bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP68: Initial NIHSS and Age Are Major Predictors for Acute Symptom Progression: Exploratory Analysis of the Pentagon Study
Authors: Hirano Teruyuki , Yonehara Toshiro , Terasaki Tadashi , Takita Tomohiro , Hashimoto Yoichiro
Published: July 2021

Background and Purpose:
Early neurological deterioration occurs in 25-48% of patients with acute ischemic stroke resulting in poor outcome. We have conducted an exploratory analysis of the PrevEntioN using cilosTazol from Acute stroke proGressiON (Pentagon) study to elucidate the predictor of progressing stroke.

Methods:
Pentagon was a multi-center, open, randomized, prospective comparative study (UMIN Clinical Trial ID: UMIN000004016). Patients with non-cardioembolic stroke were administered either cilostazol 200 mg daily or aspirin 200 mg daily within 48 hours of onset. Other stroke managements were in accord with guideline recommendation throughout the follow up until 3 months. Primary endpoint was occurrence of acute symptom progression (ΔNIHSS ≥2) within 7 days. Main secondary endpoint was independence at 3 months (mRS 0-2). After comparing baseline characteristics, vascular risk factors and treatment allocation, multivariate logistic regression analysis were performed to evaluate the factors related to acute symptom progression and 3-month outcome.

Results:
Among 201 patients (124 men, 71.2±11.4 years, NIHSS median 3, IQR 1-5), symptom progression was observed in 21 patients (10.5%). Age ≥75 years (p=0.0006) and initial NIHSS ≥5 (p=0.0010) were significantly related. When treated with aspirin (n=95), more patients with severe NIHSS experienced symptom progression (NIHSS ≤4: 7.1%, 5-7: 25.0%, ≥8: 22.2%). In patients treated with cilostazol (n=106), on the other hand, no patients with NIHSS ≥8 experienced symptom progression (NIHSS ≤4: 5.0%, 5-7: 33.3%, ≥8: 0%). In total, 138 patients (68.7%) achieved mRS 0-2 at 3 months. Age ≥75 years (p<0.0001) and initial NIHSS ≥5 (p=0.0002) were negatively associated. A logistic regression model revealed that younger age (p<0.0001), lower NIHSS (p<0.0001) and cilostazol treatment (p=0.0437) were related to mRS 0-2 at 3 months.

Conclusions:
Initial NIHSS ≥5 and advanced age ≥75 years are major predictors for acute symptom progression. Although effect on preventing symptom progression was comparable, better long-term outcome might be expected with acute cilostazol treatment.
Abstract TP78: Down-regulation Of Vascular Na+/k+ ATPase In Oophorectomized Rats Feeding A High Salt Diet Is Associated With The Cerebral Aneurysm Formation
Authors: Matsushita Nobuhisa , Tada Yoshiteru , Yagi Kenji , Kitazato Keiko T , Shimada Kenji , Sumiyoshi Manabu , Kanematsu Yasuhisa , Satomi Junichiro , Nagahiro Shinji
Published: July 2021

Background and Purpose—
Hypertension is thought to be associated with a high incidence of stroke. However, not all patients with unruptured cerebral aneurysms are hypertensive. In the DOCA-salt rats the increase in body water-free Na+ storage associated with hypertension is suggested. We hypothesized that in oophorectomized rats fed a high salt diet, body water-free Na+ accumulation may be increased, leading to the formation of cerebral aneurysms. To address the relationship between the increase in the body Na+-to-water ratio that characterizes water-free Na+ accumulation and the formation of cerebral aneurysms, we focused on vascular Na efflux pump Na+/K+ ATPase.

Methods—
Thirteen-week old female Sprague-Dawley rats subjected to carotid artery ligation were fed a high-salt diet and divided into 3 groups; a group without- (HSD) and another with bilateral oophorectomy (HSD/OVX) and a 3rd group that underwent additional renal artery ligation (HSD/OVX/RL) to induce hypertension.

Results—
Compared to HSD rats, the incidence of cerebral aneurysms and the body Na+-to-water ratio were significantly higher in HSD/OVX- and HSD/OVX/RL rats independent of hypertension. In their aneurysmal wall, ATP1α2, a subtype of Na+/K+-ATPase were down-regulated and renin-angiotensin system- and inflammation related molecules were up-regulated. In HSD/OVX/RL rats treatment with low dose olmesartan up-regulated ATP1α2 without affecting blood pressure and reduced the body Na+-to-water ratio and the incidence of cerebral aneurysm formation.

Conclusions—
These results suggest that a reduction in the vascular Na efflux pump during excessive salt intake in oophorectomized rats may be associated with the increase in water-free Na+ accumulation directing to cerebral aneurysm formation.
Abstract TP87: Comparative Analysis of 3-Dimensional Rotation Angiography versus 3-Dimensional Computed Tomography Angiography for Intracranial Aneurysm Treatment Detection and Planning
Authors: Park Jonathan , Salamon Noriko , Duckwiler Gary , Vinuela Fernando , Sayer James , Villablanca J Pablo
Published: July 2021

Introduction:
3D Rotational Angiography (3DRA) is the gold standard for intracranial aneurysm (IA) detection, but is invasive and time consuming. While 3DCTA has shown to be sensitive for IA detection, no published studies have compared 3DRA to 3DCTA in guiding clinical management. Our aim was to compare suggested treatment for IA based on 3DRA and 3DCTA vs actual final treatment and outcome.

Hypothesis:
Management recommendations based on blinded review of 3DRA and 3DCTA for IA do not differ significantly.

