bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP108: Stroke Prevention by Screening Seniors for the Silent Carotid Artery Disease, Atrial Fibrillation, and Hypertension that are the Immediate Causes of Stroke
Authors: Lavenson George S
Published: March 2022

Background—
Stroke is the leading cause of disability and health care expenditures in the United States. Carotid artery disease, atrial fibrillation, and hypertension; are the immediate primary causes of stroke. These causes are silent in 80% of cases prior to the stroke but can be discovered by screening, and with follow-up full evaluation of and preemptive management of those positive on screening, strokes can be prevented.

Methods—
A quick carotid scan (QCS) with ultrasound is used to screen for carotid artery disease and had a sensitivity of 93% in our laboratory and 97% at NYU. A stroke prevention screening protocol was employed and used the QCS for carotid artery disease, an EKG rhythm strip for atrial fibrillation, and blood pressure determination for hypertension. The protocol takes approximately 5 minutes to accomplish at a cost of $35.

Results—
Screening over 22,146 seniors in the Society for Vascular Surgery National Screening Program, at Kaweah Delta District Hospital in Central California, at New York University, and at Madigan Army Medical Center found a uniform 7.5% with possible >60% carotid stenosis, 5.1% with unknown atrial fibrillation, and 29.5% with inadequately controlled hypertension. Based on this yield of stroke potential carotid artery disease, it was estimated that screening 40 million Medicare recipients in the United States for carotid artery disease alone would prevent over 200,000 strokes annually and, when the cost of the screening, further evaluation, and management was subtracted from the cost of the strokes prevented, save nearly 13 billion dollars.

Conclusions—
Screening seniors for the silent immediate causes of stroke, carotid artery disease, atrial fibrillation, and hypertension, coupled with full evaluation of those positive on screening, and safe and effective management has the potential to prevent strokes on an epidemiological scale and should be adopted.
Abstract WMP14: Perfusion Weighted Imaging Findings in Acute TIA Patients Predict Subsequent Infarction
Authors: Lee Jun , Mlynash Michael , Kim Na-Young , Albers Gregory , Olivot Jean-Marc
Published: March 2022

Introduction:
Perfusion weighted imaging (PWI) increases the yield of MRI for the detection of ischemic lesions in TIA patients. We investigate whether PWI predicts the occurrence of acute diffusion weighted imaging (DWI) lesions on follow-up MRI.

Methods:
Consecutive patients over the age of 18 who were suspected to have a TIA were prospectively enrolled. Patients with technically adequate baseline DWI/PWI and 5 day follow-up DWI were eligible. PWI lesions were identified, blinded to clinical information, as a focal delay on MTT and/or TTP maps. Lesions were confirmed by two stroke neurologists. The baseline and follow-up MRIs were then compared to determine if a new DWI lesion had developed on follow-up and if it was located in the same brain region as the baseline PWI lesion.

Results:
Seventy percent (94/120) of the enrolled patients were eligible for these analyses. Mean age was 63 years (SD 13) and median ABCD
2
score was 5 (IQR 3, 5). The median delay from symptom onset to baseline MRI was 261 minutes (IQR 131-587); median delay to follow-up MRI was 5 days (IQR 3, 7). Acute ischemic lesions were present on the baseline DWI in 20 patients (21%). The baseline PWI revealed an ischemic lesion in 38 patients (41%). Acute PWI lesion were detected on both MTT and TTP maps in 34 (90%); MTT alone 2 (5%) and TTP alone 2 (5%). Combining DWI and PWI revealed an acute ischemic lesion in 42 patients (45%) distributed as follows: DWI+/PWI+ =16 (17%); DWI+/PWI- 4 (4%), DWI-/PWI+ 22 (23%), DWI-/PWI- 52 (55%). Every positive DWI lesion at baseline (n=20) continued to be DWI positive at follow up. In addition, 10 new DWI lesions were detected. Seven of these were in the same location as a positive baseline PWI lesion and 2 were both outside and inside the area of the initial perfusion deficit ; 1 was in a region that was normal at baseline. Therefore, 9/22 (41%) of the solated PWI lesions at baseline progressed to infarction.

Conclusions:
Early DWI lesions in patients presenting with transient neurologic symptoms were not reversible at 5 days. Early isolated PWI lesions were seen in about one fourth of these patients and nearly half progressed to infarction. These results substantiate the value of PWI for confirming the diagnosis of an ischemic lesion in patients with suspected TIA.
Abstract WMP20: Intracluster Correlation Coefficients and Reliability of Randomised Multicentre Stroke Trials within VISTA
Authors: Frank Benedikt , Fulton Rachael L , Goldie Fraser C , Hacke Werner , Weimar Christian , Lees Kennedy R ,   on behalf of the VISTA Collaboration
Published: March 2022

Background/Purpose:
Reliable estimates of intracluster correlation coefficients (ICCs) for specific outcome measures are crucial for sample size calculations of future cluster randomised trials. ICCs indicate the proportion of data variability that is explained by defined levels of clustering.

Methods:
ICCs were estimated from linear and generalised linear mixed models using maximum likelihood estimation for common measures used in stroke research, including modified Rankin Skale (mRs), National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI).

Results:
Data were available for 11841 patients with ischaemic stroke from 11 randomised trials. After adjusting for age, thrombolysis, and baseline NIHSS, the median ICC for follow-up data, using centre as the level of clustering, ranged from 0.007 to 0.041. The ICCs for follow-up data using trial, continent or year of enrolment as level of clustering were distinctly lower. Less than 1% of the variability of mRS, NIHSS, and BI was explained by any of these three cluster levels.

Conclusion:
These estimates of relevant ICCs should assist trial planning. For example the sample size for a cluster trial with 150 patients per centre using ordinal analysis of mRS should be inflated by 2.0 due to the ICC of 0.007; whereas the ICC of 0.031 using mRS dichotomised above mRS 0-1, requires inflation by 5.6. The low contribution of trials, year or continent of enrolment to overall variation in outcome offers reassurance that analyses using pooled data from multiple trials in VISTA are unlikely to suffer from bias from these sources.

