bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W P144: Association of Resting Heart Rate With Cerebrovascular Risk Factors and Carotid Artery Stenosis.
Authors: Jani Vishal B , Malik Adil , Khan Asif , Hussain Sayed , Rao Malathi , Safdar Adnan , Razak Anmar , Kassab Mounzer
Published: July 2021

Objective:
Elevated resting heart rate has been independently associated with cardiovascular and all-cause mortality, but association of it with cerebrovascular disease has been unexplored. The pathophysiological mechanisms by which this increased risk occurs are unclear. We hypothesized that elevated resting heart rate will be associated with increased development of atherosclerosis, as assessed by the incidence and progression of carotid artery stenosis and plaque morphology.

METHODS:
The Multi-Ethnic Study of Atherosclerosis is a prospective cohort study of participants free of clinical cardiovascular and cerebrovascular disease at entry. Healthy Subjects with baseline carotid stenosis by carotid duplex were stratified into five categories according to resting heart rate of: 36-55, 56 -60, 61-65, 66-71, >71bpm). Carotid stenosis incidence was assessed by relative risk regression after adjusting for comorbidities. Heart rate 36-55 was kept as a reference tier system.

RESULTS:
Of 6667 healthy individuals with an average age of 62, 3462 were men and 3511 were females. With successive increase in heart rate there was increased in associated comorbidities like hypertension, (40.3%,42%,43.2% with respective p value of 0.0001,0.0003,0.02 in tier 2,3 & 4), DM (9.7%,13.6%,20.2% with p=0.01,<0.0001 and 0.0001 respectively in tier 3, 4 & 5). Similar trend was noticed in baseline labs with increment in heart rate Total cholesterol 36.4%,36.1%,39.4% with p=0.0004,0.001,<0.0001 respectively in tier 3,4,5), CRP (4.5%,5.6%,6%,8.4% with p= ,0.0001, in each tier 2, 3,4,5). However, there did not seem to be any correlation between carotid stenosis and resting heart rate.

CONCLUSION:
Elevated resting heart rate, a well-described predictor of cardiovascular mortality with unclear mechanism, is associated with cerebrovascular risk factors, but not with the occurrence of asymptomatic extracranial carotid artery stenosis.
Abstract W P147: Occupational and Risk of Stroke: A Population-Based Study in the United States
Authors: Wang Chengwei , Mehta Bijal K , McMurtray Aaron
Published: July 2021

BACKGROUND:
Previous studies on occupational exposure for risk of stroke have been limited in the range of occupations. There has not been a population-based study on a nationally representative sample that investigates the association between a comprehensive list of occupations and risk of stroke in the United States.

Objective:
To examine the relative risk for the occurrence of stroke between different occupations in the U.S. adult population.

METHODS:
Population-based complex survey study using the National Health Interview Survey, 2004 through 2012 which included randomly sampled non-institutionalized adults (n=186,539) in the United States.The main variables measured included self-reported stroke defined as ‘Have you ever been told you had a stroke in the past 12 month” by a physician; The predictor variable, occupation, was obtained using the census occupational codes, and regrouped according to North American Industrial Classification System. Odds ratios with 95% confidence intervals were calculated. Chi-square test was used.

RESULTS:
After controlling for age, sex, ethnicity, hypertension, diabetes, angina pectoris, coronary heart disease, smoking status and alcohol drinking status, and with legal Occupations as a reference group, the likelihood of developing stroke was 1.85 times higher in Production Occupations, 1.92 times higher in Food Preparation and Serving Related Occupations, 1.93 times higher in Personal Care and Service Occupations, 1.94 times higher in Transportation and Material Moving Occupations, 2.08 times higher in Healthcare Support Occupations, and 2.11 times higher in Construction and Extraction Occupations.

CONCLUSION:
This study identifies occupation groups in US adult population with higher risk for stroke. Alleviation from workplace stress is suggested as a goal for behavioral intervention in the higher-risk occupations. Additional research on characteristics of the high risk occupations is needed for guiding prevention in these US job settings.
Abstract W P158: Permeability as a Biomarker of Cavernous Malformations
Authors: Mikati Abdul Ghani , Li Luying , Shenkar Robert , Zhang Lingjao , Guo Xiaodong , Shi Changbin , Dey Mahua , Shah Akash , Christoforidis Gregory , Awad Issam
Published: July 2021

Introduction:
Vascular hyperpermeability in lesions and nonlesional brain is a cardinal feature of cerebral cavernous malformation (CCM) pathogenesis. Thus we implemented a novel magnetic resonance imaging (MRI) technique in order to quantitate vascular permeability in CCMs and non-CCM brain tissue in humans. We hypothesize that permeability of lesions and background brain will differ between familial and sporadic patients and measurements will be consistent between observers and over time.

Method:
We used a T
1
-weighted dynamic contrast-enhanced quantitative perfusion (DCEQP) protocol in 30 patients (13 sporadic, 12 familial, and 5 non-CCM cases) in conjunction with routine MRI scans. Regions of interest (ROIs) for permeability measurement included the entire lesion and areas of 12.9 mm
2
(16 pixels) of grey and white matter near and far from the lesion. Measurements were repeated by two observers and at two time points on a subset of patients.

Results:
For each ROI category except white matter near lesions, the mean permeability was higher in the familial than in the sporadic patients with p-values of 0.04, 0.005, 0.05, and 0.007 for CCM lesions, grey matter near, grey matter far (GMF), and white matter far (WMF) from lesions respectively. No difference was seen between sporadic and non-CCM cases, however familial WMF had higher permeability than both those groups (p0.05) except GMF with p=0.04. The intrapatient coefficients of variation between measurements were 0.74 and 0.63 and interpatient coefficients of variation were 1.36 and 1.56 for sporadic and familial cases respectively. Lastly, it was found that 3 of 4 patients with two scans had stable background (WMF) brain permeability over time.