Methods:
Prospective blinded review of contemporaneous 3DRA and 3DCTA was performed for patients with suspected IA. Two interventionalists and two neuroradiologists performed blinded, prospective review of 3DRA or 3DCTA, respectively. IA size, location, and morphology were assessed. After IA characterization, each observer independently recommended optimal therapy (conservative, coil, surgery, combined/other) while blinded to other reviewers’ decisions. Findings were analyzed with Spearman, and agreement coefficient 1 (AC1) inter-rater reliability statistics.

Results:
41/52 enrolled patients had IA confirmed by 3DRA (52 IA total). 50/52 (96%) IA were initially identified by 3DCTA (both false negatives seen retrospectively). Average IA sac and neck size measured by 3DRA and 3DCTA correlated closely (p<0.01) and were 9.8 and 5.0 mm vs 9.5 and 4.5 mm, respectively. Treatment recommendations by reviewers for 3DRA vs 3DCTA correlated very strongly (AC1= 0.77), as did reader recommendations within a modality (3DRA, AC1=0.66; 3DCTA, AC1=0.79). For 39/52 (75%) of IA, majority consensus for all readers was reached (3/4 or 4/4 reviewers), which correlated well with final executed treatments (95%).

Conclusions:
Recommendations for IA treatment based on 3DCTA correlate closely with those based on 3DRA, as well as with actual treatment in a majority of patients. 3DCTA holds promise as a primary imaging tool for IA detection and clinical decision making.
Abstract TP92: Brain Activity Related To The Effects Of Augmented Feedback On Learning Movements In A Dynamic Environment In Healthy Subjects And Stroke Survivors
Authors: Mukherjee Mukul , Chang Wen-Pin , Siu Ka-Chun , Fayad Pierre , Stergiou Nicholas
Published: July 2021

Augmented visual feedback has been shown to be effective for learning reaching movements in dynamic environments after a stroke. However, the mechanisms behind such changes are not known. In addition, how brain activity changes with age as we learn novel dynamic tasks is also not clear. The purpose of this study was to examine brain activity changes that are observed when healthy younger and older adults and stroke survivors learn reaching movements in dynamic environments using augmented visual feedback.

Healthy young and older adults and chronic stroke survivors were randomly assigned to either a control or an experimental group. They all performed reaching movements with the Inmotion2 robotic system (Interactive Motion Tech Inc., MA) using the dominant/affected arm in a velocity-dependent force field. Controls received actual feedback of their movement, while experimental subjects received augmented visual feedback. Electroencephalogram recordings were analyzed to determine Event Related Desynchronization percent (ERD%). The theta, alpha, and beta frequency bands were examined during movement and pre-movement phases.

With learning, the absolute power of the frequency bands increased from the baseline to the adaptation condition, which was then washed out when the force field was removed. With age, there was a reduction in ERD% in alpha and beta bands as the motor task was learned. Stroke subjects had a further reduction in the ERD% in comparison to the healthy older adults. In addition, augmented visual feedback led to a significant increase in the ERD% in comparison to controls during the planning and execution stages of the movement.

Past studies have shown when novel dynamics are learned, ERD% reduces indicating increased cognitive processing and memory load. We found that with aging, the cognitive processing and memory required for performing the same dynamic task, increased. After a stroke, there was a further increase. However, the utilization of augmented visual feedback may reduce such requirements and lessen the load on higher centers. These results provide mechanistic support for employing augmented visual feedback for stroke rehabilitation specific to reaching movements in dynamic environments.
Abstract WMP117: Regional Homogeneity Changes In Patients With Transient Ischemic Attack: A Resting-state Functional Magnetic Resonance Imaging Study
Authors: Guo Jian , Chen Ning , Zhou Muke , Wang Pian , He Li
Published: July 2021

Background:
Transient ischemic attack (TIA) can increase the risk of some neurologic dysfunctions, of which the mechanism remains unclear. Resting-state functional MRI (rfMRI) is suggested to be a valuable tool to study the relation between spontaneous brain activity and behavioral performance. However, little is known about whether the local synchronization of spontaneous neural activity is altered in TIA patients. The purpose of this study is to detect differences in regional spontaneous activities throughout the whole brain between TIAs and normal controls.

Methods:
Twenty one TIA patients suffered an ischemic event in the right hemisphere and 21 healthy volunteers were enrolled in the study. All subjects were investigated using cognitive tests and rfMRI. The regional homogeneity (ReHo) was calculate and compared between two groups. Then a correlation analysis was performed to explore the relationship between ReHo values of brain regions showing abnormal resting-state properties and clinical variables in TIA group.

Results:
Compared with controls, TIA patients exhibited decreased ReHo in right dorsolateral prefrontal cortex (DLPFC), right inferior prefrontal gyrus, right ventral anterior cingulate cortex and right dorsal posterior cingular cortex. Moreover, the mean ReHo in right DLPFC and right inferior prefrontal gyrus were significantly correlated with MoCA in TIA patients.

Conclusions:
Neural activity in the resting state is changed in patients with TIA. The positive correlation between regional homogeneity of rfMRI and cognition suggests that ReHo may be a promising tool to better our understanding of the neurobiological consequences of TIA.
Abstract WMP118: Involvement of MMP-9 in Inflammation-induced White Matter Injury in a Novel Rat Model of Vascular Cognitive Impairment
Authors: Jalal Fakhreya Y , Thompson Jeffrey , Yang Yi , Rosenberg Gary A
Published: July 2021

Objective:
We have recently developed a rat model of white matter (WM) injury in stroke-prone spontaneously hypertensive rats (SHR-SP), which shows chronic oligodendrocyte death, blood-brain barrier (BBB) disruption, and cognitive impairment. In this study, we investigated the mechanisms of white matter damage secondary to chronic hypertensive disease.

