bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W MP117: Quantitative Susceptibility Mapping Reveals Iron Distribution in a Murine CCM Model
Authors: Tan Huan , Shi Changbin , Liu Tian , Edelman Robert , Awad Issam
Published: March 2022

Cerebral cavernous malformations (CCM) are associated with vascular leak and hemorrhage, characterized by the iron-rich hemoglobin breakdown products. Quantitative susceptibility mapping (QSM) is a new noninvasive MRI technique that has demonstrated high sensitivity to evaluate CCM lesion burden. However, accuracy of QSM to depict the iron distribution within individual CCM lesions remains unknown. In this study, we compared lesional iron distribution measured by QSM with histological iron staining in a murine CCM3 model.

Methods:
Two

Ccm3
+/–
Trp53
–/–

mouse brains were scanned on a 3T scanner using a dedicated mouse coil. Serial 1-mm-thick coronal slices of each brain were microsectioned at 5 μm and performed by Perls’ staining for iron deposition. QSM images were reformatted to obtain the same coronal slices prior to comparison. Regions of interest (ROIs) identified iron“patches” on histology (Perls’ blue staining) and QSM images (with a threshold of 1.0 ppm). Cross comparisons were performed to determine the sensitivity and specificity of QSM.

Results:
Local susceptibility distribution by QSM correlated well with the iron deposition in tissue based on qualitative comparison, as shown in the Figure below. QSM achieved a sensitivity of 0.8 (p < 0.01) and specificity of 0.94 (p < 0.01).

Conclusions:
QSM accurately detects the distribution of iron depositions within CCMs.
Abstract W MP26: Intracranial Pressure Waveforms Indicate Vasodilation During Remote Ischemic Conditioning
Authors: Hamilton Robert , Connolly Mark , Hu Xiao , Gonzalez Nestor R
Published: March 2022

Introduction:
Remote ischemic conditioning is a powerful phenomenon where brief periods of ischemia and reperfusion in a tissue such as the leg or arm can confer protective benefits from ischemic injury to distant tissues. Our previous work using intracranial pressure (ICP) waveform analysis has identified trends in the waveform shape that suggest transient cerebral vasodilation occurs as an effect of the procedure. We present a more rigorous analysis using data prospectively collected as part of our phase I clinical trial of RIC for aneurysmal subarachnoid hemorrhage (aSAH).

Methods:
During the RIC procedure ICP was measured using intraventricular monitors simultaneously recorded with ECG (Fs = 400 Hz). ICP analysis was performed using the Morphological Clustering and Analysis of Intracranial Pulse (MOCAIP) algorithm which extracts 128 metrics from the ICP pulse-waveform (Figure 1A). Previous studies in patients undergoing CO2 inhalation identified a template of 72 metrics that consistently increase or decrease during vasodilation of the cerebral vasculature. The proportion of metrics that match this template (VDI) was found for each session and compared with VDIs from a control set of normal pressure hydrocephalus (NPH) patients using a Mann-Whitney test.

Results:
Fifteen aSAH patients had ICP monitored during 29 RIC sessions of approximately 40 minutes. ICP segments of the same length were collected for 8 NPH patients. The median VDI was significantly higher in the RIC patients (0.79, 0.42, p<0.01) (Figure 1B)

Conclusion:
Pulse-waveform changes observed during the RIC procedures indicate vasodilation when compared to control patients. Intracranial pressure waveform analysis is a useful tool to detect real time changes in the state of the cerebrospinal circulatory system, providing additional insight into the mechanism and effects of RIC.
Abstract W MP28: Early Elevation of Plasma Soluble Fms-Like Tyrosine Kinase-1 is Associated With Poor Functional Outcome After Subarachnoid Hemorrhage
Authors: Chou Sherry H , Feske Steven K , Suh Sarah , Lieu Kristina , Du Rose , Henderson Galen V , Sorond Farzaneh A , Lo Eng H , Ning MingMing
Published: March 2022

Background:
Vasospasm (VSP) and brain injury following subarachnoid hemorrhage (SAH) are associated with tissue hypoxia and vascular endothelial growth factor (VEGF) release. Soluble Fms-like tyrosine kinase-1 (sFlt-1), a truncated soluble form of VEGF receptor-1, is an endogenous VEGF inhibitor released in response to hypoxia and nitric oxide deficiency. SFlt-1 is anti-angiogenic and mediates endothelial dysfunction. We hypothesize sFlt-1 elevation may be associated with VSP and poor SAH outcome.

Methods:
We prospectively enrolled consecutive SAH subjects, banked serial blood samples, and evaluated their modified Rankin scores (mRS) at 3 month intervals. Poor functional outcome was defined as mRS>2. Angiographic VSP was defined as >50% reduction in caliber of any vessel on post-SAH day 7 cerebral angiogram. In 63 SAH subjects, we compared plasma sFlt-1 by ELISA on post-SAH days 3 and 5 by VSP and outcome status using Wilcoxon rank sum or Student’s t-test depending on data distribution. Bonferroni correction was used for multiple comparisons. Logistic regression was used to adjust for confounders. Associations were measured using Pearson’s or Spearman’s correlation depending on data distribution.

Results:
Twenty-seven subjects (43%) had poor 3-month outcome and 31 (49%) developed VSP. Elevated sFlt-1 level on post-SAH day 3 was associated with poor 3-month outcome (p=0.02) while post-SAH day 5 sFlt-1 level showed no association. SFlt-1 levels were not associated with Hunt and Hess (HH) or Fisher grades or with VSP. SFlt-1 was inversely correlated to VEGF (p=0.04, r=0.26). Post-SAH day 3 sFlt-1 level was independently associated with poor SAH outcome after adjustment for HH grade, age, and VEGF level (p=0.03). VEGF was not associated with VSP or SAH outcome.