Conclusion:
Results show the higher lesional and background brain permeability of familial cases, corroborating previous findings in mice. We also demonstrate the feasibility of DCEQP in CCM disease and the potential of permeability as a biomarker of disease activity or response to treatment. It also highlights the need for further investigation into clinical factors that may impact disease activity and permeability measures.
Abstract W P16: Quantitative Analysis of Distal Emboli During Mechanical Thrombectomy With Stent-Trievers
Authors: Chueh Ju-Yu , Bzura Conrad , Puri Ajit S , Smith Stephanie , Wakhloo Ajay K , Gounis Matthew J
Published: July 2021

Introduction:
While the use of stentrievers has been shown to improve clinical outcomes compared with previous generation technology in the interventional treatment of stroke, there remains variability in clinical results. One contributor may be distal clot fragmentation during thrombectomy. Our goal is to assess various treatment strategies that can reduce the risk of distal embolization.

Materials and Methods:
Three different treatment strategies using stentrievers (Solitaire FR) included 1 Proximal flow control with a balloon guide catheter (BGC), 2 Thromboaspiration via a 5Fr distal access catheter (DAC) in the origin of the MCA, and 3 Thrombectomy through a conventional 6Fr conventional guide catheter (CGC). The vascular phantom included collateral circulation via PCom and ACom arteries and two different clot types were used(
Stroke
2013;44:1396) . For each strategy and clot type, 8 replicate experiments were performed. Large clot fragments (>1000μm) were separated from the effluent collected at each the ACA and MCA outlets and the longest dimension recorded. Particle size and number (<1000μm) were measured with a Coulter counter. A cumulative distribution of clot fragments was made with a moving average of 10μm-wide bins centered at 0.2μm intervals across a range of 25-1000μm. Exponential decay functions were fit to the data and time-constants were calculated.

Results:
For visible fragments, >1mm, both the use of the BGC and the DAC techniques produce fewer visible clot fragments (>1000μm) as compared to CGC technique (p<0.05, hard clot). For particulate sizes between 250-1000μm there was a trend towards a lower rate of hard clot embolic particulate with the DAC technique. In the size range of 25-250μm, the BGC produced less clot fragments than the DAC technique (p<0.05, hard clot). In the <25 μm group the BGC technique produced a lower rate of embolic particulates compared to the DAC or CGC technique (p<0.05). All regressions had a coefficient of determination >0.95. The BGC and DAC methods were found to have the shortest time-constants for hard and soft clots, respectively.

Conclusion:
Use of the BGC during a Solitaire FR thrombectomy is associated with statistically lower rates of distal emboli across a broad range of embolic particle sizes..
Abstract W P165: Predictors of Cerebral Microbleeds in Patients With Ischemic Stroke
Authors: Zurru Maria C , Alonzo Claudia , Brescacin Laura , Pigretti Santiago , Luzzi Ariel , Camera Luis , Waisman Gabriel , Cristiano Edgardo
Published: July 2021

Background and purpose:
similarities in renal and vascular beds could explain the relationship between impaired glomerular filtration rate (iGFR) and leukoaraiosis, white matter hiperintensities (WMH), and lacunar infarcts. We evaluated the association between microbleeds (MB) and impaired kidney function in patients with acute ischemic stroke.

Methods:
acute ischemic stroke patients were prospectively included. Pre-stroke vascular risk factors were obtained and the presence of MB and WMH were evaluated on admission MRI and analyzed as dichotomous variables.

Results:
MB were present in 128 (19%) of the 663 patients evaluated.. Table shows risk factors and comorbidities associated with MB in the univariate analysis. Only leukoaraiosis (OR 3.3; CI 95% 1.5-3.3; p 0.0001), age older than 80 years (OR 1.90; CI 95% 1.10-2.8; p 0.01), WMH (OR 9.4; CI 95% 5.6-15.6; p 0.0001) and iGFR (OR 2.2; CI 95% 1.3-3.3; p 0.01) were associated with the presence of MB in the multivariate analysis.

Conclusion:
Besides age and WMH, well-known risk factors for MB, impaired kidney function doubles the risk these lesions in a cohort of ischemic stroke patients, reassuring the hypothesis of a common pathophysiological pathway for renal and cerebral microvascular damage.
Abstract W P166: Asymmetrical Fractional Anisotropy Correlates with Verbal Fluency Task Performance at Different Stages Post-stroke
Authors: Song Jie , Nair Veena A , La Christian , Sattin Justin A , Prabhakaran Vivek
Published: July 2021

Objective:
Diffusion tensor imaging (DTI) can be used to quantify integrity of the white matter (WM) tracts by calculating the fractional anisotropy (FA) within a region of interest. Following stroke, unilateral reductions in integrity of tracts involving language function give rise to interhemispheric asymmetries in FA values. Here, we explored the relationships between asymmetrical FA measures and their ability to predict performance in verbal fluency tasks at different post-stroke stages.

Methods:
DTI data were acquired axially from 21 stroke patients at acute stage, 19 at sub-acute stage and 12 at chronic stage in a GE 3T MRI scanner. FOV = 25.6 cm х 25.6 cm, acquisition matrix = 256 х 256, slice thickness = 2 mm, number of slices = 75, number of diffusion directions = 56. Data were processed using FSL. FA values of language tracts were calculated-superior longitudinal fasciculus (SLF), sagittal stratum (SS, including inferior longitudinal fasciculus and inferior fronto-occipital fasciculus) and Uncinate fasciculus (UF). Asymmetrical FA (aFA) was computed for the affected and unaffected SLF, SS and UF in order to measure the asymmetry of WM integrity: aFA= (FAunaff - FAaff)/( FAunaff + FAaff), which yields a value between -1.0 and +1.0, where positive values indicate reduced FA in the affected WM tracts, and a value of 0 indicates symmetricial FA in the tracts. aFA was correlated with patient behavior in language task-verbal fluency (VF) with subject outliers outside of the 95% confidence interval removed.