Methods:
At 12 weeks of age, we subjected SHR-SP to permanent unilateral carotid artery occlusion (UCAO) followed by the Japanese permissive diet (JPD) and 1 % NaCl in drinking water. One group of UCAO/JPD rats received minocycline (50 mg/kg in DMSO,
i.p.
every other day for 9 weeks) and another had only UCAO/JPD with DMSO. WM lesions were characterized histologically, biochemically, and by MRI; cognitive impairment was tested by Morris water maze.

Results:
One to 3 weeks after UCAO/JPD, we found an increase in hypoxia inducible factor-1α (HIF-1α) in astrocytes, a fall in pyrol hydroxylase-2 (PHD-2), and an increase in matrix metalloproteinase-9 (MMP-9) expression. At week 1, there was infiltration of T-cells and MMP-9 co-localized with endothelial cells and neutrophils. By 3 weeks, we observed IgG leakage, indicating disruption of the BBB, with scattered hemorrhages. Long term treatment with minocycline prevented cognitive impairment along with reduction in T2-weighted image size, apparent diffusion coefficients, and fractional anisotropy compared to the vehicle-treated group. Relative cerebral blood flow was unaffected by minocycline treatment.

Conclusion:
Our results suggest that hypoxic hypoperfusion of the deep WM, which occurs secondary to hypertensive damage to blood vessels, initiates expression of MMP-9 and migration of T-cells, disrupting the BBB and damaging WM. The anti-inflammatory agent, minocycline, significantly protected the deep WM from injury.
Abstract WMP120: Long-Term Estrogen Deprivation Enhances Hippocampal Amyloidogenic Processing and Cognitive Decline after Global Cerebral Ischemia
Authors: Scott Erin L , Zhang Quan-guang , Wang Rui-min , Han Dong , Brann Darrell W
Published: July 2021

Women who enter menopause prematurely have a doubled lifetime risk of cognitive decline and dementia. The mechanism underlying this phenomenon is unclear, but it is postulated to be associated with dramatic and prolonged deprivation of the neuroprotective ovarian hormone 17beta-estradiol (E2). To shed light on this issue, 3-month-old female Sprague Dawley rats were bilaterally ovariectomized and had subcutaneous, osmotic mini-pumps containing a low, Diestrus I dose of E2 implanted either immediately (short-term E2 deprivation - STED) or 10 weeks later (long-term E2 deprivation - LTED). One week following continuous E2 replacement, all animals were subjected to 10 minutes of global cerebral ischemia (GCI) and sacrificed for tissue harvest. Intriguingly, we observed a profound induction of Alzheimer’s disease-related proteins (beta-amyloid and hyperphosphorylated-tau) throughout the hippocampus of LTED females who experienced GCI. In the same animals, we also noted a switch to amyloidogenic processing of amyloid precursor protein (APP), such that hippocampal expression of beta-amyloid cleaving enzyme 1 (BACE1) was enhanced and hippocampal expression of
A
D
isintegrin
A
nd
M
etalloprotease 17 (ADAM17) was diminished. Hippocampal expression of an alternate alpha secretase, ADAM10, remained unchanged. Furthermore, LTED females demonstrated enhanced post-ischemic cognitive decline, as they performed worse than STED females on the Morris Water Maze after GCI. Importantly, while immediate replacement of ovarian E2 was capable of preventing these events in STED females, delayed treatment with low-dose E2 was ineffective. Finally, c-Jun N-terminal Kinase (JNK) was identified as a critical mediator of post-ischemic amyloidogenesis, cognitive decline, and apoptosis in LTED females, as delayed treatment with a JNK inhibitor was able to prevent these events. These data could help explain why surgically menopausal women have an increased risk of cognitive decline and dementia and why postmenopausal women fare worse than age-matched men following a stroke. Furthermore, they lend support to the critical period hypothesis, suggesting that only perimenopausal replacement of ovarian E2 will provide neurological benefit for post-menopausal women.
Abstract WMP17: Early DWI Reversal Following Endovascular Reperfusion Is Typically Transient
Authors: Inoue Manabu , Wheeler Hayley M , Mlynash Michael , Tipirneni Aaryani , Straka Matus , Kemp Stephanie M , Zaharchuk Greg , Bammer Roland , Lansberg Maarten G , Albers Gregory W ,   The DEFUSE 2 investigators
Published: July 2021

Background and Purpose:
There are conflicting reports regarding the incidence and prognostic significance of DWI reversal following reperfusion therapy. The aim of this study was to assess the frequency and extent of early DWI reversal following endovascular therapy and to determine if early reversal is sustained or transient.

Methods:
This is a substudy of the DEFUSE 2. MRI with DWI and PWI was performed before (DWI 1) and within 12 hours after (DWI 2) endovascular stroke treatment and again at 5 days. Acute DWI lesions were outlined and quantified using mipav software (http://mipav.cit.nih.gov/). Ischemic lesion volumes were outlined on the Day 5 FLAIR then corrected for edema using a validated technique to determine the final infarct volume. Early DWI reversal was defined as (DWI 1 - DWI 2) >3 ml and permanent DWI reversal was defined (DWI 1 - final infarct volume) > 1 ml. Reperfusion was defined as a >50% reduction in PWI volume (Tmax >6 sec) on the MRI performed after endovascular therapy. The prognostic significance of early reversal was assessed in a regression model.

Results:
104 patients had a technically adequate DWI and PWI prior to endovascular therapy (performed 4.4 [3.0-6.0] hours after symptom onset). Of these, 77 had an acute DWI lesion >3 ml and a follow-up MRI (156 min [72-342] after completion of endovascular therapy) and a 5 day MRI. Seventeen percent (13/77) of the patients had early DWI reversal representing a median (IQR) of 42.4% (25.0-57.6) of the initial DWI lesion (median volume 10.9 ml [IQR 7.3-18.2]). The incidence of early DWI reversal was 21% (11/52) following reperfusion vs. 8% (2/25) in patients who did not reperfuse (p=0.20). Of the 13 patients with early DWI reversal, permanent DWI reversal occurred in only 2 (volume of permanent DWI reversal 6.9 ml and 4.7 ml). Early DWI reversal was not an independent predictor of clinical outcome.

