bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP54: Early MRI Facilitates Stroke Evaluation and Decreases Length of Stay for Ischemic Stroke Patients
Authors: Manwani Bharti , Rath Subhendu , Woodward Matthew , Staff Ilene , Fortunato Gilbert , Modak Jahanavi , Stretz Christopher , Finelli Pasquale , Lee Nora
Published: June 2021

Background:
Imaging studies are an integral part of stroke evaluation and non-contrast head CT is the initial imaging modality. Although critical for assessing acute hemorrhage, ischemic changes may not be visible on CT for up to 24 hours. MRI brain detects ischemic changes within 20 minutes of symptom onset. It is an invaluable tool to confirm an ischemic stroke and determine its etiology. A focused workup for stroke etiology or evaluation for stroke mimics accelerates management strategies and reduces length of stay in the hospital. Early discharge facilitates early rehabilitation and better functional recovery of stroke patients. Current guidelines for management of acute stroke recommend head CT within 25 minutes of presentation. However, to date, a recommendation regarding
timeline for MRI brain in stroke evaluation is lacking. Objective of this study was to investigate the correlation between time to MRI & length of hospital stay to functional outcome in stroke patients.

Methods:
648 patients (mean age 69±0.5 years; 50.4% women) admitted to Hartford Hospital (Comprehensive Stroke Center) with a focal neurological deficit in the year 2014 and got a CT head and MRI brain were enrolled in the study. Data collection was done via stroke database and retrospective chart review. Patients with any hemorrhage or age<18 years, were excluded from the study. We used Mann-Whitney U and Spearman’s correlation co-efficient to compare time from arrival to MRI and length of stay in the hospital.

Results:
There was a significant effect of time from arrival to MRI on length of hospital stay (r=0.27, p<0.01). Subgroup analysis revealed a significant decrease in length of stay if MRI was done within 12 hours of admission (p<0.02) as compared to 24 hours or above (p<0.12). Based on MRI findings, 27% patients had a new diagnosis of stroke and in 24.1% patients stroke was ruled out. This change in diagnosis had a significant effect on length of stay (Z=-2.4, p<0.02).

Conclusions:
Our study indicates that delay in MRI for a suspected stroke increases hospital length of stay.
It suggests
MRI within 12 hours of admission
to be the new standard of care for stroke patients. Ongoing work will assess the correlation of timing to MRI to functional outcomes in stroke patients.
Abstract WP58: Correlating Stroke Volume with National Institute of Health Stroke Scale as a Means of Determining Patient Prognosis
Authors: Zelnick Pamela J , Zhu Liang , McCullough Louise D , Sarraj Amrou
Published: June 2021

Introduction:
The NIH Stroke Scale (SS) is a widely used tool for directing treatment and predicting outcomes in Acute Ischemic Stroke (AIS). Severe strokes with high admission SS often correlate with long term disability, and as such, SS serves as a strong predictor of outcome. Final infarct volume (FIV) is also a pivotal predictor of stroke outcome. We aimed to evaluate the relationship between SS, FIV and outcome, and hypothesize that a combined approach evaluating both FIV and SS may more accurately correlate with patient outcomes.

Methods:
A single center, retrospective cohort study, examined AIS patients with large vessel occlusion (LVO) affecting the anterior circulation, between July 2004 and April 2013. Patients were stratified by treatment to 1) intra-arterial therapy, 2) IV tPA, 3) both or 4) neither. Primary outcomes measured were mRS at discharge and 90 days (good outcome mRS 0-2, poor 4-6). FIV was manually calculated from DWI obtained within the first 7 days of presentation. SS and FIV were compared against good and poor mRS outcomes using Wilcoxon rank sum test. Logistic regression analysis was used to evaluate the association between SS, FIV and mRS. Finally, likelihood ratio test was used to compare model fit between a model including SS alone and model including both SS and FIV.

Results:
In 332 patients, SS was significantly higher in the poor outcome group (17.3 ± 5.4) when compared to the good outcome group (13.0 ± 6.1) (p=0.0002). In the same analysis, FIVs were also larger in the poor outcome group (110.3 ± 113 cm3) when compared to the good outcome group (37.2 ± 68.3 cm3) (p<0.0001). A combined SS and FIV model correlated significantly better with discharge outcome than did SS alone (p=0.0015). Analysis of 182 patient outcomes at 90 days maintained similar findings, with SS (18 ± 5.9) and FIVs (115.4 ± 121.0 cm3) significantly higher in poor outcomes than in good outcomes; (13.0 ± 5.4) and (35.7 ± 38.2 cm3) respectively (p<0.0001). Combined SS and FIV model, again, was significantly better at modeling outcome at 90 days than was a model including SS alone (p=0.0044).

