bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3432: Sex-dependent Differences in Autophagy After Experimentally-induced Stroke
Authors: Adami Alexander J , O'Keefe Lena , Venna Venugopal R , Li Jun , Siegel Chad S , Benashski Sharon E , McCullough Louise D
Published: March 2022

Background and Purpose:
Autophagy is a catabolic process where the cell consumes pieces of itself as a part of normal cellular growth, development, and homeostasis. In response to nutrient challenge or other stressors, including ischemia, autophagy levels may rise, enabling the cell to survive. Autophagy has been shown to play a role in the cellular response to neonatal cerebral ischemia, and sex differences have been found in cell culture models of neuronal nutrient starvation. However, the role of sex in the autophagic response to stroke has not been investigated
in vivo
. The objective of this study was to examine the impact of sex on autophagy following experimental stroke.

Methods:
Stroke was induced by reversible right middle cerebral artery occlusion (MCAO - 90 minutes) in male, gonadally-intact female, and ovariectomized (OVX) WT C57BL/6 mice (20-25 gm). Autophagy activity was assessed at 6 and 24 hours following MCAO with LC3-I/II and Atg7 protein levels by western blot (n=3 MCAO; n=3 sham/group). Beta-actin was utilized as a loading control.

Results:
Atg7 levels were higher in sham males at both the 6h and 24h timepoint compared to intact females and OVX females. After MCAO, males and OXV females showed increased levels of Atg7 relative to sham at 6h, while intact female levels were unchanged. By 24h, Atg7 levels in MCAO males and OVX females remained higher than sham, while intact females showed no difference. LC3-II levels were higher in MCAO for OVX females at 6h and 24h, while intact females saw transiently-elevated LC3-II levels at 6h and no elevation by 24h. Males had higher levels of LC3-II in both MCAO and sham relative to intact females at both 6h and 24h and higher levels than OVX females at 6h.

Conclusions:
This study demonstrates that autophagy activation in response to stroke differs between the sexes. We found that males had overall higher levels of autophagy than both OVX females and intact females at both 6h and 24h. Both males and OVX females showed higher levels of autophagy at 24h and 6h after MCAO relative to sham, while females showed no change. Our study suggests that changes in autophagy may contribute to the differential outcome after stroke between the sexes. Studies examining sex differences in infarct size after MCAO after inhibition of autophagy with 3-methyladenine (3-MA, Sigma-Aldrich, St. Louis, MO) are ongoing in our laboratory.
Abstract 3433: The Effects of an 8-week Aerobic Exercise Intervention on Cardiovascular Function and Physical Performance in Sub-Acute Stroke - A Preliminary Study
Authors: Lentz Angela , Ashenden Abby , Rippee Michael , Billinger Sandra A
Published: March 2022

Purpose/Hypothesis:
Impaired vascular function and decline in cardiorespiratory (CR) fitness can result in considerable limitations in physical function in people post-stroke. These cardiovascular changes may result from reductions in oxidative capacity, blood flow, and altered muscle fiber type expression in the hemiparetic limb. CR fitness is significantly lower in people with stroke and limits walking speed, endurance and performance of daily activities. Aerobic exercise training is an excellent intervention to improve cardiovascular outcomes in people with stroke. The purpose of this preliminary study was to examine the effects of an 8-week total body recumbent stepper(TBRS) aerobic exercise intervention on vascular function using flow-mediated dilation(FMD), CR fitness, and the 6-minute walk test(6-MWT) during sub-acute stroke.

Subjects:
We have enrolled 8 participants and 5 have completed the exercise intervention. These 5 individuals (male, n = 3) were 63.0±6.3 years of age; 65.0±45.2 days post-stroke (range: 10-123) and had a total Fugl-Meyer score of 107±22.6.

Methods:
The exercise intervention consisted of aerobic exercise using the TBRS 3 times/week for 8 weeks. Using the results from the exercise test, target HR range was calculated at 50-59% of HR reserve for the first 4 weeks and then increased to 60-69% of HR reserve for the final 4 weeks. Brachial artery diameter and reactive hyperemia using FMD were assessed in bilateral upper extremities. The vessel was scanned using Doppler ultrasound with a 7.5 Mhz linear array transducer. A pneumatic cuff was placed around the forearm and inflated to suprastolic pressure for 5 minutes. After cuff deflation, images were recorded to the computer for off-line analysis using an automated edge-detection and wall-tracking software. CR fitness was assessed using a metabolic cart during an incremental peak exercise test. To assess physical performance, participants completed a 6-MWT. All outcome measures were assessed at baseline and post-intervention.

Results:
Preliminary results demonstrated improvements in vascular function, CR fitness and the 6-MWT. Although brachial artery diameter was smaller in the stroke-affected side (3.63±0.52 vs 4.04±0.66), both sides increased in diameter (stroke affected: 3.68±0.44; non-affected: 4.37±0.55) and FMD increased by 7.2% (stroke affected) and 8.6% in non-affected side after the intervention. CR fitness increased by 10%(baseline:15.6±2.8 to 17.2±4.6 ml*kg
-1
*min
-1
). The 6-MWT increased from 281±144.1 to 314.3±160.4 (12%) meters.

Conclusion:
Aerobic exercise in sub-acute stroke appears to be beneficial for improving cardiovascular function and physical performance. Aerobic exercise interventions should be considered an integral component of stroke rehabilitation.
Abstract 3443: No Exacerbation of Perihematomal Edema or Ventricular Volume with Intraventricular Tissue Plasminogen Activator in Patients with Spontaneous Intraventricular Hemorrhage
Authors: Moullaali Tom J , Ullman Natalie L , Brooks James S , Morgan Tim , Hanley Daniel F , Ziai Wendy
Published: March 2022

Introduction:
In severe spontaneous intraventricular hemorrhage (IVH), intraventricular (IVR) administration of tissue plasminogen activator (tPA) results in more rapid clearing of blood from the ventricles than with external ventricular drainage (EVD) alone. However, experimental studies suggest tPA may be neurotoxic in compromised brain tissue and may exacerbate perihematomal edema.