Conclusion:
Early DWI reversal occurs in about 15-20% of patients following endovascular therapy and can involve a substantial percentage of the initial DWI volume. However, early DWI reversal is usually transient and does not appear to signify tissue salvage.
Abstract WMP18: CT Work-Up of Patients Suspected of Acute Ischemic Stroke: Perfusion-CT Adds Value Compared to Clinical Evaluation, Noncontrast Head CT and CT-Angiogram in Terms of Predicting Outcome
Authors: Zhu Guangming , Michel Patrik , Aghaebrahim Amin , Patrie James T , Xin Wenjun , Eskandari Ashraf , Zhang Weiwei , Wintermark Max
Published: July 2021

BACKGROUND AND PURPOSE:
To determine whether Perfusion-CT (PCT) adds value to Noncontrast head CT (NCT), CT-Angiogram (CTA) and clinical assessment in patients suspected of acute ischemic stroke.

METHODS:
We retrospectively reviewed the clinical and imaging data collected in 165 patients with acute ischemic stroke. ASPECTS score was calculated from NCT. CTA was reviewed for site of occlusion and collateral flow score. PCT was used to calculate the volumes of infarct core and ischemic penumbra on admission. Recanalization status was assessed on follow-up imaging. Clinical data included age, time from onset to baseline imaging, time from baseline imaging to reperfusion therapy, time from baseline imaging to recanalization imaging, NIHSS at baseline, treatment type and modified Rankin score (mRS) at 90 days. In a first multivariate regression analysis, we used volume of PCT penumbra and infarct core as outcome, and assessed whether they could be predicted from clinical variables, NCT and/or CTA. In a second multivariate regression analysis, we used mRS at 90 days as outcome, and determined which imaging and clinical variables predicted it best.

RESULTS:
165 patients were identified. Mean±SD time from onset to baseline imaging was 6.7±8.7 hrs. 76 had a good outcome (90-day mRS 0-2), 89 had a poor outcome. Mean±SD PCT infarct was 44.8±46.5 ml. Mean±SD PCT penumbra was 47.0±33.9 ml. PCT infarct could be predicted by clinical data, NCT, CTA, and combinations of this data (P<0.05); the best predictive model included the clinical data, plus NCT and CTA. PCT Penumbra could NOT be predicted by clinical data, NCT, and CTA. In terms of predicting mRS at 90 days, all of variables but NCT and CTA were significantly associated with 90-day mRS outcome. The single most important predictor was recanalization status (P<0.001). PCT penumbra volume (P=0.001) was also a predictor of clinical outcome, especially when considered in conjunction with recanalization through an interaction term (P<0.001).

CONCLUSION:
PCT penumbra represents independent information, which cannot be predicted by clinical, NCT, and CTA data. PCT penumbra is an important determinant of clinical outcome, and adds relevant clinical information compared to a stroke CT work-up including NCT and CTA.
Abstract WMP3: Predictors And Outcomes Associated With Rescue Therapy In SWIFT
Authors: Lazzaro Marc A , Zaidat Osama O , Saver Jeffrey
Published: July 2021

Introduction:
In the Solitaire With the Intention For Thrombectomy (SWIFT) trial, rescue therapy was used when the Solitaire or Merci device was unable to restore vessel patency. Markers for non-recanalization in acute stroke have been reported for IV tPA, however similar predictors are not known for endovascular therapy. We sought to identify predictors and outcomes associated with rescue therapy in the SWIFT trial.

Methods:
Rescue therapy was defined per SWIFT study protocol, and included the use of an alternative device, agent, or maneuver following failure to recanalize with 3 retrieval attempts using the initial device. Clinical, angiographic, and demographic data was reviewed. Statistical analysis was performed using t-test or Wilcoxon methods and multivariate logistic regression analyses.

Results:
Among a total of 144 patients enrolled (31 roll-in phase Solitaire patients, and 113 randomized patients, 58 Solitaire, 55 Merci), 43 (29.9%) required rescue therapy. Baseline demographics for patients with and without rescue therapy were no different. Rescue therapy was used in a higher percentage of patients randomized to Merci than Solitaire (43% vs 21%, p = 0.009). Patients with rescue therapy experienced longer time to recanalization (p < 0.001), a lower percentage of successful recanalization (p < 0.001), and a lower percentage of good outcome (p = 0.009). In multivariate analysis, predictors of rescue therapy were those patients randomized to the Merci group (OR 3.99, 95% CI 1.58, 10.10) and patients over age 80 years (OR 3.51, 95% CI 1.06, 11.64). Non-significant trends toward an increased need for rescue therapy were observed in patients with hypertension (p = 0.09), and occlusions of the carotid terminus and M1 MCA compared with other locations (p = 0.10). No association was observed with rescue therapy and afib (p = 0.47) or IV tPA failure (p = 0.49), and rescue therapy was not associated with symptomatic ICH (p = 0.43).

Conclusions:
Predictors of rescue therapy included Merci treatment group and age, while trend toward an increased need of rescue therapy was observed with hypertension and proximal clot location. Rescue therapy was associated with fewer good outcomes. These findings may reflect targets for improvement in endovascular therapy.
Abstract WMP37: Methodological Quality and Meta-Analysis of Animal Studies of Mesenchymal Stromal Cells for Ischemic Stroke
Authors: Xie* Kate , Vu* Quynh , Eckert Mark , Zhao Weian , Cramer Steven C
Published: July 2021

INTRODUCTION:
Mesenchymal stromal cells (MSC) are multipotent cells that support numerous restorative processes after stroke. The ease of isolation and immunoprivileged status of MSC have stimulated numerous preclinical stroke studies. We performed a meta-analysis to estimate study quality, size of behavioral effects, and the impact of variables such as timing of MSC administration in relation to stroke onset.