Table:
Adjusted ICCs with various levels of clustering for outcome at 90 days.
Abstract WMP24: Thrombolysis within 48 hours after Basilar Artery Occlusion
Authors: Lindsberg Perttu J , Strbian Daniel , Sairanen Tiina , Kaste Markku
Published: March 2022

Introduction:
Recanalization therapies and their time window in basilar artery occlusion (BAO) remain empirical and vary among hospitals. Our institutional protocol for BAO does not follow the strict RCT-guided guidelines in hemispheric stroke, and advices thrombolysis up to 12 hours after sudden onset of severe symptoms, and 48 hours after onset of gradually progressing symptoms, provided that extensive infarction changes have not yet occurred.

Objective:
The aim was to analyse the importance of two fundamental variables, symptom duration and the extent of baseline infarction, on the outcome of thrombolysis-treated BAO.

Methods:
We prospectively gathered data from 184 consecutive patients with angiography-proven BAO in the Helsinki University Central Hospital, which receives all candidates for stroke thrombolysis in a catchment area of 1.5 million. We took advantage of frequent non-adherence to our management protocol and grouped patients according to "protocol violations" (PVs): exceeded symptom duration (time PV) and large-infarct PV. Patients were divided into 4 categories based on onset-to-treatment time (OTT). Intravenous alteplase (0.9 mg/kg) and concomitant full-dose heparin was administered in the majority of patients. Outcome variables were recanalization of BA, 3-month modified Rankin Scale (mRS) and 1-year mortality.

Results:
Patients with no PV had the best outcome (when recanalized, 51% had good outcome [mRS 0-2], and 62% were non-dependent [mRS 0-3]), followed by patients with time PV (42% and 58%, respectively). Over 90% of patients with large-infarct PV were dependent, institutionalized, or dead (mRS 4-6), even when recanalized. Compared with 37% in patients with no PV, 1-year mortality was higher in patients with both PVs (68.8%, p<0.05) and large-infarct PV (64.7%, p<0.01); but similar to patients with time PV (45.5%, p=0.61). Importantly, the outcome of recanalized BAO was similar among OTT categories.

Conclusions:
In the absence of extensive baseline infarct signs, recanalization of BAO up to 48 hours was seldom futile (mRS 4-6) and produced non-dependent outcomes in 60% of patients, which was virtually independent of the exact time window. We recommend a dedicated protocol for BAO in stroke patients screened for thrombolysis.
Abstract WMP41: Induced Pluripotent Stem Cell Derived Neural Progenitor Therapy for Treatment in a MCAO Ischemic Brain Injury Pig Model
Authors: West Franklin D , Yang Jeong Yeh , Duberstein Kylee Jo , Holmes Shannon P , Chilton Jamie M , Stice Steven L , Hill William D , Hess David C , Platt Simon R
Published: March 2022

Background:
Adult and embryonic stem cell derived neural progenitor (aNP and eNP) treatments have shown significant promise in rodent models of ischemic brain injury leading to decreased infarct size and improved cognitive and sensorimotor function. However, aNPs are challenging to isolate from live patients and have restricted expansion capabilities and transplant of eNPs would result in immune rejection and bring significant ethical encumbrances being embryonic stem cell derived. Induced pluripotent stem cells (iPSCs) are a new class of stem cells that differentiate into NPs (or iNPs) and can be easily expanded, overcome immune rejection and have no ethical concerns. However, the ability of iNPs to treat ischemic injury remains to be tested.

Objective:
We proposed to assess iNP function in a middle cerebral artery occlusion (MCAO) pig model that is potentially more predictive of outcomes in human patients than rodents as pigs and humans have similar brain size, white matter composition and both have gyrencephalic brains.

Results and Conclusions:
We have recently generated iNPs from human and pig iPSCs and have developed a pig MCAO stroke model. Human and pig iNPs show classical NP morphology and express the NP markers SOX1. Further differentiation of NPs demonstrated they were capable of forming all three major lineages of the central nervous system producing βIII-Tub+ neurons, GFAP+ astrocytes and O4+ oligodendrocytes. To test the function of these iNPs in vivo, a Yucatan miniature pig MCAO model was developed by cauterization of the MCA. Diffusion weighted and apparent diffusion coefficient MRI images confirmed stroke damage 1 day post MCAO. Behavioral and motor function analysis supported MRI results with pigs showing reduced neurological capacity indicated by impaired limb movement, abnormal gait, decreased contralateral menace reflex and ipsilateral head turn. The development of a pig MCAO model will allow stringent assessment of efficacy and safety of iNP therapies in a large animal system, providing a critically needed intermediate animal model of stroke that shares key features with humans.
Abstract WMP48: Usefulness of High-Resolution MRI in the Investigation of Intracranial Stenosis
Authors: Chan Bernard P , Hong Xin , Yap Tien S , Teoh Hock L , Seet Raymond C , Venketasubramanian N , Chen Christopher L , Sharma Vijay K , Chuang Kai H
Published: March 2022

Objective:
High-resolution dark-blood MRI (HR-MRI) is recently applied for investigation of intracranial stenosis. We aim to study the usefulness of HR-MRI in a group of stroke patients with intracranial stenosis detected on TOF-MRA.

Methods:
Consecutive patients with ischemic stroke or TIA presented to a teaching hospital in Singapore were recruited into a long-term follow-up study and underwent MRI of the brain including TOF-MRA with a 3T scanner at the convalescent stage. Symptomatic intracranial stenoses >/=50% were further investigated with T2 and T1 3-dimentional HR-MRI, and post-contrast T1 HR-MRI were also performed in subjects with normal renal function. Additional scan times required for HR-MRI were 6’22” for each of the non-contrast sequences and 4’33” for the post-contrast sequence.

