominator to these risk factors, the biological mechanisms underlying this phenomenon need to be elucidated.
Abstract WP446: Urine Albumin-to-Creatinine Ratio and Cognitive Impairment in Korean Adults
Authors: Jeong Seul-Ki , Kweon Sun-Seog , Shin Min-Ho , Lee Young-Hoon , Choi Jin-Su , Nam Hae-Sung , Park Kyeong-Soo , Seo Man-Wook
Published: March 2022

Background:
Renal artery shares many features with cerebral arteries: low resistance, high bloodd flow, and microvascular autoregulation. Urinary albumin excretion or urine albumin-to-creatinine ratio (UACR) has been reported to be associated with cognitive function. This study aimed to investigate the association between cognitive function using both cognitive global measure and domains and UACR in Korean adults.

Methods:
We performed a cross-sectional study in adults aged 45 to 74 years who were living in Namwon City, South Korea. Cognitive function was measured with the Korean version of modified Mini-Mental State Examination (K-mMMSE) and scores of cognitive domains including memory and frontal executive functions were extracted. Cognitive impairment was defined as below the 20th percentile of the K-mMMSE according to age, sex, and educational attainments. UACR values were categorized into 5 groups: <6.0, 6.0-14.9, 15.0-29.9, 30.0-299.9, and ≥300 mg/g, respectively. The association between the 5 groups of UACR values and cognitive function and cognitive impairment were analyzed after a stratification of sex.

Results:
A total of 10,231 participants (4009 men and 6222 women) were analyzed in the present study. The scores of K-mMMSE were negatively and independently associated with the UACR values in both sexes, even after adjusting for potential confounders. Among the cognitive domains, memory, abstract thinking, and frontal executive functions showed significant associations with the UACR values in both sexes, but language function showed significant associations only in women. Compared to the reference group (UACR <6.0 mg/g), the slight increase of UACR in men (6.0 to 14.9 mg/g) showed odds ratio of 1.50 (95% confidence intervals, 1.13-2.00) for cognitive impairment. The subjects with macroalbuminuria (UACR ≥300mg/g) showed OR of 2.51 (1.40-4.50) and 1.66 (1.00-2.74) in men and women, respectively.

Conclusion:
Cognitive functions were negatively and independently associated with the UACR values in the general Korean population. The UACR values were significantly associated with memory and frontal executive functions in both sexes. But, some cognitive domains showed inconsistent findings of association with UACR according to sex.
Abstract WP48: Antegrade Flow Across Intravascular Thrombus On 4-dimensional CTA Predicts Early Vessel Recanalization After Thrombolysis
Authors: Fröh Andreas M , Psychogios Marios M , Schramm Ramona , Wasser Katrin , Knauth Michael , Schramm Peter
Published: March 2022

Introduction
In acute stroke patients with large vessel occlusion, demonstration of antegrade flow across thrombus on catheter angiography has been associated with higher rates of vessel recanalization after intra-arterial thrombolysis. 4-dimensional CT angiography (4-dimensional CTA) obtained from a perfusion CT exam has recently been used for non-invasive detection of antegrade flow across intracranial thrombus. We sought to determine whether antegrade flow on 4-dimensional CTA may predict early vessel recanalization after intravenous thrombolysis.

Methods:
From a prospectively collected database of acute stroke patients undergoing endovascular treatment, we identified patients with the following inclusion criteria: (1) anterior circulation vessel occlusion, (2) intravenous thrombolysis (“bridging lysis”) and (3) availability of thin-section 4-dimensional CTA reconstructed from a volume perfusion CT scan. 4-dimensional CTA was reviewed for antegrade flow traversing the occlusion site. Digital subtraction angiograms (DSA) obtained at the beginning of the endovascular procedure were assessed for early partial or complete recanalization after bridging thrombolysis.

Results:
67 patients met the inclusion criteria. On 4-dimensional CTA, there was evidence of antegrade flow in 12 of 67 patients (17.9 %). Patients with and without antegrade flow had similar mean age (75±10 vs. 71±14 years; p=0.188), median presenting NIHSS (15.5 [range 8-26] vs. 17 [6-26]; p=0.249), mean time from symptom onset to i.v. thrombolysis (176±147 vs. 136±84; p=0.209) and mean time from i.v.thrombolysis to DSA (79±25 vs. 89±30 minutes; p=0.265). Early partial or complete recanalization on DSA was seen in 6 patients (9%) and was significantly more likely in patients with antegrade flow (4/12, 33.3%) versus those without (2/55, 3.6%; p=0.008 according to Fisher’s exact test).

Conclusion:
The finding of antegrade flow across thrombus on 4-dimensional CTA is associated with an increased rate of early recanalization after intravenous thrombolysis.
Abstract WP50: Defining the Hyper-acute Infarct Core in Porcine Model of Cerebral Ischemia: A Multi-modality Imaging Study
Authors: d’Esterre Christopher D , Fainardi Enrico , Lee Ting Yim
Published: March 2022

Background:
Defining the hyper-acute infarct core can inform thrombolysis treatment. Clinical outcome and hemorrhagic transformation are correlated with infarct volume at admission. CT perfusion (CTP)-derived parameters and MR-diffusion weighted imaging (DWI) are currently used to delineate infarct volume; however, reversibility of such defects has been shown for both modalities.