Conclusion:
Early elevation of plasma sFlt-1 on post-SAH day 3 is independently associated with poor 3-month SAH outcome after adjustment for clinical predictors of SAH outcome and for VEGF. Inverse correlation suggests possible negative feedback control between sFlt-1 and VEGF in SAH. Future studies are necessary to determine the source of sFlt-1 in SAH and its role in SAH-associated brain injury. Replication in a larger cohort is necessary to validate sFlt-1 as a potential biomarker for SAH outcome.
Abstract W MP34: Safety and Efficacy of Hydrosoft Coils in the Treatment of the Aneurysm Neck: Preliminary Results From the GEL THE NEC Registry
Authors: Brinjikji Waleed , Connelly Beth B , Tubman David , Hoh Brian , Jensen Mary E , Kelly Michael , Jabbour Pascal , Chaudry Imran M , Hui Ferdinand , Kallmes David F
Published: March 2022

Background and Purpose:
The HydroSoft coil was developed to be placed along the aneurysm neck to enhance intracranial aneurysm healing. In order to better understand the safety and efficacy of Hydrosoft coils in treating the aneurysm neck, the GEL THE NEC multicenter registry was developed. We report immediate angiographic and clinical results of this prospective registry.

Methods:
The GEL THE NEC study was undertaken at 30 centers in 5 countries. Patients aged 21-90 years with a ruptured or unruptured aneurysm 3-15 mm in size were eligible for enrollment. For each patient the following data were obtained: demographics and comorbidities, aneurysm geometry, use of adjunctive devices, immediate angiographic outcomes, and early (<30 days) adverse events. Postoperative anatomic results were graded by on-site neuroradiologists using the Modified Raymond Scale (Raymond 1=complete obliteration of aneurysm including the neck, Raymond 2=contrast filling the neck of the aneurysm without opacification of the aneurysm sac, Raymond 3=contrast filling the sac of the aneurysm). Predictors of good angiographic outcome were studied using chi-squared and t-tests.

Results:
A total of 571 patients with 571 aneurysms have been treated thus far in the study (196 ruptured, 375 unruptured). HydroSoft coils were successfully deployed in 549 (96.3%) of these patients. Adjunctive devices were used in 307 cases (53.8%) (212 balloon assistance, 89 stent). Aneurysmal occlusion rates were the following: 261 patients (47.3%) exhibited Raymond 1 occlusion, 257 patients (47.0%) had Raymond 2, and 29 patients (5.3%) had Raymond 3. Early post-operative stroke occurred in 10 patients (1.8%). Aneurysm perforation occurred in 11 patients (1.9%). Coil prolapse/migration occurred in 8 patients (1.4%). Early post-operative death occurred in 3 patients, all of whom presented with SAH (0.5%). Small aneurysm neck size was a significant predictor of good angiographic outcome (P=0.0003).

Conclusions:
Endovascular treatment of intracranial aneurysms with HydroSoft coils resulted in high rates of satisfactory occlusion (94.3%) and low rates of major clinical complications. Aneurysm neck size was a significant predictor of angiographic outcomes.
Abstract W MP50: Risk Prediction of Incident Acute Ischemic Stroke (AIS): Pooled Data Analysis of Cohort Studies
Authors: Pandey Dilip K , Gorelick Philip B
Published: March 2022

Introduction:
Risk assessment and estimation can be used to support the choice of behavioral and therapeutic interventions.

Objective:
To derive and validate a race and sex sensitive risk prediction algorithm for incident AIS.

Methods:
Risk prediction functions for incident AIS were developed and validated using ARIC, CHS, and MESA research databases obtained from the NHLBI BioLINCC. ARIC and CHS cohort members with prior stroke/TIA or cancer at baseline examination and CHS cohort members above age 84 years were excluded. A random 60% sample of the ARIC and CHS cohorts, separately, were pulled and combined to form the derivation cohort. The remaining 40% of ARIC and CHS data were pooled and used as the validation cohort. MESA was used as an external validation cohort. Subjects with missing data on established cardiovascular risk factors were excluded. Cox proportional hazards regression was used to develop best fitting prediction model in the derivation cohort. Performance of the model was assessed at 5 and 10 years. Measures of calibration and discrimination were undertaken in both validation cohorts.

Results:
The derivation cohort included 9,762 subjects (54.4% women, 23.8% blacks) with 708 cases of AIS with a median follow-up of 18.3 years. The ARIC-CHS validation cohort included 6,538 subjects (55.6% women, 22.8% blacks) with 475 AIS and a median follow-up of 18.3 years. The MESA validation cohort included 6,566 subjects (52.6% women, 27.9% blacks) with 106 AIS and a median follow-up of 7.6 years. The final risk equation demonstrated very good discrimination (concordance statistics: Harrell’s C = 0. 80, Somer’s D =.59). The accuracy of probabilistic predictions for 10-year stroke risk in the derivation cohort was 0.820 (p<.001) for ROC area, and 0.039 for Brier score; corresponding values in ARIC-CHS validation cohort were 0.807(p<.001) and 0.040. Similar measures for 5-year stroke risk in the derivation cohort were 0.828 (p<.001) for ROC area, and 0.016 for Brier score; and corresponding values in MESA validation cohort were of 0.810(p<.001) and 0.011.

Conclusion:
We have derived and validated a new race and sex sensitive prediction equation based on readily available predictors in clinical practice that quantifies absolute risk of first AIS at 5 and 10 years.
Abstract W MP51: ICD-9 Code Positive Predictive Value for Stroke Subtype in a Population-Based Epidemiology Study
Authors: Alwell Kathleen , Khoury Jane C , Kleindorfer Dawn O , Moomaw Charles J , Eilerman Jane , Woo Daniel , Flaherty Matthew , Ferioli Simona , DeLos Rios La Rosa Felipe , Martini Sharyl , Kissela Brett M
Published: March 2022

Introduction:
Population-based epidemiological studies contribute substantially to the knowledge of stroke incidence, temporal trends, stroke subtype distribution, and risk factor prevalence. Often data are gathered from ICD-9 codes in administrative databases. We instead gathered data through labor-intensive inspection of medical records to examine the positive predictive values (PPV) of stroke ICD-9 codes.