Findings:
35 stroke patients underwent study MRI at a mean of 123 days after stroke onset, and 12 were found to have symptomatic stenoses on TOF-MRA. 2 of them did not reveal any obvious disease on HR-MRI, while intracranial stenoses were confirmed in 10 patients (mean age: 57 years, 8 were male). Distributions include 7 with M1 stenosis/occlusion, 1 with tandem petrous ICA and M1 stenoses, 1 with cavernous ICA stenosis and 1 with petrous ICA stenosis. HR-MRI were not evaluable in one patient with M1 stenosis due to movement artifacts, and for the distal petrous ICA stenosis in the patient with tandem stenoses due to susceptibility artifact from the paranasal sinus. For the remaining 9 symptomatic stenoses, HR-MRI provided additional information with better definition of the distribution and extent of plaques in all cases, reclassification of total occlusion to severe stenosis in 3 cases, demonstration of significant plaque enhancement in 5 of 6 cases when gadolinium was given, and detection of plaque in the asymptomatic contralateral artery in 4 cases.

Conclusion:
HR-MRI is a promising technique that can reveal potentially useful information in the majority of patients with stroke due to intracranial stenosis. However, further technological advance to overcome the current limitations of long acquisition time and restricted brain coverage is required before adoption of this technique into routine clinical practice.
Abstract WMP53: Vitamin D Levels Are Lower In Acute Ischemic Stroke Patients Compared To Matched Controls
Authors: De Silva Deidre A , Talabucon Loreto P , Ng Ebonne Y , Tan Eng King , Wong Tien Yin , Ikram Mohammad Kamran , Lee Wei Ling
Published: March 2022

Introduction:
Vitamin D deficiency is increasingly recognized as a global pandemic. In longitudinal healthy population studies, vitamin D deficiency is associated with increased incidence of ischemic stroke. We compared serum 25-OH vitamin D levels between Asian ischemic stroke patients within 1 week of stroke onset with age and gender matched healthy individuals.

Methods:
We prospectively recruited 133 consecutive Asian acute ischemic stroke patients admitted to the Singapore General Hospital. Blood samples were collected within seven days of stroke onset. Stroke patients were matched for age and gender to individuals with no history of stroke from a database of healthy Asian controls. Serum 25-OH vitamin D was measured using Roche competitive electrochemiluminescence immunoassay for both stroke patients and healthy controls in the same laboratory. Vitamin D deficiency was defined as serum 25-OH vitamin D <20 μg/L and insufficiency as 20-40 μg/L. Matched statistical analyses were performed using Wilcoxon and McNemar tests.

Results:
Among the 133 matched pairs of ischemic stroke patients and healthy controls, median age was 60 years and 75% are males. Median serum 25-OH vitamin D

level was lower among stroke patients (23.2 IQR 16.65-29.60 μg/L) compared to healthy controls (28.9 IQR 21.75-35.50 μg/L) (p<0.0001). Stroke patients had a higher prevalence of vitamin D deficiency (39%) compared to healthy controls (20%) (p<0.0001). A high proportion of stroke patients had insufficient vitamin D compared to healthy controls (95% vs 84%, p=0.007). Corrected serum calcium was lower in stroke patients (median 2.26 mmol/L IQR 2.21-2.35) than controls (median 2.34 mmol/L IQR 2.28- 2.41) (p<0.0001). There was no difference in serum phosphate (p=0.266) and parathyroid hormone levels (p=0.807).

Conclusion:
This cross-sectional study of 25-OH vitamin D levels in Asian patients within 1 week of ischemic stroke onset contributes to the growing evidence that vitamin D insufficiency/ deficiency is a stroke risk factor. Vitamin D measurement within 1 week of stroke onset likely reflects pre-stroke levels and is not influenced by post-stroke effects. Our findings provide impetus for future studies to investigate if vitamin D supplementation reduces stroke incidence.
Abstract WMP67: Plasminogen Deficiency And Gender Dimorphism After Thromboembolic Stroke
Authors: Zemskova Marina A , Hoda Md Nasrul , Kadle Nikhil , Hess David C , Sazonova Irina Y
Published: March 2022

Background:
Stroke is a sex dimorphic disease with males and post-menopausal females having worse outcomes. Plasminogen (Pg) system plays a major role in post-stroke outcomes, affecting clot lysis and MMP-9 regulation. Activation of MMP-9 occurs by both Pg-dependent and Pg-independent mechanisms. However, the role of Pg-dependent molecular pathways in stroke remains unclear. The aim of this work was to determine if there is a sex-specific change in post-stroke neurologic outcomes in mice with Pg deficiency.

Methods:
Pg knockout (Pg
-/-
) and wild type (Pg
+/+
) mice of both sexes (n=8-14 animals/group; 26±4 weeks old) were subjected to embolic stroke. At 24 hours, behavioral evaluation, infarct area and edema volume were assessed.

Results:
Plasminogen deficiency caused pathological fibrin deposition in the microcirculation, inducing a similar systemic inflammatory response in males and females with significantly increased levels of monocytes (1.7-fold, p<0.01) and granulocytes (3.5-fold, p<0.001) in the circulation compared with Pg
+/+
mice. Moreover, all pro-thrombotic Pg
-/-
mice had microcytic anemia due to low red blood cell volume (36.7 fl vs. 41.6 fl, p<0.001). Pg
-/-
females had lower estrogen levels compared with Pg
+/+
females (10.2±12.6 pg/ml vs. 31.5±51 pg/ml; p=0.23). Pg deficiency did not affect the level of MMP-9 in the brain nor in the circulation. Despite the similar levels of systemic pro-thrombotic inflammation in Pg
-/-
mice of both sexes, we observed a significant gender disparity in stroke outcomes. Pg deficiency in males improved behavioral outcomes (1.6 vs. 3.2; p<0.001), reduced infarct size (32.8% vs. 43.1%; p<0.05) and edema volume (5.7% vs. 15.4%; p<0.001) compared with Pg
-/-
mice. On the other hand, Pg
-/-
females had a higher mortality (60% vs. 18%) and a poorer neurologic score (4.6 versus 2.3; p<0.001) due to severe brain injury with an increased volume of infarct (64.8% vs. 19.9%; p<0.001) and edema (13.3% vs. 5.6%; p<0.05) compared with Pg
+/+
females.