Conclusions:
A combined model including FIV and SS better correlates with clinical outcomes at discharge and 90 days in patients with AIS due to LVO, than does a model using SS alone.
Abstract WP7: Impact of Stent-Retrievers on Real World Stroke Outcomes Utilizing the National Inpatient Sample
Authors: Behera Anit K , Adjei Boakye Eric , Armbrecht Eric , Alshekhlee Amer , Edgell Randall
Published: June 2021

Introduction:
In 2015, mechanical thrombectomy (MT) with stent-retrievers became a standard of care treatment for acute ischemic stroke (AIS). Data on the impact of stent-retrievers on clinical outcomes in non-trial settings is limited. This study examines the association between the transition from first generation devices to stent-retrievers and clinical outcomes in a large inpatient sample.

Methods:
We used data from the 2010 - 2013 National Inpatient Sample for patients (n=3553) with a diagnosis of AIS using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9 CM) diagnosis codes who underwent MT using ICD-9-CM procedure code of 39.74. Patients in the 2010-2011 time period (Period 1) were categorized as first generation device patients and patients in the 2012-2013 time period (Period 2) were categorized as second generation device patients. Outcomes were in-hospital mortality (alive/dead), discharge disposition (favorable/unfavorable), and length of stay (normal/prolonged). Weighted binary logistic regression models adjusting for patient and hospital level factors were developed.

Results:
The number of procedures increases from 679 in 2010 to 1128 in 2013. In Period 1, 1443 patients were treated with MT and in Period 2, 2110 patients were treated with MT. In the adjusted model, compared to patients in Period 1, patients in Period 2 were 31% less likely to be deceased (aOR = 0.69; 95% CI = 0.58-0.83) and 22% less likely to be discharged to an unfavorable location (aOR = 0.78; 95% CI = 0.64-0.95). There was no statistically significant association between treatment period and length of stay (aOR = 0.95; 95% CI = 0.82-1.10).

Conclusion:
Patients that had an MT performed during the stent-retrievers years were less likely to expire and be discharged to an unfavorable location than patients in the first generation device years. This confirms the past literature on the beneficial effects of a second generation of stent-retrievers in the treatment of acute ischemic stroke in a real world setting.
Abstract WP73: Comparison of Clinical Scores for Symptomatic Intracerebral Hemorrhage After Intravenous Thrombolysis
Authors: Homma Kazunari , Takizawa Shunya , Ohnuki Youichi
Published: June 2021

Background:
Stroke guidelines recommend that thrombolytic therapy should be carried out within 60 minutes from the arrival at the hospital. CT may decrease door-to-treatment interval compared to MRI. However, MRI may provide more information on brain pathology to select the treatment than CT. Thus, it remains controversial which is informative for selecting thrombolysis and endovascular treatment in acute ischemic stroke between CT and MRI.

Purpose:
Purpose of this study is to evaluate which clinical risk score using CT or MRI presents the best predictive performance for symptomatic intracranial hemorrhage (SICH).

Methods:
Consecutive stroke patients suffering anterior circulation were analyzed, who were received IV rt-PA therapy between October 2005 and March 2016. We calculated nine scores for each patient: DRAGON, MRI-DRAGON, HAT, SEDAN, SITS-ICH, SPAN-100, ASTRAL, PRS, and GRASPS. The area under the receiver operating characteristic curve was calculated to determine the predictive performance of each SICH predictive score according to two criteria: NINDS and ECASS-II. Logistic regression determined the odds ratio for two SICH criteria.

Results:
A total of 166 acute ischemic stroke patients were analyzed (113 men, 72±12 years old). SICH defined following NINDS criteria occurred in 14 patients, SICH defined following ECASS criteria occurred in 11 patients. 144 patients were performed both CT and MRI [median time between CT and MRI, 11; IQR 8-16]. Only 2 scores predicted SICH (NINDS criteria) with good accuracy (ROC area> 0.7, Figure1). Only one score predicted SICH (NINDS criteria) with good accuracy (Figure2).