Methods:
The Greater Cincinnati/Northern Kentucky Stroke Study measures temporal trends in the incidence rates in a biracial population of 1.3 million. Discharge lists with primary and secondary ICD-9 codes 430-436 from the 15 area hospitals for 2010 were obtained. Detailed information from medical records of stroke and TIA cases was abstracted by trained research nurses and reviewed by a stroke physician, who determined if the event was a case and, if so, the stroke subtype (SAH, ICH, infarct, or TIA).

Results:
A total of 7691events were reviewed. Positive predictive values (PPV) for the primary ICD-9 codes for specific subtypes varied from 48.6% to 90.1%. All primary and secondary ICD-9 codes, stroke subtypes, and percent yield are presented in the Table. Interestingly, 293 cases were found coded under a different primary ICD-9 subtype. An additional 497 cases were found under secondary ICD-9 codes. Most events coded under 433.x0 were non-cases, as expected. Many cases coded 435 were not found to be true TIAs, and code 436 yielded very few cases.

Conclusions:
Stroke cases captured through codes 430-436 were not necessarily in the primary position or coded to the correct stroke subtype. Complete medical record review revealed varying degrees of accuracy for each code. This could cause stroke incidence rates to be significantly misreported if based solely upon primary subtype-defined ICD-9 codes. Population-based epidemiology studies generate the most reliable incidence estimates by combining stroke ICD-9 codes with medical record review.
Abstract W MP56: Left Atrial Septal Pouch as a Stroke Risk Factor: Association With Cryptogenic Stroke
Authors: Wong Jonathan , Lombardo Dawn , Wong Nathan , Fisher Mark
Published: March 2022

Background:
The left atrial septal pouch (LASP) is an anatomic variant of the interatrial septum, and its pathophysiological significance is uncertain (J Am Coll Cardiol Intv 2010;3:98-104). We examined the potential association between LASP and ischemic stroke subtypes in patients undergoing transesophageal echocardiography (TEE).

Methods:
In this cross-sectional study, we determined the prevalence of LASP (
Figure
) using a database of patients who underwent TEE at our institution between July 2008 and June 2011. Patients with ischemic strokes were evaluated by a vascular neurologist (blinded to the presence of LASP) for stroke subtyping using standard and modified TOAST (excluding ischemic stroke patients with multiple competing etiologies from the cryptogenic category) criteria. We compared the prevalence of LASP in ischemic stroke, cryptogenic stroke, and non-stroke patients.

Results:
The mean age of all 212 patients studied (including stroke and non-stroke patients) was 57 years. The overall prevalence of LASP was 17% (n=35). We studied 75 ischemic stroke patients. There were no significant differences in demographics or stroke risk factors comparing patients with or without LASP, except for hypertension (LASP 49% vs. no LASP 66% among all patients, p = 0.05). The prevalence of LASP among cryptogenic stroke (using standard and modified TOAST criteria) was increased compared to the prevalence among other ischemic stroke patients (26% vs. 9%, RR=1.8, 95% CI 1.1-3.1; and 30% vs. 9%, RR=2.3, 95% CI 1.2-4.1, respectively). There was no significant difference between LASP prevalence among all ischemic stroke patients (16%) and patients with no history of stroke or TIA (14%).

Conclusion:
In this population of relatively young patients, prevalence of LASP was increased in cryptogenic stroke compared to stroke patients of other subtypes. These findings suggest LASP may be a risk factor for stroke, which should be verified by further large-scale studies.
Abstract W MP63: Diagnostic Yield of an Extended Ambulatory Cardiac Rhythm Monitor in Patients With TIA or Stroke
Authors: Tung Christie E , Lansberg Maarten G , Turakhia Mintu P
Published: March 2022

Background:
In the evaluation of patients with TIA or stroke, the detection of AF changes the recommended anti-thrombotic regimen from treatment with an antiplatelet agent to oral anticoagulation. Detection of supraventricular tachycardia (SVT) may also be relevant as it is associated with an increased risk of AF. This study describes the feasibility and diagnostic yield of the Zio® Patch, a leadless, single-use, small, lightweight, and water-resistant cardiac rhythm monitor that provides continuous cardiac monitoring for up to 14 days.

Methods:
We obtained de-identified monitoring data from the manufacturer and servicer of the ZioPatch (iRhythm Technologies). Patients who were monitored between January 2012 and June 2013 and whose indication for monitoring, as entered by the ordering provider, was TIA or stroke were included. The duration of monitoring, the number and type of arrhythmias, and the time to first arrhythmia were documented. AF was defined as R-R irregularity for more than 30 seconds in duration.

Results:
1,171 monitoring reports were analyzed. The average patient age was 67.9 years. Fifty-five percent of patients were male. The mean monitor wear time was 10.9 days and the median wear time was 13.0 days (interquartile range 7.2-14.0). The median analyzable time relative to the total wear time was 98.7% (IQR 96.0-99.5%). AF was present in 4.8% of all reports (4.2% PAF and 0.6% chronic AF). The mean duration before the first episode of PAF was 1.5 days and the median duration was 0.4 days. 14.3% of first PAF episodes occurred after 48 hours. The mean PAF burden was 12.7% of the total monitoring duration. SVT of 8 beats or more was present in 51% of the records.