Conclusion:
Unlike males, Pg
-/-
females had disproportionately poor outcomes compared with Pg
+/+
females. Our data demonstrates that Pg
-/-
female mice may represent an experimental model that mimics females in an early menopausal stage with chronic pro-thrombotic disease.
Abstract WMP7: Clinical, Angiographic, and Radiographic Outcomes Differences Amongst Mechanical Thrombectomy Devices: Initial Experience of a Large-Volume Center
Authors: Kass-Hout Tareq , Kass-Hout Omar , Frankel Michael , Nahab Fadi , Belagaje Samir R. , Anderson Aaron A. , Yepes Manuel , Gershon Rafael , Sun Chung-Juan Johnny , Isakov Alex , Glenn Brenda A. , Gupta Rishi , Nogueira Raul G.
Published: March 2022

Background and Purpose:
Early reperfusion is the keystone in (AIS) therapy. Here, we compare the angiographic, radiographic, and clinical outcomes amongst the three device categories currently available.

Methods:
Retrospective review of a prospective collected database of large vessel AIS in a large academic center. Data from all consecutive patients who underwent clot retrieval using Merci, Penumbra, or Stent-Retrievers (Solitaire, n=31 or Trevo, n=20) from September 2010 to July 2012 were analyzed. Baseline characteristics were compared across the 3 groups. The outcome measures included the rates of recanalization (TICI 2b-3), symptomatic intracebral hemorrhage (sICH, defined as any parenchymal hematoma e.g. PH-1/PH-2), final infarct volume, 90-day mortality, and independent functional outcomes (modified Rankin Scale, mRS 0-2) at 90 days.

Results:
The entire cohort included 242 patients with a mean age of 65.5 and median baseline NIHSS 20. The median ASPECTS score was 8. There were no significant differences in terms of baseline characteristics amongst the 3 device groups. No differences in the rate of sICH (5.9% vs. 6.02% vs. 7.41%, for Stent retrieval, Penumbra and Merci respectively, P= 0.91), mean procedure time (90.6, 76.23 and 75.3 min for Stent retrieval, Penumbra and Merci respectively, P= 0.05), and the volume of infarction (70.4, 58.02, and 65.61 cc for Stent retrieval, Penumbra and Merci respectively, P = 0.47) between the Stent-Retriever, Penumbra, and Merci groups, respectively. However, the rates of reperfusion (88.2 % vs. 77.1% vs. 69.1 %, p= 0.041) and 90-day functional independence (54.9 % vs. 43.4 % vs. 24.7%, p=0.0015) were significantly higher with Stent-Retrievers as compared to Penumbra or Merci treatments. There was no significant difference in the rate of 90-day mortality amongst the different devices (33.33%, 26.51% and 40.74% for Stent-Retriever, Penumbra, and Merci groups, respectively, P= 0.1549).

Conclusion:
Our initial data suggest a potential superiority of the Stent-Retriever technology to both Penumbra and Merci devices. Differences between Stent-Retrievers and Penumbra were much smaller in our experience and additional comparison in a randomized prospective fashion is warranted.
Abstract WMP72: Effects of Remote Ischemic Preconditioning on the Coagulation Profile of Patients with Aneurysmal Subarachnoid Hemorrhage
Authors: Mayor Fernando , Bilgin-Freiert Arzu , Katsnelson Michael , Dusick Joshua R , Vespa Paul , Koch Sebastian , Gonzalez Nestor
Published: March 2022

Background:
Several animal studies have suggested that ischemic preconditioning (IP) may prolong the coagulation times of the subjects treated. This presents a potential challenge for the translation of the technique into clinical settings as abnormal coagulation profiles may negatively affect the outcomes of IP in patients with ischemic stroke or intracerebral hemorrhage. This study evaluates the immediate and late effects of remote ischemic preconditioning (RIPC) on coagulation in patients enrolled in two trials of RIPC after aneurysmal subarachnoid hemorrhage (SAH).

Methods:
21 patients with SAH (mean age 56, range 38-81) underwent 137 RIPC sessions, 2-12 days following SAH. RIPC was induced by 3-4 cycles of 5-10 minutes of lower limb ischemia followed by reperfusion using a blood pressure cuff inflated to a pressure of 200 mmHg or 30 mm Hg above the systolic blood pressure. Vascular occlusion was confirmed with Doppler. Blood samples for partial thromboplastin time (PTT), prothrombin time (PT), and INR were collected before and after each session. Patients were followed for potential hemorrhagic complications.

Results:
The coagulation profile was analyzed in 47 samples. No significant immediate effect was identified on PTT (mean pre RIPC 27.6 sec vs. post RIPC 27.5 sec, p=0.8), PT (mean pre RIPC 10.8 sec vs. post RIPC 10.8 sec, p=0.6) or INR (mean pre RIPC 1.03 vs. post RIPC 1.034, p=0.6) after each session. However, a significant increase of PT and INR but not PTT was identified after exposure to the complete series of at least 4 sessions (mean PT pre RIPC 11.3 sec vs. post RIPC 12.1, p=0.01; mean INR pre RIPC 1.02 vs. post RIPC 1.09, p=0.014, mean PTT pre RIPC 27.4 sec vs. post 27.85, p=0.092). There was also a significant direct correlation between the number of sessions and the increase in PT (Pearson=0.59, p=0.007) and INR (Pearson=0.57, p=0.01). Average follow up of 26 days demonstrated no hemorrhagic complications associated with RIPC.