Methods:
We used computerized volumetrics to assess change in intracerebral hemorrhage (ICH), IVH, ventricular and peri-ICH edema (PHE) volumes at 2-5 (T1) and 5-9 (T2) days following diagnostic CT scans (T0) of 20 patients (10 tPA treated; 10 controls) with IVH requiring EVD. Control patients from a hospital database treated with EVD alone were matched by IVH and ICH volume to tPA-treated patients. Treated patients came from two multicenter trials involving 100 patients with IVH, and spontaneous ICH volume <30cc and received a median of 4 doses (range 1-8) of tPA.

Results:
There were no significant differences between matched pairs in terms of age, admission Glasgow Coma Score, Graeb IVH score, PHE volume, total ventricular volume, or ICH volume. Median IVH volume was larger in the tPA-treated group (26.2 cc iqr10.2 vs. 23.1 cc iqr9.2; P=0.02). IVR tPA resulted in more rapid clearance of IVH as determined by T2-T0 decrease in Graeb score and median IVH volume (tPA: -18.7 (10.8) cc; control:-7.6 (3.2) cc; P=0.005). Ratios of PHE to ICH volume were non-significantly higher in control vs. tPA treated patients at T1 and T2 [control:tPA = 0.82:0.77 (T1);P=0.44 and 0.64:0.56 (T2);P=0.48]. Total ventricular volume was significantly larger in the control group at T2 (median: 41.7 (36.9) cc vs. tPA: 24.5 (11.9) cc; P=0.02) and cumulative median cerebrospinal fluid drainage was non-significantly higher (control: 1079 (463) cc vs. tPA: 639 (428) cc; P=0.08). Ventriculitis was more frequent in the control group (4 vs. 2 episodes; P=0.08) as was shunt dependence (4 vs. 0 cases; P=0.04).

Conclusions:
For case matched large IVH with small ICH volume, IVR tPA enhances lysis of intraventricular blood clots, accelerates resolution of post-hemorrhagic hydrocephalus and has no significant impact on perihematomal edema.
Abstract 3445: Predictors and Outcomes of Merci Device Fracture during Mechanical Thrombectomy for Acute Ischemic Stroke
Authors: Shi Zhong-Song , Saver Jeffrey L , Loh Yince , Liebeskind David S , Gonzalez Nestor R , Tateshima Satoshi , Jahan Reza , Duckwiler Gary R , Viñuela Fernando
Published: March 2022

Background and Purpose:
Merci device fracture is an adverse event during mechanical thrombectomy for acute ischemic stroke. The purpose of this study was to describe the frequency and predictors of this complication in acute stroke patients after thrombectomy and its impact on clinical outcome.

Methods:
We retrospectively analyzed acute ischemic stroke patients treated by mechanical thrombectomy with the Merci Retriever and identified the presence of device fracture. The predictors of device fracture were assessed. We evaluated the impact of device fracture on potential hemorrhage and clinical outcome.

Results:
Of 136 patients treated by thrombectomy, 6 (4.4%) experienced intra-procedural device fracture. Internal carotid artery occlusion was associated with device fracture (OR 13.06; 95% CI 1.47 to 115.62,
P
=0.01). The fractured X and L series devices were successfully ensnared by a Merci device or a microsnare in 4 patients. Compared with patients with non-fractured devices, those with fractured devices had similar rates of Thrombolysis and Myocardial Infarction (TIMI) grade II and III revascularization (66.7% versus 72.3%;
p
=0.67), decreased rates of arterial occlusive lesion (AOL) grade III recanalization (0% versus 48.5%;
p
=0.03) and longer mean procedure time (2.5 hours versus 1.8 hours;
p
=0.03). In patients with fractured devices, no parenchymal hematomas were found, while hemorrhagic infarction and subarachnoid hemorrhage were found in 3 and 2 patients, respectively. Decompressive craniectomy following thrombectomy for malignant edema was associated with device fracture (
P
=0.02). Patients with fractured devices had similar rates of independence at discharge (modified Rankin Scale≤2, 0% versus 25%;
P
=0.34) and in-hospital mortality (16.7% versus 23.4%;
P
>0.99).

Conclusions:
Device fracture is relatively infrequent in acute ischemic stroke patients treated by Merci thrombectomy. Target occlusion in the internal carotid artery is an independent predictor of intra-procedural device fracture. This complication is not associated with parenchymal hematomas or poor clinical outcomes after thrombectomy.
Abstract 3448: Moderate Hypertension Increases Potassium Loss from Ischemic Cortex and Reduces Infarct Volume in Experimental Stroke
Authors: Jones Stephen C , Kharlamov Alexander , Yushmanov Victor E
Published: March 2022

After experimental focal ischemia, pronounced changes of brain tissue sodium, MAP2, water content, and potassium concentration ([K
%
]
br
) occur in the periphery of the ischemic region which we have defined as the ‘Ischemic Edge’ (IE) (Kharlamov et al., JCBFM, 2009: S230). We hypothesize that the lower [K
%
]
br
in the IE is related to residual collateral flow and that an increase in this collateral flow will result in a further decrease in [K
%
]
br
in the IE.