Conclusion:
We concluded that MRI-DRAGON presented the best predictive performance for SICH, and MRI may be more useful for selecting thrombolysis and endovascular treatment in acute ischemic stroke than CT.
Abstract WP91: Long-Term Risk of Stroke after Stent-Assisted Coiling of Unruptured Intracranial Aneurysms
Authors: Salehi Omran Setareh , Navi Babak B , Kamel Hooman
Published: June 2021

Background:
Long-term comparative data are limited regarding stent-assisted coiling versus coiling alone for unruptured intracranial aneurysms. We compared the risks of ischemic stroke and intracranial hemorrhage after stent-assisted coiling versus coiling without stenting.

Methods:
Using administrative claims data on all admissions to nonfederal acute care hospitals in CA, FL, and NY from 2005-2013, we identified adult patients who underwent stent-assisted coiling or coiling without stenting for an unruptured intracranial aneurysm. Our primary outcome was a composite of ischemic stroke or intracranial hemorrhage (intracerebral, subarachnoid, or subdural hemorrhage). Our secondary outcomes were ischemic stroke and intracranial hemorrhage. Outcomes were ascertained by previously validated ICD-9-CM diagnosis codes. To focus on the long-term safety of these techniques, we excluded patients with an outcome during the index hospitalization. Kaplan-Meier survival statistics and Cox regression were used to compare stroke risk after stent-assisted coiling versus coiling alone.

Results:
We identified 5,398 patients (mean age, 58 [±13] years; 79% female) treated with endovascular coiling, of whom 254 (4.7%) underwent stent-assisted coiling. Over 4.2 (±2.0) years of follow-up, 357 outcomes were identified (205 ischemic strokes, 152 intracranial hemorrhages). By 8 years, the cumulative rate of stroke or hemorrhage was 8.5% (95% confidence interval [CI], 5.3-13.6%) with stent-assisted coiling versus 9.2% (95% CI, 7.8-10.9%) with coiling alone. Most outcomes occurred in the first year (3.6% after stent-assisted coiling versus 3.9% after coiling alone). After adjustment for demographics and vascular risk factors, the risk of ischemic stroke or intracranial hemorrhage was similar after stent-assisted coiling compared to coiling alone (hazard ratio [HR], 1.1; 95% CI, 0.7-1.7). Our results were unchanged when assessing the secondary outcomes of ischemic stroke (HR, 1.4; 95% CI, 0.8-2.4) or intracranial hemorrhage (HR, 0.7; 95% CI, 0.3-1.7).

Conclusions:
After uncomplicated coiling of an unruptured aneurysm, long-term rates of stroke and intracranial hemorrhage were similar for stent-assisted coiling and coiling without stenting.
Abstract 110: RNA Sequencing Reveals Novel Macrophage Transcriptome Favoring Neurovascular Plasticity After Ischemic Stroke
Authors: Shi Yejie , Wang Rongrong , Liu Yaan , Ye Qing , Hassan Sulaiman H , Zhao Jingyan , Hu Xiaoming , Leak Rehana K , Rocha Marcelo , Wechsler Lawrence R , Chen Jun
Published: June 2021

Introduction:
Blood monocytes/macrophages (MΦ) infiltrate the brain in massive numbers after ischemic stroke, but their functional roles in the post-stroke brain remain elusive.

Methods:
We sorted CD11b
+
CD45
high
monocytes/MΦ from mouse blood and brain 5d after distal MCAO (dMCAO) and investigated their transcriptomic profiles by RNA-seq (n=3/group).

Results:
Robust genomic changes occurred in MΦ invading the post-dMCAO brain compared to their counterparts in the blood (3196 differentially expressed genes with >2 fold changes; FDR<0.05). In addition to their canonical role in immune responses, brain MΦ expressed unique transcriptomic programs which may favor post-stroke neurovascular repair. Functional enrichment analysis of brain MΦ transcriptome revealed significant overrepresentation (p<0.01) of 110 biological processes linked to neurovascular remodeling and plasticity (e.g., angiogenesis and axonal regeneration), suggesting a previously underappreciated role for MΦ in post-stroke brain repair. Upstream Regulator analysis predicted PPARγ as a master regulator (z-score=2.64, p<10
-15
) that drives the transcriptional reprogramming in post-stroke brain MΦ and dictates their functional phenotype. Accordingly, tamoxifen-induced, myeloid cell-specific PPARγ knockout mice demonstrated less post-stroke angiogenesis (BrdU+CD31 staining) and neurogenesis (BrdU+NeuN) than WT mice (n=9/group, p<0.01), which correlated significantly with the exacerbation of neurological deficits in these mice (n=9/group, p<0.01 vs WT in foot fault and adhesive removal tests) at 35d after dMCAO.