Methods:
Six domestic pigs (mean weight 34.7kg) had a CTP scan prior to intracranial injection of endothelin-1 (ET-1; 0.01mL/kg) into the left striatum. Subsequent CTP scans at 30min, 1hr, 1.5hrs were done to monitor stroke progression. A second dose of ET-1 (0.01mL/kg) was injected at 2hrs from the first injection. Twenty minutes after the second ET-1 injection, 18F-FDG was injected. The animal was moved to a 3T MRI scanner where MR-DWI was performed. The animal was then moved back to the CT scanner for a final CTP/PET acquisition. The brain was quickly removed, cut into 10mm slices and stained with tetrazolium-chloride (TTC), the gold standard for defining final infarct volume. Using custom software, the infarct volume defined by low intensity TTC stain, low CBF (< 9.3ml•min-1•100g-1), low CBV (< 1.07ml•100g-1), DWI hyper-intensity and low F-18 FDG uptake were determined. A linear regression model was used to correlate the infarct volume measured by each imaging modality to that by the histological gold standard and the coefficients of correlation (R2) compared.

Results:
R2 values for CBF, CBV, DWI and FDG versus TTC-histology were 0.83, 0.69, 0.95 and 0.61, respectively. For the CBF and DWI parameters the slope of the fitted line was greater than 1, while the slope of the fitted line for the CBV and CBFxCBV parameters was less than 1. Mean normalized (relative to the histologically defined infarct) values were 1.38, 0.82, 0.99, and 0.67 for CBF, CBV, DWI and FDG, respectively.

Conclusion:
In this small sample study, the CTP-CBF and the imaging gold standard DWI both overestimated the TTC-infarct in 100% and 50% of cases, while CTP-CBV and FDG-PET both underestimated the final infarct volume in 100% of animals.
Abstract WP58: Early Recanalization Rates Do Not Differ among Stroke Subtypes when treated with Argatroban and intravenous tPA: a Subanalysis of the Argatroban TPA Stroke Study
Authors: Barreto Andrew D , Guerrero Waldo R , Alexandrov Andrei V , Lyden Patrick D , Alderazi Yazan J , Lee Jessica , Martin-Schild Sheryl , Shen Loren , Sisson April , Balucani Clotilde , Peng Hui , Savitz Sean I , Gonzales Nicole R , Wu Tzu-Ching , Rahbar Mohammad H , Tsivgoulis Georgios , Demchuk Andrew M , Grotta James C
Published: March 2022

Background and Objectives:
Argatroban is a direct thrombin inhibitor that safely augments the benefit of tPA in animal stroke models. The Argatroban tPA Stroke Study (ARTSS-1), was a recently completed NIH sponsored, Phase IIa, prospective, open-label, safety and activity study of Argatroban and tPA in patients with ischemic stroke (
NCT00268762
). Symptomatic hemorrhage occurred in 4.6% and rates of complete recanalization were 30% and 63% at 2 and 24 hours, respectively. We hypothesized that stroke subtypes might respond differently to the treatment combination.

Methods:
A total of 65 patients with intracranial large vessel occlusive disease were given standard dose (0.9mg/kg) tPA and a 100 μg/kg bolus of argatroban followed by infusion of 1 μg/kg per minute for 48 hours adjusted to a PTT of 1.75 times baseline. Pre-tPA vessel imaging using TCD or CTA confirmed intracranial occlusions. A multivariate logistic regression was performed to test whether stroke subtype independently influenced recanalization after controlling for: NIHSS, antithrombotic use, diabetes, age and clot location (ICA, MCA, Vertebrobasilar).

Results:
Recanalization data was available for 47 patients at 2-hours. Baseline characteristics are displayed in the table. After adjusting for age, NIHSS, diabetes, clot location and previous antithrombotic use, there was no difference between any recanalization at 2-hours in the different stroke etiologies. Interestingly, M1 clots were more likely to recanalize compared with M2 (OR 6.2; 95% CI 1.3-25, p=0.019). Results were similar when only analyzing 2-hours complete recanalization.

Conclusion:
Although all large vessel stroke subtypes recanalize at similar rates when treated with combination Argatroban and rtPA, larger thrombi may benefit to a greater degree. A randomized, controlled clinical trial of this promising adjunctive therapy is warranted and ongoing (ARTSS-2 trial,
NCT01464788
).
Abstract WP63: Safety and Efficacy of Modest Blood Pressure Reduction with Valsartan in Acute Ischemic Stroke
Authors: Yu Kyung-Ho , Oh Mi-Sun , Hong Keun-Sik , Kang Dong-Wha , Park Jong-Moo , Bae Hee-Joon , Koo Ja-Seong , Koh Im-Seok , Lee Byung-Chul
Published: March 2022

Background and purpose
Recently, the lowering of blood pressure (BP) with angiotensin-receptor blocker did not show the beneficial effect in patients with acute stroke. However, the management of BP in acute ischemic stroke has still been a matter of debate in clinical practice. We designed a prospective, randomized, open-labeled, blinded endpoints, multi-center study to evaluate Valsartan Efficacy oN modesT blood pressUre REduction in Acute Ischemic Stroke (VENTURE).

Methods
Eligible patients were randomly assigned to receive valsartan or no anti-hypertensive agents as a control for 7 days after symptom onset by the central computerized system. Inclusion criteria were 1) age older than 18 years, 2) admission within 24 hours from onset, 3) treatment initiation within 48 hours, 4) NIH stroke scales 2-21, and 5) Systolic BP 150-185 mmHg. Primary endpoint was death or dependency measured as modified Rankin Scale score ≥ 3 at 90 days. Safety endpoints were early neurological deterioration within 7 days and mortality at 90 days. Thirty centers have participated since October 2008 in South Korea. Analyses were based on intention to treat. This study is registered as number
NCT00874601
in ClinicalTrials.gov.