Focal ischemia was induced by MCA transection and bilateral CCA occlusion in Sprague-Dawley rats (isoflurane, N
2
O) for 4 h. CBF (% of control) was monitored by laser speckle imaging in three different regions on the stroke side (NC, normal cortex; IE region at the periphery of the ischemic region; and IC, ischemic core) and in corresponding regions of non-lesioned hemisphere. In phenylephrine group (Phe, n=5) mild hypertension (132 mmHg) was maintained by constant (2 h) phenylephrine infusion (0.5 mg/ml, 0.02 ml/m, IV) started at 5 m after ischemia (Shin et al., Stroke, 2008: 1548). In the control group (Con, n=3) saline was similarly infused (blood pressure, 102 mmHg).

The cortical distribution of [K
%
]
br
from calibrated images of brain sections histologically stained for K
%
was analyzed using a “ribbon” tool. CBF and [K
%
]
br
over treatment group, side, zone and time were analyzed using SAS Proc Mixed. To assess the loss of K
%
in the IE region, we determined the IE volume and calculated (V * [K
%
]) the amount of K
%
lost for each group.

Moderate hypertension (Phe group) doubled CBF in IC and IE regions of the ischemic hemisphere compared to the Con group (p<0.05) and decreased infarct volume (11.2% vs 6%, p=0.03).
Fig. 1
shows the K
%
-depletion from the IE 4 hr after MCAo. The IE volume is ∼40% of the hemispheric volume and ∼80% of the ischemic region volume (
Fig. 1
A), the amount of K
%
lost in the Phe group was x2 that lost in the Con group (
Fig. 1
B), and was ∼20% of the amount of K
%
in the hemisphere (
Fig. 1
C). There were no differences in the minimal amount of K
%
lost in the central ischemic core, underscoring the importance of collateral flow at the Ischemic Edge.

We suggest that the lower [K
%
]
br
in IE in the Phe group results from higher residual collateral flow. These data demonstrate that the IE is a major component of stroke pathology, suggest that moderate hypertension’s effect to reduce infarct volume (Shin et al., Stroke, 2008, 1548) and improve patient outcome (Hillis et al., Cerebrovasc Dis, 2003, 236) is partially based on K
%
-depletion at the IE, and give support to the importance of K
%
-loss in ischemic stroke.

Support: NIH NS30839, NS66292 1
Abstract 3452: Antiphosphatidylserine-prothrombin Antibodies Are Associated With Outcome After TIA
Authors: Mullen Michael T , Messe Steven R , Kasner Scott E , Sansing Lauren H , Husain M R , Norman Gary L , Shums Zakera , McIntire Chandani , Cucchiara Brett L
Published: March 2022

Background and Purpose:
Newly defined subclasses of antiphospholipid antibodies (aPLs) have been associated with thrombotic and atherosclerotic vascular events. We aimed to determine if they predict outcome after TIA.

Methods:
Detailed clinical data and blood samples were obtained prospectively from subjects with TIA hospitalized <48 hours from symptom onset. In a retrospective analysis standard aPLs, anti-cardiolipin (ACL) and β-2-glycoprotein-1 (β2GP1), and newer aPLs, anti-phosphatidylserine-prothrombin (aPS-PT), β2GP1 D4/5 subunit and β2GP1 D1 subunit, were measured by ELISA. The primary outcome was a composite endpoint of stroke or death within 90 days or identification of a high-risk stroke mechanism (defined as >50% stenosis in a vessel referable to symptoms or cardioembolism warranting anticoagulation). A secondary outcome was the presence of clinical or sub-clinical atherosclerosis.

Results:
Over 4.5 years, 167 patients were enrolled. Mean age was 62±14 years; 55% were female. Mean time from symptom onset to blood sampling was 26.2 ± 12.7 hours. Overall, 41 patients (25%) had the composite endpoint: 25 (15%) with a >50% stenosis, 14 (8%) with cardioembolism and 8 (5%) with clinical events (5 strokes, 3 deaths). The results of aPL testing using predefined cut-points to define positivity are summarized in the
table
. Using a cutoff of 30 units aPS-PT IgG antibodies were significantly associated with stroke/death (OR 17.3 95% CI 2.4-123.8 p=0.004) with a trend towards an association with the composite endpoint (OR 4.9 95% CI 0.8-30.4 p=0.09). In multivariate analysis adjusting for ABCD2 score, aPS-PT IgG remained associated with stroke/death (OR 16.6 95% CI 2.1-133.7 p=0.008). Using a data derived cut-off of 20 units (∼95% percentile within study population) aPS-PT IgG antibodies were significantly associated with stroke/death (OR 7.2 95% CI 1.2-42.5 p=0.03) and the composite endpoint (OR 4.2 95% CI 1.1-16.6 p=0.04). After adjusting for ABCD2 score, the association with stroke/death remained significant (OR 6.1 95% CI 1.0-38.5 p=0.05) and the composite endpoint approached significance (OR 3.8 95% CI 0.9-15.4 p=0.06). Elevated aPS-PT IgG levels occurred more frequently in subjects with clinical or sub-clinical atherosclerosis than those without (9% vs 0%, p=0.012). Other aPLs were not associated with atherosclerosis.

Conclusion:
In contrast to other aPLs, anti-phosphatidylserine-prothrombin IgG antibodies are elevated in high-risk TIA patients.
Abstract 3467: Disappearance Of The Acute Diffusion Weighted Imaging Lesion After Treatment With tPA
Authors: Freeman Jason W , Luby Maire , Warach Steven
Published: March 2022

Background:
MRI with diffusion weighted imaging (DWI) is significantly more sensitive than head CT in the determination of acute ischemic stroke. In patients presenting with acute ischemic cerebrovascular syndrome (AICS), we sought to determine the probability of finding a normal DWI post treatment with tPA, despite a clinical syndrome and pretreatment MRI consistent with acute ischemia. While previous studies report a rate of stroke mimic (SM) of 3 to 10%, a more recent report estimates up to 21% of patients treated based on head CT were either stroke mimic or neuroimaging negative cerebral ischemia.

