bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W P367: Anterior Cerebral Artery Diameter Predicts Anterior Cerebral Artery Territorial Stroke.
Authors: Shoamanesh Ashkan , Masoud Hesham , Weed Katrina , Duerfeldt Kaylyn , Lau Helena , Romero Jose R , Pikula Aleksandra , Teal Philip , Nguyen Thanh , Kase Carlos S , Babikian Viken L
Published: July 2021

Background:
Anterior cerebral artery strokes (ACAS) account for only 1-2% of cerebral infarctions, and typically result from embolism in western populations. The cause of the low frequency of ACAS in relation to MCA strokes (MCAS) is uncertain, but differences in arterial anatomy may affect flow-directed embolism rates. We aimed to determine whether variability in ACA A1 diameters (A1D) and A1D/MCA M1 diameter (M1D) ratios predict ACAS

Methods:
Consecutive patients admitted to Boston Medical Center with a diagnosis of ACAS between 01/2008-10/2012 were reviewed. Patients with an interpretable CT angiogram (CTA) or magnetic resonance angiogram (MRA) of the cerebral vasculature were eligible. Excluded were patients with ACAS ipsilateral (ipsi) to an aplastic ACA, concomitant ipsi MCAS, and those with lacunar, watershed, aneurysm clipping or local intracranial atherosclerosis as stroke etiology. Patient demographics were compiled. Ipsilateral and contralateral (contra) A1D, M1D, as well as ICA-ACA and ICA-MCA angles were measured from CTA and MRA images. Consecutive MCAS admitted between 01/2011-10/2012 served as controls.

Results:
The study comprised 55 individuals (27 ACA, 28 MCA) with mean age of 69 years. Stroke etiology was cardioembolism in 56%, internal carotid artery embolism in 16% and idiopathic in 27%. Patients with ACAS had larger mean ipsi A1D (2.47 vs. 2.05 mm,p<0.01), ipsi A1D/M1D ratios (0.95 vs. 0.73,p<0.001) and were more likely to have a contra aplastic/hypoplastic ACA (41 vs. 4%,<0.001). Ipsi A1D (OR per 1 mm increment: 8.52 [95% CI 1.36, 53.26]) and ipsi A1D/M1D ratio (OR per 10% increment: 1.83 [95% CI 1.15, 2.91]) remained significant following multivariate analysis. Ipsilateral M1D was protective for ACAS (OR per 1 mm increment: 0.17 [95% CI 0.03, 0.90]) after adjusting for ipsi A1D. There were no significant differences in demographic variables, stroke etiologies, terminal ICA-ACA or ICA-MCA angles between ACAS and MCAS.

Conclusions:
Larger ipsilateral A1D and A1D/M1D ratio are independent predictors of ACAS. These findings concur with the notion that A1D and M1D are important in determining the path of emboli that reach the terminal ICA.
Abstract W P371: Cerebral Microbleeds and Renal Impariment in Acute Lacunar Stroke
Authors: Sato Takahiro , Saji Naoki , Aoki Junya , Kobayashi Kazuto , Uemura Junichi , Shibazaki Kensaku , Kimura Kazumi
Published: July 2021

Background and purpose:
Cerebral small vessel disease is associated with chronic kidney disease. Although cerebral microbleeds (CMB) are common in patients with lacunar stroke, the association between CMB and renal impairment remains unclear. The aim of this study was to clarify whether CMB are associated with renal impairment in patients with acute lacunar stroke.

Methods:
We evaluated consecutive first-ever lacunar stroke patients who were admitted to our hospital within 24 hours after stroke onset. Lacunar infarcts were defined as <15 mm in diameter detected on initial diffusion-weighted imaging scans and depended on the criteria for small artery occlusion based on the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification. CMB were defined as a focal area of signal loss in brain parenchyma <5 mm on T2*-weighted imaging scans. We divided patients into two groups according to the presence or absence of CMB.

Results:
Among 152 patients (66% male, mean age 69 years), 45 (30%) had CMB. The presence of silent lacunar infarcts (SLI; 87% vs 41%, P <0.001), white matter disease (WMD; 67% vs 26%, P <0.001), and hypertension (84% vs 66%, P <0.05) were higher and estimated glomerular filtration rate (eGFR) on admission (67.7 vs 79.0 mL/min/1.73 m
2
, P <0.01) was lower in patients with CMB than in those without. The frequency of CMB showed a significant difference among tertiles of eGFR (highest, middle, and lowest; 14%, 35%, and 40%, P <0.01). On multivariable logistic regression analysis, SLI (odds ratio, 95% confidence interval; 11.1, 3.8-37.7), hypertension (5.1, 1.6-18.9), WMD (4.6, 1.6-13.8), eGFR on admission (lowest and middle tertiles vs highest tertile, 3.3, 1.1-10.9), NIHSS score on admission (1.3, 1.0-1.6), and diabetes mellitus (0.1, 0.04-0.41) were independently associated with CMB.

Conclusions:
In lacunar stroke patients, the presence of CMB should be associated with renal impairment.
Abstract W P48: Marked Regional Variation in Acute Stroke Treatment in Medicare Beneficiaries
Authors: Burke James F , Skolarus Lesli E , Adelman Eric E , Scott Phillip A , Meurer William J
Published: July 2021

Objective:
Regionalization of stroke care has occurred sporadically across the U.S, so determining realistic goal treatment rates for individual regions or the nation as a whole is challenging. Studies of a single hospital or region vary widely in estimates of eligibility for acute therapy and may have limited generalizability or biases. We hypothesized that the proportion of U.S. Medicare beneficiaries receiving acute stroke therapy varies by region. Treatment rates in high performing regions may represent realistic national goals and inform policy to increase treatment rates.