Conclusion:
Virtually the entire duration of monitoring with the ZioPatch yields analyzable data that allows for the detection of cardiac arrhythmias. Among TIA and stroke patients, AF was present in approximately 5% of the records and SVT in 50%. The first episode of PAF frequently occurred more than 48 hours after the start of monitoring. This suggests that Holter (24-48 hour) monitoring is insufficient and supports extended cardiac monitoring in TIA and stroke patients. Further studies are needed to determine which stroke patients are at greatest risk for AF and to assess the clinical significance of SVT.
Abstract W MP76: Ischemic Postconditioning Protected Against Stroke by Inhibiting NADPH Oxidase-Mediated ROS Activity
Authors: Joo Sungpil , Xie Weiying , Fan Yifang , Zhao Heng
Published: March 2022

Background:
The underlying protective mechanisms of ischemic postconditioning (IPostC) remain elusive. Although previous studies have shown that IPostC generates protection by attenuating ROS activity, how this protection is achieved is not known. We hypothesize that inhibition of NADPH oxidase-mediated reactive oxygen species (ROS) is essential for the neuroprotective effects of IPostC.

Methods:
We used both wild type mice and mice mutant for the NADPH oxidase gene. Stroke was induced by middle cerebral artery (MCA) suture occlusion and IPostC was conducted by repeated, brief occlusions immediately after reperfusion. Glucose was injected to promote NADPH oxidase, while apocynin and 2-deoxyglucose (2-DG) were used to inhibit it. FACS was used to quantify inflammatory cells in the brain, and to assess ROS activity in macrophage/microglia subsets stained by 2′-7′-dichlorodihydrofluorescein diacetate (DCFH-DA).

Results:
IPostC reduced infarction as a function of the numbers of cycles of brief MCA occlusion. Glucose injection enlarged the infarction induced by the control stroke and abolished the protective effects of IPostC. Both 2-DG and apocynin injection reduced infarction, but only apocynin, and not 2-DG, acted synergistically with IPostC against stroke. Moreover, neither IPostC nor glucose altered the infarction in NADPH oxidase gene mutated mice. FACS results suggest that glucose injection exacerbated while IPostC inhibited inflammatory cell infiltration. Furthermore, IPostC blocked ROS activity in both macrophages and microglia.

Conclusions:
IPostC attenuated infarction by inhibiting NADPH oxidase-mediated ROS activity.
Abstract W MP79: The Sex Chromosome Complement Contributes to Ischemic Stroke Sensitivity and Inflammatory Responses in Aged FCG Mice
Authors: Liu Fudong , Bentivegna Kathryn , Mirza Mehwish , Steffens Eleanor B , Xu Yan , McCullough Louise D
Published: March 2022

Introduction:
Aging is the most important non-modifiable risk factor for ischemic stroke; modeling stroke in aged animals is of clinical relevance and translational value. Stroke is a sexually dimorphic disease. Elderly women not only have higher stroke incidence than age-matched men, but also have poorer recovery, higher morbidity and mortality once a stroke occurs. Much of this has been attributed to the loss of estrogen with menopause. However, stroke incidence does not begin to climb until well after natural menopause, suggesting there are hormone independent effects on ischemic sensitivity. As hormone levels are relatively equivalent between sexes at the age post-menopausal, tissue damage and functional outcomes must be influenced by biologic sex (XX vs. XY) in addition to the hormonal milieu.

Hypothesis:
We hypothesized that sex differences in ischemic stroke in aged brains are shaped by the sex chromosome complement.

Methods:
The Four Core Genotype (FCG) mouse model was utilized to dissociate the effects of sex chromosome compliment from hormone exposure on ischemic sensitivity. XXF, XXM, XYF, and XYM aged mice (18-20 months) were subjected to 90-minute middle cerebral artery occlusion (MCAO). Stroke outcomes were examined at 24h and 7d of stroke. Inflammatory responses were also evaluated by flow cytometry, immunohistochemistry, and multiplex cytokine analysis.

Results:
At 24h and 7d of stroke, more microglial activation and higher levels of pro-inflammatory cytokines (IL-1β and IL-6) were seen in XXF and XXM than in XYF and XYM mice respectively. Accordingly, XXF and XXM mice had significantly larger infarct volumes than XYF and XYM cohorts respectively (XXF vs.XYF: 43.26 ± 5.63% vs. 24.22 ± 3.48%; XXM vs. XYM: 50.44 ± 6.11% vs. 26.24 ± 3.91%;
P
<0.05, n=7~9/group) at 7d of stroke. There was no significant difference in hormone levels in aged FCG mice. Although no significant difference in neurological deficit scores (NDS) were seen between any two genotypes 24 hours after stroke, XXF and XXM mice exhibited worse NDS than XYF and XYM cohorts respectively at 7 d of stroke.

Conclusions:
The sex chromosome complement contributes to ischemic sensitivity in aged animals, which is likely mediated in part by innate immune responses.
Abstract W MP84: Erythropoietin Inhibits Oxidation of Tetrahydrobiopterin and Restores Bioavailability of Endothelial Nitric Oxide in Cerebral Microvessels of Hph-1 Mice
Authors: Santhanam Anantha Vijay R , d'Uscio Livius V , Smith Leslie A , Katusic Zvonimir S
Published: March 2022

Background:
While reported neuroprotective effects of erythropoietin (EPO) make it an appealing candidate for its evaluation in protection of neurovascular unit during cerebrovascular or neurodegenerative disorders, effects of EPO on cerebral microvessels, the vascular component of neurovascular unit, have not been studied to date. The present study was designed to determine the effects of EPO in cerebral microvessels derived from wild-type mice and also from hph-1 mice, a genetic mouse model of BH4 deficiency.

Methods:
Hph-1 mice and wild-type littermates (C57BL/6 background) were administered recombinant human EPO (1000 U/kg/day) intraperitoneally for 3 days. Following treatment, mice were killed by injection of an overdose of pentobarbital, brains were removed and cerebral microvessels were isolated.

