bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP67: Micro- and Macroalbuminuria After Intravenous Thrombolysis May Predict Hemorrhagic Transformation in Acute Ischemic Stroke
Authors: Kim Joon-Tae , Cho Bang-Hoon , Choi Kang-Ho , Ryu Su-Ra , Oh Dong-Seok
Published: March 2022

Introduction:
Endothelial disruption might be one of the mechanisms related to the development of hemorrhagic transformation (HT) in cerebral ischemia. Dysfunction of the vascular endothelium may be explained by a link between micro/macroalbuminuria and increased risk of cardiovascular disease.

Hypothesis:
We hypothesized that micro- and macroalbuminuria could be a predictor of HT after intravenous thrombolysis (IVT) in acute ischemic stroke. Therefore, this study assessed the hypothesis that micro- and macroalbuminuria might be associated with HT after IVT in patients with acute ischemic stroke and sought to investigate whether the value of urinary albumin-to-creatinine ratios (UACR) would correlate with the degree of HT.

Methods:
This was a retrospective study of stroke patients who had undergone IVT within 3 hours of symptom onset. Albuminuria assessment was based on random morning spot urine collection with patients in a fasting state, the first morning after IVT. HT was assessed by means of follow-up DWI obtained 24 and 72 hours after IVT. HT was classified as HI and parenchymal hematoma according to the ECASS criteria. We defined symptomatic intracranial hemorrhage (SICH) according to the definitions in the NINDS-tPA trials.

Results:
154 patients were included in the study. Fifty-one patients had HT and 12 ones had SICH. The presence of micro- or macroalbuminuria was associated with HT after adjustment for variables with clinical significance (OR, 2.521; 95% CI, 1.105-5.751;
p
= 0.028). In addition, the presence of micro- or macroalbuminuria was independently associated with SICH after adjustment for variables. There were significant relationships between the presence of micro- and macroalbuminuria and types of HT.

Conclusion:
In conclusion, the results of this study suggest that the presence of micro- and macroalbuminuria after IVT could be a predictor of HT in patients with acute ischemic stroke and that treatment of albuminuria might prevent HT after IVT in patients with acute ischemic stroke.
Abstract TP69: Minimum NIHSS Score To Qualify For IV tPA
Authors: Choe Jessica , Raman Rema , Ernstrom Karin , Meyer Dawn M , Guzik Amy , Meyer Brett C , Hemmen Thomas
Published: March 2022

BACKGROUND:
Frequently patients with ischemic stroke are excluded from IV tPA therapy because of mild deficits. Often a minimal score on the NIHSS is used to identify mild stroke patients, but some argue to specially weight motor and language deficits. We examined the outcomes of patients with Acute Ischemic Stroke (AIS) who did not receive IV tPA using four definitions of a “mild” deficit using the total and itemized NIHSS at baseline with the aim to identity patients with a mild deficit that highly predicts good outcome when not treated with thrombolysis. Additionally we examined if any single item on the NIHSS in mild stroke patients predict poor outcomes.

METHODS:
We included all adult patients with mild (NIHSS 0-4) AIS from the UCSD SPOTRIAS Database from 2004-2012; excluded patients who received thrombolysis (IV or IA) or had a pre-stroke mRS >0. We analyzed baseline demographics (age, sex, race, HTN, DM, afib), total NIHSS, NIHSS items (normal or abnormal) and 90-day mRS. We evaluated four definitions of mild deficits: 1) total NIHSS 0-4; 2) NIHSS 0-4 AND arm (Q5) AND leg weakness (Q6) 0-1, AND aphasia (Q9) 0-1; 3) NIHSS 0-4 AND Q5,6,9=0; 4) NIHSS 0-4 AND Q5+6+9<2. Good outcome was defined as 90-day mRS 0-1.

RESULTS:
A total of 147 patients were included (definition #1), under mild #2 we identified 111, #3 78 and #4 106 patients. Good outcome was achieved in 70.8%, 70.3, 74.4% and 70.8% of each definition. No NIHSS item (0 vs >0) correlated with poor outcome in mild patients.

CONCLUSION:
We found no significant difference in outcome prediction when weighing motor and language deficit over the overall NIHSS <5. In the patients with mild stroke, no specific NIHSS scoring item predicted poor outcome.
Abstract TP81: Flow Independent Dynamics in Aneurysm (FIDA): Pressure Measurements within an Aneurysm Before and After Partial and Complete Flow Impairment
Authors: Majidi Shahram , Watanabe Masaki , Qureshi Adnan I
Published: March 2022

BACKGROUND:
The correlation between different hemodynamic variables and aneurysm growth and rupture has not been fully understood. We aimed to study intravascular and peri-vascular pressure in the aneurysm after partial and complete flow impairment within the aneurysm.

MATERIALS AND METHODS:
A silicone model of an 8 mm sized aneurysm (neck diameter: 5mm, vessel size: 4 mm) was used. The aneurysm wall was encapsulated and sealed within a 5ml syringe filled with saline and a pressure sensor guidewire (PrimeWire, Volcano Corp.) providing pressure changes in the peri-vascular compartment (outer aneurysm wall). Through a 5 F guiding catheter, a second pressure sensor guidewire was advanced inside the aneurysm sac. The aneurysm connected to a pulsatile fluid pump. Both pressure sensors continuously measured pressure inside and outside the aneurysm under pulsatile flow under the following conditions: 1) baseline (reference); 2) a 16 mm by 3.75 mm flow diverting stent (ev3, Irvine, California) deployed in front of the aneurysm; 3) two flow diverting stents (16 mm by 3.5 mm) were deployed; and 4) a covered stent (4 mm by 16 mm VeriFlex cronory artery stent covered with rubber sheet) was deployed.