Methods:
All Medicare beneficiaries with a principal diagnosis of ischemic stroke (ICD-9 433.x1, 434.x1, 436) admitted through the emergency department were identified using MEDPAR files from 2007-2010. Receipt of IV tPA (DRG 559, MS-DRG 61-63, ICD-9 procedure code 99.10) or IA thrombolysis (CPT code 37184-6, 37201, 75896 via linked Medicare Carrier files) was determined. Patients were assigned to one of 3,436 Hospital Service Areas (HSA; local health care markets for hospital care) by zip code. Regional acute stroke treatment rates were calculated and the lowest and highest quintiles were compared. Multi-level logistic regression was used to adjust for individual demographics as well as regional population density, education, median income, and unemployment using linked census data. Model-based adjusted regional acute stroke treatment rates were estimated.

Results:
Of 916,232 stroke admissions 3.6% received IV tPA only and 0.6% received IA or combined therapy. Unadjusted treatment rates by region ranged from 0.8% (minimum) to 14.8% (maximum). Regional rates ranged from 1.7% (quintile 1) to 5.4% (quintile 5). Regions with higher education, population density and income had higher treatment rates (p <= 0.001). After adjustment, regional differences were attenuated slightly _ 1.9% (quintile 1) to 5.1% (quintile 5).

Conclusions:
Marked variation exists in acute stroke treatment rates by region, even after adjusting for patient and regional characteristics, supporting the perception that a major opportunity exists to improve acute stroke treatment within many HSAs.
Abstract W P6: North American Solitaire Stent-Retriever Acute Stroke Registry: Choice of Anesthesia and Outcomes
Authors: Abou-Chebl Alex , Zaidat Osama O , Castonguay Alicia C , Dabus Guilherme , Froehler Michael T , Janardhan Vallabh , Nanda Ashish , Nguyen Thanh N , Sun Chung-Huan , Nogueria Raul G
Published: July 2021

Background and Purpose:
Previous work has suggested that general anesthesia (GA) may have a negative impact on outcomes in acute ischemic stroke (AIS) patients undergoing endovascular therapy, however, those data predated the availability of the safer and possibly more effective stentriever devices.

Methods:
The investigator-initiated NASA Registry recruited North American sites to submit demographic, clinical, procedural (including use of GA versus local anesthesia [LA]), and site-adjudicated angiographic and clinical outcome data on consecutive patients treated with the Solitaire™ FR device. The primary outcomes were mRS at 90-days, mortality, and sICH.

Results:
A total of 281 patients from 18 centers were enrolled in this sub-study. GA was utilized in 69.8% (196/281) of patients. Baseline demographics were comparable between the LA and GA groups, except the former demonstrated a longer time to groin puncture (395.4±254 versus 337.4±208min, p=0.04) and slightly lower NIHSS (16.2±5.8 versus 18.8±6.9, p=0.002). Procedural factors were also similar, although lower balloon-guide catheter usage (22.4% versus 49.2%, p=0.0001) and longer fluoroscopy times (39.5±33 versus 28±22.8min, p=0.008) were seen in the LA versus GA cohorts, respectively. Recanalization (TICI≥2a) success (91.8 versus 86.8%, p=0.3) and the rate of sICH (7.1% versus 11.2%, p=0.4) were similar between the LA and GA patients, respectively. The primary outcome of mRS≤2 was achieved in 52.6% and 35.6% (OR 1.4[1.1-1.8], p=0.01) of LA and GA patients, respectively. In a multivariate analysis, hypertension, NIHSS, unsuccessful revascularization, and GA use (OR 3.3(1.6-7.1), p=0.001) were associated with death. To account for potential confounders, when only anterior circulation patients and patients who were electively intubated were included, there was a persistent difference in good outcomes in favor of the LA patients (50.7% versus 35.5%, OR 1.3[1.01-1.6], p=0.04).

Conclusions:
The NASA Registry has demonstrated that clinical outcomes and survival are significantly better in patients treated without GA without any increase in sICH. Future AIS trials should prospectively evaluate the effect of GA on outcomes.
Abstract W P86: Photo-stimulation of the Striatum Promotes Functional Recovery and Neurogenesis after Focal Ischemic Stroke
Authors: Song Mingke , Mohamad Osama , Gu Xiaohuan , Wei Shipeng , Wei Ling , Yu Shan Ping
Published: July 2021

Introduction and Purpose:
The striatum region of the brain supports self-repair process after experimental cerebral ischemia. Optogenetics is a temporally and spatially precise method to manipulate targeted neuronal populations. We tested whether optogenetic technique can be translated into stroke treatment by photo-stimulation of the striatum after focal cerebral ischemia.

Methods:
Adult male channelrhodopsin-2 (ChR2) transgenic mice were utilized, taking the advantage of that the cation channel ChR2 is abundantly expressed in the striatum. Before stroke, mice were trained 5 times per day for 3 days with a modified adhesive removal test. Mice were then subjected to the ischemic insult targeting the right sensorimotor (barrel) cortex. Four days after stroke, optical fibers were implanted into the striatum and fixed with a cannula on the skull. In control group, stoke mice received optical fiber implantation but without photo-stimulation. In treatment group, daily photo-stimulation pulses (473 nm blue laser) were started at 5 days after stroke and sustained for 8 days. The adhesive removal test on forepaws was performed 3, 10, 17, 24, and 31 days after stroke.

Results:
The impaired forepaw sensorimotor function in these two groups progressively recovered over the timeline. Stroke mice treated with photo-stimulation showed significantly better recovery assessed 31 days after stroke compared to stroke control. Our study also shows that the activity of neurogenesis in the brain was augmented by photo-stimulation, which may be responsible for enhanced functional recovery.