METHODS:
Studies of MSC and stroke were identified through PubMed and Web of Science. Studies of hemorrhage, not in English, or using modified MSC were excluded. A Quality Score was determined for each study, estimating methodological quality using 10 criteria derived from STAIR guidelines, with higher Quality Scores reflecting greater compliance with issues such as randomization and outcome blinding. Outcome data extracted for MSC and control arms were used to derive estimates of effect size using Cohen’s d.

RESULTS:
A total of 46 studies met criteria, with 39 studying rats, 6 mice, and 1 primates. There were 61 treatment groups, as some studies had >1 independent MSC treatment arms; MSC were introduced intravenously in 41, intracerebrally in 15, and intraarterially in 6. MSC source was rat in 24, human in 16, and mouse in 6. Time of MSC administration ranged from 5 weeks pre- to 1 month post-stroke. MSC dose ranged from 1x10^4 to 3.25x10^7. The median Quality Score was 6 (IQR 5-7). Quality Score was not related to time of MSC administration relative to stroke or to behavioral effect size. Median effect size was 2.05 for the Modified Neurological Severity Scale (n=23), 1.88 for Adhesive Removal Test (n=19), and 2.70 for the Rotarod Test (n=14). Effect sizes were substantial across all routes of administration and differed only for the mNSS (p<0.04), favoring the IC route. Effect size did not vary with time of MSC administration relative to stroke for any behavioral measure.

CONCLUSIONS:
The quality of preclinical MSC stroke studies has generally been good. MSC consistently provide very large behavioral benefits, across scales and routes of administration. The magnitude of behavioral effects was not related to the Quality Score or to the time of MSC administration relative to stroke. These findings support translation of MSC to human trials.
Abstract WMP43: The Natural History of Vertebral Artery Origin Stenosis and Long-term Survival
Authors: Thompson Matthew , Issa Mohammad , Lazzaro Marc , Zaidat Osama
Published: July 2021

Methods:
We retrospectively reviewed clinical data on patients admitted at a single institution for possible stroke between 2004 and 2007, and selected subjects who underwent angiography of the neck. We classified subjects as having vertebral artery origin stenosis (VAOS) by ‘moderate’ to ‘severe’ (≥50%) occlusion. Age, sex, and race-matched control subjects were selected from our study population as having no evidence of VAOS on angiography. Long-term follow-up data was collected and death certificates were searched for comparison among cases and controls. A Kaplan-Meier curve was plotted based on time to event (stroke or death).

Results:
The proportion of subjects that were found to have VAOS was 58 per 358 cases, or 16.2%. Four subjects were excluded because of stenting, so a total of 54 cases and 54 matched controls were included for long-term follow-up analysis. In our study population, we calculated the relative risk of having a stroke or dying in patients with VAOS to be 6.0 times that of patients without VAOS (
p
<0.02). The observed 5-year survival for patients with VAOS was 67% (36/54) compared to 89% (48/54) in control subjects (
p
<0.01).

Conclusions:
Patients with vertebral artery origin stenosis are at a significantly higher risk of having a stroke or dying. Subsequent prospective, multicenter studies are needed to validate our results.
Abstract WMP5: Predictors and Clinical Relevance of Hemorrhagic Transformation after Endovascular Therapy for Acute Ischemic Stroke: a Multicenter Retrospective Analysis of 1122 Patients
Authors: Nogueira Raul G , Gupta Rishi , Jovin Tudor G , Levy Elad I , Liebeskind David , Zaidat Osama , Rai Ansaar , Hirsch Joshua , Hsu Daniel , Rymer Marilyn M. , Tayal Ashis H. , Lin Ridwan , Kass-Hout Omar , Kasshout Tareq , Natarajan Sabareesh K. , Nanda Ashish , Tian Melissa , Hao Qing , Kalia Junaid S. , Chen Michael , Abou-Chebl Alex , Nguyen Thanh N. , Yoo Albert
Published: July 2021

Background and Purpose:
Endovascular techniques are frequently employed to treat large artery occlusion in acute ischemic stroke (AIS). We sought to determine the predictors and clinical impact of intracranial hemorrhage (ICH) after endovascular therapy.

Methods:
Retrospective analysis of consecutive patients presenting to 13 high-volume stroke centers with AIS due to proximal occlusion in the anterior circulation who underwent endovascular treatment within 8 hours from symptom onset. Logistic regression was performed to determine the variables associated with ICH, hemorrhagic infarction (HI), and parenchymal hematomas (PH) as well as 90-day poor outcome (mRS≥3), and mortality.

Results:
A total of 1122 patients (mean age, 67±15 years; median NIHSS, 17 [IQR13-20]) were studied. Independent predictors for HI included diabetes mellitus (OR 2.27, 95%CI [1.58-3.26], p<0.0001), pre-procedure IV tPA (1.43[1.03-2.08], p<0.037), Merci thrombectomy (1.47[1.02-2.12], p<0.032), and longer time to puncture (1.001[1.00-1.002], p<0.026). Patients with atrial fibrillation (1.61[1.01-2.55], p<0.045) had a higher risk of parenchymal hematomas (PH) while the use of intra-arterial tPA (0.57[0.35-0.90], p<0.008) was associated with lower chances of PH. Both the presence of HI (2.23[1.53-3.25], p< 0.0001) and PH (6.24[3.06-12.75], p< 0.0001) were associated with poor functional outcomes; however, only PH was associated with higher mortality (3.53[2.19-5.68], p<0.0001).