Methods:
We queried the LESION database for patients who presented with clinical syndrome consistent with AICS, underwent acute MRI screening and then underwent follow-up MRI at either 2hrs or 24hrs post treatment with iv-tPA. Experienced Stroke neurologist interpreted the follow up scans and identified those with absence of the initial DWI lesion. We excluded patients whose TOAST was small vessel disease or those with brainstem infarcts, given the higher incidence of false negative MRI in these types of stroke.

Results:
There were 195 patients who met inclusion criteria. Of these there were a total of 4 patients in whom early follow up imaging failed to reveal the previously seen DWI lesion for which they were treated. This represents 2.0% of patients. The causative lesion did reappear on subsequent imaging in 2 out of the 4 patients. In an additional 6 patients, the initial MRI was negative prior to treatment with none of these patients developing a DWI lesion post iv-tPA. Four of the six patients were determined to be stroke mimics after their work-up was completed.

Conclusions:
We found that 2.0% of patients with positive DWI prior to iv-tPA had follow-up imaging that failed to show the initial DWI lesion. In addition, 2.7% of patients treated had negative pre and post tPA imaging. We conclude that the true incidence of neuroimaging negative stroke post iv-tPA is unlikely to be greater than 5% in those patients screened with MRI. While the pathophysiological basis is not yet know, the transient disappearance of the DWI lesion may give rise to a higher rate of patients being interpreted as stroke mimics in those initially screened with head CT.
Abstract 3470: A Simple Score (ACVS) to Identify Patients at High Risk of Recurrent Stroke or Death during 1Year after Transient Ischemic Attack or Minor Ischemic Stroke.
Authors: Yamagami Hiroshi , Kawamoto Michi , Todo Kenichi , Yamamoto Shiro , Yoshimura Hajime , Sugo Norifumi , Sekiya Hiroaki , Ishii Junko , Tamaki Yoshitaka , Higashida Kyoko , Kohara Nobuo
Published: March 2022

Background and Purpose:
Transient ischemic attack (TIA) and minor ischemic stroke is critical warning sign of following disabling stroke. Recently, the concept of acute cerebrovascular syndrome (ACVS) is advocated for early diagnosis and management of TIA or minor stroke. We thought to determine whether the early examination findings at admission can predict the recurrent stroke or death during 1 year after the qualifying event.

Methods:
Between April 2006 and July 2009, 621patients with TIA or minor ischemic stroke (defined as an National Institutes of Health Stroke Scale [NIHSS] score ≤3) were admitted to our stroke center within 7 days after the onset. Among them, 494 patients obtained outcome at 1year were analyzed. Background data including the findings of laboratory examination, brain MRI diffusion weighted image (DWI), brain MRA and carotid ultrasound were obtained within 3 days after the admission. Information about recurrent stroke and/or death from any cause within 1 year after the qualifying event was obtained from clinical record or telephone interview.

Results:
During 1 year after the qualifying events, further stroke were identified in 46 (9.3%) patients, 19 (3.9%) patients died, and a total of 60 (12.2%) patients had composite incident of recurrent stroke or death. Multivariate logistic regression analysis showed that age ≥ 60 years old (hazard ratio, 3.00), female sex (hazard ratio, 1.98), history of previous stroke (hazard ratio, 2.10), serum CRP level ≥ 0.2mg/dL (hazard ratio, 2.59), intracranial or carotid artery stenosis ≥ 50% (hazard ratio, 1.76) and acute infarction on DWI (hazard ratio, 3.62) were found to be independent risk factors for recurrent stroke or death. A four-point score derived from these results (acute infarction on DWI [present = 1], CRP level [≥ 0.2mg/dL = 1], vascular stenosis of intracranial or carotid artery [≥ 50% = 1], and stroke history [present = 1]: ACVS) was highly predictive of 1-year risk of recurrent stroke or death (p < 0.001,
Figure
).

Conclusions:
Risk of stroke or death during 1 year after TIA or minor stroke seemed to be highly predictable. Although further validations are needed, the ACVS score may be useful in clinical practice to identify high-risk individuals who need careful treatment and follow up.
Abstract 3479: Prediction of Outcome in Cerebellar Infarction by Diffusion MRI
Authors: Tchopev Zahari , Zhuo Jiachen , Betz Joshua , Gullapalli Rao , Sheth Kevin N
Published: March 2022

Background and Purpose -
Early identification of patients at risk for neurological deterioration after stroke remains a challenge. MRI based volumetric assessments of infarct have been shown to predict poor outcome amongst patients with large middle cerebral artery infarcts. However, no such quantitative imaging measure exists to predict outcome following cerebellar stroke. In this study, we tested the hypothesis that the volume of cerebellar infarction and its associated apparent diffusion coefficient (ADC), as estimated from diffusion-weighted images (DWI), can provide reliable information for the prediction of neurological deterioration.

Methods -
We retrospectively identified twenty-eight consecutive patients (age 58.2±13) with cerebellar stroke who underwent MRI (median 40.8 hours) with DWI. Patients were divided into poor (N=7) and good (N=21) outcomes. Patients with poor outcome were defined as those who required posterior fossa decompression or died as a result of their cerebellar infarct. Lesion and cerebellar volume were defined on ADC maps. The ratio of the lesion volume to the whole cerebellum volume was calculated (rVolume) as well as the ratio of the lesion mean ADC to normal cerebellum mean ADC (rADC). The National Institutes of Health Stroke Scale (NIHSS) score, as well as age, sex and race were collected. Binary logistic regression was used to identify predictors of poor outcome. The sensitivity and specificity of rVolume and lesion volume were determined in predicting poor outcome using ROC analysis.