Conclusions:
Optogenetic stimulation of the striatum promotes functional recovery and neurogenesis after focal ischemic stroke.
Abstract 102: Coregistration of Serial Angiograms Using Point Cloud Matching
Authors: Scalzo Fabien , Stier Noah , Liu Jingyu , Bi Weike , Liebeskind David S
Published: July 2021

Introduction:
Digital subtraction angiography (DSA) is the gold standard to assess reperfusion during endovascular procedures. Visualization and quantification of changes between successive runs is challenged by patient motion and variations in acquisition parameters such as zoom and pose of the x-ray receptor. Automated coregistration of successive DSA sequences would allow for the visualization of serial changes in perfusion during the procedure. The objective of this study is to develop a fully automated framework for the coregistration of patient-specific DSA acquired at different time points during an endovascular reperfusion procedure.

Methods:
The dataset was established retrospectively from patients admitted at a stroke care center and diagnosed with acute ischemic stroke. Included patients underwent a clot retrieval procedure. Biplane DSA was performed before and after endovascular reperfusion intervention. A neurologist manually coregistered the anterior-posterior (AP) view of successive DSA sequences from each patient using anatomical reference landmarks. The developed computer vision framework processed each DSA to extract the vasculature using a vessel detector, followed by resampling of the responses. The resulting set of points in the pre- and post-intervention DSA were then matched using a point cloud matching algorithm. In this study, we provide an experimental analysis with the conventional RANSAC algorithm. Evaluation was performed by measuring the error between the estimated affine transform, that relates the pre- to the post-intervention DSA, and the groundtruth established manually.

Results:
A total of 20 patients were included in the analysis. Mean age was 66.8 (range 34-91). Distribution of the TICI scores was as follows: TICI 0(3), TICI 1(0), TICI 2a(5), TICI 2b(10), TICI 3(2). Overall coregistration error was as follows: angle (8.6+- 3.1 degrees), shift (24.8 +- 19 mm), respectively.

Conclusions:
RANSAC point cloud matching algorithm can be used to accurately coregister serial angiograms during endovascular procedures. This could lead to near real-time visualization and quantification of revascularization.
Abstract 11: Persistent Risk Of Venous Thromboembolism After Discharge Among Stroke Survivors - A Seven-Years Longitudinal Study
Authors: Moradiya Yogesh , Dharaiya Devanshi , Murthy Santosh , San Luis Christa , Modi Sneha
Published: July 2021

Background and Purpose:
Risk of venous thromboembolism (VTE) in stroke patients persists after discharge from hospital due to residual deficits. Quantification of VTE risk at various post-discharge intervals may have implications for surveillance and/or prophylactic strategies for high-risk individuals. We therefore, studied incidence rates and risk factors of deep venous thrombosis (DVT) and pulmonary embolism (PE) among stroke survivors after discharge from the hospital.

Methods:
Adults with principle diagnosis of ischemic stroke discharged alive from acute care hospitals in California State between January 2005 and December 2010 were followed up until December 2011 using state inpatient and emergency department databases for development of DVT and/or PE. Case ascertainment was done using International Classification of Diseases -9 codes. We calculated incidence rates of DVT and PE during first 30 days, 31-90 days, 91-365 days and >1-year after the discharge. We calculated independent risk factors for VTE within 90 days after discharge by using logistic regression controlling for baseline demographics, comorbidities, inpatient complications and procedures.

Results:
A total of 168,194 stroke survivors were followed up for a mean duration of 3.6+/-1.9 (SD) years after discharge. Among these, 6,179 (3.7%) developed DVT and 2,487 (1.5%) developed PE resulting in incidence rate of 1.02 and 0.41 per 100 person year for DVT and PE respectively. The incidence rates of DVT during first 30 days, 31-90 days, 91-365 days and >1-year post-discharge were 6.53, 2.91, 1.24 and 0.66 per 100 person year respectively. Similarly, the incidence of PE was 3.04, 1.13, 0.46 and 0.26 during first 30 days, 31-90 days, 91-365 days and >1-year after discharge respectively. Factors independently associated with VTE within 90 days were age>65 years, African-American race, higher Charlson comorbidity index, metastatic cancer, anemia, obesity, acute myocardial infarction, pneumonia, sepsis, hemodialysis, gastrostomy and mechanical ventilation during index admission.

Conclusions:
VTE risk remains high among stroke survivors even after discharge from the hospital. The risk is highest during first 30 days and remains high as long as 1 year after discharge.
Abstract 124: Impact Of Adherence With Antiplatelet Monotherapy On The Mortality After Ischemic Stroke: A Nationwide Multicenter Follow-up Study
Authors: Kim CK Chi Kyung , Kim Yerim , Jung Seunguk , Kim Jun Yup , Jeong Han-Gil , Ko Sang-Bae , Lee Seung-Hoon , Bae Hee-Joon , Yu Kyung-Ho , Lee Byung-Chul , Yoon Byung-Woo
Published: July 2021

Introduction:
Antiplatelets are the most important drugs to prevent ischemic stroke. These drugs are prescribed for nearly life long period. However, few studies have elaborated on the significance of adherence with antiplatelet monotherapy in ischemic stroke.

Methods:
We enrolled 36,128 patients with ischemic stroke from Jan 2008 through Dec 2011 from 40 hospitals which were participated in a nationwide research project in Korea. The whole drug information was obtained from the Health Insurance Review and Assessment Service in Korea. Among them, 8,299 patients had taken antiplatelet monotherapy over 6 months with one of the most popular antiplatelet drugs (aspirin, clopidogrel or cilostazol). The adherence with antiplatelet monotherpay was defined as % adherence = (n of days’ supply) / (actual n of days to refill) х 100. Nonadherence was defined as < 80% adherence. The mortality and drug information were censored on 31 Dec 2012.

Results:
From 8,299 patients using a single antiplatelet drug over 6 months, 1056 (12.7%) patients were included in nonadherence group. The factors related to nonadherence were severe neurological deficits and the atherosclerotic stroke subtype. Compared with the good adherence group, the adjusted hazard ratio (HR) of the nonadherence group for all-cause mortality was 1.49 (95% CI, 1.28-1.73), after controlling age, stroke severity, stroke subtype, and the presence of hypertension, diabetes, hyperlipidemia, and smoking. In subgroup analyses, the adjusted HRs for mortality after ischemic stroke were increased in the aspirin or clopidogrel monotherapy group respectively, compared with good adherence group (HR and 95% CI in nonadherence with aspirin, 1.22 and 1.01-1.46; HR and 95% CI in nonadherence with clopidogrel, 2.07 and 1.53-2.82).