Results
405 patients were randomly assigned to valsartan (n=203) or control group (n=202), and primary endpoints were available for 373 patients (187 valsartan, 186 control). The BP reduction was significantly greater in valsartan group than in control group during the 7-day treatment (mean diastolic BP was 84.7±2.5 mmHg in valsartan group and 87.1±2.67 mmHg in control group; P=0.022). However, there was no difference in the primary endpoint between valsartan (n=46, 24.6%) and control (n=42, 22.6 %) groups (Odds ratio 1.13, 95% CI 0.79-1.63; p=0.643). In addition, safety endpoints including early neurological deterioration within 7 days (20 (10.7%) in valsartan and 11 (5.9%) in control group, p=0.137) and mortality at 90 days (2 in valsartan and 0 in control group, p=0.333) were similar between the two groups.

Conclusion
The modest BP reduction with valsartan did not suggest any beneficial effect in patients with acute stroke and raised blood pressure. However, These findings might be because this study was underpowered owing to early termination.
Abstract WP64: Mild Strokes: To Treat or Not To Treat
Authors: Rymer Marilyn M , Ratnasingam Denesh
Published: March 2022

Background:
Over half of the ischemic strokes in the US are "mild" by NIHSS scores at presentation.The most common reason for witholding tPA in patients who arrive in time is that the stroke is "too mild."Based on mounting evidence that mild strokes may cause significant disability, the stroke team at Saint Luke’s Neuroscience Institute (SLNI) began to consider mild strokes (NIHSS 0-5) eligible for treatment with intravenous tissue plasminogen activator (IVtPA) in 2009.This analysis evaluated whether more aggressive treatment of mild strokes with IVtPA resulted in better overall outcomes measured by a greater percentage of patients being discharged home with fewer discharges to skilled nursing (SNF) and lower mortality.

Methods:
We retrospectively reviewed strokes in the SLNI database with presenting NIHSS scores of 0-5 in 2007/2008, and in 2010/2011 by treatment status and discharge disposition.

Results:
In 2007/2008, there were 342 mild strokes; 11(3.2 %)received tPA.In 2010,2011 there were 432 mild strokes; 62(15.7%)received tPA (p=0.001).Overall discharge to home: 218/342(63.7%) in 07/08 and 310/432(71.8%) in 10/11 (p=0.017). Discharge to SNF: 45/342(13.2%)in 07/08; 42/432(9.7%) in 10/11 p=0.133. In cases treated with IVtPA in both cohorts, discharge to SNF=5/79(6.3%); no IVtPA=82/695(11.8%)p=0.108. Mortality: 9/342 (2.6%) in 07/08 and 3/342(0.7%) in 10/11 (p=0.030).Of the 12 total mortalities, 2 were treated with IVtPA.There were no statistically significant differences in the percentage of discharges to rehabilitation in the two cohorts.

Conclusions:
It is safe to administer IVtPA to patients with mild strokes.There is a trend toward more aggressive treatment of mild strokes with tPA being associated with a higher likelihood of being discharged to home, fewer discharges to SNF, and lower mortality in the group as a whole.A randomized prospective trial would be useful to further direct decision making in this group of patients.
Abstract WP68: Extending the Time Window with Low Dose IV Abciximab in Acute Non-Lacunar Stroke
Authors: Mandava Pitchaiah , Weir Raymond U , Shah Shreyansh D , Hannawi Yousef , Murthy Santosh B , Anderson Jane A , Dalmeida William , Fabian Roderic H , Kent Thomas A
Published: March 2022

Background:
Proven options to treat ischemic stroke patients ineligible for IV t-PA are limited. Our focus is on treatments to spare the penumbral microcirculation. Evidence indicates that Glycoprotein (GP) IIb/IIIa inhibitors when given with heparin, as used in coronary intervention, increases macro- and distal micro-vascular patency in the heart and animal stroke models. We hypothesized that the cardiac dose of IV abciximab (ABX) used in the halted AbESTT trial was too high leading to hemorrhage, while exclusion of heparin reduced efficacy. We previously showed that a 30% lower ABX dose achieved target GP IIb/IIIa platelet inhibition of 92% in stroke patients and hypothesized a lower dose when given with short term heparin would be safe and effective.

Methods:
After consent, patients with non-lacunar stroke ineligible for t-PA were offered low dose IV ABX (bolus:0.2 mg/kg & infusion:0.05 ug/kg/hr) along with IV heparin (36 hrs) for ant. circulation strokes within 6 hrs and post. within 12 hrs of onset. In place of a control arm, we adapted our pPAIRS matching strategy to obtain best matches from non-lacunar placebo patients in the NINDS dataset at the 2 hr post-randomization NIHSS. Age, glucose and gender were other factors that were matched.

Results:
Forty five patients have been treated. t-PA ineligibility was mostly due to time of onset, recent surgery or anticoagulation. Mean time to treatment was 5.2 h (Ant:4.1h; Post:9.3h). Matching with NINDS placebo subjects was excellent: median NIHSS: ABX: 18 vs NINDS: 17; age: ABX: 66.6 ± 13 vs NINDS: 66.3 ± 11; and glucose: ABX:148 ± 58 vs NINDS:144 ± 52; all p>0.05. There was 1 symptomatic hemorrhage in ABX patients (2.2%) vs none in NINDS; p=1.0. Ninety day mRS 0-1 and 0-2 in the ABX arm (42.2% and 55.6%) were higher than in NINDS matched placebo subjects (15.6% and 31.1%); all p<0.05. Mortality was 24% after ABX and 40% in NINDS; p>.05.