Results -
Logistic regression analysis revealed that rVolume (p=0.018), lesion volume (p=0.034), NIHSS score (p=0.020) and whole cerebellar ADC value (p=0.043) were significant predictors of poor outcome. The rADC (p=0.073) approached significance. The rVolume (p=0.047) remained a significant predictor of outcome even when controlling for age, NIHSS score, and hours to scan, while a trend towards significance for lesion volume (p=0.072), cerebellar ADC (p=0.069) and rADC (p=0.061) were also observed. ROC analysis revealed that both rVolume as a percentage and lesion volume had a specificity of 95% and a sensitivity of 57% in predicting poor outcome. The respective cut-off values were 30% and 41 cc.

Conclusions -
Quantitative measurement of rVolume, lesion volume, and cerebellar ADC values are significantly correlated with patient outcomes following cerebellar stroke. Although cerebellar ADC provided additional sensitivity, the rVolume appears to be a strong predictor of outcome when controlling for age, NIHSS score and time to scan. Quantitative analysis of diffusion MRI may assist in identification of patients with cerebellar stroke at highest risk of deterioration. Prospective validation is warranted.
Abstract 3487: Back To Basics: A Revised Approach To Fall Prevention In The Right Brain CVA / TBI Patient
Authors: Howell Denise , Reddan Margaret
Published: March 2022

Background and Purpose:
In December 2009, Mercy Medical Center’s Acute Inpatient Rehabilitation unit suffered an unprecedented rise in the number of patient falls to an unacceptable level of 17.3%. The national benchmark for falls on an acute rehabilitation unit is 8-10%. Of the 10 patients that had fallen, 9 had been admitted for post CVA rehabilitation, and of that number, 7 of them had a right brain sided injury. This caused us to question what it was that made this particular patient population so susceptible to falling. We looked into what effect on behavior a brain injury would cause. Based upon the area that was affected, either right or left brain, there were definite behaviors that would characterize the patients in either category. Left brain injured patients have physical deficits on the right side of their bodies, they may have speech or swallowing disorders and because of disorganized thinking they act very slow and cautiously when approaching tasks. They are the type of patient that needs constant feedback to participate in rehabilitation therapies, so they do not constitute a higher then normal fall risk. The patient with a right sided brain injury has left sided physical impairments, poor impulse control, spatial-perception difficulties and is more prone to having left body sided “neglect” where they are not aware of anything on their left side¼including their own body. This type of patient is at an exceptionally high risk for falling.

Method:
Based upon the behavioral characteristics of the right brain injured patient, we developed a new safety program for all right brain injured patients, whether from a traumatic brain injury or a CVA. An immediate staff inservice was initiated on how a brain injury affects behavior. In addition to our usual hourly rounding, bed and chair alarms became mandatory for these patients to alert the staff that the patient is trying to get up unassisted, they wear a different color of slipper sock to differentiate them from the other patients at a glance, their “falling star” fall risk star room sticker now has a “Happy Face” drawn on it. As an added benefit all of these interventions, with the exception of the chair alarms, did not cost the unit anything extra to implement.

Results:
By identifying these right CVA patients as being at exceptionally high risk for falls upon admission, making it easy to differentiate them from the other rehabilitation patients and initiating our new fall prevention program, our falls have decreased significantly in this patient population, down 27% in January 2010.

Conclusion:
A focused approach to fall prevention based upon behavioral characteristics of the right brain injured CVA patient has been highly successful in reducing the number of patient falls in our acute inpatient rehabilitation unit for this particular patient population.
Abstract 3494: LOXblock-1 Provides Efficient, Specific, And Long-lasting Neuroprotection Against Transient Focal Ischemia In Mice By Inhibiting 12/15-Lipoxygenase
Authors: Yigitkanli Kazim , Pekcec Anton , Pallast Stefanie , Mandeville Emiri , Joshi Netra , Smirnova Natalya , Gazaryan Irina G , Ratan Rajiv R , Witztum Joseph L , Holman Theodore R , Lo Eng H , Van Leyen Klaus
Published: March 2022

Background and Purpose -
Acute phase stroke treatment options are currently very limited. We have previously demonstrated 12/15-lipoxygenase (12/15-LOX) to initiate an apoptotic cell death cascade, contributing to neuronal cell death, but also vascular leakage and edema formation in the ischemic brain. The current study was designed to test if a novel inhibitor LOXBlock-1, can specifically reduce 12/15-LOX activity in vivo, and provide efficient and long-lasting protection against stroke-induced injury.

Methods -
In vitro protection by LOXBlock-1 was tested in HT22 cells. A cell-based reporter assay determined activation of HIF1a and NRF2. The lipoxygenase metabolite 12-HETE was measured using a commercial EIA kit, and confirmed by HPLC/mass spectrometry. We injected LOXBlock-1 intraperitoneally in mice subjected to middle cerebral artery occlusion (MCAO). Immunohistochemistry was used to detect MDA-modified lysine in the ischemic brain, TTC and H&E stains were used to determine infarct size. Neurological severity score and corner test were used to evaluate behavioral outcome. Intracerebral hemorrhage was induced by collagenase injection.

Results -
Nanomolar LOXBlock-1 protected HT22 cells against oxidative glutamate toxicity. LOXBlock-1 reduced 12-HETE levels, without activating HIF1a- and NRF2-dependent pathways. One day after MCAO, MDA-modified lysine co-localized with 12/15-LOX in the peri-infarct cortex, and LOXBlock-1 reduced hemispheric swelling, levels of 12-HETE, and infarct size. After 14 days, infarct size remained reduced, and behavioral outcome was improved. LOXBlock-1 did not increase collagenase-induced hemorrhage.