Conclusions:
Our study reveals a novel repair-enhancing transcriptome in brain MΦ during post-stroke neurovascular remodeling. As a master molecule controlling genomic reprogramming, PPARγ is a rational therapeutic target for promoting beneficial MΦ functions, and facilitating neurorestoration and long term functional recovery after ischemic stroke.
Abstract 111: Myeloid Specific Deletion of CD36 Increases Microglia-Like CD45
Low
Subset and Exacerbates Stroke-Induced Brain Injury
Authors: Park Keun Woo , Balkaya Mustafa , Yang Jiwon , Cho Sunghee
Published: June 2021

Objective:
CD36 regulates biological and pathological processes including inflammation, resolution, phagocytosis, and angiogenesis. Highly expressed in monocytes/macrophages (MM), MM CD36 has been implicated in both detrimental and beneficial effects in acute stroke outcome and recovery. Using myeloid specific deficiency of CD36 (CD36KO

MM

) mice, the present study addresses the role of MM CD36 on subset composition of MM in the acute and recovery phases of stroke.

Methods:
WT (CD36

fl/fl

) and CD36KO

MM

(M/F, 12w old) mice were subjected to transient focal ischemia. Brain immune cells were collected at 3d, 7d and 2m (n=8-12/timepoint). Infarct volume and hemispheric swelling were measured at 3d (n=13/genotype). In the isolated brain immune cells, CD11b+ cells were further distinguished by CD45

Hi

and CD45

Low

subsets. The extent of MM trafficking was determined by an intravenous infusion of control GFP+ splenocytes into the stroked WT and CD36KO

MM

mice 1d prior to sacrifice and MM subset analyses.

Results:
Compared to WT mice, CD36KO

MM

mice showed no difference in CD45

Low

subset at 3d, 7d and 2m after stroke. However, CD36KO

MM

mice displayed a significant reduction of CD45

Hi

subset, presumably infiltrating cells, at these time points (n=4-8 /group, P<0.01). Adoptive transfer of control GFP+ splenocytes to stroked CD36KO

MM

mice resulted in an increase of GFP+ cells in CD45

Low

but a profound reduction in CD45

Hi

subset. Despite the near absence of CD45

Hi

and increased CD45

Low

population in the post-ischemic brain, CD36KO

MM

mice displayed exacerbation of brain injury (15.1±13.7 vs 25.8±17.5 mm
3
, p<0.05) and brain swelling (12.1±10.3 vs 18.4±12.7 %, p=0.1).

Conclusion:
The observed reduction of CD45

Hi

subset and exacerbation of brain injury in CD36KO

MM

mice suggests a beneficial role of infiltrated CD45

Hi

MMs in limiting stroke injury. The sustained trafficking at 2m indicates potential involvement of MM CD36 in the recovery process. Further studies to assess long-term outcomes of CD36KO

MM

mice will provide critical insights on the role of macrophage CD36 in stroke recovery.
Abstract 115: Current Status of Acute Stroke Management in Korea: A Nationwide Report Based on 19,608 Patients Treated in 216 Hospitals
Authors: Kim Jun Yup , Lee Keon-Joo , Kang Jihoon , Kim Beom Joon , Kim Seong-Eun , Oh Hyunji , Park Hong-Kyun , Cho Yong-Jin , Park Jong-Moo , Park Kwang-Yeol , Lee Kyung Bok , Lee Soo Joo , Kim Tackeun , Lee Ji Sung , Lee Juneyoung , Yang Ki Hwa , Choi Ah Rum , Kang Mi Yeon , Bae Hee-Joon
Published: June 2021

Introduction:
There have been few reports on status of acute stroke management at a national level worldwide, and none in Korea. This study is aimed to describe the current status and disparities of acute stroke management in Korea.

Methods:
Data from 5th (2013) and 6th (2014) national surveys for assessing quality of acute stroke care were used. Patients with principal diagnosis codes indicating subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), ischemic stroke (IS), who were admitted via emergency rooms within 7 days of onset at hospitals treating 10 or more stroke cases during the each 3-month survey period were selected.