Conclusion:
Our study demonstrated that nonadherence with antiplatelet monotherapy is an independent predictor of all-cause death after ischemic stroke from nationwide multicenter follow-up study.
Abstract 154: Heritability of Ischemic White Matter Lesions in a Family Population with Increased Susceptibility of Vascular Disease
Authors: Nyquist Paul A , Yanek Lisa R , Becker Lewis C , Kral Brian G , Vaidya Dhananjay , Becker Diane M
Published: July 2021

Introduction:
Ischemic strokes are more likely to occur in the subcortical region of the brain, and also cluster strongly in families. However, the extent to which ischemic white matter lesions (WML) are heritable in a high risk healthy population remains unknown. We thus examined the heritability of ischemic WML volumes in both the periventricular (PV) and subcortical (SC) brain regions in apparently healthy European American (EA) and African American (AA) families with increased susceptibility for vascular disease .

Methods:
We measured traditional risk factors, and imaged the brains of 579 healthy first degree relatives of probands with early onset CAD prior to 60 years of age. PV and SC WML volumes were directly measured using 3T cranial MRI. The location and volume of lesions were characterized using standard automated software. Maximum-likelihood estimates of polygenic heritability were performed on the unadjusted and adjusted transformed WML traits with the use of variance components models in the ASSOC subroutine of SAGE.

Results:
Heritability was analyzed in 359 EA from 122 pedigrees as well as in 220 AA from 75 pedigrees. Participants were 58% women, 37% AA; mean age 51.5±11 (range of 29-74 years). Adjusting for age, sex, systolic blood pressure, and intracranial volume we determined the heritability for total WML volumes in EA’s (h2=0.62, SE 0.135, p<0.00001), and AA (h2=0.16, SE 0.24, p=0.25); for PV WML in EA’s (h2=0.31, SE 0.145, p=0.00167) in AA’s (h2=0.037, SE 0.165, p=0.4118); and for SC WML in EA’s (h2=0.581, SE 0.166, p=0.0002) and AA’s (h2=0.582, SE 0.182, p=0.0007).

Conclusions:
Total WML volumes were highly heritable in EA, as were both PV, and SC WML volumes. In AA, only SC WML volumes were significantly heritable. In general, heritability estimates where greater for the SC than for the PV WML volumes. These findings suggest a heritable precursor state of stroke-related small vessel cerebrovascular disease in EA, generally greater for the subcortical region where subsequent strokes are more likely to occur, and a similar state only in the SC region in AA high risk healthy family members with susceptibility to vascular disease.
Abstract 166: Spleen Contraction in Patients With Ischemic Stroke and Brain Hemorrhage: Validating Animal Studies
Authors: Vahidy Farhaan S , Rahbar Mohammad H , Lee MinJae , Parsha Kaushik N , Sahota Preeti , Nguyen Claude B , Bui Thanh-Tung , Barreto Andrew D , Bambhroliya Arvind B , Aronowski Jaroslaw , Grotta James C , Savitz Sean I
Published: July 2021

Objectives:
Animal models have shown that the spleen contracts and contributes to post-ischemic inflammation that may exacerbate brain injury and impair recovery. Translation of these findings in patients is challenging because of a lack of normative spleen volume (SV) data. We created normograms of SV for an adult at-risk population, quantified splenic contraction (SC) in stroke patients, and characterized patients with SC.

Methods:
We enrolled 158 healthy volunteers (HV) with matching age and gender distribution with that of our stroke center registry. Spleen ultrasounds were performed on 5 consecutive days. We used quantile regression models to identify predictors of SV for HV. Gender and body surface area (BSA) were used to construct percentile based normograms of SV, and the expected pre-stroke SV were calculated, from which SC was quantified. We also enrolled a cohort of 170 patients with acute stroke and intracerebral hemorrhage within 24 hours of symptom onset and performed serial spleen ultrasound measurements during hospitalization. Logistic regression was used to determine factors associated with SC.

Results:
Normograms for SV in healthy males and females based on BSA were created (Figure 1). Over a 5-day consecutive period of daily spleen measurements, the maximum day to day variation was 10.6 cm3. Based on these findings, stroke patients with a normalized SV below 20 cm3 of their expected SV, were classified as having SC. Excluding stroke mimics, 158 patients were included in the analyses, of which 64 (40.5%) had SC detected within 24 hrs of symptom onset. African-American race, older age, and history of previous stroke were significantly associated with SC (Table 1).

Conclusion:
The spleen does appear to reduce in size after stroke in some specific subgroups of patients with acute stroke and brain hemorrhage. The biological relevance of SC to the inflammatory response and functional outcomes of stroke patients are currently being studied in our study cohorts.
Abstract 182: Time is Brain on the Collateral Clock! Collaterals and Reperfusion Determine Tissue Injury
Authors: Liebeskind David S , Liu Dezhi , Sanossian Nerses , Sheth Sunil A , Liang Conrad , Johnson Mark S , Ali Latisha K , Kim Doojin , Hinman Jason D , Rao Neal M , Starkman Sidney , Jahan Reza , Gonzalez Nestor R , Tateshima Satoshi , Duckwiler Gary R , Saver Jeffrey L , Yoo Bryan , Alger Jeffry R , Scalzo Fabien ,   on behalf of the UCLA Stroke Investigators
Published: July 2021

Background:
The pace of ischemic injury due to stroke may vary due to collaterals and degree of reperfusion. Previous linear models that estimate time is brain have not incorporated individual patient data from advanced imaging such as diffusion-weighted imaging (DWI) and angiographic assessment of collateral grade or reperfusion. We developed a realistic model of ischemic injury using detailed imaging data in a homogenous cohort of isolated M1 middle cerebral artery occlusions.