Conclusion:
Low dose ABX appeared safe and potentially effective when compared with NINDS placebo subjects assessed 2 hrs after their initial presentation so as to provide a comparable baseline. Since low dose ABX achieves sufficient platelet inhibition and the combination with short term heparin appeared well tolerated, we suggest these findings deserve confirmation in a prospective RCT.
Abstract WP77: Safety and Efficacy of Endovasucular Treatment of Superior Hypophyeal Artery Aneurysms: A Review of 86 Cases
Authors: Haruma Jun , Sugiu Kenji , Tokunaga Koji , Hishikawa Tomohito , Kin Kyouhei , Kidani Naoya , Shimizu Tomohisa , Ohkuma Yu , Hiramatsu Masafumi , Date Isao
Published: March 2022

BACKGROUND AND PURPOSE:
Given the challenges posed by surgical clipping, endovascular techniques have been increasingly used to treat superior hypophyeal artery(SHA) aneurysms. The purpose of this study was to assess the safety and efficacy of endovascular techniques in the treatment of SHA aneurysms.

MATERIAL AND METHODS:
Medical charts and initial and follow-up magnetic resonance angiography(MRA) were reviewed retrospectively for all patients treated with endovascular procedures at our institution between January 2000 and July 2012.

RESULTS:
We identified 86 patients with SHA aneurysms who were treated with endovascular techniques. Of these patients, 75 were women and only 11 were men (87.2% female predominance). Patients age ranged between 23 and 86 years with a mean of 53.4. Ruputured aneurysms accounted for 9.3% (8/86) of all aneurysms. Average aneurysm size was 5.9 mm and raged from 3.6 to 16.4mm. Ten patients were treated with coil embolization; 72, with balloon-assisted coil embolization; 3, with stent-assisted coiling; 1, with balloon and double catheter coiling; one patient was given up. Complete or near-complete aneurysm occlusion (>95%) was achieved in 96.5% (83/86). Procedure-related complications occurred in 3.4% (3/86). Thromboembolic complication was seen in one patient, one patient also suffered an intra-procedural aneurysm rupture, one patient occurred puncture hematoma. Imaging follow-up was available for 64% (55/86) of patients (MRA) at a mean time point of 24 months (range, 6-101). 3 patients had a recurrence (3.4%), but none of the patients had a retreated.

CONCLUSION:
SHA aneurysms have the lowest recurrence rate with endovascular treatment compared with aneurysms in other locations by using historical data. Because of its safety and efficacy, endovascular therapy should be considered the procedure of choice for the treatment of SHA aneurysms.
Abstract WP8: Determinants Of Benefit From Endovascular Recanalization In Acute Ischemic Stroke: A Meta-Analysis
Authors: Yallapragada Anil V , Ahluwalia Amrit S , Federer Lisa , Saver Jeffrey L
Published: March 2022

Background:
While endovascular recanalization therapy for acute ischemic stroke has made substantial technical advance, demonstration of clinical benefit has to date been elusive. We performed a systematic meta-analysis of all clinical trials and large series of endovascular recanalization to identify features associated with good clinical outcome.

Methods:
We searched MEDLINE and Cochrane Registry of Clinical Trials to identify all randomized trials and large cohort series of endovascular recan for acute stroke published from 1999 - 2012. Reports were included if they used any endovascular recanalization technique in a sample of 50 or more subjects. Studies confined to patients with post circulation or ICA occlusions were excluded.

Results:
A total of 22 studies reporting 2185 patients met selection criteria. Interventions were intra-arterial fibrinolysis (IAF) in 6 series (467 patients), the Merci retriever in 5 (508 patients), the Penumbra system in 3 (373 patients), and stent retrievers in 5 (571 patients). Across series, average patient age was 66, 49% were female, median pretreatment NIHSS was 17, and avg time from onset to recanalization was 293 minutes. Target occlusion locations included the ICA in 17% and MCA in MCA 63%. Independent final clinical outcome (mRS ≤ 2 or nearest equivalent) was achieved in 41%, SICH occurred in 8%, and mortality rate was 23%. Factors associated with independent clinical outcome were: lower NIHSS pretreatment (r = 0.5), achievement of partial or better recanalization (r = 0.4), and onset to recanalization time (r =-0.4). A factor associated with mortality was longer time to recan (r = 0.4). With individual interventions, rates of good outcome were: IAF 51%, Merci 29%, Penumbra 32%, and stent retrievers 51%. Rates of mortality were: IAF 15%, Merci 33%, Penumbra 26%, and stent retrievers 22%.

Conclusions:
Independent clinical outcome after endovascular recanalization therapy is associated with lower pretreatment deficit severity, achievement of recanalization, and shorter time to recanalization. Differences in functional outcomes are noted between different endovascular recanalization techniques, likely reflecting differences in case mix and in recanalization efficiency.
Abstract WP89: Hemodynamic Differences Found in Ruptured and Unruptured Aneurysms - Quantitative Comparison of 41 Cases from a Single Location
Authors: Chien Aichi , Sayre James , Vinuela Fernando
Published: March 2022

Introduction:
Brain aneurysm growth and rupture has been reported to relate to hemodynamic properties. To understand the characteristics of high rupture risk blood flow, research has studied flow differences between ruptured and unruptured aneurysms. Although it is known that flow characteristics also vary between different aneurysm locations, due to the rarity of data for ruptured cases, previous reports which showed differences between ruptured and unruptured aneurysms have relied on the inclusion of cases from multiple locations for the comparison.

Hypothesis:
Our aim is to test the hypothesis that hemodynamic differences between ruptured and unruptured cases can be found in aneurysms at the same location.