Results:
At acute stage, higher values of aFA in SLF (R2 = 0.606, p = 0.008) and SS (R2 = 0.624, p = 0.004) were significantly correlated with poor VF performance. At sub-acute stage, higher values of aFA in SS (R2 = 0.431, p = 0.028) were inversely correlated with poor VF performance. At chronic stage, higher values of aFA in SLF were inversely correlated with poor VF performance (R2 = 0.517, p = 0.008).

Conclusion:
Results show that asymmetries in white matter tract integrity (i.e., SLF, SS and UF), generally considered as language-function tracts, are significantly correlated with verbal fluency performance at different stages post-stroke, implying changes in WM integrity in these tracts over time may lead to changes in behavioral performance.
Abstract W P171: Intracranial Blood Flow Changes After Extracranial Carotid Stenting
Authors: Shakur Sophia F , Amin-Hanjani Sepideh , Bednarski Caroline , Du Xinjian , Aletich Victor , Charbel Fady , Alaraj Ali
Published: July 2021

Objectives:
To determine the effects of extracranial carotid stenting on intracranial blood flow.

Methods:
Records of patients who underwent stenting for extracranial carotid stenosis at our institution between 2004-2012 and had flow rates obtained pre and post stenting using quantitative magnetic resonance angiography were retrospectively reviewed. Measurements of degree of stenosis, stenosis length, and residual lumen were made from cerebral angiography images.

Results:
18 patients with complete anatomic and flow data were included. Mean age was 66 years with 61% presenting with symptomatic stenosis. Degree of stenosis ranged from 60% to 90%. Internal carotid artery (ICA) mean flow improved significantly post stenting from 174.9 +/- 83.6 mL/min to 250.7 +/- 91.2 mL/min (
P
=0.011). Ipsilateral middle cerebral artery (MCA) flow, however, was not significantly altered post stenting (101.8 +/- 47.7 mL/min vs. 111.3 +/- 37.4 mL/min;
P
=0.15). Multiple regression analysis revealed that improvement in residual lumen, but not percentage stenosis (p=0.45) or stenosis length (p=0.992), is an independent predictor of increased change in ipsilateral ICA flow (
P
=0.005). Degree of stenosis, stenosis length, residual lumen, and ICA flow post-stenting were not predictive of ipsilateral MCA flow (
P
=0.65,0.37,0.25,0.79). The ratio of ipsilateral to contralateral ICA flow improved from 0.67 +/- 0.36 at baseline to 0.94 +/- 0.34 after stenting (
P
=0.007). The ratio of ipsilateral to contralateral MCA flow was 1.08 +/- 0.59 at baseline, and was unchanged at 1.09 +/- 0.46 after stenting (
P
=0.91).

Conclusions:
ICA flow compromise was evident in the setting of carotid stenosis, which improved by 43% on average post stenting. Improvement in residual lumen at the site of stenosis was the strongest predictor of increased flow, indicating that this parameter is the best indicator of a hemodynamically successful intervention. Unlike ICA flow, intracranial flow measured in the MCA was not significantly compromised at baseline compared to the contralateral hemisphere, nor significantly altered after stenting. This reflects compensatory intracranial collateral supply pre-stenting, which redistributes once the ipsilateral ICA is revascularized.
Abstract W P172: Prevalence of Positive Dwi Findings in Relation to Tia Etiology
Authors: Gon Yasufumi , Sakaguchi Manabu , Okazaki Syuhei , Mochizuki Hideki , Kitagawa Kazuo
Published: July 2021

Objective:
Previous studies have shown that the prolonged duration of TIA symptoms or ABCD2 score are associated with DWI abnormality, and the presence of DWI abnormality is associated with an increased early risk of stroke. However, there are few reports that show the relation between TIA clinical etiology and DWI abnormality. Our aim of this study is to clarify the prevalence of positive DWI in relation to characteristics of patients and TIA.

Methods:
The subjects were enrolled from patients who were admitted to our stroke unit within 7 days after symptom onset from January 2006 to July 2013. The diagnosis of TIA was done by NINDS criteria, and we classified TIA etiology by TOAST classification based on clinical symptoms, ECG monitoring, carotid ultrasound, MR angiography and transesophageal echocardiography. All patients underwent DWI-MRI within 7 days after symptom onset. We examined an association between TIA etiology, symptom, duration of symptoms and DWI abnormality.

Results:
A total of 141 patients (mean 64 years; 63% men) were admitted with TIA during this period. Those included lacuna TIA (n=17, 12.1%), atherothrombotic TIA (n=32, 22.7%), cardioembolic TIA (n=23, 16.3%), TIA due to other causes (n=35, 24.8%), and TIA with unknown etiology (n=34, 24.1%). Prevalence of positive DWI findings were 47.1% in lacunar TIA, 43.7% in atherothrombotic TIA, 52.1% in cardioembloic TIA, 42.8% in TIA due to other causes, and 23.5% in TIA with unknown etiology. DWI abnormality was the most frequent in cardiogenic TIA. In relation to symptom duration, the prevalence of DWI positive findings were 45.2% in less than 1 hour (N=53), 36.6% in 1-3 hour (N=41), 25.0% in 3-6 hour (N=12) and 42.9% in 6-24 hours (N=35). In relation to motor symptoms, there was no difference in prevalence of DWI abnormality between patient with motor symptoms (39.8%, N=113) and without (42.8%, N=28). There was no relation between DWI abnormalities and age, a history of stroke/TIA episode or vascular risk factors.