Methods:
Retrospective analysis of a consecutive series of isolated M1 occlusions was conducted at an expert core lab. ASITN collateral grade was assessed at baseline and extent of reperfusion after endovascular therapy (EVT) was scored with 3 distinct versions of TICI. A separate imaging expert measured DWI lesion volumes on serial MRI acquired from admission to discharge. Graphical analyses illustrated curves demarcating extent of injury over time, based on both collateral grade and extent of reperfusion.

Results:
126 patients (median age 73; 88 women; median NIHSS 17; median time to 1
st
DWI, 4h08min) with acute stroke due to M1 occlusion (61 proximal, 65 distal) underwent EVT during a 6-year period. Median collateral grade was 2 (range 0-4) and median TICI, 2B (range 0-3). mTICI scores were 0 (n=18), 1 (6), 2A (25), 2B (73), and 3 (4) with 24 TICI 2C scores when evaluated in detail. Total number of DWI scans was 323, with mean 2.5 per patient. Collateral grade strongly influenced pace of development of initial tissue injury (ASITN 0, 0.445 cc/min; 1, 0.276 cc/min; 2, 0.178 cc/min; 3, 0.106 cc/min; 4, 0.031 cc/min). The relationship between time and DWI lesion growth was not linear, but best fit logarithmically (R
2
= 0.985, RMSE 2.1 for log fit; R
2
= 0.757, RMSE 8.1 for linear fit). Individual lesion growth varied markedly with both collateral grade (ANOVA p<0.001) and the degree (TICI 2B/3 vs. 0,1,2A) of reperfusion (ANOVA p=0.013).

Conclusions:
Collateral grade and the degree of reperfusion strongly dictate the timecourse of ischemic injury in the brain after stroke onset. Advanced imaging and angiographic assessment of collaterals and reperfusion confirm a logarithmic, not linear, model that can be used to differentiate stroke patients and streamline therapeutic strategies.
Abstract 191: Persistent Infiltration of Active Microglia in Brain Arteriovenous Malformation Causes Unresolved Inflammation and Lesion Progression
Authors: Zhang Rui , Degos Vincent , Kang Shuai , Wong Michael , Zhan Lei , Su Hua
Published: July 2021

Background and Purpose:
Monocytes are present in human brain arteriovenous malformation (bAVM), but their roles and origin are not clear. Endoglin (Eng, a bAVM causative gene) mutation extends CD68+ cell retention in the mouse stroke brain. Using 2 mouse bAVM models, we tested the hypothesis that CD68+ cells in bAVM are mostly active microglia, which cause unresolved inflammation and lesion progression.

Methods:
In Model 1, using Rosa-CreER;Eng-floxed mice, AVM was induced through global Eng deletion, and brain focal angiogenesis stimulated by an adeno-associated viral vector expressing vascular endothelial growth factor (AAV-VEGF). In Model 2, using CCR2RFP/+/CX3CR1GFP/+;Alk1 (another bAVM causative gene) floxed mice, AVM was induced through focal Alk1 deletion, and angiogenesis by intra-brain injection of Ad-Cre and AAV-VEGF. The RFP+ and GFP+ and CD68+ cells in the bAVM were quantified.

Results:
The mice in both models had bAVM 8 weeks after model induction. The bAVM lesions had more CD68+ cells than the normal angiogenic region of wild-type (WT) mouse brain (Model 1 vs. WT: 562±182/mm2 vs. 353±86, P=0.049; and Model 2 vs. WT: 890±289 vs. 549±72, P=0.058). Most (95%) CD68+ cells in Model 2 were GFP+ microglia. Model 2 mice also had more RFP+ bone marrow (BM)-derived macrophages than WT controls (P=0.065), suggesting that unmutated BM-derived macrophages also participate in bAVM pathogenesis. A similar number of CD68+ cells was detected in the brain angiogenic foci in Model 1 mice (P=0.29) 2 weeks after model induction.

Conclusions:
These data indicate a consistent infiltration of active microglia in bAVM that causes unresolved inflammation, which then promotes abnormal angiogenesis and lesion progression. Unmutated BM-derived microphages also participate in this process.
Abstract 196: Polymorphisms in Cerebral Cavernous Malformation Signaling Pathway Genes Associated With Severity of Cerebral Cavernous Malformation Type 1
Authors: Choquet Hélène , Pawlikowska Ludmila , Nelson Jeffrey , McCulloch Charles E , Akers Amy , Baca Beth , Khan Yasir , Hart Blaine , Morrison Leslie , Kim Helen
Published: July 2021

Objective:
Familial cerebral cavernous malformation (CCM) is an autosomal dominant disease caused by mutations in
CCM1
,
CCM2
or
CCM3
, and characterized by multiple brain lesions that can lead to intracerebral hemorrhage (ICH), seizures, and neurological deficits. Carriers of the same mutation can manifest variable symptoms and severity of disease, suggesting the influence of modifiers. As the three CCM proteins form a trimeric complex
in vitro
and interact with many other proteins, we hypothesized that variants in
CCM1-2-3
and in other genes encoding proteins involved in CCM signaling modify disease severity, as manifested by ICH and greater total or large lesion counts.

Methods:
We analyzed 188 Hispanic CCM1 patients harboring the common Hispanic mutation (CHM,
CCM1
Q455X). ICH and lesion counts at enrollment were obtained by clinical assessment and MRI. Samples were genotyped on the Affymetrix Axiom Genome-Wide LAT1 Human Array. We analyzed 504 variants (MAF≥1%) within +/- 5kb of 42 genes for association with ICH, total and large (≥5 mm in diameter) lesion counts, adjusting for age, gender and family structure.