Conclusion -
12/15-LOX inhibition by LOXBlock-1 provides effective and long-lasting protection against transient focal ischemia in mice, without worsening hemorrhage. LOXBlock-1 may be a suitable acute phase stroke treatment.
Abstract 3530: Low yield of Transthoracic and Transesophageal Echocardiography in the Management of Patients with Acute Ischemic Strokes
Authors: Bal Simerpreet , Coulter Jonathan I , Godzwon Catherine , Almekhlafi Mohammed , Weeks Sarah , Hutchison Stuart , Menon Bijoy K , Coutts Shelagh B
Published: March 2022

Background
Echocardiography has become ubiquitous in the diagnostic armamentarium of ischemic strokes. There is however insufficient evidence to recommend transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) in every patient with ischemic stroke. We sought to determine diagnostic yield of TTE and TEE in determining cardiac etiology for ischemic strokes.

Methods
This is a retrospective chart review of patients with diagnosis of ischemic stroke admitted to the Foothills Medical Center, Calgary from Jan 2009 to June 2010. These patients had TTE and/or a TEE as part of inpatient diagnostic evaluation. Patients with previous history of atrial fibrillation and anticoagulation were excluded. Clinical findings,baseline cardiac exam and ECG were noted. High yield findings on TTE and TEE were defined using American Heart association guidelines( mitral stenosis,LV/LA thrombus/aneurysym,apical akinesia/septal aneurysym,severe LV dysfunction,ASD,vegetation).Topographical distribution of infarcts on follow-up brain imaging and vascular imaging findings within 7 days after the event were documented. These imaging findings were categorized in following groups: normal, infarcts with presumed cardioembolic source (single cortical, multiple cortical, bilateral infarcts with normal vascular imaging), lacune (single subcortical) and infarcts due to large artery atherosclerosis (single or multiple infarcts in the territory of an abnormal large artery).

Results
397 patients with TTE and 67 with TTE/TEE as a workup for ischemic stroke were included in the study. High yield TTE findings were seen in 34/397(8.6%) patients. High yield TEE findings were found in 5/65 (7.7%) patients. Thirteen of 34 (38%) patients with high yield TTE findings had abnormal ECG or baseline cardiac exam at presentation in comparison to 10/423(2%) patients with no high yield findings (p=0.02). There was a suggestion that imaging patterns with presumed cardioembolic source showed association with high yield TTE findings [19/39 (50%) patients in comparison to 144/423(19%)] patients with no high yield findings.(p=0.07 OR 1.84 95% CI 0.95-3.84). Among the various topographical patterns, single cortical infarct with normal vascular imaging was significantly associated with high yield TTE findings. (p<0.03, OR 2.20 95% CI 1.04 - 4.64).

Conclusion
The diagnostic yield of TTE and TEE in determining cardio-embolic sources is relatively low. Baseline abnormal ECG and clinical exam along with specific patterns of imaging may help to determine cardioembolic etiology. A more rational approach to use of cardiac imaging is required in settings with limited resources.
Abstract 3540: Characteristics Of The Hypertrophic Olivary Degeneration Following Aggressive Treatment Including Surgical Resection And Gamma Knife Radiosurgery Of The Brainstem Cavernous Malformations
Authors: Yun Jung-Ho , Ahn Jae- Sung , Kwon Do Hoon , Kwun Byung Duk
Published: March 2022

Introduction:
Hypertrophic olivary degeneration (HOD) is an unusual phenomenon involving hypertrophy of the olivary nucleus, which occurred due to a neuronal connection injury to the dentato-rubro-olivary pathway of the brainstem. The purpose of this study is to explore the characteristics of the HOD following surgical resection and Gamma Knife radiosurgery of the brainstem cavernous malformation.

Methods:
The medical records from January 2001 through May 2011 were reviewed retrospectively to identify patients who underwent surgical resection or Gamma Knife radiosurgery in the brainstem cavernous malformation. Total 77 cases (including 32 in surgical group and 45 in Gamma Knife radiosurgery group) of the brainstem cavernous malformations were treated in our institute except for the patients who received conservative treatment and we selected and investigated in 13 patients who developed HOD at T2 high signal intensity on follow-up MRI. We divided into 2 groups as the surgical group and the radiosurgery group. The detailed informations of the two each groups were carefully reviewed.

Results:
The HOD group was composed of 5 men and 8 women, ranging in age from 9 to 67 years with mean of 44.6 years. Among 13 HOD patients, 7 patients were cases who were developed after surgical resection and 6 patients after Gamma Knife radiosurgery. The mean follow-up period was 32 months (2∼108 months). Bilateral HOD patients were 7 including 4 in the surgical group and 3 in the radiosurgery group. The HOD associated symptoms were showed in 6 of 13 patients including 3 patients (2 palatal tremors, one ataxia) in the surgery group and the same in the radiosurgery group. All 6 patients that had these symptoms had recovered incompletely until the last clinical follow-up period (mean 22.6 months). There are significant differences including the time interval between HOD diagnosis and treatment, and mean age in each two groups.

Conclusions:
It is concluded that HOD should be recognized as a potential complication of the aggressive surgery within the brainstem. It is important not to confuse HOD for a new ischemic event, neoplastic disease and inflammatory or infectious diseases through the following special features: typical symptom (palatal tremor), the remote primary lesion, non enhancing lesion and delayed occurrence months after insult.
Abstract 3554: GP IIb/IIIa Inhibitor Use during Endovascular Coil Embolization: A Single Center Experience
Authors: Pandya Dhruvil J , Darkhabani Ziad , Biesboer Annie , Lazzaro Marc A , Issa Mohammad A , Taqi Muhammad , Smith Heidi , Fitzsimmons Brian-Fred , Zaidat Osma O
Published: March 2022

Introduction:
Acute thromboembolic event (TEE) remains a considerable complication of endovascular aneurysm treatment. We sought to evaluate the safety of Glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors for TEE during endovascular aneurysm embolization (EAE).