Methods:
To include sufficient ruptured and unruptured cases, aneurysms located at the internal carotid artery-ophthalmic artery, the most common aneurysms in our center, were analyzed. A total of 41 (12 ruptured and 29 unruptured) cases treated from January 2004 to August 2011 were included. Aneurysms were studied using patient-specific hemodynamic analysis. Flow changes in different aneurysm regions and their association with rupture were analyzed quantitatively. Statistical methods including multivariate test and paired t-tests were used to investigate the flow differences between ruptured and unruptured groups.

Results:
Concentrated high blood flow pulsatility was discovered in ruptured aneurysms. In contrast, the blood flow pulsatility was found to be lower and increased gradually from the neck to dome in unruptured aneurysms. Pulsatility index at regions of neck, body, and dome averaged 1.5, 1.7, and 1.5 for ruptured cases, and 1.0, 1.2, and 1.3 for unruptured cases. Quantitative comparisons of inflow and outflow that analyzed the temporal characteristics of the flow showed that significant changes within the aneurysm sac may be a key indicator related to aneurysm rupture risk (P<0.05).

Conclusions:
The different hemodynamic characteristics between ruptured and unruptured cases found in our study suggest that the high pulsatility and the relationship between inflow and outflow may be useful to characterize rupture risk for aneurysms at the same location.
Abstract WP90: Immunohistochemical Analysis Of A Ruptured Basilar Top Aneurysm Treated With Coil Embolization In 1990
Authors: Yuki Ichiro , Spitzer Daniel , Fujimoto Motoaki , Takao Hiroyuki , Murayama Yuichi , Vinuela Fernando
Published: March 2022

Purpose:
A ruptured basilar top aneurysm was treated with pre-market GDC in 1990. The fourteenth patient since the initial clinical use of the GDC survived the subarachnoid hemorrhage and deceased in 2012 due to unrelated medical condition. Immunohistochemical analysis of the aneurysm was performed.

Materials and Methods:
A 61 year old female who suffered SAH due to a ruptured basilar top aneurysm majoring 6mm in largest diameter was treated with GDC in 1990. The patient survived the SAH without any neurological deficit, and the last angiogram performed in 1996 showed complete obliteration. The patient recently deceased in 2012 due to unrelated medical condition, and autopsy was performed. The aneurysm was removed with the surrounding tissue, fixed and embedded in paraffin. Histologic analysis using H&E staining, Masson Trichrome staining, alfa smooth muscle actine (αSMA) staining as well as factor VIII staining was performed.

Results:
The gross findings showed no adhesion between the treated aneurysm and the adjacent brain tissue. The orifice of the aneurysm was completely covered by a layer of neointima, and patency of bilateral P1 perforators was confirmed. Microscopic findings showed a prominent collagen deposition with minimal cellular component in the aneurysm. A thick layer of neointima covering the orifice of the aneurysm was composed of a layer of thick collagenous tissue and a layer of SMA positive sub intimal tissue. There was no major histologic change observed in the adjacent brain tissue such as cerebral peduncles.

Conclusion:
A histologic / immunohistochemical analysis of a ruptured basilar top aneurysm which was treated 22 years ago was performed. A neointima covering the orifice of the aneurysm was composed of a thick layer of collagenous tissue and a layer of SMA positive subintimal tissue. Patency of the perforating arteries from the bilateral P1 segment was confirmed, and no major histologic change was seen in the adjacent brain tissue.
Abstract WP96: Age Related Decline Of Oligodendrogenesis After White Matter Injury
Authors: Miyamoto Nobukazu , Hayakawa Kazuhide , Pham Loc-Duyen D , Matsuzaki Toshinori , Seo Ji Hae , Kim Kyu-Won , Magnain Caroline , Boas David , Lo Eng H , Arai Ken
Published: March 2022

Background and Purpose:
Adult white mater retains endogenous repair mechanisms. But how aging affects this ability for self-repair remains to be fully understood. Here, we assessed the hypothesis that aged white matter loses the capacity for oligodendrogenesis, and hence is more vulnerable to external stress.

Methods:
A mouse model of chronic cerebral hypoperfusion was prepared by bilateral common carotid artery stenosis in young (2-month old) and middle-aged (8-month old) mice (n=30 each). White matter integrity and injury were assessed with myelin staining, myelin-basic-protein staining, and optical coherence tomography. Cognitive function was assessed by spontaneous Y-maze test. Proliferation and differentiation of oligodendrocyte precursor cells (OPCs) were evaluated using a bromodeoxyuridine assay.

Results:
While there was no clear difference in myelin density of the corpus callosum between young and middle-aged mice under normal conditions, the latter showed larger white matter injury and working memory deficits after chronic cerebral hypoperfusion insults (P<0.05). The numbers of newly-born oligodendrocytes and OPCs in young mice were both increased by the hypoxic stress, but these responses in middle-aged mice were lower with less activation of cAMP response element binding protein (CREB) (P<0.05). Notably, activating CREB by a type-III phosphodiesterase inhibitor cilostazol in middle-aged mice enhanced the differentiation of OPCs, which alleviated myelin loss and cognitive dysfunction (P<0.05).

Conclusions:
An age-related decline in oligodendrogenesis may compromise endogenous repair mechanisms, and CREB-activating therapies may rescue white matter after chronic cerebral hypoperfusion. Approaches that promote OPC function and repair may be useful for treating white matter rendered vulnerable by age in stroke or vascular dementia.
Abstract WP99: Post-stroke PPARγ Activation Promotes The Proliferation And Differentiation Of Innate- And Bone Marrow-derived Stem Cells In Subventicular Zone, Leading To Vasogenesis And Neurogenesis In Cortex
Authors: Kinouchi Tomoya , Kurashiki Yoshitaka , Kitazato Keiko T , Shimada Kenji , Yagi Kenji , Tada Yoshiteru , Matsushita Nobuhisa , Sumiyoshi Manabu , Satomi Junichiro , Sata Masataka , Nagahiro Shinji
Published: March 2022

Background and Purpose—
Neuroprotection after ischemia by pretreatment with a peroxisome proliferator-activated receptor gamma (PPARγ) agonist was associated with the transcriptional activation of anti-apoptotic- and survival genes via p-STAT3 in oophorectomized (OVX) rats. Based on this finding, we hypothesized that post-stroke PPARγ activation contributes to neurogenesis.