Results:
At baseline, 30.3% of CCM1-CHM patients had a history of ICH. Mean total lesion count was 60.1 ± 115.0 (range 0 to 713). Mean large lesion count was 4.9 ± 8.7 (range 0 to 104). Two
NTRK1
variants (rs41267423 and rs1800879) as well as
SLMAP
rs7621574 and
PCDHGA1
rs17097189 were significantly associated with ICH (
P
≤0.014). Suggestive associations with ICH (
P
≤0.05) were observed for additional 15 variants in 11 genes.
RAP1GAP
rs2625408 was associated with both total and large lesion counts (
P
≤0.004) and additional 4 variants in 4 genes were associated with one of these phenotypes. No single variant was associated with both ICH and total or large lesion count; however, different variants in
RAP1GAP
and
KDR
genes were associated with all three phenotypes tested.

Conclusions:
Variants in genes involved in CCM signaling may contribute to variability in CCM1 disease severity. Genotypes that replicate in other cohorts might be useful as predictors in clinical management.
Abstract 208: Vascular Risk Factors But Not Transesophageal Echocardiography (TEE) Features Are Associated With Stroke Recurrence in Patients With Cryptogenic Stroke (CS) and Patent Foramen Ovale (PFO)
Authors: Mono Marie-Luise , Kahles Timo , Thaler David E. , Michel Patrik , Weimar Christian , Serena Joaquin , Thijs Vincent , Engelter Stefan , Krämer Markus , Luft Andreas , Eberli Franz , Mallmann Achim , Müller-Eichelberg Andreas , Collins Lester , Hemelsoet Dimitri , Zedde Maria Luisa , De Pauw Adinda , Armon Carmel , Arnold Marcel , Meier Bernhard , Mattle Heinrich P. , Nedeltchev Krassen
Published: July 2021

Background and purpose:
Recurrent ischemic stroke in patients with CS and PFO has been proposed as a marker of increased risk for paradoxical embolism. It is unclear, whether the excess risk is driven by specific features of the PFO (right-to-left shunt (RLS) size, RLS at rest, associated atrial septum aneurysm (ASA)) or the presence of vascular risk factors (vRF). We compare the prevalence of vRF, TEE features, and baseline medications in PFO patients with first-ever versus multiple CS.

Methods:
From September 2008 to March 2013, the International PFO Consortium enrolled 993 patients with ischemic stroke or transient ischemic attack (TIA) and newly diagnosed PFO. In this analysis of baseline data, we included 386 patients with first-ever CS and no radiological evidence of prior cerebral ischemia (first-ever CS group, mean age, 52y) as well as 71 patients with recurrent CS and multiple ischemic lesions on CT and/or MRI (multiple CS group, mean age, 59y). Patients with TIA as index event, those with first-ever CS but additional “silent” ischemic lesions on imaging as well as those with recurrent CS without radiological findings of prior cerebral ischemia were excluded. We used nonparametric tests for independent samples and the Bonferroni correction for multiple comparisons.

Results:
Age > 55y (63% vs. 44%, P=0.001), hypertension (52% vs. 30%, P=0.001), hyperlipidemia (64% vs. 44%, P=0.003), and coronary artery disease (15% vs. 3%, P=0.001) were significantly more frequent in the multiple CS than in the first-ever CS group. The frequencies of male gender, current smoking, diabetes, migraine with or without aura, associated ASA, RLS size, and RLS at rest did not differ between groups. At baseline, patients with multiple CS were more likely to be on antiplatelets (50% vs. 18%), antihypertensive (51% vs. 22%) or lipid lowering drugs (44% vs. 10%, P=0.001 for each comparison) than patients with first-ever CS. The frequency of anticoagulant treatment did not differ between groups.

Conclusions:
In patients with CS, vRF but not specific PFO features were associated with recurrent cerebral ischemic events. The ongoing prospective part of the International PFO Consortium will likely shed light upon the role of vRF control for secondary stroke prevention in patients with PFO.
Abstract 21: Infarct Distributions Differ in Pediatric Sickle Cell Patients With or Without Large Vessel Vasculopathy
Authors: Guilliams Kristin P , Ragan Dustin K , Fields Melanie E , McKinstry Robert C , Shimony Joshua S , Rhodes James N , Hulbert Monica L , Vo Katie D , Lee Jin-Moo , Ford Andria L
Published: July 2021

Introduction:
Children with sickle cell disease (SCD) have a high risk of ischemic strokes in diverse spatial distributions, but mechanisms responsible for these different patterns are unclear.

Methods:
MRIs and MRAs from 2006-2014 were retrospectively collected on SCD children with an overt stroke history. Hemispheres were categorized based on presence or absence of large vessel vasculopathy (Vsc) on MRA. Manually delineated infarcts on FLAIR were individually co-registered to the corresponding T1 MPRAGE maps, and then co-registered onto a common space. Left and right hemispheres were separated with a mask in the common space. Hemispheres were flipped so all with Vsc were oriented as right hemispheres, and those without Vsc as left. Co-registered infarct maps were warped into the final anatomic space and averaged to create a lesion density map. A cerebral blood flow (CBF) map was created from average pseudocontinuous arterial spin labeled measurements prospectively collected on 7 children with SCD and no Vsc.

Results:
Of 22 children with SCD and overt stroke history (median 15.5y, 41% male), 14 had Vsc (median 16 y, 50% male) in 19/44 hemispheres. Both non-Vsc and Vsc hemispheres had infarct hot-spots in a predominantly deep white matter watershed distribution, but Vsc hemisphere infarcts were more numerous, more extensive and encompassed more gray matter (Figure). Hot-spots overlapped with regions of lowest flow within the deep white matter on the CBF map. Vsc hemispheres also had infarcts in classic large artery territories, not seen in non-Vsc hemispheres.