RESULTS:
Mean baseline pressures inside and outside the aneurysm were 55 mmHg (range 120-40 mmHg) and 15 mmHg (range 40-8 mmHg), respectively. There was no change in pressure inside and outside the aneurysm after deploying the first and second flow diverting stents (partial flow impairment) and pressure remained at 55 mmHg and 15 mmHg inside and outside the aneurysm, respectively. The pressure recording from outside the aneurysm dropped from 15mmHg to zero after deploying the covered stent (complete flow impairment). There was no change in pressure inside the aneurysm after deploying the covered stent. Mean pressure within the aneurysm was 55 mmHg and it remained the same after covered stent deployment.

CONCLUSION:
Our findings suggest a major discordance between the pressures within the aneurysm and partial or complete flow impairment (flow-independent). The outer wall pressure is reduced after covered stent placement. These finding may assist physicians in better understanding of aneurysm hemodynamics and rupture after flow diverting stent deployment.
Abstract TP96: A Genomic Profile of Immune Mediated Mechanisms Associated with Stroke Recovery.
Authors: Barr Taura L , VanGilder Reyna , Rellick Stephanie , Brooks Steven , Doll Danielle , Lucke-Wold Ann Noelle , Chen Dongquan , Denvir James , Warach Steven J , Singleton Andrew B , Matarin Mar
Published: March 2022

Objective:
We recently identified a profile of genomic biomarkers related to the inflammatory and immune signaling mechanisms in human ischemic stroke. The objective of this study was to identify novel biomarkers for ischemic stroke recovery through gene expression profiling and pathway analysis.

Methods:
Peripheral whole blood samples were collected from n=34 MRI diagnosed ischemic stroke patients’ ≥18 years of age at two time points: within 24 hours from stroke symptom onset and 24-48 hours later. Modified rankin scale (MRS) was used to determine 30 day stroke outcome. Total RNA was extracted from whole blood stabilized in Paxgene RNA tubes, amplified, and hybridized to Illumina HumanRef-8v2 bead chips. Gene expression was compared in a univariate manner between stroke patients at both time points and good versus bad outcome using t-test in GeneSpring. Inflation of type one error was corrected by Bonferroni and Ingenuity Systems Pathway analysis (IPA) was performed. A validation cohort of ischemic stroke patients was recruited from WVU Ruby Memorial Hospital (WVUH).

Results:
Three genes were significantly downregulated over time (LY96, IL8, and SDPR) ( Bonferroni corrected p<0.05) Pathway analysis revealed cytotoxic t-lymphocyte antigen 4 (CTLA4) and dopamine signaling as highly significant canonical pathways present in the peripheral whole blood of ischemic stroke patients 24-48 post onset of symptoms. When controlling for age and hypertension, high baseline expression of ARG1, MMP9, TLR2 and TLR4 significantly predicted worse scores on the MRS. Validation in a separate cohort of subjects at WVUH confirms these findings.

Conclusions:
In this study we have demonstrated that ischemic injury to the brain produces an immune response that can be observed in the peripheral blood following stroke. Markers of immune dysfunction in the early post-stroke phase, such as arginase, TLR signaling and T-cell activity may prove useful for identifying patients with increased risk of post-stroke immune suppression and poor recovery.
Abstract WMP100: State Based Stroke Center Designation Increases their Availability and Thrombolytic Administration Rates
Authors: Janjua Nazli , Moradiya Yogesh , Ramirez-Abreu Darwin , Xavier Andrew R , Zaidat Osama S , Yavagal Dileep Y
Published: March 2022

Background:
The Joint Commission (JC) recently proposed criteria for certification of comprehensive stroke centers (CSCs), which have capabilities for stroke care in addition to those of primary stroke centers (PSCs). CSCs may be ideal facilities to care for patients ineligible for intravenous thrombolysis (IT). We sought to assess the availability of PSCs and CSCs and variability in their designation mechanisms in the United States (US).

Methods:
Numbers of designated stroke centers were determined from state Departments of Health (DOH) and JC listings and DOH surveys. These were integrated with 2010 US Census bureau data. Minimum hospital volumes for annual procedures and disease specific admissions required for CSCs (IT for 25 stroke patients, care of 20 subarachnoid hemorrhage patients, endovascular embolization of 15 cerebral aneurysms and surgical clipping of 10 aneurysms) were extracted per state from the 2009 Nationwide Inpatient Sample (NIS).

Results:
Projected number of CSCs are low (.28+/-0.54 per million capita). States with their own DOH based PSC designation had significantly higher numbers of all stroke centers per million capita (7+/-2 vs 3+/-2, p<0.001), primarily constituted by DOH designated PSCs. These states also had a non-significant trend towards higher numbers of CSCs per million capita, (0.81+/-0.72 vs 0.18+/-0.47). NIS data demonstrate only 1.6% (82 of 5128) of hospitals meet all 4 volume criteria, with the most deficient item being required aneurysm clippings (3.9%). Among hospitals lacking only 1 of the 4 criteria (n=131), IT volume was the major deficiency (51.8%). States with DOH based PSC designation had significantly higher numbers of hospitals achieving this goal for IT (10.8% vs 3.0%, p<0.001) even after controlling for bed size and teaching status (OR: 1.77; 95% CI: 1.49-2.11).

Conclusion:
Projected numbers of CSCs are low. Hospital deficiencies must be investigated in order to meet the public’s needs. States with DOH designation mechanisms have higher numbers of all stroke centers, which administer thrombolysis at higher rates. More widespread adoption of these successful state policies may increase stroke centers’ ability to care for acute ischemic stroke.
Abstract WMP11: The Association between Endovascular Reperfusion and Favorable Clinical Response Is Similar in Older and Younger Stroke Patients
Authors: Liggins John , Mishra Nishant K , Wheeler Hayley M , Inoue Manabu , Straka Matus , Kemp Stephanie , Mlynash Michael , Bammer Roland , Albers Gregory W ,   The DEFUSE 2 investigators
Published: March 2022

Background:
Older stroke patients generally have poorer clinical outcomes than younger stroke patients. We aimed to determine if the clinical response following endovascular reperfusion differs between older and younger patients with the Target Mismatch profile.