Method:
We reviewed a single-center retrospectively collected database of EAE from 7 / 2005 to 12/2010. All patients who received a GPIIb/IIIa inhibitor (abciximab or eptifibatide) were included in the analysis. Clinical, demographic, and radiographic data were retrospectively collected through chart review. TEE was defined as a partial or complete occlusion of the parent vessel at the aneurysm neck, and/or distal vessel within the parent vessel territory. Recanalization was defined as near-complete or complete resolution of vessel thrombus on angiogram. New intracerebral hemorrhage (ICH) was defined as new intraparenchymal hemorrhage finding on head CT or new area of subarachnoid hemorrhage (SAH) >1mm in thickness.

Result:
Among a database of 701 cases, a GPIIb/IIIa inhibitor was used in a total of 61 (8.7%) cases, of these 57 were treated for TEE and 4 were treated prophylactically for sub therapeutic platelet point of care testing. There were 41 males, and the mean age was 54 ±13 years. The TEE occurred slightly higher during ruptured aneurysm coiling (57% and 43%, p=0.07). Thirty-nine (64%) cases were treated with adjunctive devices, which included a stent (29) or balloon (10), p-value=0.001. Close to half of the TEE was not occlusive (54%). A total of 55 (90%) cases received abciximab with a mean bodyweight base dose of 0.17mg/kg, and 6 (10%) cases received eptifibatide with a mean body weight base dose of 0.15mg/kg. Nine (16%) cases required additional therapy for ongoing clot (stent (3), balloon (3), penumbra (1), intra- arterial thrombolysis (1), and vessel sacrifice (1). Forty-two (74%) cases had complete angiographic recanalization (77% using abciximab and 25% using eptifibatide, (p=0.051)). There were 10 (16%) new ICH; 3 (5%) which were symptomatic. Patients with new ICH had non significant higher mean bodyweight dose compare to patients without new ICH 0.26 0.32 mg/kg and 0.15 0.07 mg/kg respectively.

Conclusion:
GP IIb/IIIa inhibitor use in EAE as single and multimodal therapy for acute TEE may have acceptable safety and recanalization rates (symptomatic ICH of 5% and complete recanalization of 74%). Further study to confirm the current study findings and identify optimal dosing is needed; however these data suggest that a lower dose may be favorable.
Abstract 3568: Natural History Of Dissecting Vertebral Artery Aneurysms
Authors: Kobayashi Norikata
Published: March 2022

[Purpose]
To evaluate the natural history of dissecting vertebral artery aneurysm without hemorrhage or ischemic stroke.

[Methods]
Between October 2003 and June 2011, a total of 131 patients were diagnosed with vertebral artery dissecting aneurysm in our institution. Of these, 91 patients who were presented only pain or asymptomatic and they were observed with consecutive image studies. Clinical outcomes as well as image findings of these patients were retrospectively analyzed.

[Results]
All 91 patients underwent consecutive image studies during the follow up period including MRI and / or 3D-CT angiography. No medical / surgical intervention was performed. Mean follow-up time period was 2.42 years. During the observation time, one patient (1.1%) developed an ischemic stroke (Wallenberg syndrome) followed by a subarachnoid hemorrhage (Hunt and Hess grade 2). 4 patients(4.4%) showed mild clinical worsening due to mass effect. Rest of 94.5% were clinically unchanged. Seventy two patients (79.1%) showed no change in the image findings during the observation time and 12 (13.2%) showed improvement. Enlargement of the aneurysm was seen in 5 patients (5.5%).

Of these.
[Conclusion]
With limited observation time in this study, vertebrobral artery dissecting aneurysms without stroke patients showed minimal hemorrhagic / ischemic event during the observation. For those who presented with asymptomatic or minute headache dissecting vertebral artery aneurysm, course observation with consecutive image studies may be a good management option unless they develop symptoms associated with significant mass effect.
Abstract 3582: Procedural Duration Impacts Clinical Outcome Following Intra-arterial Stroke Therapy
Authors: Leslie-Mazwi Thabele M , Chandra Ronil V , Mehta Brijesh P , Oh Daniel C , Chaudhry Zeshan A , Hirsch Joshua A , Yoo Albert J
Published: March 2022

Background:
Recanalization rates of large vessel occlusions (LVO) are higher with intra-arterial therapy (IAT) than with intravenous tPA. However, there are often time delays to IAT. Multiple pre- and intra-hospital factors impact on time from last seen well (LSW) to recanalization. We sought to compare standard time intervals prior to and during IAT to assess whether there is a differential influence on outcome in LVO.

Methods:
We analyzed our prospective observational IAT database for patients with anterior circulation stroke undergoing IAT between February 2005 and November 2010. Times of LSW, imaging, groin puncture and recanalization were collected and analyzed. Functional outcome was assessed with 3 month modified Rankin scale (mRS), and was trichotomized into mild (mRS 0-2), moderate (mRS 3) and severe disability (mRS 4-6).

Results:
Of 174 patients, 50% were female. Mean age was 63.7 years, median NIHSS 17. TICI 2-3 recanalization was strongly associated with improved outcome (p<0.0001), with recanalization occurring in all 43 patients with 3 month mRS 0-2. The time from groin puncture to recanalization had a strong impact on outcome (
Figure
). Among patients with mild, moderate and severe disability, the mean times were 93.4 minutes, 87.2 minutes, and 130.6 minutes, respectively (p=0.001). Time from baseline CT to recanalization was also associated with outcome: 211.9 minutes for mild, 213 minutes for moderate and 250 minutes for severe disability (p=0.036). Time intervals prior to imaging evaluation did not have a significant effect on outcome.