Results:
A total of 19,608 stroke cases (age, 67.7±13.5years; female, 45%; IS, 76%; ICH, 15%; SAH, 9%) treated in 216 hospitals were analyzed. Thirty-one percent of hospitals had stroke units and 41% of stroke cases were treated at hospitals without stroke units. In IS, IV thrombolysis (IVT) and endovascular treatment (EVT) rates were 10.7% and 3.6%, respectively. Thirty-nine percent of IVT and fifty-two percent of EVT cases were performed in hospitals with annual volume of <25 IVT and <15 EVT. Centralization of EVT showed disparities by region (Figure). Carotid endarterectomy, carotid artery stenting, decompressive, bypass surgery was conducted in 0.2%, 1.4%, 1.0%, 0.2% of IS cases; decompressive surgery was done in 28.1% of ICH cases; surgical clipping, endovascular coiling was done in 17.2%, 14.3% of SAH cases, respectively. There were noticeable regional disparities in various interventions, use of ambulance, arrival time and provision of stroke unit service.

Conclusions:
This study is the first report on the status of acute stroke care in Korea on a national level. Large number of recanalization therapies were performed in low-volume-hospitals. Expansion of stroke unit service, stroke center certification or accreditation, and connections between stroke centers and EMS are highly recommended.
Abstract 121: Visualization and Quantification of Post-Stroke Neural Connectivity in Mice Using Serial Two-Photon Tomography
Authors: Poinsatte Katherine , Ramirez Denise M , Ajay Apoorva , Betz Dene , Plautz Erik , Kong Xiangmei , Meeks Julian P , Stowe Ann , Goldberg Mark P
Published: June 2021

Background:
It is a challenge to characterize post-stroke changes in neural connectivity at microscopic scale across the entire rodent brain. Serial two-photon tomography (STPT) is an advanced laser-scanning microscopy technique which collects serial fluorescence images across the brain and reconstructs 3D datasets. We examined changes in motor connectivity after cortical infarcts in mice, using retrograde viral tract tracing, STPT imaging, automated registration workflow, and machine learning algorithms.

Methods:
Young male C57/B6 mice received a photothrombotic motor cortex (M1) stroke (n=3) or sham surgery (n=3). 15 days later, a retrograde pseudorabies trans-synaptic virus encoding fluorescent protein was injected into the left forelimb flexor muscles to label motor system projections. Mice were sacrificed 3 weeks post-stroke. STPT images were analyzed using supervised machine learning (pixel-wise random forest via the “ilastik” software package) and datasets were mapped to the Allen Mouse Brain Atlas for region-specific visualization and quantification of fluorescent signals.

Results:
Machine learning algorithms successfully identified neuronal cell bodies, neuronal processes, and ischemic tissue throughout the brain. The fluorescent signal of cells and neuronal processes was higher in the right M1 and SS of uninjured mice than the left M1 and SS. After stroke, this signal was diminished in the right M1 and SS. Labeled neurons were also reduced in the left M1 suggesting the presence of secondary transcortical connections.

Conclusions:
STPT generates whole brain datasets that when analyzed with ML algorithms show early alterations in post-stroke neural connectivity in the corticospinal tract. Further studies utilizing monosynaptic and conditional viral tracers will better assess the full spectrum of connectivity changes during post-stroke functional recovery.
Abstract 122: Selective Intra-Arterial Cooling (SI-AC) Improve Recovery in a Nonhuman Primate Model of Ischemic Stroke
Authors: Wu Di , Wu Longfei , Chen Jian , Ding Yuchuan , Ji Xunming
Published: June 2021

Background and Purpose:
Recent findings from our group prove that selective intra-arterial cooling (SI-AC) treatment leads to prominent and persistent functional improvements after stroke in both rodents and non-human primate (NHPs) stroke models. In this study, neuro-protective potentials of SI-AC treatment were further explored at brain network and histopathological levels in preclinical higher-order brains.

Methods:
Cerebral ischemia/reperfusion was induced by thrombus and thrombolysis (t-PA) in adult rhesus monkeys (n=10). SI-AC treatment was randomly given to 5 models. Conventional MRI and diffusion tensor imaging scans were performed 4 h, 7 and 30 days post focal ischemia. Effects on functional recovery were also assessed through longitudinal neurologic scores and behavior tests. Animals were euthanized after the final scan for histological analysis.