Methods:
Stroke patients enrolled in the DEFUSE 2 study underwent MRI diffusion (DWI) and perfusion (PWI) weighted imaging prior to endovascular treatment. Target Mismatch was defined as a ratio of PWI (Tmax >6s) over DWI volume >1.8, DWI volume <70ml, and a PWI (Tmax >10s)

volume <100ml. Favorable clinical response was defined as a >8 point improvement on the NIHSS or an NIHSS score of 0-1 at 30 days. The relationship between baseline clinical and neuroimaging variables and favorable clinical response, was assessed using logistic regression. In addition, we evaluated the interaction of age and reperfusion on favorable clinical response and compared the effect of reperfusion between younger (age ≤ 80 years) and older (age > 80 years) patients.

Results:
Seventy-eight patients had a Target Mismatch and forty-two patients had a favorable clinical response. Age (p<0.01), reperfusion status (p<0.01), baseline DWI volume (p=0.07), hypertension (p<0.01) and history of stroke or TIA (p<0.01) were associated with favorable clinical response in univariate analyses. In multivariate analysis, age (p<0.05), reperfusion (p<0.01) and baseline DWI volume (p<0.05) were independent predictors of favorable clinical response. The age by reperfusion status interaction was not significant in the multivariate model (p = 0.3). Additionally, there was no significant difference between the odds ratio for favorable clinical response with reperfusion in patients ≤80 years (n = 58; OR = 6.2, 95% CI = 1.7 - 24.4) and those above 80 years (n = 20; OR = 2.1, 95% CI = 0.2 - 21.1) (p = 0.3 for the difference between the odds ratios).

Conclusion:
Target Mismatch patients who are younger have overall better clinical outcomes than older patients with the Target Mismatch. The association between endovascular reperfusion and favorable clinical response did, however, not differ between younger and older stroke patients. These results argue against the use of an age cutoff for endovascular stroke therapy.
Abstract WMP110: Effectiveness of EEG Ischemia Monitoring in Clinical Practice for the Detection of Delayed Cerebral Ischemia after Subarachnoid Hemorrhage
Authors: Rosenthal Eric S , O’Connor Kathryn , Westover M. B
Published: March 2022

Background:
Quantitative EEG trend monitoring has shown high sensitivity in pilot studies for early detection of delayed cerebral ischemia (DCI) after aneurysmal SAH. Little is understood, however, about its performance in the prospective clinical environment. We hypothesized that clinical confounders and mimics of ischemic EEG patterns may result in high false alarm rates.

Methods:
Patients undergoing EEG ischemia monitoring within 4 days of SAH were identified from a prospectively documented clinical database and evaluated for any EEG ischemic signs (EEG-IS) denoted by the clinical neurophysiologist (NPhys-EEG-IS), including deterioration by one grade in percent alpha variability (PAV) over 8 hours, >50% decrement in alpha-delta ratio (ADR) exceeding 1 hour, >10% decrement in ADR exceeding 5 hours, or new focal EEG slowing on the raw EEG. We separately performed a wholly computational retrospective assessment for EEG-IS (Comp-EEG-IS). DCI was retrospectively ascertained as an unexplained focal clinical or radiologic decline.

Results:
19 patients underwent EEG monitoring (median 10 days, IQR 9-11). Late epileptiform or rhythmic patterns emerged in 14 patients (74%). There was a strong trend towards NPhys-EEG-IS being associated with DCI (univariate OR 8.4, p=0.15), which persisted (multivariate OR 7.5, p=0.08) after adjusting for the association of Hunt-Hess grade >4 and DCI (multivariate OR 3.4, p=0.27). Of 11 patients (58%) with NPhys-EEG-IS alarms, 6 developed DCI (Se 86%, Sp 58%, PPV 55%). DCI was not associated with longer NPhys-EEG-IS alarm duration (5.0 vs. 4.8 alarm-days; NS). The Comp-EEG-IS method was problematic, resulting in multiple false alarms per patient-day; we identified several clinical variables contributing to false alarms.

Conclusions:
When applied purely quantitatively, published EEG trend analysis methods result in unacceptably high false alarm rates. Neurophysiologist integration of quantitative and raw EEG data modestly improves the predictive value of EEG ischemic signs and affords relatively high sensitivity. Better understanding of specific EEG signatures of confounding variables, and real-time integration of parallel clinical data are required for more accurate EEG DCI detection in clinical practice.
Abstract WMP12: Final Infarct Volume Is A Stronger Predictor Of Outcome Than Recanalization In Patients With Proximal Middle Cerebral Artery Occlusion Treated With Endovascular Therapy
Authors: Jovin Tudor , Zaidi Syed , Aghaebrahim Amin , Urra Xavier , Jumaa Mohammad , Jankowitz Brian , Hammer Maxim , Nogueira Raul , Horowitz Michael , Reddy Vivek , Jadhav Ashutosh P
Published: March 2022

Background and Purpose:
The rationale for recanalization therapy in acute ischemic stroke (AIS) is to preserve brain through penumbral salvage and thus improve clinical outcomes. We sought to determine relationship between recanalization, clinical outcomes, and final infarct volumes in AIS patients presenting with middle cerebral artery (MCA) occlusion who underwent endovascular therapy and post procedure Magnetic Resonance Imaging (MRI).

Methods:
We identified 201 patients with MCA occlusion. Patients with other occlusive lesions were excluded. Baseline clinical/radiological characteristics, procedural outcomes (including Thrombolysis in Myocardial Infarction -TIMI scores), clinical outcome scores (modified Rankin scores - mRS), and final infarct volumes on Diffusion Weighted Imaging (DWI) were retrospectively analyzed from a prospectively collected database. Favorable outcome is defined as 90-day mRS≤2.