Conclusions:
RIPC by limb ischemia appears to prolong the PT and affect INR in human subjects with subarachnoid hemorrhage after at least 4 sessions, a change that correlates with the number of sessions. However, PT and INR values remained within normal range and there were no hemorrhagic complications.
Abstract WMP73: Extracellular Newly Identified Receptor for Advanced Glycation End Products Binding Protein Predicts the Outcome in Patients with Acute Ischemic Stroke: Research for Biomarkers in Ischemic Stroke
Authors: Wakisaka Yoshinobu , Ago Tetsuro , Kamouchi Masahiro , Kuroda Junya , Matsuo Ryu , Gotoh Seiji , Isomura Tetsuro , Awano Hideto , Suzuki Kazuo , Fukuda Kenji , Okada Yasushi , Ooboshi Hiroaki , Kitazono Takanari ,   REVIOS Investigators
Published: March 2022

Background:
Extracellular newly identified receptor for advanced glycation end products binding protein (EN-RAGE) contributes to inflammation and is associated with poor outcome after ischemic heart disease. We assessed the plasma EN-RAGE levels in acute stroke patients and examined their relation with functional outcome after stroke.

Methods:
Blood samples and clinical information were obtained from 171 patients with ischemic stroke at 5 points (days 0, 3, 7,14, and 90) after the onset. Age- and sex-matched healthy 171 controls were enrolled from the Hisayama study in Japan. Stroke severity was assessed with the National Institute of Health Stroke Score (NIHSS). Functional outcome at 90 days was assessed by modified Rankin scale (mRS). To analyze the effects of EN-RAGE levels on stroke severity and outcome, patients were divided into high and low EN-RAGE groups according to whether the level was above or below the median of the whole patients at day 0.

Results:
EN-RAGE levels at day 0 were higher in patients [1.6 (0.8-3.5), median (IQR)] than in controls [0.9 (0.4-1.6)] (p<0.01). Patients with poor outcome (mRS: 2-6, n=73) showed higher EN-RAGE levels at day 0 [2.1 (1.2-5.1)] than those with good outcome (mRS: 0-1, n=97) [1.1 (0.5-2.0)] (p<0.01). Multivariate analysis revealed that EN-RAGE levels at day 0 independently associated with poor outcome (OR:1.2, 95%CI: 1.1-1.5). Although NIHSS were not different between high (n=87) and low (n=84) EN-RAGE groups at day 0 [4 (2-8) vs 4 (2-6)], low EN-RAGE group showed significantly lower NIHSS than high EN-RAGE group at days 3, 7, 14, and 90. Low EN-RAGE group showed preferable outcome than high EN-RAGE group (figure).

Conclusions:
Our study suggests that EN-RAGE predicts poor outcome in patients with acute ischemic stroke.
Abstract WMP77: Persistent Post Stroke Hyperglycemia Should Accelerate The Early Development Of Brain Infarct Volume: A Prospective Study Using By A Continuous Glucose Monitoring Device (CGMS).
Authors: Shimoyama Takashi , Uemura Junichi , Shibazaki Kensaku , Inoue Takeshi , Iguchi Yasuyuki , Kimura Kazumi
Published: March 2022

Background:
Previous studies suggested that hyperglycemia was associated with infarct volume expansion in acute ischemic stroke patients. However, most studies have used a single time point measure (usually at admission) of blood glucose to define glycemia. The aim of the present study is to clarify the influence of persistent hyperglycemia after stroke assessed by a continuous glucose monitoring device (CGMS).

Methods:
Acute ischemic stroke patients with ICA and MCA occlusion within 24h of onset were prospectively studied. Continuous glucose monitoring was performed with a CGMS for 72h after admission.The patients were divided into two groups according to mean CGMS glucose value during 72h; persistent hyperglycemic group (mean CGMS glucose value ≥135mg/dl) and normoglycemic group (mean CGMS glucose value < 135mg/dl). Infarct volume was measured at admission, 24h and 72h after admission using DWI. We compared the change in infarct volume after 24h and 72h between the two groups. Multiple regression analysis was performed to identify variables that predicted the infarct volume expansion.

Results:
33 patients were enrolled in the present study. During 72h monitoring, 17 patients (51.5%) had persistent hyperglycemia. Admission glucose value (129.0 mg/dl vs. 116.0 mg/dl, P=0.276) and HbA1c (5.6% vs. 5.5%, P=0.901) did not differ in the persistent hyperglycemic group and the normoglycemic group.The baseline infarct volume was similar in the two groups (59.1ml vs. 43.9 ml, P=0.709). However, the change in infarct volume after 24h was larger in the persistent hyperglycemic group than the normogycemic group (23.9 ml vs. 6.8ml, P=0.009). On the other hand, the change in infarct volume after 72h was not statistically different (41.7 ml vs. 28.7 ml, P=0.260). Multiple regression analysis indicated that persistent hyperglycemia (P=0.007) and no recanalization (P=0.027) were independently associated with infarct volume expansion after 24h.

Conclusion:
Persistent post stroke hyperglycemia independently affects infarct volume expansion after 24h but not 72h. These findings suggest that persistent hyperglycemia in the patients with large vessel occlusion should have a deleterious effect accelerating the early development of cerebra ischemia.
Abstract WMP81: Prostaglandin E2 EP1 Receptor Deletion Exacerbates Brain Injury And Behavioral Deficits After Experimental Induced Intracerebral Hemorrhage.
Authors: Singh Nilendra , Ma Bo , De Oliveira Gabriela , Narumiya Shuh , Dore Sylvain
Published: March 2022

Background:
Prostaglandin E2 (PGE2) has been reported to have various cytoprotective or toxic properties in acute and chronic neurological conditions. The role of the PGE2 EP1 receptor in intracerebral hemorrhage (ICH) induced brain injury has not yet been fully investigated. Thus, this study is performed to investigate the role of the EP1 G-protein-coupled receptor in hemorrhagic stroke.