Results:
Treatment of wild-type mice with EPO did not affect BH4 bioavailability, superoxide anion production or basal cGMP levels. We have reported that cerebral microvessels of hph-1 mice demonstrated reduced bioavailability of BH4, increased production of superoxide anions and impaired endothelial NO/cGMP signaling. Treatment of hph-1 mice with EPO attenuated the levels of 7,8-dihydrobiopterin (7,8-BH2; P<0.05, n=5), oxidized product of BH4, and significantly increased the ratio of BH4 to 7,8-BH2 (P<0.05, n=5), indicative of increased bioavailability of BH4 for eNOS activation. Increased superoxide anion production in cerebral microvessels of hph-1 mice were attenuated by EPO treatment (P<0.05, n=5). While eNOS expression remained unchanged, levels of cGMP were significantly increased on EPO treatment in hph-1 mice (P< 0.05, n=6). Furthermore, EPO treatment selectively increased expression of manganese superoxide dismutase.

Conclusion:
The ability of EPO to attenuate oxidative stress and restore bioavailability of endothelial NO in cerebral microvessels may help to explain mechanisms responsible for cerebrovascular protective effects of EPO.
Abstract W MP95: CCR2+ Monocytes Contribute to Hematoma Clearance After Experimental Intracerebral Hemorrhage
Authors: Hammond Matthew D , Taylor Roslyn A , Ai Youxi , Sansing Lauren H
Published: March 2022

Background:
Inflammation is a key contributor to injury and recovery after intracerebral hemorrhage (ICH). CCR2+ monocytes were recently identified as mediators of early injury in a rodent ICH model, but their potential roles in ICH recovery have not been addressed. The purpose of this study was to determine how CCR2+ monocytes influence repair and recovery after ICH

Methods:
Ccr2-/- bone marrow was transplanted into wild type congenic mice to create chimeras with normal microglia, but few circulating monocytes. Control mice received wild type bone marrow. Mice were subjected to the blood injection ICH model, whereby 20 μl of blood were injected into the striatum. The resulting motor weakness was quantified using the cylinder and beam balance tests. Residual hemoglobin was quantified in brains at day 7 using Drabkin’s reagent. In wild type mice, 1-μm fluorescent beads were injected with the blood as a phagocytosis substrate. An imaging flow cytometer was used to visualize phagocytic cells.

Results:
Mice with Ccr2-/- bone marrow have less severe motor deficits up to day 3, but both genotypes were equally recovered at day 7. Despite normal behavior, mice with Ccr2-/- bone marrow had significantly more residual hemoglobin in their brains (8.92 ± 1.03 vs. 3.96 ± 2.80 μl, p<0.05; Fig.), suggesting a role for monocytes in ICH clearance. To determine if monocytes have the capacity to phagocytose debris after ICH, we injected fluorescent beads with the ICH blood. CCR2+ monocytes engulfed more beads than resident microglia at day 1 (4.35 ± 2.23 vs. 0.23 ± 0.45 beads, p<0.0001; Fig.), suggesting a more active role in phagocytosis.

Conclusions:
Hematoma clearance has been attributed mainly to microglia, but these results indicate that CCR2+ monocytes are also involved. Interestingly, the lack of a motor deficit at day 7 indicates that the presence of a hematoma does not inhibit functional recovery in the absence of CCR2+ inflammatory monocytes.
Abstract W P100: Alterations of γδT Cell Subsets in Stroke Patients with White Matter Disease
Authors: Hao Qing , Adamski Mateusz G , Yu Hua , Wagner Erin , Seales-Bailey Chloe , Baird Alison
Published: March 2022

Background:
γδT cells have been shown in experimental models to play a role in the evolution of ischemic brain injury by increasing cerebral infarct volumes and neurological deficits. We have previously reported decreased levels of γδT cells in the subacute phase of human stroke. In this study we aimed to determine the functional significance of alterations in levels of γδT cells and other T cell subsets on the extent of ischemic brain injury.

Methods:
Blood was drawn from ischemic stroke patients within 24 hours of recruitment and stained with CD3 (PE-TR), γδTCR (PE), CD4 (FITC) and CD8 (PE-Cy5) monoclonal antibodies. γδT cells were also divided into functional subsets - CD4+ γδT, CD8+ γδT and null γδT cells. Percentages of circulating lymphocytes were measured by a fluorescent activated cell counter. The extent of acute ischemic injury was measured using lesion volume on diffusion weighted images by Image Processing Analysis and Visualization (MIPAV), while the extent of chronic ischemic injury which is manifested as white matter changes(WMC) was assessed using the Age Related White Matter Changes (ARWMC) rating score. Independent T-tests and non-parametric tests were used for between group comparisons.

Results:
Of the 41 patients recruited, the mean age was 66.8±13 years and 18 (43.9%) were men. Blood was drawn at a mean time of 47 ±30 hours after symptom onset. Compared to patients with absent-mild WMC (ARWMC score of 0-1), patients with moderate-severe WMC (ARWMC of 2-3) had higher percentages of CD8+ γδT cells (6.6% vs. 12.0%, p=0.005) and CD8+ T cells (22.2% vs. 28.5% p=0.036), and lower percentages of CD4+ T cells (71.0% vs. 63.5%, p=0.048) and null γδT cells (72.7% vs. 59.6%, p=0.03). However γδT percentages did not differ significantly. The volumes of acute ischemic stroke lesions did not correlate with γδT levels or with other T cell subsets.

Conclusions:
Alterations of T cell subsets, most notably, CD8+ γδT and CD8+ T cells were present in stroke patients with cerebral white matter disease. Their role in the formation of cerebral small vessel disease needs to be further studied.
Abstract W P102: Emboli Detection Within the Posterior Circulation
Authors: Cutting Shawna , Cabrera Frank , Cabrera Yosdely , Campo Nelly , Romano Jose , Koch Sebastian
Published: March 2022

Objective:
To describe the frequency and clinical significance of microembolic signals in the posterior circulation following acute stroke.

Background:
Although transcranial Doppler (TCD) is frequently used in the anterior circulation following ischemic stroke, TCD use for microembolic signal detection (MES) in the posterior circulation has not been validated.