Results:
Successful recanalization (TIMI grade 2/3) was achieved in 83% and favorable outcomes in 46% of cases. Mean infarct volume was 69.5 ml in recanalized vs. 129.6 ml in non-recanalized patients (p<0.01) and 40.4 ml in patients with favorable outcomes vs. 111.8 ml in patients with unfavorable outcomes (p<0.01). In multivariate analysis TIMI ≥ 2, baseline NIHSS, ASPECTS scores and age were identified as independent predictors of outcome. However, when infarct volumes were included in analysis only final infarct volume and age remained significantly associated.

Conclusions:
Successful recanalization leads to improved functional outcomes through a reduction in final infarct volumes. In our series, age and final infarct volume but not recanalization was found to be independent predictors of outcome, supporting the use of final infarct volume as surrogate marker of outcome in acute stroke trials.
Abstract WMP15: Hemispheric Asymmetry of Frontoparietal Control Network in Acute Ischemic Stroke Correlates with Stroke Severity
Authors: Alcauter Sarael , Gao Wei , An Hongyu , Ford Andria L , Powers William , Lee Jin-Moo , Lin Weili
Published: March 2022

Introduction:
Recent resting-state fMRI (rsfMRI) studies revealed a frontoparietal control (FPC) network specialized in cognitive control and decision-making. In this study, we hypothesize that acute hemispheric asymmetry of functional connectivity within the FPC network predicts clinical severity and long-term functional outcome.

Methods:
RsMRI was performed in nine ischemic stroke patients (mean age: 75.33 ± 7.6 y; 6 male; 7 MCA, 2 ACA affection) within 3 hrs after onset. NIH Stroke Scale was obtained at admission, 24 hours and 72 hours after symptom onset. Modified Rankin Scale (mRS) was obtained 1 month after onset. FPC network was defined using a seed-based approach (ipsilesional hemisphere seed) and thresholded at the 95th percentile. FPC asymmetry index was defined as the absolute difference of the proportion of voxels within the network between the two hemispheres. Linear partial correlations were calculated between FPC asymmetry index and clinical scores controlling for NIHSS at admission (significance: P < 0.05).

Results:
Asymmetry index of the FPC network showed a significant positive correlation with NIHSS at 24 hours (R2=0.5113, P=0.0462), 72 hours (R2=0.5406, P=0.0376) and marginally significant correlation with MRS at 1 month (R2=0.2799, P=0.1775).

Conclusions:
Significant correlations between FPC asymmetry index and subsequent clinical assessments suggest that the integrity of FPC network during acute ischemia may impact stroke recovery. Acute functional connectivity measurements pertaining to the high order, FPC network, may have potential for early prediction of outcomes in acute ischemic stroke.
Abstract WMP19: Are “Drip and Ship” Patients Different than Other rt-PA Treated Patients? Clinical Characteristics and Patient Outcomes.
Authors: Kleindorfer Dawn , Smith Eric E , Fonarow Gregg C , Grau-Sepulveda Maria M , Olson DaiWai M , Hernandez Adrian F , Peterson Eric D , Schwamm Lee
Published: March 2022

Introduction:
Many large stroke centers provide remote acute stroke consultation to partner hospitals via telephone or video, followed by transfer of the patient to the central hospital (“drip and ship” (DS)). We used data from a large, quality-oriented database to describe the characteristics and outcomes of drip and ship patients compared to patients that received rt-PA and were admitted at the same institution (“front door” (FD) cases).

Methods:
We analyzed acute ischemic stroke cases treated with rt-PA in Get With The Guidelines-Stroke (GWTG-Stroke) between April 2003 and October, 2010. Data were included from fully participating GWTG-Stroke hospitals with discharge information available. Categorical data were analyzed by Pearson chi-square test and continuous data by Wilcoxon test.

Results:
A total of 44,667 rt-PA treated ischemic stroke pts from 1440 hospitals were included in this analysis, of which 34,192 were front door cases, and 10,475 were drip and ship. DS cases were slightly younger (69yo vs. 72yo), and were more likely male (46% vs. 50%), white (81% vs. 75%), and had lower NIHSSS (11 vs. 12), p<0.001 for all comparisons. The DS patients were statistically less likely to report hypertension, atrial fibrillation, and prior stroke history, but absolute differences were small (see Table). In-hospital mortality was similar for DS vs. FD (10.9% vs. 9.6%), as was the symptomatic intracranial hemorrhage rate <36hrs (5.8% vs. 5.2%), and discharge to home (41% vs. 40%).

Discussion:
Within the GWTG-Stroke database, 23% of rt-PA-treated ischemic stroke are “drip and ship” patients, and have similar demographics and co-morbidities to “front-door” treated patients. Clinical outcomes, including in-hospital mortality and symptomatic hemorrhage are also similar. These data demonstrate that the current national paradigm of remote consultation for acute ischemic stroke thrombolysis is as safe as in-person consultation.
Abstract WMP34: Endogenous Plasminogen is Essential for Motor Functional Recovery and Axonal Remodeling after Stroke in Mice
Authors: liu zhongwu , Li Yi , Zhang Ruilan , Cui Yisheng , Shang Xia , Chopp Michael
Published: March 2022