Conclusion:
Prevalence of DWI positive findings was high in cardiogenic TIA, and low in TIA with unclassified etiology. There were no relation between DWI abnormality, duration of symptom, and motor symptom.
Abstract W P183: Testing the Utility of an Emergency Room-Based Stroke Evaluation Protocol
Authors: Kim Gyeong-Moon , Helenius Johanna , Arsava E Murat , Ay Hakan
Published: July 2021

Background and purpose:
A fundamental goal in diagnostic stroke evaluation is to identify the underlying etiology. We sought to determine the yield of an emergency department-based diagnostic evaluation protocol for identifying the etiology of stroke.

Methods:
We determined etiologic stroke subtypes using the automated Causative Classification System (CCS, available at https://ccs.mgh.harvard.edu) in 2422 consecutive patients with ischemic stroke at admission and discharge. Admission assessment was based on information from clinical evaluation, ECG, brain imaging (CT or MRI), and vascular imaging (CTA/MRA). Discharge CCS was performed blinded to the admission CCS subtype using information from additional tests such as echocardiography, cardiac monitoring, and special blood and CSF tests.

Results:
Table 1 shows the distribution of CCS subtypes. Overall, admission and discharge CCS subtypes were different in 29% of the patients. The size of “undetermined” category decreased from 37% at admission to 12% at discharge. The shift from “undetermined” to a known etiology was primarily due to detection of cardiac sources with low or uncertain risk of stroke (94%). The yield of investigations performed after admission in identifying a major known subtype was only 4.1% (p=0.008).

Conclusions:
A careful clinical evaluation and first-line diagnostic testing including brain and vascular imaging in the emergency department identify > 90% of those with a major stroke etiology. The low yield of additional testing suggests a need for developing cost-effective evaluation strategies in suspected patients.
Abstract W P192: A Direct Telecommunication Between Doctors of a Comprehensive Stroke Center and Local Hospitals Significantly Shortened the Door-to-Puncture Time for Intraarterial Thrombectomy
Authors: Jeong Hye Seon , Kwon Hyunjo , Koh Hyunsong , Yu Heesun , Yun Nayoung , Oh Sang-Geun , Kwag Hyun Jeong , Song Hee-Jung , Kim Jei
Published: July 2021

Background:
We evaluated whether a direct doctor-to-doctor telecommunication (D2D-Call) between a comprehensive stroke center and local hospitals was effective to rapidly start intraarterial thrombectomy (IAT) for acute ischemic stroke patients, who first visit local hospital.

Methods:
Clinical data of 92 consecutive patients (male:female, 63:29; mean age±standard deviation, 68.6±11.4 years), who underwent IAT for terminal internal carotid and/or middle cerebral artery occlusions, were analyzed. The patients were classified by arrival manners at Stroke Center; 1) Direct-Arrival at Center (n=59), 2) Arrival after D2D-Call (n=20), and 3) Arrival without D2D-call (Non-D2D-Call, n=13). The D2D-call system had three parts; 1) D2D-Call for transfer, 2) activation of IAT team before arrival, and 3) immediate start of IAT after arrival of a patient. Time intervals from arrival to IAT start (Arrival-to-IAT) and from symptom onset to recanalization (Onset-to-Recanalization) was compared between three groups. The rates of recanalization and good clinical outcome (0-3 of the modified Rankin Scale) of three groups were also compared.

Results:
The Arrival-to-IAT time was significantly shorter in D2D-Call than other two groups (Direct-Arrival, 103.3±21.6; D2D-Call, 41.3±15.1; Non-D2D-Call group, 107.5±19.0 minutes, p<0.001).

The Onset-to-Recanalization time was also shortened in D2D-call (Direct-Arrival, 286.4±89.5; D2D-Call, 324.5±61.2; Non-D2D-Call group, 402.5±67.1 minutes, p=0.001).

Even though recanalization rate (Direct-arrival, 88%; D2D-call-transfer, 75%; Non-D2D-call-transfer group, 77%, p=0.302) was similar between three groups, D2D-Call patients showed similar good clinical outcomes like as Direct-Arrival patients at 3 months after IAT (Direct-Arrival, 64%, D2D-call, 60%; Non-D2D-call group, 39%, p=0.080).

Conclusion:
The direct telecommunication between doctors of a Stroke Center and local hospitals could significantly shorten the start time for IAT and achieved better clinical outcomes for transferred ischemic stroke patients.
Abstract W P198: Sphingomyelin Synthases Regulate Neuronal Cell Proliferation and Cell Cycle Progression
Authors: Wesley Umadevi V , Tremmel Daniel , Dempsey Robert
Published: July 2021

Introduction:
The molecular mechanisms of cerebral ischemia damage and protection are not completely understood, but a number of reports implicate the contribution of lipid metabolism and cell-cycle regulating proteins in stroke out come. We have previously shown that tricyclodecan-9-yl-xanthogenate (D609) resulted in increased ceramide levels after transient middle cerebral artery occlusion (tMCAO) in spontaneously hypertensive rat (SHR). We hypothesized that D609 induced cell cycle arrest probably by inhibiting sphingomyelin synthase (SMS). In this study, we examined the direct effects of SMS on cell cycle progression and proliferation of neuroblast cells.

Methods:
Ischemia was induced by middle cerebral artery occlusion (MCAO) and reperfusion. Expression levels were measured by western blot analysis, RT-PCR, and Immunofluorescence staining. SMS1 and 2 expressions were silenced by stable transfection with SMS1/2-targeted shRNA. Cell cycle analysis was performed using Flow cytometry. Data were analyzed using MODFIT cell cycle analysis program. Cell proliferation rate was measured by MTT assay.