Methods:
ICH was induced randomly in 2.0-2.5 month-old male C57BL/6 (WT) and EP1 knockout mice by intrastriatal injection of collagenase. Following 72h after ICH, neurological outcomes were evaluated using: adhesive removal, rotarod, open field and neurological deficits on a 24-point scale. Thereafter, the mice were sacrificed and brains were taken out to quantify the lesion volume, brain swelling, cell death/survival, and microglial activation following this ICH model. All values are expressed in (mean±SEM), and the number of cells/field was provided by averaging four different regions around the hematoma.

Results:
Collagenase injection produced a reproducible hematoma that was primarily restricted to the striatum. Neurological deficit was worsened in EP1 knockout (18.7±1.7) compared to WT mice (11.1±0.9) after 72h of ICH. Interestingly, deletion of EP1 receptor aggravates brain injury lesion volume (17.8±1.7 vs. 12.5±1.6mm
3
) and brain swelling (18.7±1.6 vs. 11.1±0.9mm
3
) compared to WT mice. Behavior analysis (EP1 vs. WT) using adhesive removal (91.7±4.3 vs. 52.3±3.9sec), open field (1120.0±155.9 vs. 1837.0±82.8sec), and rotarod performance (46.0±4.2 vs. 66.3±4.0sec) tests indicate that WT mice recovered faster compared to EP1 mice. Fluoro Jade staining indicated that cell death was higher in EP1 than WT mice (117.3±7.3 vs. 71.5±4.6 cells/field), and 8-hydroxyguanosine staining showed that neuronal survival was reduced in EP1 mice (19.4±2.4 vs. 33.9±2.1cells/field) at 72h after ICH. Thereafter, quantification using Iba1 immunostaining demonstrated a 72% increase in the number of immunoreactive microglia appearing in WT than in EP1 mice.

Conclusion:
These results suggest that EP1 receptor deletion aggravates brain injury, induces neurological dysfunction with decreased neuronal survival, and activates microglia in this ICH preclinical model.
Abstract WMP86: Novel, High-tech Walking Recovery Program Improves Motor Recovery
Authors: Banta Melissa W , Wilks Matt , Pidcoe Peter E , Sima Adam , Devers Amber
Published: March 2022

Introduction:
Although there are a number of research studies investigating walking recovery after stroke, most focus on one intervention or piece of equipment in order to achieve a controlled experimental environment. Such studies have yet to produce a comprehensive clinical practice guideline (CPG) for gait training. To fill this void, we implemented a clinical program for walking recovery, iWalk™, using a variety of advanced technologies, and an evidence-based CPG to assist in making assessment and intervention decisions. This study compares outcomes of patients treated using a traditional therapy program to those treated with the iWalk program.

Hypothesis:
The systematic application of a novel, evidence-based CPG for walking recovery will result in superior motor performance when compared to traditional therapy in patients post stroke.

Methods:
This study included all stroke survivors admitted to a rehab facility during a 24 month period, with the cohort split into two groups. The control group received traditional rehabilitation (n=152) and the experimental group received the iWalk protocol (n=165). Since full implementation of the protocol could not be assigned a specific date, a buffer group (n=50) between the two groups was excluded from this analysis.

Results:
Functional Independence Measure: An interaction between age and treatment program was detected (p<0.001). Motor FIM scores showed greater improvement for younger patients in iWalk than in the traditional therapy program.

Length of Stay:
When examining LOS as an outcome, an interaction between treatment group and total FIM score was detected (p=0.073). Patients who were lower functioning on admission were more likely to be discharged home if they were in the iWalk program. Examining LOS as a predictor, the difference in timed-up-and-go scores between the treatment groups reveals that iWalk seems to be better for a LOS around 3 weeks, but is not significant (p>0.05).

Conclusions:
This study demonstrates outcome differences that favor iWalk. Additionally, there may be a LOS range which optimizes motor recovery. It is unclear whether a patient’s LOS is a reflection of the improvement of clinical variables or practical reasons. Further work is necessary on this topic.
Abstract WMP91: The Mortality Rate Of Stroke Patients Is Less When Treated At Telestroke Spokes Vs. Non Telestroke Sites
Authors: Hall-Barrow Julie C , Bird Tommy M , Yaghi Shadi , Imus Terri L , Bianchi Nicolas ,   ARSAVES Group
Published: March 2022

Background:
Most rural hospitals in Arkansas did not administer t-PA prior to participating in a telestroke program. With the growing number of telestroke networks, it is crucial to determine the effectiveness of these programs in improving the outcome of ischemic stroke patients.

Methods:
The Arkansas Stroke Assistance through Virtual Emergency Support (AR SAVES) team reviewed the hospital discharge data of AR SAVES hospitals versus propensity score matched control hospitals linked with death certificates from 2006 to 2010 provided by the Arkansas Department of Health. All patients with primary ICD-9 codes for ischemic stroke were included. Hospitals with less than 10 admissions for ischemic stroke during the study period were excluded. ARSAVES hospitals were included in the evaluation if they started participating in the first 12 months of program initiation. All hospitals in the state that were not in the ARSAVES program prior to Jan 1, 2011 were the control group. Analyses were done using chi-square tests and t-tests. We used multivariable logistic regression models to compare differences in dichotomous outcomes.

Results:
A total of 18 hospitals and 3,728 ischemic stroke patients were included in the final analysis. Patients treated in participating hospitals had reduced mortality rates at 30 days (ARR 0.58, 95% CI 0.40-0.85), 6 months (ARR 0.57, 95% CI 0.42-0.77) and 12 months (ARR 0.66, 95% CI 0.48-0.90), as well as reduced rates of discharge to hospice care (ARR 0.53, 95% CI 0.29-0.99). There were no statistically significant differences in either length of hospital stay (AME 0.35 days, 95% CI -0.31 to 1.01) or hospital cost (AME $629, 95% CI -834 to 2,091).