Conclusions:
In AIS patients undergoing endovascular therapy, diabetes mellitus, longer time to treatment, and Merci thrombectomy appear to be associated with a higher risk for HI while atrial fibrillation appears to result in a higher risk for PH. While both HI and PH are associated with poor outcomes only PH is associated with higher mortality.
Abstract WMP52: Sustained Long Term Lifestyle Modifications Regress Carotid Artery Atherosclerosis - Insights from a Meta-Analysis
Authors: Jhamnani Sunny , Patel Dhavalkumar , King Fred , Heimlich S. Layla , Walitt Brian , Lindsay Joseph
Published: July 2021

Background and Purpose:
Carotid artery plaque progression has been associated with significant cerebrovascular morbidity and mortality. Even though, lifestyle modifications are the cornerstone of the management of atherosclerotic disease, the long term effects of a healthy diet and regular exercise on the atherosclerotic burden of carotid arteries is not clear. This meta-analysis was undertaken to assess this possibility.

Methods:
Randomized controlled trials comparing the efficacy of intensive lifestyle measures (diet and/or exercise) and usual care were identified by a systematic search. Three independent researchers searched MEDLINE, OVid, PUBMED, EMBASE and CINAHL for eligible studies. We included studies which provided baseline and quantitative carotid intimal medial thickness (IMT) data measured after at least 3 years. Comprehensive Meta-Analysis Version 2.0 was used for statistical analysis.

Results:
We identified 4 eligible studies of which 2 studies looked at the effect of diet alone while 1 looked at the effect of diet and exercise. One study was excluded from the analysis because of lack of sufficient data. There was no significant heterogeneity between the 3 studies analyzed (p: 0.699). A total of 980 patients were analyzed; 492 patients in the intervention group and 488 patients in the control group. After at least 3 years of follow up, lifestyle changes were negatively correlated with carotid IMT with a difference of mean of -0.023; SE: 0.007 (95% CI: -0.036 to -0.010, p: 0.001 ) when compared with the control group, reflecting the pooled effect size (Figure).

Conclusion:
Sustained long terms lifestyle changes i.e. diet and exercise, not only prevent the progression but also regress carotid artery atherosclerosis after at least three years of follow up.
Abstract WMP57: Fully Automated CT-based Quantification Of Microangiopathic Density Reduction In White Matter And Comparison To Gold Standard MRI
Authors: Hanning Uta , Homann Georg , Niederstadt Thomas , Heindel Walter , Kemmling Andre
Published: July 2021

Purpose:
Severity of white matter (WM) lesion load is difficult to quantify precisely in computed tomography (CT) even though it is the most frequently used imaging modality for brain. This pilot study addressed the need for reliable automated observer-independent quantification of white matter disease in CT. The purpose was to present and evaluate a CT-based automated rater independent method for assessment of microangiopathic WM changes.

Methods and Materials:
A probabilistic WM-tissue-map in standad MNI-152 space was obtained from 600 normal MRI scans from two large population studies (published previously). Robust registration of the WM-tissue-map to individual CT space was accomplished by affine linear registration with non-linear refinement (FSL4.1). The tissue- specific density (Hounsfield Unit, HU) within WM-space of the CT image was determined by the mean of all voxel densities weighted by WM content: Σ (HUxyz × Pxyz (WM))/ Σ (Pxyz (WM) ; (HUxyz = density of voxelxyz ; Pxyz = partial WM content at voxelxyz). The reduction of HU over WM-space in 40 CT images with visible WM disease was correlated with gold standard MR-based WM lesion volume measurements.

Results:
Automated WM-specific segmentation of brain CT was reliable in 40 cases with varying occurrence of WM-disease. Microangiopathic reduction of density within WM-space showed high correlation with MRI FLAIR-based WM-lesion volume (Pearson correlation coefficient 0.87).

Conclusion:
Automated quantification of density reduction within WM-space in CT images is feasible and may be used as a surrogate for gold standard MR based WM lesion load. The presented method needs further validation with larger datasets and different CT scanner protocols.
Abstract WMP61: TWOACES: TIA Work-up As Outpatient, Assessment Of Clinical Efficacy And Safety
Authors: Castle James , Green Jenifer , Olivot Jean-Marc , Albers Gregory
Published: July 2021

Background:
Much controversy exists as to the appropriate triage of acute TIA patients. One commonly used tool is the ABCD
2
score. This tool is helpful for patients at low risk (score of 0-3) or high risk (score of 6-7) of stroke, but leaves a large moderate risk population (score of 4-5) for whom no clear guidance can be given. As previous studies have found large artery atherosclerosis to be a potent risk factor for stroke after TIA, we attempted to further delineate low and high risk TIA populations with the addition of non-invasive arterial imaging.

Methods:
All patients referred to the Stanford Stroke Service for possible TIA within 72 hours of symptom onset between July 2007 and February 2010, and all patients referred to the Highland Park Stroke Service for possible TIA within 72 hours of symptom onset after October 2009 were screened for enrollment in this observational study. 406 patients were invited to enroll, 5 refused. Of the 401 enrolled, follow-up was obtained in 398 patients. Patients were placed into two groups: 1) ABCD
2
scores of 0-3 or 4-5 AND no sign of hemodynamically significant stenosis (<50%) "Low Risk Group"; and 2) those with ABCD
2
scores of 6-7 or 4-5 AND hemodynamically significant stenosis (≥50%) "High Risk Group". Non-invasive arterial imaging included CTA, MRA, and Carotid US - all chosen by the treating physician. 30 day stroke rates with 95% CIs were recorded.