Results:
We have identified that the expression of SMS1is significantly up-regulated in the ischemic hemisphere following MCAO. Neuro-2a cells transfected with SMS specific ShRNA acquired more neuronal like phenotype and exhibited decreased proliferation rate. Also, silencing of both SMS1 and 2 induced cell-cycle arrest as shown by significantly increased percentage of cells in G0/G1 and decreased proportion of cells in S-phase as compared to control cells. This was accompanied by up-regulation of cyclin-dependent kinase (Cdk) inhibitors p21 and decreased levels of phophorylated AKT levels. Furthermore, loss of SMS inhibited the migratory potential of Neuro 2a cells.

Summary:
Up-regulation of SMS under ischemic/reperfusion conditions suggests that this enzyme potentially contributes to cell cycle regulation and may contribute to maintaining neuronal cell population. Further studies may open up a new direction for identifying the molecular mechanisms of cell cycle regulation and protection following ischemic stroke
Abstract W P203: Clot Injection Speed Differentially Affects Infarct Volume and Neurological Outcome in Vehicle Versus tPA Treated Rats
Authors: Marinescu Marilena , Bouley James , Chueh Juyu , Fisher Marc , Henninger Nils
Published: July 2021

Introduction:
Embolic stroke models closely mimic the pathophysiology of human stroke. Numerous models have been developed in an attempt to reduce lesion variability. However, while close attention has been paid to clot properties and site of injection, no study has considered the potential impact of the injection technique. We sought to investigate the relation between clot injection (CI) speed and neurological outcome following vehicle or recombinant tissue plasminogen activator (tPA) infusions.

Methods:
Male Wistar Kyoto rats operated by a single experienced surgeon were randomly assigned to one of four groups: Slow CI-vehicle (n=49); slow CI-tPA (n=30); fast CI-vehicle (n=50); fast CI-tPA (n=37). Real-time flow during CI was measured in a subset of animals (fast n=11, slow n=11). Saline or tPA (10 mg/kg body weight) was given 60 min post CI for a duration of 60 min. Clot properties as well as animal setup and surgery were identical in all experiments. At 24 h edema corrected infarct volume and neurologic outcomes were assessed.

Results:
Volume flow curves during CI were similar within respective slow and fast CI experiments indicating reproducible injection speed (Figure1A, data are mean±S.D.). Slow CI resulted in significantly smaller infarct volumes (p=0.024, Figure 1B, data are mean±S.E.M.) and better neurological outcomes (p=0.01, Figure 1C) compared to fast CI at 24 h. Unexpectedly, rtPA treatment attenuated infarct size in fast (p<0.001) but not slow CI experiments (p=0.382, Figure 1C).

Conclusion:
Investigators should assess their CI technique because it can critically determine infarct extent and response to thrombolysis after rat embolic stroke. Further investigations into cerebral blood flow changes as well as severity of edema formation and hemorrhagic conversion are ongoing to elucidate potential mechanisms underlying our observation.
Abstract W P211: Investigating the Cause for “Collateral Failure” in Stroke-in-Progression: Intracranial Pressure Elevation Reduces Flow Through Collateral Vessels
Authors: Beard Daniel , McLeod Damian , Spratt Neil J
Published: July 2021

Background:
Adequacy of the collateral circulation is a major determinant of outcome in stroke patients. Recent human imaging data indicates that collateral failure, rather than reperfusion-reocclusion is the most common cause for early progression in minor stroke. Our previous experimental data shows that intracranial pressure (ICP) rises transiently 24 h after even minor stroke. Herein, we investigated the effect of ICP manipulation on blood flow through collateral vessels during MCA occlusion.

Methods:
We developed and validated a method to quantify flow velocity and vessel diameter of anterior-middle cerebral artery (ACA-MCA) leptomeningeal collaterals in rats during stroke, using fluorescent microspheres. BIood flow velocity and diameter was quantified in individual collateral vessels and used to calculate absolute flow during MCA occlusion and reperfusion (n = 6). In separate experiments, ICP was increased after MCA occlusion by fluid infusion into the lateral ventricles and effects on relative collateral flow were determined (n = 4).

Results:
In vitro validation indicated accurate flow quantification (R
2
= 0.99, P<0.0001). Collateral flow was seen to switch from bidirectional to unidirectional flow (toward occluded vessel) and increase by 595 ± 134 % within 10 min of vessel occlusion. Direction and flow changes were variable after MCA reperfusion, however there was a mean flow reduction of 52 ± 15 % by 5 mins. Artificially elevating ICP during MCA occlusion caused a reduction of cerebral perfusion pressure which was strongly correlated with collateral flow reduction (R
2
= 0.90, p<0.0001).

Discussion:
Our method permits real time quantification of flow through individual collateral vessels during stroke and reperfusion. Intracranial pressure elevation reduced collateral flow, proportional to its effect on cerebral perfusion pressure. Coupled with our previous data indicating significant ICP elevation after even minor stroke, this suggests that transient ICP elevation is the possible cause of the collateral failure recently described in patients with stroke-in-progression.
Abstract W P214: Neuroregenerative Effects of the Peptide Hormone Ghrelin After Cerebral Ischemia
Authors: Diederich Kai , Schmidt Antje , Strecker Jan-Kolja , Schäbitz Wolf-Rüdiger , Minnerup Jens
Published: July 2021

Introduction:
The peptide hormone Ghrelin is known as the ligand of the growth hormone secretagogue receptor and affects pituitary hormone secretion, gastrointestinal function and the cardiovascular and immune system. Recently it has been shown that Ghrelin also influences key mechanisms of the CNS. Ghrelin crosses the blood-brain barrier and binds to hippocampal neurons thereby promoting dendritic spine synapse formation and proliferation of progenitor cells. These finings led to the assumption that Ghrelin might exert neuroprotective and neuroregenerative effects in the brain.