Conclusion:
Stroke patients treated at telestroke spoke hospitals had a significantly lower mortality rate than those treated at a non telestroke hospital, with the same cost of care. This may be a reflection of increased t-PA use and improved stroke education and stroke patient care in telestroke hospitals.
Abstract WMP92: Health Insurance Coverage is Associated with Mortality after Stroke
Authors: McManus Michael , Ovbiagele Bruce , Markovic Daniela , Towfighi Amytis
Published: March 2022

Background:
Management of treatable risk factors is of paramount importance to decrease stroke mortality and improve outcomes after stroke. Optimizing healthcare access serves as a foundation for risk factor management. The association between health insurance type and mortality after stroke warrants investigation.

METHODS:
Using data from the National Health and Nutrition Examination Surveys 1999-2004 with follow up mortality assessment through 2006, we examined the relationship between health insurance and (1) stroke mortality among all adult participants (n=15,049) and (2) vascular and all-cause mortality among participants with self-reported stroke (n=563). The relationship between insurance type and the aforementioned outcomes were evaluated using Cox regression after adjusting for covariates (age, sex, race, income, BMI, and major medical comorbidities).

RESULTS:
Among 10,786 participants <65 years (representing 163,891,359 individuals in the US) 69% had private insurance, 21% were not insured and 4% had Medicaid. Among 4,263 participants ≥ 65 years (representing 33,375,771 individuals in the US), 43% had Medicare + private insurance, 41% had Medicare only, 8% had private insurance only and 4.2% had Medicare + Medicaid. Stroke survivors ≥65 years with private insurance were less likely to die from vascular causes compared to those with Medicare alone (adjusted HR 0.38, CI 0.23-0.63, p<0.001). The same subjects had lower all-cause mortality if they had Medicare + private insurance compared to Medicare alone (adjusted HR 0.63, CI 0.37-1.08, p=0.07). Uninsured stroke survivors <65 years had similar all-cause mortality to those with insurance (adjusted HR 0.97, CI 0.29-3.23). In the general population, uninsured individuals <65 years were more likely to die of stroke than those with insurance (adjusted HR 3.13, CI 0.96-10.23, p=0.06); however, insurance status did not affect stroke mortality among individuals ≥65 years.

CONCLUSION:
In this nationally representative sample of the US population followed for up to 7 years, insurance status appears to have a profound, independent impact on mortality rates after stroke. These findings highlight the importance of health insurance coverage in post-stroke outcomes.
Abstract WMP95: U.S. Trends in the Cost and Charges for a Hospital Admission for Acute Ischemic Stroke (AIS): Do the Trends Track with the Consumer Price Index (CPI) for Medical Care Services?
Authors: Simpson Annie N , Simpson Kit N
Published: March 2022

Introduction
Care for AIS patients have improved over the last decade, with increased use of high technology interventions. The use of effective but high cost interventions, as well as the resulting improvement in survival, may affect the costs for a hospital admission. Thus, hospital costs for AIS may be expected to increase more than the average cost of medical care, as measured by the CPI. Furthermore, increases in bad debt for AIS patients may force hospitals to increase charges for AIS admissions to cover the cost of providing care to non-paying cases.

Hypothesis
Trends in costs for hospital admissions for AIS will increase the same as the CPI, while costs for patients treated with tPA will rise faster. Increased use of tPA and/or mechanical thrombectomy (MT), and improved survival will explain increases in costs, while insurance status will explain changes in charges.

Methods
A total of 499,661 hospital admissions for AIS were extracted from the Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP) data for 2005 through 2010. Cost per admission was estimated from total charges using each hospital’s cost-to-charge ratio and were compared with CPI trends in changes in healthcare costs provided by the US Bureau of Labor and Statistics. Use of tPA and/or MT was examined using multiple regression analyses. Number and percent of patients, per year, with tPA therapy and MT were calculated.

Results
Cost of an acute care admission for AIS increased at a greater rate than the CPI from 2005 through 2008, but appeared to level of in 2009, with tPA admission most closely following the CPI. Utilization of tPA increased in 2005 from 1.84% to 5.47% in 2010. The number of admissions with MT increased from 0.87% to 8.09% over the same time period. Charges for AIS admissions have increased much more rapidly that the CPI observed from 2005 to 2010, with admission receiving tPA having the greatest gain in charges.

Conclusions
Cost of care for AIS patients who receive tPA follows the CPI trend, while costs for non-tPA patients increase at a greater rate. This disparity could indicate a widening gap between cost and reimbursement for non-tPA admissions, and/or a failure of many hospitals to accurately record the use of tPA for billing purposes.
Abstract WP108: Effect Of Human Amnion Epithelial Cell Therapy On Stroke Outcome In Mice
Authors: Broughton Brad , Lim Rebecca , Wallace Euan , Drummond Grant , Sobey Christopher
Published: March 2022