Results:
Of the 398 patients in whom follow-up data was obtained, 340 (85.4%) fell into the “Low Risk Group”. Within that group, the stroke rate at 30 days was 1.76% (6 strokes, 95% CI 0.72-3.89%). Within the “High Risk Group”, the stroke rate at 30 days was 5.17% (3 strokes, 95% CI 1.21-14.7%). The overall stroke rate was 9/398 (2.26%, 95% CI 1.13-4.31%).

Conclusions:
In our observational study we continue to find that the overall 30 day stroke rate after TIA was quite low (2.26%). The percentage of all TIA patients falling into the “Low Risk Group” was quite high (85.4%), and these patients had a particularly low rate of stroke at 30 days. Given the high number of “Low Risk” patients and the low rate of stroke in that group at 30 days, the vast majority of TIA patients could likely be safely evaluated in a rapid outpatient setting provided that the treating physician is confident of the diagnosis.
Abstract WMP66: Enrollment in a Pre-hospital Stroke Trial: Common Reasons for Patient Non- Enrollment
Authors: Sanoff Randy , Cherin Samantha B , Krause Joan , Chatfield Fiona , Sanossian Nerses , Starkman Sidney , Saver Jeffrey , Liebeskind David , Restrepo Lucas , Ali Latisha , Valdes-Suerias Miguel , Kim May , Obviagele Bruce , Kim Doojin , Conwit Robin , Eckstein Mark , Pratt Frank , Hamilton Scott , Stratton Sam ,   For the FAST-MAG Investigators and Coordinators
Published: July 2021

Background:
Enrolling patients in the field is a promising strategy to facilitate entry of subjects within the first 1 to 2 hours after symptom onset into clinical trials for acute stroke treatment. The Field Administration of Stroke Therapy Magnesium (FAST-MAG) Trial is the first multicenter study to implement eliciting informed consent by cell phone between patients or their legally authorized representatives (LARs) and off- site enrolling physician-investigators. Call yield and profile of screen failures observed over the course of the study are reported.

Methods:
FAST-MAG is a phase 3 trial to evaluate field-initiated magnesium sulfate as a neuroprotective agent to improve the long-term functional outcome in acute stroke. The outcomes of these attempted enrollment calls from 362 participating ambulances to the eight central English and Spanish-speaking enrolling physician-investigators were tracked prospectively from 1/2012 to 1/2005.

Results:
Over seven years, 3,726 calls were made to enrolling physicians. Of these, 1478 (40%) resulted in trial enrollments. Among 2248 non-enrollment calls, the five most common reasons for were: physician’s determination of last known well time was longer than two hours (19%), pre-existing condition which could confound outcome evaluation (18%), patient deemed not competent to provide informed consent and no LAR available (12%), rapidly improving neurological deficit (9%), patient not English or Spanish speaking (6%). Phone connection difficulties accounted for only 2.7% of screen failures, whereas 4.2% were competent patients and 11% were LARs refusing participation. Yearly enrollment yeilds did not change significantly throughout the study

Conclusion:
Two of every five calls from the field to FM enrolling physicians resulted in trial enrollment. Enrollment yields were consistent throughout the study.
Abstract WMP85: Recovery Rate vs. Recovery Capacity: A Mathematical Model and its Implications for Rehabilitation
Authors: Schweber Adam B , Dunn Lauren E , Lendaris Andrea R , Minzer Brandon M , Lazar Ronald M , Marshall Randolph S
Published: July 2021

INTRODUCTION:
Recovery of most hemiparetic patients at 90 days can be well predicted as a fixed proportion (70%) of initial motor deficit. However, recent work has shown considerable variability in the
rate
of recovery among proportional recoverers, prompting consideration of whether rate of recovery and recovery capacity are independent and whether a single rate dynamic governs proportional recovery.

HYPOTHESIS:
Among proportional recoverers, recovery rate variability can be accounted for by a single mathematical model in which: 1) recovery rate is independent of recovery capacity and 2) recovery has a sigmoid trajectory parameterized only by initial stroke severity.

METHODS:
We studied 23 patients with first-ever unilateral hemiparetic stroke previously identified as proportional recoverers. Fugl-Meyer Upper Extremity Motor Exam (FM-UE) had been measured at <72h, 1 week, and 90 days. A non-linear model predicting patients’ FM-UE score at any time after stroke onset was posited and model parameters were estimated by regressing one-week FM-UE scores against initial scores. Statistical significance and goodness of fit were evaluated.

RESULTS:
The model accounted for 86% of variability in motor recovery achieved by patients at 1 week after stroke onset (pseudo-R
2
=0.863,
F
23,21=
418.0,
p
<.0001) and predicted that more severely impaired patients will have a slower maximum recovery rate and a recovery period that is longer in duration and more delayed in onset.

CONCLUSION:
The model provides evidence that proportional recovery is governed by a single rate dynamic and that recovery rate is independent of recovery capacity. It provides a tool for predicting motor impairment at any time following stroke onset and suggests a framework for characterizing the biology of recovery and the role of therapeutic interventions as either capacity-enhancing or rate-enhancing.
Abstract WMP94: Root Cause Analyses of Preventable Causes of Readmission after Stroke: The University Hospitals- Case Medical Center (UH-CMC) and University Hospitals System Stroke Program (UHSSP) Experience
Authors: Kim Benny S , Fussner Julie , Sila Cathy
Published: July 2021

Root Cause Analyses of Preventable Causes of Readmission after Stroke:
The University Hospitals- Case Medical Center (UH-CMC) and University Hospitals System Stroke Program (UHSSP) Experience

Objective:
Metrics, such as the 30 day readmission rate after stroke, are increasingly used by consumers and payors to reflect hospital quality of care. Benchmarks determined by large administrative databases lack detailed root cause analyses which are crucial in determining preventable causes.