Other than hepatic derived plasminogen (Plg) in the circulation system for intravascular thrombolysis, Plg is also synthesized in neuroendocrine tissues, and may play a role in neuritogenesis and axonal outgrowth. To demonstrate the contribution of Plg to neurological recovery after stroke, we examined functional recovery and axonal remodeling between wild type (WT) and plasminogen knockout (Plg
-/-
) mice. In the 1
st
experiment, adult male WT and Plg
-/-
mice (n=10/group) were subjected to permanent right middle cerebral artery occlusion (MCAo). A single pellet reaching test and a foot fault test were performed before and on day 3 after stroke and weekly thereafter. Biotinylated dextran amine (BDA) was injected into the left motor cortex to anterogradely label the corticorubral tract (CRT) and corticospinal tract (CST). Mice were euthanized 4 weeks after stroke. In the 2
nd
experiment, Western blot was employed to examine expression level of neurotrophins and inhibitory proteins in the brain and spinal cord in WT and Plg
-/-
mice euthanized at day 0, 3, 7 and 14 after MCAo, respectively (n=5/group). There was no significant difference in volume of cerebral infarction between groups. In WT mice, the motor function deficits after stroke progressively recovered with time. In contrast, the motor recovery post stroke in Plg
-/-
mice was significantly impaired compared to WT mice (p<0.01). BDA-positive axonal density of both CRT and CST in the denervated side of the red nucleus and cervical gray matter originating from the contralesional cortex were significantly reduced in Plg
-/-
mice compared with WT mice (p<0.05). In WT mice, Western blot analysis showed that expression level of growth cone filamentous actin in the ischemic brain and spinal cord, and nerve growth factor (NGF) in the bilateral cerebral hemispheres and the spinal cord were increased 7-14 days after stroke, and myelin-associated glycoprotein in the brain and neurocan in the spinal cord increased 3 days after stroke and then returned to normal levels. However, the up-regulation of NGF and clearance of the inhibitory molecules were impaired in Plg
-/-
mice (p<0.05). Our data suggest that plasminogen promotes neurological recovery after stroke by, at least in part, stimulating axonal remodeling in the CNS.
Abstract WMP4: THRACE: Randomized Trial and Cost Effectiveness Evaluation on Thrombectomy in Acute Ischemic Stroke
Authors: bracard serge , ducrocq xavier , guillemin francis , hosseini kossar ,   THRACE investigators
Published: March 2022

THRACE is a controlled, multicenter (31 hospital centres in France) and randomized parallel group study, with a cost-effectiveness analysis.

Objectives:
The primary objective is to determine whether a combined approach intravenous (IV) thrombolysis and mechanical thrombectomy, is superior to the reference treatment with IV thrombolysis alone. The second objective is to determine the cost-effectiveness of this new procedure compared to the standard.

Methods:
All patients aged between 18 and 80 years with an acute ischemic stroke occurred within 4 hours are eligible for the study. Inclusion criteria are an occlusion of the intracranial carotid artery, the M1 portion of the middle cerebral artery or the upper third of the basilar and with a NIHSS score between 10 and 25. All the patients are treated with the reference IV treatment (0,9 mg/kg of rTpa). In the thrombectomy arm, thrombectomy is performed at the end of IV perfusion, with one of the thrombectomy device available. The modified Rankin Score at 3 month after treatment is the primary outcome. Secondary outcomes are the Barthel score at 3 month and the Quality of Life with Euroqol EQ-5D generic questionnaire at 3 and 12 months after treatment. The sample size was estimated at 480 patients. 200 are already included and the intermediate analysis is planned in the end of 2012.
Grant: French Ministry of Health. STIC program 2009
Abstract WMP68: Loss Of Programmed Cell Death Ligand 1 And 2 Reduces Total Infarct Volume In Male Mice Following Experimental Stroke
Authors: Chen Yingxin , Bodhankar Sheetal , Offner Halina , Alkayed Nabil J , Murphy Stephanie J
Published: March 2022

The programmed cell death 1 receptor (PD-1) is an immunoglobulin superfamily member whose expression is induced in activated T cells, B cells, natural killer cells and monocytes. Binding of PD-1 to either of its two known ligands, programmed cell death ligand 1 and 2 (PD-L1 and PD-L2), induces inhibitory signals that regulate peripheral T cell tolerance and immune homeostasis. We have shown increased PD-1 expression in brain macrophages and glia as well as increased PD-L1 and PD-L2 expression in peripheral and brain B cells in mice after experimental stroke. Furthermore, we have observed increased infarct volume in PD-1 deficient mice, thus potentially implicating the PD-1/PD-L co-inhibitory pathway in post-stroke CNS inflammation. Using PD-L1 and PD-L2

deficient mice, we determined if PD-L1 or PD-L2 was also important in modulating stroke infarct volume. Young adult male wild-type (WT; n=11) and PD-L1 (n=9) and PD-L2 (n=12) knockout (KO) mice underwent 60 min of middle cerebral artery occlusion via intraluminal filament. Laser-Doppler flowmetry was used to monitor cortical perfusion. All mice were euthanized and brains collected at 96 h of reperfusion. Total infarct volume (% corrected contralateral hemisphere) was determined by image analysis of coronal brain slices stained with 2,3,5-triphenyltetrazolium chloride (TTC). Relative laser Doppler flowmetry changes (% baseline) during and after middle cerebral artery occlusion were equivalent among groups. Compared to male WT mice (WT vs. KO), genetic deletion of either PD-L1 (51+3% vs. 20+5%; p<0.001) or PD-L2 (51+3% vs. 35+4%; p=0.007) reduced total infarct volume. We also observed that total infarct volume was smaller in PD-L1 vs. PD-L2 KO mice (20+5% vs. 35+4%; p=0.017). Our findings along with our previous work in PD-1 deficient mice suggest that ligands other than PD-L1 or PD-L2 might be involved with PD-1 signaling in ischemic brain and that PD-L1 and PD-L2 might have other functions independent of PD-1 binding affecting infarct volumes. Future studies will evaluate the roles of PD-1, PD-L1, and PD-L2 in regulatory immune cell subsets that affect ischemic brain outcomes. This study was supported by National Institutes of Health grant NS075887.
Abstract WMP69: Monocyte-derived Macrophages Can Reduce Damage After Experimental Ischemic Stroke
Authors: Nishiyama Yasuhiro , Arac Ahmet , Bliss Tonya M , Steinberg Gary K
Published: March 2022

Background
Post-ischemic inflammation plays an important role in stroke pathology. Understanding the details and mechanisms of post-stroke inflammation is essential to develop therapeutics that can reduce the damage and promote recovery. Macrophages are known to promote both injury and repair in various pathologies, and these divergent properties may be due to different macrophage subtypes. Here, we identify different macrophage subtypes in the brain after ischemic stroke and investigate their effects on stroke outcome.