Conclusions:
The etiology of ischemia in SCD is likely multifactorial, involving reduced oxygen delivery (anemia), impaired CBF (Vsc), and possible associated thrombosis (Vsc with low/turbulent flow distal to stenosis). Differential patterns of infarction reflect these different layers of compromise.
Abstract 212: Factors Associated with Symptom Development in Asymptomatic Carotid Artery Stenosis: Multimodal Carotid and Perfusion Imaging Study
Authors: Kwon Soonwook , Lee Mi Ji , Kim Keon-Ha , Jeon Pyoung , Kim Young-wook , Kim Dong-Ik , Kim Suk Jae , Bang Oh Young , Chung Chin-Sang , Lee Kwang Ho , Kim Gyeong-Moon
Published: July 2021

Background:
The predictors of symptom development in asymptomatic carotid stenosis are still unclear. We sought to identify factors associated with symptom development in asymptomatic carotid stenosis using multimodal imaging technique.
Methods:
We retrospectively collected patients who had carotid artery revascularization procedures (carotid endarterectomy [CEA] or carotid artery stenting [CAS]) from April 2007 to May 2013. Patients who had event of cerebral ischemic stroke during 6 months before CEA or CAS were categorized as a symptomatic carotid stenosis. Results from carotid Duplex sonography, CT angiography, brain MRI and MRA, perfusion-weighted MRI (PWI), and demographic profiles were compared. Multivariate logistic regression analysis was performed to identify factors associated with symptom carotid stenosis.

Results:
A total of 684 patients (asymptomatic 58%, symptomatic 42%) with carotid stenosis more than 50% were included. The presence of ischemic heart diseases, peripheral artery occlusive disease and use of statin were higher in the asymptomatic carotid stenosis. On Duplex scan, ulceration, echolucent plaque, and heterogeneous components of plaque were more frequent in symptomatic carotid stenosis. Angiographic data showed the length of plaque was longer in symptomatic carotid stenosis. Presence of deep white matter hyperintensity, FLAIR vessel sign and GRE vessel sign were more frequently observed in symptomatic carotid stenosis. Patients with symptomatic carotid stenosis had increased cerebral blood flow, cerebral blood volume (CBV), and delayed time to peak when compared to the asymptomatic stenosis. Multivariate analysis revealed length of plaque (>20mm), deep white matter hyperintensity and increased CBV were associated with symptomatic carotid stenosis (Odd ratio [OR]=2.339, 95% confidence interval [CI] 1.312-4.169, P=0.004; OR=2.315, 95% CI 1.160-4.619, P=0.017; OR=2.242, 95% CI 1.127-4.463, P=0.021, respectively).

Conclusion:
Plaque burden, deep white matter hyperintensity, and increased CBV were independent predictors of symptom development in carotid stenosis. Multimodal imaging may be useful to identify high risk patients of ischemic stroke among asymptomatic carotid stenosis.
Abstract 3: Genetic Factors And Motor Status After Stroke
Authors: Cramer Steven C , See Jill , Aizik Shlomit , Shahbaba Babak , Wolf Steven L , Dromerick Alexander W , Winstein Carolee J ,   ICARE Investigators
Published: July 2021

BACKGROUND:
Genetic factors may help identify biological subgroups of patients with stroke. The current study focused on two specific genetic polymorphisms and examined each in relation to baseline values for the two primary behavioral measures used in the Interdisciplinary Comprehensive Arm Rehab Evaluation (ICARE) After Stroke study: [1] the Stroke Impact Scale (SIS-16), a measure related to impairment, disability, and handicap after stroke, and [2] the Wolf Motor Function Test (WMFT) time, which measures arm disability. Specifically, the current substudy hypothesized that [1] the val66met polymorphism for brain-derived neurotrophic factor (BDNF) and [2] the ApoE e4 polymorphism are each associated with poorer motor status by the SIS-16 and the WMFT.

METHODS:
Of the 361 subjects in the ICARE study, genetic samples were acquired in 216. BDNF polymorphism and ApoE e4 polymorphism status were determined, then compared with scores on SIS-16 and WMFT as determined at baseline in the ICARE study, adjusting for age.

RESULTS:
The 216 enrollees in this genetics substudy had age 61 +/- 13, were 67% male, and did not differ from the other 145 ICARE participants in age or race. The BDNF val66met polymorphism was present in 19.7% of subjects, and ApoE e4 in 29.8%; both polymorphisms were in Hardy-Weinberg equilibrium. Among those with the BDNF val66met polymorphism, baseline scores on the SIS-16 were significantly poorer (58 +/- 18 vs. 67 +/- 16, p=0.007); BDNF polymorphism status explained 6.5% of the variance in SIS-16 score. BDNF polymorphism status did not correlate with WMFT, and ApoE e4 polymorphism status did not correlate with the score on either behavioral measure.

CONCLUSION:
Among enrollees in a phase III clinical trial of motor therapy after stroke, genetic variation related to BDNF polymorphism status accounted for a significant difference in baseline status for SIS-16, one of the trial’s two primary endpoints, to a degree (9 points) that approaches minimum clinically important difference. Genetic factors may be an important source of variance to consider in studies of restorative stroke therapy after stroke.
Abstract 37: Refining of the Association of Fever with Functional Outcome in SAH
Authors: Pegoli Marianna , Kramer Christopher L , Mandrekar Jay , Lanzino Giuseppe , Rabinstein Alejandro
Published: July 2021

Background:
Fever has been associated with worse clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH). However, the impact of the cause, severity, and duration of fever is not clear. We conducted this study to evaluate the impact of fever and subfebrile load and fever characteristics on functional outcome.

Methods:
We collected detailed information on fever onset, cause, severity, and duration during the ICU stay in a cohort of 586 consecutive patients with aSAH. Fever was defined as core body temperature ≥ 38.3°C. Subfebrile measurements were those between 37 and 38.2°C. Febrile and subfrebile loads were defined as number of hours with fever or subfebrile measurements. Poor outcome was defined as modified Rankin score (mRS) > 2. Univariate and multivariate logistic regression models were developed to define predictors of outcome using various categorizations of fever cause, severity, and duration.