Methods:
In 2010, the UHSSP Quality Initiative developed a MIDAS™ report alerting the Stroke Coordinator of all inpatient encounters to any UH hospital within 30 days of a stroke discharge from UH-CMC. A focus study guided a detailed case review including demographics, index admission stroke subtype, discharge treatment and disposition, follow up appointments, medical compliance, readmission diagnosis and location, and Root Cause Analysis of preventable causes.

Results:
Of 1093 stroke discharges from January 2011 - June 2012, 84 (7.7%) were readmitted within 30 days; 5.7% to UH-CMC and 2% to other UH hospitals. During this period, compliance with evidence-based guidelines for stroke exceeded benchmarks. Readmitted patients were 54% female, 30% aged ≥ 80 years and 45% were transferred from facilities. Stroke subtypes reflected total discharges with 78% ischemic stroke, 9.6% TIA, 8% intracranial hemorrhage and 3.6% subarachnoid hemorrhage. Of the various causes of readmission, the most common were recurrent vascular events in 22% (TIA, stroke 14%, myocardial 8%) and infection in 20% (pneumonia 11%, urinary tract 7%). Bleeding complications of anti-thrombotic therapy occurred in 8% (hemorrhagic transformation 6%, GI 2%). Other frequent events included new onset seizure (7%) or cardiac arrhythmia (5%). Scheduled, elective readmissions accounted for 6% and medically unnecessary transfers from facilities an additional 6%.

Conclusions:
Single center data would have missed 26% of the readmissions that went to hospital system community hospitals. Root Cause Analyses of readmitted patients discovered evidence relevant to the readmitting diagnosis prior to index hospital discharge in 7% but only 6% of all readmissions were preventable by the discharging team.
Abstract WP100: Hydrogen Sulfide Increases Angiogenesis And Improves Functional Outcome After Stroke
Authors: Oh Mi-Young , Jang Hyunduk , Lee Seung-Hoon , Ryu Wi-Sun , Yoon Byung-Woo
Published: July 2021

Background:
Hydrogen Sulfide is a potent inducer of angiogenesis. In this study, we investigate whether NaHS (H2S donor) induces angiogenesis and thereby improves functional outcome in rat cerebral ischemic/reperfusion model.

Methods:
Adult male rats were subjected to middle cerebral artery occlusion and were treated with 5mg/kg of NaHS or normal saline starting 48 hours after middle cerebral artery occlusion and daily for 14 days. Neurological functional tests were performed. The volume of von willebrand factor(vWF)- positive area was measured. Newly proliferated vascular endothelial cell were counted. Angiogenic factor expressions were measured by immunohistochemistry and western blot. In vitro, endothelial tube formation was examined.

Result:
NaHS significantly promoted vWF-positive area (30.1±10.1% vs. vehicle, 12.3±7.1 %, p<0.01) and proliferation of vascular endothelial cell (7.3/2*105 um2 vs. vehicle, 3.1/2*105um2, p<0.01) in the ischemic brain. and improved functional outcome after stroke. Mechanisms underlying the NaHS-induced vascular remodeling were investigated. NaHS increased the expression of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang1), angiopoietin-2(Ang-2) and phosphorylation of Akt, and ERK-1/2.

Conclusions:
NaHS promoted angiogenesis, which may contribute to improvement of functional outcome after stroke. The VEGF/VEGF receptor, phosphoinositide 3-kinase/Akt, and ERK-1/2 pathways appear to mediate NaHS-induced angiogenesis.
Abstract WP102: Interleukin-21 Promotes Neuronal Autophagy Following Cerebral Ischemia
Authors: Clarkson Ben , Ollar Samual J , Walker Alec , Fabry Zsuzsa
Published: July 2021

Currently there is no treatment for the inflammatory responses that develop following cerebral ischemia. We have previously shown that the CD4+ T cell derived inflammatory cytokine IL-21 is highly upregulated in ischemic mouse brain following transient middle cerebral artery occlusion (tMCAO) and promotes neuronal tissue injury. We also found IL-21+ CD4+ cells in perivascular spaces of ischemic human brain tissue; however, the primary effects and cellular targets of IL-21 remain unknown. Thus, we compared genome-wide whole brain gene expression in wild-type (WT) and IL-21
-/-
mice following 1 hour tMCAO (n=3-5). RNA from whole brain was analyzed by Mouse Gene 1.0 ST microarray (Affymetrix) revealing that 2019 gene fragments representing 1505 genes had >3 fold higher expression in WT brain compared to IL-21
-/-
after 24 hours reperfusion. Gene score resampling of annotated probe scores identified biological process gene ontology (GO) terms with 3-8 member genes most significantly over-represented including: GO:0010507 Negative Regulation of Autophagy, GO:0090174 Organelle Membrane Fusion, GO:0000046 Autophagic vacuole fusion, and GO:0016242 Negative regulation of macroautophagy (p <0.001). These findings suggested a role for IL-21 in neuronal autophagy_consistent with our earlier reports of reduced expression of autophagy related gene 6 (ATG6) in infarcted brain tissue of IL-21
-/-
mouse compared to WT mice. Thus, we hypothesized that IL-21 could directly induce autophagy in hypoxic neuronal cells. IL-21 receptor was expressed on 10% of CD45- cells isolated from healthy mouse brain. Furthermore, using RT-PCR we detected Il21r mRNA expression on neuronal (Neura2A), astrocytic, and endothelial cell lines (MB114) with highest expression levels on Neuro2A cells. Surface expression on Neuro2A cells and primary neurons was confirmed by immunofluorescence. In preliminary experiments primary neurons treated with 256 ng/mL rIL-21 for 4 hours following 1-2 hour oxygen glucose deprivation showed increased expression of ATG6 compared to control treated cells (p<.05). In conclusion, these data suggest that IL-21 could directly promote neuronal autophagy following cerebral ischemia.