Methods:
We retrospectively reviewed all patients who had a TCD performed for a posterior circulation ischemic stroke between 2009-2012. Either the basilar, vertebral or posterior cerebral artery was monitored by TCD for 30 minutes. Characteristics of vessels affected, patient demographics, and occurrence of MES was recorded. Good outcome was defined as discharge home or to an acute rehabilitation facility.

Results:
Of the 80 patients (age 61± 15 years, 65% male) who underwent TCD monitoring of the posterior circulation, 22 (27.5%) had MES. The mean number of emboli detected was 1.6 per 30 minutes. Average length of time between symptom onset and TCD was 27 days (outpatient 101.5 days; inpatient 7.3 days). Medical comorbidities were similar in those with and without MES. Vertebral or basilar stenosis >50% was found in 32 patients (40%). Moderate (50-70%) or severe (>70%) stenosis was associated with presence of MES (p=0.002), although the number of MES was similar in those with moderate vs. severe stenosis (p=0.50). Patients with MES were more likely to have experienced a TIA (36.3% vs 12.0%, p=0.01), but not stroke (27.3% vs 29.8%, p= 0.75), prior to the index event. The presence of MES was not associated with time from event to TCD (<7 vs. ≥7 days, p=0.48), length of hospital stay (7 vs. 11 days, p=0.14), recurrent neurologic events while hospitalized (6.7% vs. 12.5%, p=.47) or discharge disposition (15.4% vs. 28.9% with good outcome, p=0.276).

Conclusions:
Presence of MES in the posterior circulation is associated with large vessel intracranial stenosis >50% and TIA prior to index event, but does not correlate with a worse clinical outcome. Further studies are needed to establish the utility of TCD monitoring for MES after posterior circulation stroke.
Abstract W P107: Predictors of Outcome in Patients With Acute M2 Occlusion
Authors: Khan Muhib A , Zhang Jiaying , Moonis Majaz , Goddeau Richard , Henninger Nils
Published: March 2022

Background:
Limited information is available regarding the outcomes after distal middle cerebral artery stroke. To gain a better understanding, the aim of our study was to assess for factors associated with outcome following M2 middle cerebral artery occlusion infarcts.

Methods:
We retrospectively reviewed admission computed tomography (CT)-angiography (CTA) of consecutive acute ischemic stroke patients admitted to a single academic center from January 2010 to August 2012. Only patients with isolated M2 occlusion (defined as an occlusion distal to the bifurcation and proximal to further division) were included. We assessed for factors associated with a good 90-day outcome (modified Rankin Scale [mRS] score ≤2). Factors associated with an mRS ≤2 in univariable analyses (p<0.05) were entered into multivariable logistic regression analysis. Admission National Institutes of Health Stroke Scale (aNIHSS), age, and infarct volume were also entered as dichotomized variables. Receiver operating characteristic (ROC) curves were plotted to determine the optimal aNIHSS score, infarct volume, and age cut points predicting an mRS ≤2. Optimal thresholds were determined by maximizing Youden’s index.

Results:
90 patients with isolated M2 occlusions were included in final analyses. Of these, 69% had a 90-day mRS ≤2. Age ≤80 years (OR 0.37, 95%-CI 0.003-0.416, p=0.008), aNIHSS ≤10 (OR 0.05, 95%-CI 0.009-0.36, p=0.002), and infarct volume <27 ml (OR 0.009, 95%-CI 0.001-0.15, p=0.001) were independent predictors of a good 90-day outcome. Entering age, aNIHSS, and infarct volume as continuous variables did not meaningfully change these results. Notably, 20% patients (64% of those with a poor outcome) had died by 90-days. We then repeated all analyses for predictors of 90-day mortality. This analysis indicated that age ≤80 years (OR 4.7, 95%-CI 1.25-18, p=0.02) and infarct volume <26 ml (OR 7.3, 95%-CI 1.4-38.5, p<0.001) were independently associated with 90-day mortality.

Conclusion:
The majority of patients with isolated M2 occlusion strokes have a good 90-day outcome, which is predicted by younger age, lower aNIHSS, and smaller infarct size. Further investigations are required to identify specific factors predicting death in this patient population.
Abstract W P109: CT Angiography of Symptomatic Intracranial Atherosclerosis: Anatomical Predictors of Fractional Flow
Authors: Liebeskind David S , Leng Xinyi , Scalzo Fabien , Johnson Mark S , Fong Albert K , Ip Hing L , Fan Florence , Soo Yannie , Leung Thomas , Liu Liping , Wong Ka S , Feldmann Edward
Published: March 2022

Background:
Current use of CT angiography (CTA) for intracranial atherosclerosis (ICAD) focuses solely on measurement of maximal degree in isolated stenosis, a parameter that poorly predicts subsequent stroke. Noninvasive modeling with computational fluid dynamics (CFD) measures hemodynamic impact of stenoses based on fractional flow. We tested a novel method to compare anatomy- and CFD-based hemodynamics.

Methods:
A geometric mesh of ICAD lesions was derived from CTA. Semi-automated seed placement and centerline calculation across stenotic segments was used to automatically identify luminal stenoses, tandem lesions, plaque length and associated volumes. Fractional flow, the pressure drop across lesions, was calculated and compared to CFD-derived values using Ansys CFX and CFD-post, with boundary conditions for laminar flow.

Results:
CTA of 73 patients (mean age 72.7 ± 10.2 years; 58% men) with recently symptomatic ICAD were analyzed by semi-automated anatomical measures and CFD. Lesions included 45 M1, 14 ICA, 11 Bas and 3 VA intracranial lesions with median stenosis of 62.0% (40-93). Median plaque length was 12.2 (2.9-29.9) mm. Total plaque volumes measured median 75.1 (19.2-325.3) mm
3
with focal stenoses accounting for 40.0 (6.3-168.5) mm
3
. Pressure drop across the lesion calculated anatomically based on maximal stenosis averaged 34.7% (IQR 18.1-76.9) and 12.7% (IQR 5.0-40.2), the latter accounting for plaque length. These correlated moderately with fractional flow measured by CFD (ρ=0.545 and ρ=0.561, respectively). Plaque volumes of the entire lesion or the focal stenosis, the presence of tandem lesions or irregular surface morphology did not correlate with CFD-derived fractional flow.