Conclusions:
Acute stroke prognostication models should incorporate reliable and easily derived factors. Among patients selected for IAT using favorable imaging profiles, the time from groin puncture to recanalization is a strong predictor of 3 month outcome, and may be useful for early prognostication.
Abstract 3588: Induced Pluripotent and Fetal Derived Neural Stem Cells Differ in Chemokine and Receptor Expression.
Authors: Auriat Angela M , Smith Tenille N , Wang Nancy , Wang Kendrick , Guzman Raphael
Published: March 2022

Introduction:
Cell based therapies have shown a considerable ability to improve functional outcome when administered after experimental stroke. Intra-arterial (IA) cell transplantation has been shown to be a valuable alternative transplantation method for cell treatment. The success of IA therapy depends on the targeted homing and subsequent migration of cells to the injured brain area. This process is reliant on neural stem cell (NSC) expression of chemokines and their receptors. Understanding the differences in cell expression of these molecules and the resulting differences in chemotaxis will help identify ideal cell types for transplantation. Previously, we compared mRNA from human and mouse NSCs and found that only a 10% overlap in chemokine expression. We wanted to determine if there are also variations between different cell types from the same species. We compared NSCs obtained from induced pluripotent stem cells (iPS NSCs), to fetal NSCs (F NSC). We used RT-qPCR, in vitro cell migration, and quantification of cell secretion to compare chemokine and ligand expression in F NSCs and iPS NSCs.

Methods:
Secondary neurospheres originating from FVB mice were generated from either fetal primary NSCs from E17.5 mice (F NSC), or derived by transducing neurospheres originating from E3 mice with Oct4 (iPS NSC). Cells were grown as neurospheres in growth media treated with EGF and FGF. RT-qPCR was performed on extracted RNA using microarray technology for chemokine receptors and ligands. Luminex immunological assay was completed to assess secreted cytokines and inflammatory proteins. The Boyden chamber migration assay was used to determine migration to SDF-1 or MCP-1 at varying concentrations.

Results:
RNA expression was detected for 58% of the factors assessed. F NSCs alone expressed 6% (e.g. mmp2, Cxcl10), iPS NSCs alone expressed 16% (e.g. CCL2, CCL7, LIF), and both iPS NSCs and F NSCs expressed 20% (e.g. BDNF, HIF1a, CXCR4) of the detected factors. We assessed 26 secreted proteins, 73% occurred at detectable levels, of these 74% were expressed more highly in F NSCs than in iPS NSCs, including, il-1α, CCL3, CCL5, TNF-α, and VEGF; iPS NSCs secreted higher levels of MCP3, Il-3, and substantially more MCP-1 (113.7 ± 1.44 vs 52.78 ±4.221 pg/ml). iPS NSCs also had a higher migratory response to MCP-1 than F NSCs did (p < 0.001). Cell migration to SDF-1 did not differ between cell types (p = 0.905).

Conclusions:
Several chemokines and their receptors were differentially expressed in mouse iPS and F NSCs. These differences may result in variations in the NSC response to the ischemic brain. The profile of chemokine and chemokine receptor expression on NSCs should be strongly considered when selecting cell types for post stroke treatment.
Abstract 3590: Quantification of Resources Needed for Successful Recruitment for Multiracial Stroke Randomized Controlled Trials
Authors: Edwards Dorothy F , Coles Regina , Farr Deeonna , Gibbons Michael C , Loftin Sara , Wein Andrea , Fatima Sabiha , Fernandez Stephen , Shara Nawar , Jayram-Trouth Anapurni , Kidwell Chelsea S , Dromerick Alexander W
Published: March 2022

Background:
Many stroke trials fail to meet recruitment goals or need additional time to accrue sufficient subjects to support hypothesis testing. Many investigators also report difficulties recruiting diverse samples. One cause may be a lack of understanding of the complexity of the process and insufficient resources devoted to recruitment efforts. We s quantified and analyzed the number of interactions needed to present study materials and obtain a final response to an invitation to participate in a stroke intervention trial seeking a diverse sample.

Methods:
Patients with acute ischemic stroke or TIA admitted to five hospitals in the District of Columbia were screened for enrollment in PROTECT-DC (Prevention of Recurrent Throboembolic Events District of Columbia). All participants were approached during the acute phase of stroke treatment. No recruitment occurred in the ED. Recruitment staff were trained for cultural competency, culturally tailored recruitment materials and scripts were provided. Detailed logs of each encounter were made. Data included number of face-to-face contacts and telephone conversations with potential participants and family members.

Results:
from June 2009 to June 2011, 1915 patients were admitted with stroke, 619 (32%) met inclusion criteria, mean age 65, 52 % female and 66 % African American. Of, these 286 (46%) patients were discharged before being approached. Of the total eligible 333 (54%) were approached ; 130 (39%) consented, 109 (33%) refused the remaining 94 (28 %) made no decision.. The mean number of contacts before obtaining a decision was 2.81 ± 1.15 (range 1-6). There were no significant differences in consent rates by gender (p=0.44) or race (p=0.64), however blacks required significantly more contacts (p<0.04) than whites before consenting or refusing participation. Review of recruitment log data suggests that substantial time and effort is devoted to individuals who do not wish to volunteer, but who are unwilling to decline participation.

Conclusion:
Approximately recruitment visits were required to successfully recruit subjects for this non ED hospital based stroke prevention trial. On average recruiters spent 5 hours in direct recruitment activities per consented subject. Substantial effort is associated with “soft refusals” in patients who do not wish to volunteer. Successful recruitment requires adequate resources and appropriate staff training and support. It is important to recognize these resource needs when planning a stroke intervention trial.