Methods
C57BL/6 mice (male, 11-14 weeks old) were subjected to left transient middle cerebral artery occlusion (tMCAo). To deplete blood monocytes, clodronate-filled liposomes (CL) were used. Phosphate-buffered saline (PBS)-filled liposomes (PL) served as controls. Behavior was assessed using a neurological score. Infarct size was assessed by TTC at 2d and silver staining at 7d post-stroke. Immune cells in brain, blood, spleen and bone marrow were analyzed by flow cytometry.

Results
A time-course analysis of immune cells after stroke identified two macrophage subpopulations in the brain: Ly6Chigh and Ly6Clow. Ly6Chigh macrophages were the dominant cell population early after stroke, peaking by 3d and then decreasing in number by 5d. Conversely, the number of Ly6Clow macrophages were initially low and peaked at 5d. To investigate the effects of these macrophage subpopulations, we used clodronate depletion of monocytes with different injection paradigms. Injecting clodronate just after reperfusion, to target the Ly6Chigh macrophages, had no significant effect on infarct size at 2d and 7d post-stroke, or on functional deficit, compared to the PL group. However, when the injections were given every other day after stroke, from day 0 to day 6, CL-treated mice had significantly larger infarct sizes at 7d post-stroke (48.9±4.3 vs 35.6±5.8, % of contralateral hemisphere, n=10; p<0.01), and worse neurological scores (11.1±1.1 vs 6.2±1.1, n=10; p<0.01) than PL-treated mice. Moreover, the CL group had fewer brain macrophages at 5d. Temporal analysis of the macrophage subpopulations with this treatment paradigm is ongoing.

Conclusion
Macrophage can reduce brain damage and play a role in promoting recovery after stroke.
Abstract WMP74: Plasma Interleukin-6 Values Are Associated With Neurological Severity In Ischemic Stroke
Authors: Kuwashiro Takahiro , Ago Tetsuro , Kamouchi Masahiro , Matsuo Ryu , Kuroda Junya , Isomura Tetsu , Awano Hideto , Suzuki Kazuo , Sugimori Hiroshi , Kiyohara Yutaka , Kitazono Takanari
Published: March 2022

Introduction:
Interleukin-6 (IL-6) is a representative pro-inflammatory cytokine produced by various cells; however, it also plays multi-functional roles besides the immune function. Although several studies have shown that IL-6 levels are increased after stroke, its significance in stroke remains still controversial. We aimed to examine the temporal profile of plasma IL-6 after stroke and to investigate its significance in neurological severity. We tested the hypothesis that plasma IL-6 is associated with neurological severity in ischemic stroke patients.

Methods:
We prospectively enrolled 171 patients with ischemic stroke and age- and gender-matched healthy controls. Blood samples and clinical information were obtained at five time points (days 0, 3, 7, 14 and 90) after stroke onset.

Results:
Average IL-6 values at day 0 were significantly higher in the stroke patients than in the controls (6.3 ± 1.5 pg/mL vs. 1.2 ± 0.1 pg/mL, p = 0.0005). In the patients, IL-6 values at day 0 was positively associated with neurological severity as evaluated by National Institute of Health Stroke Scale (NIHSS) (r = 1.3292, p < 0.0001). When the patients were divided into 4 groups (Q1, Q2, Q3 and Q4 from milder to severer group) according to the interquartile range of the NIHSS on admission, Q1 (3.0 ± 1.1 pg/mL, p = 0.0075), Q2 (2.4 ± 0.6 pg/mL, p = 0.0033), Q3 (3.2 ± 0.7 pg/mL, p < 0.0001) and Q4 (17.9 ± 5.7 pg/mL, p < 0.0001) groups had significantly higher IL-6 values than the controls. IL-6 values reached the maximum at the day 3 after stroke and decreased subsequently, although they were significantly higher than those of the controls at all the 5 points (Figure). IL-6 values were significantly higher (11.0 ± 3.1 pg/mL vs. 2.7 ± 0.7 pg/mL, p = 0.0065) in the poor outcome group (modified Rankin Scale (mRS) ≥ 2 at 90 day) than the good outcome group (mRS ≤ 1).

Conclusions:
Plasma IL-6 is increased with the maximum at day 3 after ischemic stroke and is associated with neurological severity.
Abstract WMP75: Is Glycemic Control With Sliding Scale Insulin Therapy Safe For Diabetic Patients With Acute Ischemic Stroke?
Authors: Shimomura Ryo , Arihiro Shoji , Koga Masatoshi , Matsushima Hayato , Ishigami Akiko , Minematsu Kazuo , Toyoda Kazunori
Published: March 2022

Backgroundand Purpose:
There is no established glycemic control for acute ischemic stroke. Patients’ outcomes may be deteriorated by strict glycemic control with sliding-scale insulin therapy (SSIT) via hypoglycemia. We aimed to investigate baseline characteristics, frequency of hypoglycemia and outcome in diabetic patients who received SSIT in acute ischemic stroke.