Conclusions:
Detailed anatomy of intracranial atherosclerotic lesions can be extracted by semi-automated techniques, revealing extensive heterogeneity. Clinical studies are needed to discern whether CTA anatomy or CFD-derived fractional flow measures predict recurrence of stroke in the territory.
Abstract W P110: Preexisting Cerebral Small Vessel Disease Increases Cortical Infarct Volume after Distal Middle Cerebral Artery Occlusion
Authors: Khan Muhib , Zhang Jiaying , Moonis Majaz , Goddeau Richard P , Henninger Nils
Published: March 2022

Background:
Cerebral small vessel disease (cSVD) predominantly affects the subcortical white matter. However, little is known about its impact on cortical ischemic susceptibility. We sought to assess whether preexisting cSVD is predictive of the cortical infarct volume following middle cerebral artery (MCA) branch occlusion and whether it relates to a worse 90-day outcome.

Methods:
We analyzed data from 117 consecutive patients with MCA branch occlusion as documented by admission computed tomography (CT)-angiography. To avoid potential confounding, we excluded patients with subcortical infarction. Baseline clinical, laboratory, and outcome data as well as final cortical infarct volumes on follow-up imaging were retrospectively analyzed from a prospectively collected database. Severity of cSVD was assessed on admission CT using the van Swieten scale (VSS), grading the white matter lesions on a 3-point scale from 0 (absent) to 4 (severe). We also dichotomized the degree of cSVD (VSS 0-2 [absent to moderate] vs. 3-4 [severe]) for statistical purposes. Multivariable linear and logistic regression analyses were used to identify independent predictors of the final infarct volume.

Results:
A final infarct volume of ≤27 mL best predicted a favorable 90-day outcome (mRS≤2) as determined by receiver operating characteristic curves. Severe cSVD (OR 7.434; 95%-CI 1.549-35.676; p=0.012) was independently associated with infarct volume >27 mL. Patients with severe cSVD had significantly larger cortical lesion volumes compared to patients without (Figure1A). Severe cSVD (OR 3.027; 95%-CI 1.013-9.048; p=0.047) and infarct volume >27 mL (OR 9.038; 95%-CI 1.997-40.899; p=0.004) were independent predictors of a poor 90-day outcome (mRS 3-6; Figure 1B).

Conclusion:
Severe subcortical cSVD contributes to larger cortical infarct volumes and worse functional outcome adding to the notion that the brain is negatively affected beyond cSVD ‘s macroscopic boundaries.
Abstract W P113: Periprocedural Risk of Carotid Revascularization According to Delay from Neurologic Symptom Onset During the Acute Period
Authors: De Rango Paola , Lenti Massimo , Cieri Enrico , Ciucci Andrea , Farchioni Luca , Fiorucci Beatrice , Caso Valeria
Published: March 2022

Background:
Concerns on procedural risks in patients with recent transient ischemic attack (TIA) or stroke have been raised against the efficacy of early carotid revascularization performed during the acute period (<15-20days) from neurologic symptoms onset. Aim of this study was to define the 30-day risks of stroke/death after carotid endarterectomy (CEA) and carotid stenting (CAS) in symptomatic patients stratified for delay from the last neurologic event.

Methods:
During 2009-2013, 207 consecutive patients were treated with carotid revascularization within 20 days from the last neurologic event. Thirty-day stroke/death rate was analyzed in procedures performed <48h, during the first 7 days, between 7 and 15 days or after 15 days.

Results:
There were 183 CEA and 24 CAS. Overall 175 procedures were performed within the first 15 days and 32 after. Specifically, 22 patients were treated within the first 48h and 89 within the first 7 days. The 30-day stroke and death rate was 2.9% (6/207). There were 3 deaths, 2 cerebral hemorrhages and 3 ischemic strokes. 30-day stroke/death rate was comparable in patients treated within the first 15 days and those treated later : 2.9% (5/175) and 3.1% (1/32); Odds ratio , OR 0.9; 95%Confidence Interval, CI, 0.10-8.1; p=.99. 30-day stroke/death rate was 2.2% (2/89) for patients treated within 7 days and 3.5% (3/86) for those treated between 7 and 15 days. For the 22 patients receiving carotid revascularization within the first 48 hours, periprocedural risk was 0.

Conclusions:
Currently carotid revascularization can be performed safely within the acute period from neurologic symptoms onset with a stroke/death risk of 3.5% or lower.
Abstract W P116: Association Between Blood Pressure And Short-Term Prognosis of Symptomatic Intracranial Atherosclerotic Stenosis
Authors: Park Jong-Moo , Kang Dong-Wha , Yu Kyung-Ho , Koo Ja-seong , Hong Keun-Sik , Cho Yong-Jin , Kim Dong-Eog , Bae Hee-Joon , Lee Yong-Seok , Rha Joung-Ho , Kim Young A , Lee Byung-Chul , Kim Jong S. , Kwon Sun U.
Published: March 2022

Background and Purpose:
Optimal blood pressure (BP) management for the patients with intracranial atherosclerotic stenosis (ICAS) has not been clearly defined. We investigated whether BP parameters during poststroke 7 months would affect the prognosis of symptomatic ICAS.

Methods:
Patients with acute symptomatic stenosis in the middle cerebral artery or the basilar artery were enrolled in Trial of cilOstazol in Symptomatic intracranial Stenosis 2 (TOSS-2). We included patients whose BP were measured 5 time points at baseline, 1, 3, 5 and 7 months during trial. Mean, maximum, maximum-minimum, standard deviation (SD), and coefficient of variation (CV) of systolic BP (SBP) and diastolic BP (DBP) were determined. The progression of symptomatic ICAS and the occurrence of new MRI lesions were investigated as the primary outcome by 7-month follow-up MR angiogram and MRI.