Stem cells derived from human tissue, including embryonic, induced pluripotent, neural, and mesenchymal cells, have been reported to rescue injured brain tissue and improve functional recovery in experimental models of stroke. However, potentially major limitations to each of these cell types may limit their use as a treatment option for stroke patients. Conversely, stem cells derived from the placenta, namely human amnion epithelial cells (hAECs), which appear to offer several advantages over other stem cell lineages, have received almost no attention as a stroke therapy. We have tested the hypothesis that hAECs may be an effective form of cell-based therapy for stroke in male C57Bl6 mice subjected to 0.5 h middle cerebral artery occlusion-reperfusion. Mice were injected with 1x106 fluorescently-labelled hAECs or saline (vehicle) i.v. at either 1 h (acute treatment) or 72 h (delayed treatment) post-stroke and brains were removed after 3 or 14 d, respectively. Neurological and motor assessment tasks were performed every 3-4 days. hAECs injected acutely after stroke were present in the infarct, but not in the contralateral hemisphere at 72 h, and this was associated with improved neurological and motor function as well as reduced infarct damage (n = 7-12; P < 0.05). Immunofluorescence of the key marker of apoptosis, cleaved caspase-3, revealed that less apoptosis occurred in the infarct core of mice treated with hAECs versus vehicle (P < 0.05). Moreover, mice that instead received delayed post-stroke hAEC treatment had markedly improved survival and functional outcomes during 14 d compared with vehicle-treated mice (n = 10/group). Thus, early post-stroke i.v. delivery of hAECs can reduce brain injury and functional deficit. Delayed post-stroke hAEC treatment improves longer term survival and functional performance. These findings suggest that hAECs may be a viable and effective clinical therapy for promoting recovery following ischaemic stroke.
Abstract WP114: Alteration in Gene Expression Profiles in Aging Cerebral Cortex Prior to the Occurrence of Stroke in Stroke-Prone Spontaneously Hypertensive Rats
Authors: Ito Masaki , Kuroda Satoshi , Takahashi Koji , Kawabori Masahito , Miyamoto Michiyuki , Yamauchi Tomohiro , Saito Hisayasu , Shichinohe Hideo , Houkin Kiyohiro
Published: March 2022

Purpose—
Stroke is a complex disorder with a poorly understood multifactorial and polygenic etiology. However, little is known about the underlying pathogenic biomarkers. This study was aimed to reveal the antecedent events in the brain of stroke-prone spontaneously hypertensive rats (SHR-SP), by extensive microarray analysis prior to the occurrence of stroke.

Method—
Blood pressure was measured every week. 0.5% NaCl was loaded everyday from 9 wks of age to promote hypertension additionally. Male SHR-SPs were sacrificed at 6 and 12 wks of age (n=3 and 3, respectively). Wistar-Kyoto rats (WKY; male, 6-wk-old, n=3) utilized as the control sacrificed at 12 wks. Subsequently, total RNA was extracted from cerebral cortices immediately and gene expression profiles were studied using 27k rat cDNA microarray. Differentially expressed probes were determined by one-factor ANOVA (P<0.01). These probes further analyzed with k-means cluster analysis (Number of Clusters: 10). Finally, genes differentially expressed in 12-wk-old SHR-SPs were investigated using the Gene Ontology.

Result—
All animals did not develop any evidence of stroke symptom. Mean blood pressure was lower than 110 mmHg in all 6-wk-old animals, but gradually elevated up to higher than 180 mmHg only in 12-wk-old SHR-SPs. Extensive microarray analysis identified 414 differentially expressed probes. Of these, k-means cluster analysis revealed 84 probes with significant variance of expression in 12-wk-old SHR-SPs. Of these 84 probes, 39 upregulated and 18 downregulated genes were categorized as recognized genes at NCBI EntrezGene. Gene Ontology analysis of these genes showed no specific patterns. However, this study identified 4 differentially upregulated genes that play an important role in cell growth, cell adhesion, transcription regulation and unknown role, including HtrA serine peptidase 4, periostin, zinc finger protein 189, and oxidation resistance 1.

Conclusion—
Although further studies are essential to determine the specific roles of these 57 genes in the development of stroke, the present data may provide the first large scale description of alteration in gene expression profiles in SHR-SP and suggest several cues to investigate some biomarkers for cerebral stroke.
Abstract WP123: Determinants Of Cerebral Hyperperfusion Syndrome After Extracranial-intracranial Artery Bypass In Severe Intracranial Steno-occlusive Disease
Authors: sharma vijay , yeo leonard L , Ahmad Aftab , ke jia teo , lwin sein , Tsai yeo T , ning chou , sinha arvind , hock luen teoh , chan bernard
Published: March 2022

Background:
Patients with intracranial stenoses are at considerable risk for ischemic events. Recent trials on stenting for intracranial stenoses and external carotid-internal carotid (EC-IC) bypass in carotid occlusions failed to show benefit over best medical therapy. We perform EC-IC bypass in patients with severe steno-occlusive disease of intracranial internal carotid (ICA) or middle cerebral artery (MCA) with impaired cerebral vasodilatory reserve (CVR). EC-IC bypass may lead to cerebral hyperperfusion syndrome (HPS) in some cases, presenting as neurological deficits during early post-operative period. We evaluated possible predictors of HPS.

Methods:
Patients with severe intracranial ICA or MCA stenosis and impaired CVR on transcranial Doppler (TCD) derived breath-holding index (BHI) were evaluated with acetazolamide-challenged 99Tc-HMPAO-SPECT. Patients with significantly impaired CVR on SPECT were offered EC-IC bypass with close post-operative monitoring.

Results:
Of the 112 patients with severe intracranial ICA/MCA stenosis, 77 (69%) showed impaired CVR and 46 (41%) underwent STA-MCA bypass. Transient neurological deficits, mainly contralateral weakness within 7-days of surgery, were noted in 8 (17%). HPS was confirmed by CT perfusion and/or SPECT in 7 cases. Strong correlation was observed between HPS and pre-operative TCD-BHI (0% cases with BHI 0.3-0.69; 6.3% with BHI 0-0.3 and 41% with BHI <0, p=0.012). HPS patients showed more than 50% increase in the MCA mean flow velocity on TCD (compared to pre-operative values) on the operated side (63.3% vs 3.3% on control side, p<0.0005). Meticulous control of blood pressure and hydration led to complete resolution of neurological deficits in all cases (mean 3-days, range 1-6days).

Conclusion:
Symptomatic cerebral HPS is common in early post-operative period after EC-IC bypass surgery. Early diagnosis and appropriate management might prevent the complications of this syndrome