We assessed the hypothesis that a chronic pharmacological stimulation with Ghrelin promotes mechanisms of long term post-stroke neuroregeneration thereby improving functional and structural regeneration.

Methods:
In order to examine long term neuroregenerative effects, Ghrelin (40 μg/kg/d) was administered starting 24 hours after photothrombotic ischemia until the end of the experiment via osmotic pumps. Functional recovery was assessed by the adhesive tape removal test and the cylinder test performed weekly for 4 weeks. Cognitive function was analysed using the Morris water maze test. Brains were removed 4 weeks after ischemia. Post-ischemic neurogenesis was quantified in the subventricular zone (SVZ) and dentate gyrus (DG) using antibodies against Bromodeoxyuridine and Doublecortin.

Results:
Treatment with Ghrelin improved motoric and cognitive recovery following photothrombotic stroke. In close apposition to the enhanced functional recovery, the pharmacological stimulation with Ghrelin significantly increased the generation of newborn hippocampal neurons in the SVZ as well as in the DG of the hippocampus.

Conclusion:
In the present study, we demonstrated that chronic treatment with Ghrelin promotes the structural and functional recovery following ischemia. The recently discovered neurotrophic properties and the effects on post-stroke recovery demonstrated in this study substantiate the potential of Ghrelin as a promising agent for the neuroregenerative treatment of ischemic stroke.
Abstract W P215: Effects of Angiopoietin-1 on Hemorrhagic Transformation and Cerebral Edema after Tissue Plasminogen Activator Treatment for Ischemic Stroke
Authors: Shimohata Takayoshi , Kawamura Kunio , Takahash Tetsuya , Kanazawa Masato , Kanazawa Masato , Igarashi Hironaka , Nakada Tsutomu , Shimohata Takayoshi
Published: July 2021

An angiogenesis factor, angiopoietin-1 (Ang1), is known to participate in the survival of endothelial cells, vascular remodeling, and vascular stability. In addition, Ang1 has been reported to reduces postischemic vascular hyperpermeability. From the above findings, we hypothesized that Ang1 could attenuate hemorrhagic transformation and cerebral edema after tissue plasminogen activator (tPA) treatment by stabilizing blood vessels and inhibiting hyperpermeability. Sprague-Dawley rats subjected to thromboembolic focal cerebral ischemia were assigned to a permanent ischemia group and groups treated with tPA at 1 h or 4 h after ischemia. The cartilage oligomeric protein (COMP)-Ang1 protein or control protein (COMP protein) was administered immediately before tPA administration in the tPA 4 h group, because recombinant Ang1 protein is poorly soluble. At 24 h after ischemia, we evaluated the effects of the protein on the amount of cerebral hemorrhage, the cerebral edema volume, cerebral infarct volume, and the prognosis with a 6-point neurological score. Ang1 expression was observed in pericytes, astrocytes, and neuronal cells, in the healthy brain tissue of the sham group rats. It was decreased in the BBB when tPA treatment was performed after the therapeutic time window. Administering recombinant COMP-Ang1 to supplement this decrease could suppress hemorrhagic transformation as measured by hemoglobin content in a whole cerebral homogenate and cerebral edema due to BBB damage (Figure A, B). No significant differences were observed between groups for cerebral infarct volume and the neurological scale score (Figure C, D). In conclusion, Ang1 may be considered a promising target molecule for vasoprotective therapies in order to control the hemorrhagic transformation and cerebral edema that accompany tPA treatment.
Abstract W P218: Interleukin 21 receptor: A Major Modulator of Infarct Volume
Authors: Lee Han Kyu , Keum Sehoon , Lo Donald C , Marchuk Douglas A
Published: July 2021

Using the permanent middle cerebral artery occlusion (MCAO) model of stroke, we have demonstrated that different inbred mouse strains show profound differences in infarct volume, indicating that infarction is under strong genetic control. To identify natural genetic determinants modulating infarction, we employed quantitative trait locus (QTL) linkage analysis and a genome-wide association study of cerebral infarct volume. We identified a locus on distal chromosome 7 that contributes over 50% of the variation in infarct volume, as well as other loci of smaller effect.

Using interval-specific ancestral haplotype analysis, we fine-mapped the chromosome 7 locus to only 12 candidate genes. To identify the gene(s) underlying this locus, we determined the strain-specific transcript levels of all 12 genes in relevant tissues that included P1 and adult brain cortex, and embryonic macrophages, the latter due to their importance in the development of the cerebrovascular system. One gene, interleukin 21 receptor (Il21r), showed a 7-fold expression difference between strains and harbors a coding SNP difference that segregates with infarct volume.

To determine whether Il21r is a major modulator of infarction, we examined Il21r in mice for their cerebrovascular anatomy as well as the cerebral infarct volume after MCAO. While Il21r-/- mice show a moderate reduction in collateral vessel connections compared to wild-type littermate mice cerebral infarct volume in Il21r-/- mice is increased 3-fold. This suggests that Il21r has effects on both cerebrovascular anatomy and innate neuroprotection. To examine the latter, we performed an ex vivo study of brain slices under in vitro oxygen deprivation. In this system devoid of any potential circulatory effects, but retaining appropriate tissue architecture, Il21r-/- brain slices showed an increase in oxygen-deprivation induced cell death, showing that Il21r is also involved in cerebrovascular-independent neuroprotection. Biochemical studies of the brain slices show that Il21R regulates ischemia-induced apoptosis. The identification of Il21R as a cerebrovascular-independent modulator of infarct volume provides a fundamental advance in the understanding of genetic modulation of ischemic stroke.
Abstract W P222: Activated Microglia Contribute to Neurovascular Integrity and Limit Brain Injury After Acute Neonatal Focal Stroke
Authors: Fernández-López David , Faustino Joel , Klibanov Alexander , Derugin Nikita , Akassoglou katerina , Vexler Zinaida S
Published: July 2021