Methods—
To examine the proliferation and differentiation after cerebral ischemia of innate- and bone marrow (BM)-derived stem cells, we treated 13 week-old OVX Wistar rats with the PPARγ agonist. After replacing their BM cells with BM cells from green fluorescent protein transgenic (GFP) rats they were subjected to 90-min cerebral ischemia and divided into 2 groups. One was treated with pioglitazone (PGZ, 2.5 mg/kg/day) for 14 days after ischemia induction. The other was vehicle-control (VC).

Results—
Compared to VC, neurological deficits and infarct volumes were significantly reduced in rats treated with PGZ. In the VC rats innate- and BM-derived stem cells in the subventricular zone (SVZ) were slightly increased after ischemia. Notably, in the PGZ group, the proliferation of both cell types was evidently augmented with PPARγ expression. They were translocated from the SVZ into the cortical peri-infarct area. There they differentiated into neurons, glia, and blood vessels and the expression of phosphorylated Akt, VEGF, and of BrdU incorporated into the cells was increased. This suggested the PGZ-induced vasogenesis and neurogenesis via activation of cell survival- and proliferation signals, resulting in the neurological improvement and the reduction of infarct size.

Conclusions—
Our findings provide new evidence in OVX rats that PPARγ activation after ischemia promotes the proliferation and differentiation of innate- and BM stem cells, leading to good outcome.
Abstract 10: Human Placenta-Derived Adherent Cell Treatment of Stroke Induces Angiogenesis, Increases Synaptic Plasticity and Improves Functional Outcome in Older-Adult Rats
Authors: Shehadah Amjad , Chopp Michael , Pal Ajai , He Shuyang , Zeitlin Andrew , Cui Xu , Zacharek Alex , Cui Yisheng , Roberts Cynthia , Lu Mei , Hariri Robert , Chen Jieli
Published: March 2022

Background and purpose:
Human Placenta-Derived Adherent cells (PDAC
TM
) are a novel adherent mesenchymal-like cell population derived from normal, full-term human placental tissue. PDA-001 (cenplacel-L) is a clinical formulation of PDAC
TM
developed for intravenous administration. In this study, we investigated the efficacy of PDA-001 treatment in a rat model of transient middle cerebral artery occlusion (MCAo) in older-adult rats.

Methods:
Older-adult male Wistar rats (600-750g, 10-12 months) were subjected to 90 minutes of MCAo. To test the efficacy of PDA-001 treatment in older-adult rats, at 1 day after MCAo, randomly selected animals (n=12 per group) were injected, via a tail vein, with vehicle control (cell media), or with PDA-001 (4x10
6
or 8x10
6
cells). Treatment response was evaluated using a battery of functional outcome tests, consisting of adhesive-removal test, modified Neurological Severity Score (mNSS) and foot-fault test. All rats were sacrificed 29 days after MCAo, and lesion volumes were measured using hematoxylin and eosin (H&E). To assess cerebral tissue for angiogenesis and synaptogenesis, immunohistochemical stainings for bromodeoxyuridine (BrdU) and von Willebrand Factor (vWF), and synaptophysin were performed, respectively.

Results:
PDA-001 treatment at the 4X10
6
and 8X10
6
doses significantly improved functional outcome after stroke in older-adult rats (p<0.05). The neurological benefit of PDA-001 treatment was associated with significant increases in the number of BrdU immunoreactive endothelial cells, increases in vascular density and perimeter in the ischemic brain (p<0.05), as well as significantly increased synaptic plasticity as measured by increased synaptophysin expression in the ischemic border zone (IBZ) (p<0.05).

Conclusion:
PDA-001 treatment significantly improved functional outcome after stroke in older-adult rats. The neurorestorative effects induced by PDA-001 treatment may be related to the increase in angiogenesis and synaptic plasticity.
Abstract 100: Combining Prehospital Neuroprotective Therapy With Post-Hospital Arrival Recanalization Therapies: The FAST-MAG Experience
Authors: Sanossian Nerses , Liebeskind David S , Kim-Tenser May A , Eckstein Marc , Pratt Franklin D , Stratton Samuel , Conwit Robin , Starkman Sidney , Saver Jeffrey L ,   FAST-MAG Investigators and Coordinators
Published: March 2022

Background:
Prehospital neuroprotective therapy aims to preserve penumbral tissue in anticipation of recanalization therapies. We describe the population receiving recanalization treatment upon hospital arrival after enrollment in a prehospital neuroprotective trial.

Methods:
The Field Administration of Stroke Therapy Magnesium (FAST-MAG) phase 3 clinical trial randomized subjects with stroke symptom onset within 2 hours to prehospital treatment with intravenous magnesium sulfate vs. placebo. Subjects were eligible for all FDA-approved/cleared therapies as concomitant treatment, including intravenous thrombolysis and mechanical neurothrombectomy.