Results:
Of the 409 participants in TOSS-2 trial, 50 patients were excluded due to insufficient blood pressure value. Comparing 48 patients with the progression of symptomatic ICAS with 311 nonprogression group, no difference in mean SBP was observed. Values of maximum, maximum-minimum, SD and CV of SBP and DBP were not different between two groups either. All BP parameters were not different regarding the presence of new ischemic lesions on follow-up MRI. Patients with mean SBP below and above 140 mmHg during trials did not show different results in primary outcome (ICAS progression 11.6% vs. 17.6%, p=0.123; new MRI lesions 13.8% vs. 14.5%, p=0.890). Multivariable analysis revealed no specific BP parameters for the progression of ICAS or new ischemic MRI lesions during 7 months.

Conclusions:
No specific BP parameters were associated with the progression of ICAS and new lesion development on MRI during 7 months after stroke. Otherwise, no additional risks were noted in patients with symptomatic ICAS by mean BP below 140 mmHg.
Abstract W P124: Elevated Glucose Level Adversely Affects Infarct Volume Growth and Neurological Deterioration in Non-diabetic Stroke Patients, but Not Diabetic Stroke Patients
Authors: Shimoyama Takashi , Uemura Junichi , Saji Naoki , Shibazaki Kensaku , Kimura Kazumi
Published: March 2022

Background:
Hyperglycemia is recognized as a common occurrence associated with a high risk of poor outcome in ischemic stroke patients. However, little is known about the association between elevated glucose level, growth of infarct volume, and neurological deterioration in ischemic stroke patients without diabetes. The present study aimed to clarify this issue in acute ischemic stroke patients with arterial occlusion.

Methods:
We studied 375 acute ischemic stroke patients with arterial occlusion within 24 h of onset. Diabetes was diagnosed in patients with known history of diabetes or HbA1c value ≥6.5%. Infarct volume was measured on admission and at follow-up within 48 h using diffusion-weighted imaging. Neurological deterioration was defined as an increase of ≥4 points increase in National Institutes of Health Stroke Scale score within seven days of stroke onset. We examined the relationship between glucose level on admission, infarct volume growth, and neurological deterioration in three categories (all patients, non-diabetes, and diabetes) using multivariate modeling. Regression models included admission glucose level and other potentially predictive variables (NIHSS score on admission, initial infarct volume, arterial recanalization, hemorrhagic infarction, and ICA occlusion).

Results:
Diabetes was present in 104 patients (27.7%). Multivariate regression analysis showed that elevated glucose level was independently associated with infarct volume growth in all patients (P=0.034) and non-diabetes (P=0.002), but not in diabetes (P=0.871). Moreover, elevated glucose level was independently associated with neurological deterioration in all patients (odds ratio [OR], 1.010; 95% confidence interval [CI], 1.004-1.017; P=0.002) and non-diabetes (OR, 1.014; 95%CI, 1.002-1.026; P=0.022), but not diabetes (OR, 1.006; 95%CI, 0.998-1.014; P=0.151).

Conclusions:
Glucose level appears to influence infarct volume growth and neurological deterioration, particularly in non-diabetic patients with ischemic stroke.
Abstract W P13: Which Patients are Informative About Benefits of Neurothrombectomy?: Analysis of the Pooled SWIFT and STAR Trials Dataset
Authors: Saver Jeffrey L , Pereira Vitor M , Gralla Jan , Jahan Reza ,   the SWIFT and STAR Trialists
Published: March 2022

BACKGROUND:
To demonstrate treatment benefit, neurothrombectomy clinical trials should enroll patients who show better outcome with reperfusion than non-reperfusion.

METHODS:
We analyzed the pooled dataset of prospective Solitaire neurothrombectomy trials. Solitaire-treated patients were categorized as reperfusers (TICI 2a-3) and non-reperfusers (TICI 0-1).

RESULTS:
Among 271 Solitaire-treated patients, any reperfusion (TICI 2a-3) was achieved in 90.0%. Reperfusers and non-reperfusers did not differ in age (67.5 vs 69.4, p = 0.46), baseline NIHSS (16.7 vs 17.2, p=0.62), target vessel distribution, or onset to arterial puncture time (4.5h vs 4.9h, p=0.24). Across the entire cohort, reperfusion was strongly associated with freedom from disability (mRS 0-2, 57.5% vs 20.0%, p<0.001), freedom from dependence (mRS 0-3, 72.9% vs 36.0%, p<0.001), and shift in disability (mRS mean 2.3 vs 3.6, Wilcoxon Rank Sum p <0.001), but not with increased survival (90.0% vs 88.0%, p=0.73). Among 12 baseline prognostic subgroups, defined by age, NIHSS, and time to treatment quartiles, the most informative endpoint analyses were: shift analysis (informative in 10); mRS 0-3 (informative in 9); mRS 0-2 (informative in 6); and survival (informative in 2). Only 1 of the 12 subgroups was not informative on any analysis - very young patients, 25-60y (ceiling effect). While both mRS 0-2 and shift analysis were informative in patients of moderate age (61-77y), mild to moderate severity (NIHSS 8-13, 18-20), and very rapid treatment (1.6-3.5h), shift analysis was also informative in patients with older age (78-88y), an additional band of moderate stroke severity (NIHSS 14-17), and longer time to treatment (3.6 to >5.6h).

CONCLUSIONS:
Reperfusion with the Solitaire stent retriever is strongly associated with improved disability outcomes. Compared with dichotomizing at freedom from disability (mRS 0-2), analyzing all substantial reductions in disability (mRS ranks analysis) additionally detects benefit in patients of older age, greater stroke severity, and later treatment times, expanding the informative clinical trial population by over 40%.