It has been recently shown that microglial cells, which for a long time were considered purely injurious in the context of cerebral ischemia, can also exert beneficial effects following stroke in both adults and neonates1,2. Lack of tools to reliably distinguish resident microglia from infiltrated peripheral monocytes has been a major obstacle on the way to understand the relative role of these subpopulations of cells of the monocyte lineage in the pathophysiology of stroke. We subjected postnatal day 10 (P10) transgenic Cx3cr1GFP/-CCr2RFP/- mice, in which resident microglia (Cx3cr1GFP) and infiltrating monocytes (CCr2RFP) can be distinctively identified, to a transient 3 hour middle cerebral artery occlusion MCAO, a model that we recently developed3. Microglial cells were left unperturbed or were selectively depleted before MCAO by intracortical injection of clodronate-encapsulated liposomes.

Depletion of microglia exacerbated injury and significantly increased infarct volume (75.9% Vs. 56.3%, p<0.01). Furthermore, compared to mice with unperturbed microglia, depletion of microglia significantly increased the number of hemorrhages in injured regions, adversely affected vascular density and decreased the number of both adherent and infiltrated monocytes. The extent of RFP+ monocyte adhesion to vessels and infiltration in the brain parenchyma was highly variable among individual mice and did not correlate with brain infarct, whereas a significant correlation between the overall extent of microglial activation (measured by morphological transformation) and the number of infiltrated monocytes was observed.

The deleterious effect of microglial depletion on vascular integrity and function and on brain injury indicates that activated microglia act as a buffering component that limits vascular degeneration and injury severity after neonatal stroke. Our data also suggest a direct and dynamic relationship between microglial activation and monocyte recruitment into acutely reperfused neonatal brain.

Support: NS55915 (ZV), NS76726 (ZV), NS080015 (ZS, KA), AHA POST10980003 (DFL).

1. Faustino J et al. J Neurosci. 2011.

2. Lalancette-Hebert M et al. J Neurosci. 2007.

3. Woo MS et al. Annals of Neurology. 2012.
Abstract W P227: Cerebral Hyperperfusion Syndrome after Intravenous Thrombolysis for Acute Ischemic Stroke
Authors: Yeo Leonard , Rathakrishnan Rahul , Teoh Hock Luen , Paliwal Prakash , Ng Kay W , Bharatendu Chandra , Wakerley Benjamin , Ong Jonathan , Batra Amit , Ting Eric Y , Sinha Arvind K , Sharma Vijay
Published: July 2021

Background:
Cerebral hyperperfusion syndrome (CHS) is a recognized complication after surgical revascularization of a chronically atherosclerotic artery. However, this phenomenon is unexpected when an acutely occluded artery is recanalized by IV-TPA for acute ischemic stroke (AIS).In patients with discrepant neuroimaging and clinical findings, our multimodal evaluations revealed CHS in a series of 7 patientsmafter IV- TPA therapy.

Methods:
Patients in whom the occluded ICA or MCA in pre-TPA CT-angiogram (CTA) showed recanalization in the day-2 CTA, were observed for any new unexpected neuropsychiatric symptoms/signs. If these were present they underwent multimodal evaluation including serial transcranial Doppler (TCD), quantitative electroencephalography (QEEG) and HMPAO-SPECT. Patients with considerable mismatch between clinical and neuroimaging findings were also included. CHS was deemed to have occurred if the unexpected neuropsychiatric signs corresponded with TCD flow velocity >100% of the contralateral vessel, EEG showed abnormal activity and HMPAO-SPECT scan showed markedly increased cerebral perfusion compared to the contralateral side.

Results:
Out of 155 patients treated with IV-TPA, 7 (4.5%) patients fulfilled our definition of CHS. All 7 patients developed the symptoms 2-3 days after IV-TPA. Abnormalities on TCD, QEEG and HMPAO-SPECT were observed in all patients. The unexpected symptoms included generalized headache (4 cases), unexplained persistent drowsiness (3 cases), visual neglect (2 cases), aphasia (2 cases) and severe suicidal thoughts despite complete neurological recovery (1 case). All cases had hypertension prior to the index stroke. Upright posture, fluid restriction and aggressive blood pressure control resulted in rapid resolution of abnormal features in all cases within a week. All patients achieved modified Rankin score 0-1 with no intracranial hemorrhage.

Conclusion:
CHS after intravenous thrombolysis in acute ischemic stroke should be suspected in patients that achieve arterial recanalization with unexplained new neuropsychiatric manifestations. Early diagnosis and appropriate management might prevent hemorrhage and achieve good functional outcomes.
Abstract W P232: Lower Rates of Delirium in Stroke Units May Reflect Selection Bias
Authors: Liotta Eric M , Corado Carlos , Bergman Deborah L , Bernstein Richard A , Caprio Fan Z , Curran Yvonne , Guth James C , Maas Matthew B , Naidech Andrew M , Prabhakaran Shyam
Published: July 2021

Introduction:
Studies of delirium after acute stroke focus on stroke units (SUs). A protective effect of SUs against delirium has been suggested. We hypothesized that selection bias against medically complex patients accounts for this apparent effect.

Methods:
An observational cohort of acute ischemic stroke patients was screened for post-stroke delirium. Delirium was diagnosed using the Confusion Assessment Method (CAM). Key patient variables were prospectively recorded including initial NIHSS score and medical complications. Univariate associations with delirium were identified and a logistic regression model was developed for the entire cohort. Separate logistic regression models were also developed for non-stroke unit (NSU) and SU patients. The SU consisted of a specialized stroke ward, step-down stroke unit, and a neuroscience ICU.