Results:
Among the 1223 patients with acute cerebral ischemia enrolled in the trial, mean age was 71 [SD 13] , 45% were women, 78% White race, 14% Black race and 21% Hispanic ethnicity. Among the cerebral ischemia patients, 434 [36%] received IV thrombolysis and 72 [6%] received endovascular therapy, including 46 patients who received both IV and endovascular recanalization treatment.. Patients treated with IV TPA, compared to supportive care patients, had more severe deficits on ED arrival [median NIHSS 12.5 vs. 4.0, p<0.0001], were assessed by paramedics earlier [30 vs. 50 minutes, p<0.001], and arrived in the ED earlier [63 vs. 84 minutes, p<0.001], but were of similar age and ethnicity. Those who were taken for endovascular therapy had more severe strokes [NIHSS 16, IQR 9.5-23] but were no different in race-ethnicity or time to evaluation.

Conclusions:
Concomitant intravenous thrombolysis and endovascular recanalization were administered at high rates in the FAST-MAG study, reflecting expanding reperfusion practice in Los Angeles and Orange Counties during the study period. The FAST-MAG population has a sufficient volume of patients concomitantly treated with recanalization therapy to explore with good power the potential benefit of neuroprotection prior to recanalization therapy.
Abstract 108: Chronic Kidney Disease Is Associated with the Risk of Dementia in Patients with Vascular Risk Factors Independently of Cerebral Small Vessel Disease
Authors: Miwa Kaori , Tanaka Makiko , Okazaki Shuhei , Furukado Shigetaka , Yagita Yoshiki , Sakaguchi Manabu , Mochizuki Hideki , Kitagawa Kazuo
Published: March 2022

Background and Purpose:
Vascular disease is an important cause of dementia and cognitive decline. In this context, chronic kidney disease (CKD) has emerged as a possible risk factor of cognitive decline. Small-vessel pathology due to endothelial dysfunction has been evoked to explain the connection between kidney and cerebral microvasculature: they share similar anatomic and physiologic characteristics. However, to what extent CKD impact future dementia beyond cerebral small vessel disease (SVD) is unknown. We assessed the predictive value of CKD, when controlling for MRI-findings on the risk of dementia.

Methods:
Using data from a Japanese cohort of participants with vascular risk factors in an ongoing observational study from 2001, we evaluated the association between dementia and CKD (defined as estimated glomerular filtration rate [eGFR] <60 mL/min per 1.73 m2). Baseline brain MRI was used to determine SVD (lacunar and white matter hyperintensities), medial-temporal atrophy and subcortical atrophy. Cox proportional hazards analysis was performed as predictors of dementia with adjusting for age, gender, APOE ε4 allele, educational level, baseline MMSE score, clinical stroke (previous and incident), conventional vascular risk factors, and MRI-findings.

Results:
Of 600 subjects (mean: 68 ± 8.3 years, male: 57%, 12.8 ± 2.6 years of schooling, CKD: 29%, mean eGFR: 68.4 ± 17.4 mL/min per 1.73 m2), a total of 50 incident dementia cases were diagnosed (Alzheimer disease: 24 patients, vascular dementia: 18, mixed type dementia: 5, other type: 3), during median 7.5 years follow-up. Baseline eGFR and the presence of CKD were associated with an increased risk of all-cause dementia in the age, gender, education level, and APOE ε4 allele adjusted models. These associations of both eGFR (per 1-SD decrease) and CKD remained significant even after additional adjusting for MRI-findings and confounding variables (HR: 1.44, 95% CI [1.02-2.02], and HR: 2.30 [1.19-4.43], respectively).

Conclusion:
Our longitudinal study showed that CKD was independently related to the risk of all-cause dementia in patients with vascular risk factors. Our results reinforce the hypothesis that CKD exert deleterious effects on dementia incidence.
Abstract 11: Ultrasonic Vocalizations as a Tool to Model Aphasia in Murine Experimental Stroke
Authors: Trammel Cassandra J , Doran Sarah J , Venna Vennugopal R , McCullough Louise D
Published: March 2022

BACKGROUND:
Stroke is the leading cause of aphasia. One in four stroke survivors experience some form of speech impairment. Although rodents do not produce speech like humans, male mice vocalize at ultrasonic frequencies. By analyzing changes in ultrasonic vocalization (USV) patterns we assessed correlates of speech impairment in the rodent model. Further, to identify for any lateralization effect in vocalization we compared left and right sided strokes. Finally, changes in FOXP2 expression, a gene involved in the language production, were assessed.

METHODS:
Stroke was induced by 60-min middle cerebral artery occlusion (MCAO) in male C57BL/6 mice. All mice were pre-screened for baseline USVs one day prior to stroke, with an ultrasonic microphone and amplifier from Avisoft Bioacoustics for two 120-second trials, and analyzed using SAS-lab Pro. The first cohort determined if stroke led to changes in USVs and were tested on the day of stroke, post-stroke day (psd) 2, 7 and 14. The second cohort was used to assess differences between left and right MCAO (LMCAO/RMCAO) and shams, USVs were recorded psd 1 and 3. “High vocalizing” mice (>30 USVs / 120sec) were used to avoid baseline bias (n=45). FOXP2 levels were assessed by western blot at 6 and 24 hrs after stroke.

RESULTS:
Repeated measures ANOVA revealed a significant effect of stroke on USVs across the days [F(1,8)=8.181; p<0.05] in the first cohort. Stroke reduced USVs on psd 2 and psd 7, but mice recovered to sham levels by psd 14. Results from the second cohort identified that, on psd1 LMCAO mice had significantly reduced USVs compared to mice subjected to RMCAO (p<0.10), and RMCAO mice vocalized less than sham mice (p<0.05). Infarct analysis showed no difference between RMCAO and LMCAO. Shams showed full recovery to baseline USVs by psd 3. FOXP2 levels were elevated at 6 hrs after stroke, but fell to below sham levels at 24 hrs.