Methods:
Consecutive ischemic stroke patients with diabetes mellitus (DM) admitted to our hospital within 7 days of onset from 2008 through 2010 were studied. DM was defined as having prior diabetic medications, fasting plasma glucose (PG) of 126mg/dl, 2-h PG of ≥200 mg/dl during a 75g OGTT, random PG of ≥200 mg/dl, or HbA1c (NGSP) of ≥6.5%. Physicians in charge decided whether the patient was treated with sliding scale insulin therapy (SSIT) at admission. Hypoglycemia was defined as having PG of ≤80 mg/dl during hospitalization. Favorable outcome was defined as mRS 0-1 at 3 months.

Results:
Of a total 258 ischemic stroke patients with DM (193 men, 72 ± 10 yo), 130 (96 men, 71±10 yo) received SSIT (SSIT group) and the remaining 128 (97 men, 73±9 yo) did not (N group). Patients in the SSIT group more frequently took prior diabetic medication (72% vs 53%, p=0.001), had higher initial PG (199±85 mg/dl vs 156±78 mg/dl, p<0.001), higher HbA1c (7.8±1.9% vs 6.8±1.2%, p<0.001) and higher initial NIHSS [median 4 (IQR 2-7) vs. 3 (IQR 1-5), p=0.028] than those in the N group. Hypoglycemia tended to be more common (15% vs 7%, p=0.050) and favorable outcome tended to be less common (43% vs 54%, p=0.081) in the SSIT group than in the N group. In the SSIT group, 19 patients showing hypoglycemia were older (76±8 years vs 71±10 years, p=0.031), more frequently took prior diabetic medication (95% vs 68%, p=0.015), and had lower admission levels of PG (163±68 mg/dl vs 206±86 mg/dl, p=0.040) and HbA1c (6.9±1.3% vs 7.9±2.0%, p=0.035) than those in the remaining 111 patients without hypoglycemia.

Conclusions:
Acute ischemic stroke patients with prior diabetic medication, poor glycemic control before onset and severer stroke symptom often received SSIT. Hypoglycemia was found in one seventh of patients treated with SSIT. We have to be careful especially when aged patients or diabetic medication users receive SSIT.
Abstract WMP87: Effectiveness of Mirror Therapy in Stroke Patients with Unilateral Neglect- A Randomized Controlled Trial
Authors: Arora Rajni , Kaur Paramdeep , K.V. Dheeraj , Mathangi Santhosh , Sharma Deepika , Pandian Jeyaraj
Published: March 2022

Specific Aims:
To study the effectiveness of mirror therapy and limb activation vs limb activation alone in the treatment of stroke patients with unilateral neglect.

Significance:
Hemi spatial neglect is a major disability after stroke. There are no effective therapies available so far. This study is a randomized controlled trial and has been carried out since January 2011 in Stroke Unit & College of Physiotherapy, Christian Medical College & Hospital. All stroke patients with thalamic and parietal lobe lesions and unilateral neglect after 48 hours of stroke were included in the study.

Approach:
Patients were randomized to treatment and control groups. Treatment group was given mirror therapy with limb activation and the control group received only limb activation. The treatment sessions were 1-2 hours/day for 5 days/week, for 4 weeks period. Unilateral neglect and outcome measures were assessed using picture identification task, star cancellation & line bisection tests, Catherine Bergego scale & Functional Independence Measure (FIM). The outcome was documented by a blinded assessor at 6 months. Fishers exact test & independent t-test was used (SPSS version 16.0) for statistical analysis. The mean difference in baseline scores & at follow-up was compared between the two groups.

Innovation:
Twenty five patients were enrolled; analysis was confined to 23 patients (14 in treatment group & 9 in control group; 2 patients died). The treatment group performed better in the picture identification task (treatment group: mean difference 4.9 confidence interval (CI): 3.9-5.8) vs control group (2.1, CI: 1.4-2.8; p<0.001). The mean change in the star cancellation score in the treatment group was 31.5 (CI: 24.4-38.6) vs control group 14.3 (CI: 7.7-20.9); p=0.001. The mean change in line bisection test was 11.0 (CI: 9.0-13.1) in the treatment group vs 6.7 (CI: 4.3-9.2); p=0.008 in the control group. The proportion of patients with no neglect in Catherine Bergego scale in the treatment group was 12 (85.7%) vs 0 (0%); p=<0.001 in the control group. Three patients (21.4%) were independent in FIM in the treatment group vs. 0 (0%); p=0.25 in the control group. Mirror therapy with limb activation is effective in improving unilateral neglect in stroke patients in this ongoing trial.
Abstract WP101: Localization of Stereotactic Injections of Human iNP cells One Week Post-MCAL Stroke is Critical in Reducing Stroke Lesion Injury
Authors: Zhu Andy , Ma Jun , Grace Harrison , Stice Steven L , West Franklin D , Hoda Md N , Kondrikova Galina , Periyasamy-Thandavan Sudharsan , Johnson Maribeth H , Hess Mathew , Carroll James E , Hill William D , Hess David C
Published: March 2022

There is interest in therapeutic approaches to improve stroke injuries beyond the current 4.5 hour window of opportunity available for tPA treatment. We are interested in determining if neural progenitor cells can provide protection one week out from a stroke injury, and if the location of the cells relative to the core or penumbra of the injury site is important.

Methods:
We used a unilateral permanent middle cerebral artery ligation (MCAL) stroke injury model in C57B6 mice (male 3 months old) that generates a modest cortical lesion with limited subcortical injury. A single 3 ul Stereotactic injection was made either in the stroke core, or outside the injury site penumbra under the ipsilateral hippocampus. We injected 100,000 neural progenitor cells (iNPs) differentiated from induced pluripotent stem cells derived from human fibroblasts. Previous work showed that injection in a matrix enhanced iNP survival, therefore, the cells were injected either in a hydrogel matrix (n=4) or in matrigel (n=5) one week post-MCAL. Hydrogel (n=5) and Matrigel (n=4) only control groups were also used. Mice were sacrificed three weeks post-MCAL (two weeks post-transplant) and evaluated for lesion size as a percent of cortex.