Results:
Over 10 months 246 patients (56% male, mean 65 years, 29% in NSUs) met inclusion criteria. Delirium occurred in 30 (12%) patients and was less frequent in the SU (8.0% vs 22.5%, p=0.002). Frequency of CAM checks differed between NSU and SU (median 4.1 vs 3.7 per day; p=0.03). NSU patients had similar NIHSS scores as SU patients (median [interquartile range], 3 [1-8] vs 3 [1-5]; p=0.18) but more ICU admissions (48% vs 27%, p=0.001) and more infections (18% vs 9.7%, p=0.06). In the entire cohort, initial NIHSS (OR 1.07, 95% CI 1.02-1.13; p=0.006), cardioembolic stroke mechanism (OR 3.0, 95% CI 1.3-6.9; p=0.009) and SU care (OR 0.39, 95% CI 0.17-0.88; p=0.02) predicted delirium after correcting for covariates, including frequency of CAM checks. In the NSU model, age (OR 1.06, 95% CI 1.01-1.11; p=0.02) and infections (OR 6.8, 95% CI 1.5-30.2; p=0.01) were associated with delirium. Only cardioembolic stroke mechanism (OR 5.4, 95% CI 1.7-16.7; p=0.003) was associated with delirium in the SU model.

Conclusion:
Associations with delirium after acute ischemic stroke differ between NSU and SU patients. Stroke patients treated in NSUs are fundamentally different than SU patients. Given the potential for residual confounding, the lower incidence of delirium after stroke in SUs than NSUs may reflect selection bias rather than a specific effect of SU care.
Abstract W P251: Clinical and Imaging Characteristics of Hyper-Acute Intracerebral Hemorrhage
Authors: Sanossian Nerses , Burgos Adrian M , Liebeskind David S , Villablanca J P , Hamilton Scott , Starkman Sidney , Saver Jeffrey L ,   FAST-MAG Investigators and Coordinators
Published: July 2021

Background:
Most descriptive studies of intracerebral hemorrhage (ICH) use cases from hospital registries or large stroke databases. The clinical, imaging, and outcome characteristics for patients presenting acutely after symptom onset, and found to have primary ICH on imaging in the emergency department (ED) is not well described.

Methods:
Cases presenting to the ED via ambulance in the first 2 hours after symptom onset with intracerebral hemorrhage on initial imaging were identified from the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) phase 3 clinical trial of intravenous magnesium vs. placebo. All subjects provided consent in the field and were transported to their usual care hospital, and no guidance was provided on treatment.

Results:
Of 1700 stroke cases presenting <2 hours from onset, there were 369 (22%) cases with primary ICH. Primary ICH cases had a mean [SD] age of 65 [13] years, 34% women, 79% White race, 34% Hispanic ethnicity, 80% pre-exisitng hypertension, 20% diabetes, 18% smokers; they were assessed in the field by paramedics a median [IQR] of 23 [15-40] and arrived in the ED 58 [46-77] minutes after onset. Median Glasgow Coma Scale was 15 [15-15] in the field and 15 [10-15] in the ED. Initial CT demonstrated ICH on the right in 61%, left in 39% and bilateral in 1. There was concurrent intraventricular hemorrhage in 41%, subarachnoid hemorrhage in 11%, and subdural hemorrhage in <1%. Mean [SD] hematoma volume was 29.2 [38.6] cc. At three months 30% had a good outcome [MRS 0-2] and 44% were dead or bedridden [MRS 5-6]. Younger age, absence of diabetes, smaller volume of hemorrhage, absence of intraventriuclar hemorrhage, and less severe clinical deficit in the field and in the ED was associated with good outcome.

Conclusions:
We describe the characteristics of hyper-acute primary ICH presenting to the ED, the population most likely to respond to acute treatments aimed at improving outcomes.
Abstract W P26: Meta-analysis Of Studies Using Solitaire And Trevo Pro Stent Retriever Devices For Mechanical Thromboembolectomy In Acute Cerebral Ischemia
Authors: Jadhav Vikram , Qureshi Mushtaq H , Adil Malik M , Zarar Amna , Mian Nidaullah , Zafar Taqi T , Umair Muhammad , Qureshi Adnan I
Published: July 2021

Objective:
To report rates of recanalization and symptomatic intracerebral hemorrhage (SICH) after mechanical thromboembolectomy using Solitaire and Trevo Pro devices in acute cerebral ischemia using meta-analysis of published studies.

Methods:
We identified all studies that used Solitaire or Trevo devices for mechanical thromboembolectomy in treatment of acute cerebral ischemia using a search on PubMed and Cochrane libraries, stroke trials database, proceedings of neurology and neurosurgery related conferences, and supplemented by a review of bibliographies of selected publications. Recanalization was assessed using TICI >2a and rates of SICH were recorded. For the meta-analysis, forest plots and statistical analysis including event rates [ER] with 95% confidence intervals [CI] based on both fixed and random models were performed using Comprehensive Meta-Analysis Software. The presence of publication bias was interrogated by funnel plot of Standard Error by log odds ratio.

Results:
Eighteen studies with Solitaire device and five with Trevo device were identified and included in the meta-analysis. There were a total of 433/505 (85%, ER 0.85 [CI] 0.80-0.88, P<0.001) successful recanalizations with Solitaire device whereas 196/243 (80%, ER 0.80 [CI] 0.74-0.85, P<0.001) successful recanalizations were noted with Trevo device. The incidence of SICH was 45/505 (9%, ER 0.09 [CI] 0.06-0.14, P<0.001) with Solitaire device and 17/243 (6%, ER 0.06 [CI] 0.049-0129, P<0.001) with Trevo device after mechanical thrombectomy. There was no publication bias.

Conclusions:
Meta-analysis of studies reveals similar rates for recanalization and SICH after mechanical thromboembolectomy using Solitaire or Trevo Pro devices.