Results:
532/586 patients (90.9%) had fever for a mean of 2.1±3.0 days. Fever started within 24 hours in 69 (11.8%) and within 72 hours in 110 (18.8%). Poor outcome occurred in 175 patients (29.9%). On univariate analysis, days of fever, febrile load, fever onset within 24 hours, and fever onset within 72 hours were associated with poor outcome (all p<0.001), but subfebrile load was not (p=0.58). On multivariate model constructed with all variables associated with outcome on univariate analyses (including age, WFNS grade, modified Fisher grade) days of fever remained independently associated with poor outcome (OR 1.14 of poor outcome per day of fever, 95% CI 1.06-1.22; p=0.0006) displacing all other fever measures from the final model.

Conclusions:
The great majority of patients with aSAH are febrile during their ICU stay. Early onset of fever, number of hours with fever, and especially days of fever are associated with poor functional outcome. Conversely, the number of hours with elevated but subfebrile temperature does not influence clinical outcome. These data suggest that prolonged fever should be avoided, but subfebrile temperatures do not justify intervention.
Abstract 39: Decreased Ferroxidase Activity in Cerebrospinal Fluid Following Subarachnoid Hemorrhage
Authors: Gomes Joao A , Love Anna , Cotleur Anne , Provencio Javier
Published: July 2021

Introduction:
We previously reported on the relationship between unbound CSF iron and brain injury following SAH. The ferroxidase ceruloplasmin (Cp) regulates iron levels in the CNS and prevents free radical injury. Paradoxically, oxidative stress is known to cause structural modifications that result in decreased enzymatic activity of Cp. We sought to determine if CSF of patients with SAH exhibits impaired ferroxidase activity (FA).

Methods:
Samples of CSF were obtained on day 5 following aneurysm rupture and levels of malondialdehyde (MDA; a marker of lipid peroxidation) and ferroxidase activity (defined as the amount of enzyme that converts 1 μM of substrate into product per minute) were determined by means of absorbance and colorimetric assays. Ceruloplasmin concentration in CSF was measured with ELISA. Demographic and clinical data were recorded. Values are expressed as mean ± SEM. Comparisons were made using Wilcoxon rank sum test. Simple linear regression analysis was performed for comparison of continuous variables.

Results:
A total of 5 patients and 4 control subjects were included in this pilot study. Median Hunt-Hess and modified Fisher scores were 4 (IQR 1.5) and 4 (IQR 1), respectively. Levels of MDA in CSF (9.2 ± 0.9 vs. 0.09 ± 0.01 μM,
p
=0.02) were significantly higher in SAH patients, while FA was significantly reduced (64.8 ± 17.1 vs. 284.1 ± 64.9 U/L,
p
=0.01). Ceruloplasmin concentration was higher in SAH samples (49.4 ± 12 vs. 1.72 ± 0.7 mg/L,
p
=0.04), and patients who developed delayed cerebral ischemia had lower CSF FA (43.2 ± 6.3 vs. 97.2 ± 32.4 U/L,
p
=0.07), compared to those who did not.

Conclusions:
The ferroxidase activity of CSF following SAH is significantly impaired, in spite of higher ceruloplasmin concentrations. Evidence of increased CNS oxidative damage was also demonstrated in our cohort. We postulate that structural modifications in Cp mediated by an oxidative milieu occur in SAH and are associated with decreased enzymatic function.

There is a possible inverse relationship between ferroxidase activity and risk of development of delayed cerebral ischemia. Further studies are needed to explore the significance of these findings.
Abstract 54: Reduction in time to Imaging and intravenous Thrombolysis by in-field Evaluation and Treatment in a Mobile Stroke Treatment Unit
Authors: Taqui Ather , Cerejo Russell , Itrat Ahmed , Uchino Ken , Donohue Megan M , Briggs Farren , Organek Natalie , Buletko Andrew Blake , Sheikhi Lila , Buttrick Maureen , Khawaja Zeshaun , Wisco Dolora , Winners Stacey , Reimer Andrew , Frontera Jennifer , Manno Edward , Swickard Scott , Hustey Fredric , Kralovic Damon , Rasmussen Peter , Hussain Muhammad S
Published: July 2021

Background:
A Mobile stroke treatment unit (MSTU) with on-site treatment team can provide thrombolysis successfully in a pre-hospital setting more quickly than traditional treatment in the hospital. We compared our experience of patients treated with the mobile stroke unit to treatment of patients brought to emergency department via a traditional ambulance

Methods:
We implemented a MSTU at our institution starting July 18, 2014. The unit includes a registered nurse, paramedic, emergency medical personnel, and CT technologist. A stroke physician evaluated each patient via telemedicine and a neuroradioloigst and stroke physician remotely assessed images obtained by CereTom mobile CT (Neurologica, Danvers, USA). Data were entered in medical records and a prospective registry. The evaluation and treatment in the first 3 weeks of implementation of MSTU was compared to a control group of patients brought to the emergency department via a traditional ambulance in the preceding 3 months. The time of alarm was the dispatch time by the city emergency medical service.

Results:
23 patients were treated in the MSTU group and 34 in the control group. There were no significant differences in age or gender between the groups. The median time for alarm-to-MSTU-arrival-at-scene was 13 minutes (Interquartile range 9-17). There was a significant reduction of median alarm-to-CT scan completion times (41 min in MSTU vs 62 min in controls, p<0.0001) and median alarm-to-thrombolysis times (64 min in MSTU vs 104 min in controls, p<0.008). Six patients (26%) received thrombolysis in MSTU group and 5 (14%) in the controls. There were no early complications of thrombolysis in the MSTU group.

Conclusion:
Compared with traditional ambulance model, ambulance-based thrombolysis resulted in decreased time to imaging and treatment.