Results:
Mice that received stem cells placed into the core of the lesion, regardless of the specific matrix, had significantly smaller cortical lesions (p=0.0021) than those who did not receive stem cells (hydrogel alone control 36.0% mean cortical lesion (10.7% SD); Hydrogel + iNP cells 15.6% (3.1%); Matrigel alone control 30.4% (10.0%), matrigel + iNP cells 19.4% (8.6%). There was no difference between the controls: saline only, matrigel only, or hydrogel only. Using the same approach a second set of mice received 100,000 iNP cells outside of the lesion site, below the ipsilateral hippocampus (matrigel + iNPs (n=9), matrigel alone (n=9), or saline (n=8). In contrast there was no reduction in lesion size.

Conclusion:
This suggests that iNPs in the region of greatest injury can provide protection even one week following stroke, but that these effects are spatially limited. Future studies will focus on aged male and female populations.
Abstract WP120: Granuloctye-Colony Stimulating Factor in Ischemic Stroke Trial (GIST): A Pilot Study
Authors: Sharma Michael , Gladstone David , Black Sandra , Blacquiere Dylan , Hogan Matthew , Stotts Grant , Walker Lisa , Atkins Harry
Published: March 2022

Introduction:
Granulocyte-colony stimulating factor (G-CSF) is upregulated in models of cerebral ischemia. This may promote hematopoietic stem cell (HSC) mediated central nervous system repair. We hypothesize that exogenous G-CSF may promote recovery after acute ischemic stroke. We examined the safety and feasibility of this therapy with a double-blind, randomized pilot study of G-CSF in patients with acute stroke.

Methods:
Patients with ischemic stroke and motor deficits greater than 2 on the National Institutes of Health Stroke Scale (NIHSS) were randomized to receive a four-day course of G-CSF (10 μg/kg sc) or matching placebo within ten days of stroke occurrence, followed by a second cycle after six weeks. Primary outcomes were safety measures including recurrent stroke, mortality, toxicity as measured by the NCI Common Toxicity Scale, and worsening of disability as measured by modified Rankin Scale (mRS), Barthel index, NIHSS and Glasgow Outcome Scale (GOS). Testing occurred at 1.5, 3, 6 and 12 months after treatment. MRI, CT perfusion and functional MRI were obtained at 3 months with repeat MRI scan at 12 months, and neuropsychological testing was conducted at 6 and 12 months.
Results:
Nine patients were randomized; mean pre-treatment NIH Stroke Scale was 8.8. Elevation of circulating leukocytes and CD34+ cells were observed after G-CSF administration compared to placebo. Adverse events including diarrhea, dehydration, bone pain, and asymptomatic leukocytosis were seen more frequently in the G-CSF treated cohort, but there were no recurrent strokes or deaths in either group. Disability did not worsen in any patients, with no significant change in median mRS, NIHSS, GOS or Barthel index between groups at 1.5, 3, 6 or 12 months after treatment. No significant changes in neuropsychological testing or imaging parameters were observed.

Conclusions:
G-CSF administration in ischemic stroke patients appears to be safe and feasible, with no increase in mortality or worsening of disability observed in this pilot study. Larger randomized trials would be needed to determine efficacy of this potential novel therapy for stroke recovery.
Abstract WP128: Blood Sampling Oxygen Extraction Fraction As Predictors Of Hyperperfusion Phenomenon Following Carotid Artery Stenting
Authors: Iwata Tomonori , Mori Takahisa , Miyazaki Yuichi , Nakazaki Masahito , Takahashi Yoichiro , Mizokami Koji
Published: March 2022

Backgrounds and Purpose:
Hyperperfusion syndrome following carotid artery stenting (CAS) may occur in patients suffering from stage 2 hemodynamic failure, where oxygen extraction fraction is elevated. The purpose of our retrospective study was to investigate whether or not blood sampling OEF has some relation to hyperperfusion phenomenon (HP) following CAS.

Materials and Methods:
Included for analysis were patients (1) who were admitted to our institution from 2010 to 2012, (2) who underwent elective CAS and (3) who underwent blood sampling for OEF calculation and single-photon emission computed tomography (SPECT) before and immediately after CAS. Oxygen extraction fraction (OEF) was calculated from arteriovenous oxygen difference as follows: OEF = (Ca02-Cv02) / Ca02 where Ca02 is arterial oxygen content and CvO2 is the jugular vein oxygen content. Cerebral blood flow (CBF) was measured in bilateral middle cerebral artery (MCA) territory and in the affected side cerebellar hemisphere by SPECT. Asymmetry index (AI) was defined as CBF in the affected side / CBF in the unaffected side, and MCA-to-cerebellar activity ratio as the CBF in the affected side / the CBF in the ipsilateral cerebellar hemisphere. HP was defined as 10% or more of increase in MCA-to-cerebellar activity ratio following CAS.

Results:
During the study period, 90 patients matched our criteria for retrospective analysis and 21 patients presented post-CAS HP. Procedures were successful in every case. There was no relation of pre-CAS OEF to asymmetry index and MCA-to-cerebellar activity ratio. There was no relation of post-CAS OEF to asymmetry index, but post-CAS OEF had relation to MCA-to-cerebellar activity ratio (r=0.26, p<0.05). Patients’ features were compared between HP and non_HP groups. Although there were no significant differences in pre-CAS OEF between two groups, patients in HP group had higher post-CAS OEF (0.46 vs 0.41, p<0.01). Cut-off value of post-CAS OEF was 0.45 or more, which yielded 57% of sensitivity and 81% of specificity for post-CAS HP (p<0.01).

Conclusion:
Elevation of blood sampling OEF immediately after CAS is related to post-CAS HP.