CONCLUSIONS:
The findings of this study suggest that screening for USVs may offer a novel tool for post-stroke behavioral recovery assessment. Stroke induced differential changes in USVs between RMCAO and LMCAO indicate lateralization of vocalization in rodents. In conclusion, decreased USVs parallels FOXP2 expression at 24 hrs suggests that rodent MCAO could be a practical model to study aphasia.
Abstract 124: Quantifying Intracranial Aneurysm Wall Permeability for Risk Assessment Using Dynamic Contrast Enhanced MRI: A Pilot Study
Authors: Vakil Parmede , Ansari Sameer A , Eddleman Christopher S , Bendok Bernard , Batjer H. H , Carroll Timothy J
Published: March 2022

Introduction:
Aneurysmal subarachnoid hemorrhage is the leading cause of non-traumatic hemorrhagic strokes. We propose a technique for assessing intracranial aneurysm (IA) rupture risk by quantifying wall permeability with dynamic contrast enhanced (DCE) MRI. We determine the correlation between IA wall permeability and established metrics of rupture risk.

Methods:
Twenty aneurysms in 19 patients were imaged with DCE-MRI and wall permeability parameters (kTrans and vL) were quantified adjacent to the aneurysm wall using Tofts’ permeability model (Figure 1). The DCE time course (1a), the AIF (red), and observed signal, S(t) (white) are measured. The permeability signal, P(t) (c) is modeled and fitted using Toft’s equation allowing quantitation of kTrans (d), shown superimposed on the DCE image. Three risk paradigms based on size indices (size, aspect ratio) and clinical criteria (progression to rupture, symptomatic presentation, dome irregularities) were used to split aneurysms into high and low-risk groups. Mean kTrans and vL were calculated in each risk group for each paradigm and compared using a student’s t-test. In addition, correlation analysis was used to compare kTrans and vL against size and aspect ratio.

Results:
In all IAs, there was pronounced increase in wall permeability compared to a paired healthy normal vessel (kTrans - 0.0922 vs. 0.0096 min-1, p<0.001; vL - 11 vs. 0.30 %, p<0.001). KTrans is significantly larger in high versus low risk aneurysms when risk is based on size (0.13 min-1 vs 0.06 min-1, p=0.01) and clinical endpoints (0.12 min-1 vs 0.05 min-1, p <0.01), but vL did not differ significantly. KTrans correlated strongly with size (p=0.005, r2=0.57) but vL did not (p=0.08, r2=0.19).

Conclusions:
Increased wall-permeability in intracranial aneurysms correlates with rupture risk and may indicate instability, growth, or remodeling. Further studies with histological correlation on harvested IA wall specimens are necessary.
Abstract 127: Genetic Ablation of Alternatively-spliced Extra Domain A of Fibronectin Protects Hypercholesterolemic Mice from Acute Stroke Injury
Authors: Ahmad Ajmal , Gandhi Chintan , Chauhan Anil
Published: March 2022

Background and Hypothesis:
Fibronectin containing the alternatively-spliced extra domain A (EDA
+
-FN) is absent in the arteries or circulation of healthy humans and mice; but is specifically expressed in the endothelium of atherosclerotic arteries, and elevated in circulation during pathological settings, including stroke. We tested the hypothesis that deletion of EDA in FN protects hypercholesterolemic apolipoprotein E-deficient (ApoE
-/-
) mice from acute stroke injury.

Methods:
We generated EDA
hi/hi
/ApoE
-/-
mice (constitutively overexpress EDA
+
-FN in plasma) and EDA
-/-
/ApoE
-/-
mice (EDA-deleted allele of FN). ApoE
-/-
mice (express EDA
+
-FN in plasma (~3-5 μg/mL) similar to levels found in human pathological settings) were used as control. Susceptibility to thrombosis was assessed using FeCl
3
-induced carotid thrombosis model. Stroke outcome was evaluated in male mice following 60 min of ischemia/ 23 h of reperfusion injury by measuring infarct size, neurological deficit and markers of inflammation within the infarct and surrounding regions (immunohistochemistry).

Results:
Using intravital microscopy, we found that the time to stable occlusion of the carotid artery was accelerated in EDA
hi/hi
/ApoE
-/-
mice (P<0.05 vs ApoE
-/-
mice), whereas EDA
-/-
/ApoE
-/-
mice showed opposite effect. EDA
-/-
/ApoE
-/-
mice had smaller infarcts and improved neurological outcome (P<0.01 vs. ApoE
-/-
mice), concordant with decreased vascular inflammation (neutrophils, macrophages, and NF-κB p65 expression). Conversely, EDA
hi/hi
/ApoE
-/-
mice had larger infarcts and more severe neurological deficits, concordant with increased vascular inflammation (P<0.01 vs. ApoE
-/-
mice). Because EDA
+
-FN activates toll-like receptor 4 (TLR4)
in vitro
, we investigated the role of TLR4 in the EDA
+
-FN-mediated aggravated stroke injury. Genetic ablation of TLR4 in EDA
hi/hi
/ApoE
-/-
mice completely reversed aggravated stroke injury (P<0.05 vs. EDA
hi/hi
/ApoE
-/-
mice), whereas TLR4 deficiency in EDA
-/-
/ApoE
-/-
had no effect.

Conclusions:
EDA
+
-FN is pro-thrombotic and pro-inflammatory, and promotes acute stroke injury via a TLR4 -dependent mechanism. We suggest that monitoring plasma EDA
+
-FN levels may have prognostic value for patients at high risk for stroke.