Results:
SI-AC treatment led to a higher rate of infarct reversal, significantly mitigated neurologic deficits, and more preserved dexterity when compared with those only receiving t-PA during a 30-day observation period. More fiber numbers, a higher FA values based on DTI analysis, and a higher integrity of white matter based on immunochemistry in ipsilateral side were observed in models receiving t-PA plus SI-AC during the same observation period. Histological findings, consistent with MRI images in the infarct size and reversal, indicated that myelin damage, spheroids, and spongiosis were significantly improved in models receiving SI-AC treatment than those with t-PA alone treatment.

Conclusions:
Our findings further supported that SI-AC as an adjunctive treatment could significantly improve neural tissue and functional preservation in a large animal model, suggesting its potential application in ischemic stroke treatments.
Abstract 133: White Matter Hyperintensity and Cardiovascular Disease Outcomes: A Secondary Analysis of the SPRINT MIND Trial
Authors: de Havenon Adam H , Turan Tanya , Yeatts Sharon , Gottesman Rebecca , Prabhakaran Shyam , Rost Natalia
Published: June 2021

Background:
The Systolic Blood Pressure Intervention Trial (SPRINT) randomized patients to a goal SBP <120 mm Hg vs. <140 mm Hg . A subset of patients enrolled in SPRINT MIND, which performed a baseline MRI and measured white matter hyperintensity volume (WMHv). We evaluated the association between WMHv and cardiovascular events.

Methods:
The primary outcome was a composite of stroke, MI, ACS, decompensated CHF, or CVD death. The secondary outcome was stroke. The WMHv was divided into quartiles. We fit Cox models to the outcomes and report adjusted hazard ratios for the quartiles of WMHv, and stratified by SPRINT treatment arm.

Results:
Among 719 included patients, the mean WMHv in the quartiles was 0.34, 1.09, 2.61, and 10.8 mL. The primary outcome occurred in 51/719 (7.1%) and the secondary outcome in 10/719 (1.4%). The WMHv was associated with both outcomes (Table 1, Figure 1). After stratifying by treatment arm, we found the association persisted in the standard, but not intensive, treatment arm (Table 2). However, the interaction term between WMHv and treatment arm was not significant.

Conclusions:
We observed that degree of WMH was associated with CVD and stroke risk in SPRINT MIND. The risk may be attenuated in patients randomized to intensive BP lowering. Trials are needed to determine if intensive BP lowering can prospectively reduce the high cardiovascular risk in patients with WMH.
Abstract 142: Quantitative Susceptibility Mapping and Vessel Wall Imaging as Screening Tool to Detect Microbleed in Sentinel Headache
Authors: Ishii Daizo , Nakagawa Daichi , Zanaty Mario , Roa Jorge A , Kasab Sami A , Shaban Amir , Hudson Joseph S , Osorno-Cruz Carlos , Byer Stefano , Allan Lauren , Torner James C , Awad Issam A , Carroll Timothy J , Samaniego Edgar A , Hasan David M
Published: June 2021

Objective:
Imaging via MR-quantitative susceptibility mapping (QSM) can identify reliably microbleeds (MBs) associated with intracranial aneurysms (IAs) in subjects presenting with severe headache suggestive of sentinel headache (SH) preceding subarachnoid hemorrhage. However, its use is limited due to associated skull base bonny artifact. Vessel wall imaging (VWI) is not limited by bonny artifact and therefore could be an alternative to QSM in detecting MBs. The purpose of this study is to examine the correlation between QSM and the MR-VWI in detecting MBs associated with severe headache suggestive of SH.

Methods:
We performed a prospective single-center study of subjects with unruptured IAs with initial presentation of headaches. All subjects underwent evaluation using 3T-MRI protocol which included MRA, QSM, and pre- and post-contrast VWI of the IAs. Presence/absence of MBs detected by QSM was correlated with aneurysm wall enhancement (AWE) on MR-VWI.

Results:
In the interval of November 2017 to June 2019, a total of 40 subjects harboring 51 unruptured IAs were enrolled in the study. MBs and AWE were detected in 12 (23.5%) and 22 (43.1%) IAs, respectively. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of QSM detecting MBs associated with recent/remote SH was 100% for all, respectively. The sensitivity, specificity, PPV, and NPV of AWE on VWI for detecting MBs confirmed by QSM was 91.7%, 71.8%, 50%, and 96.6%, respectively.

Conclusions:
The combination of imaging findings of MR-VWI and QSM can be used reliably for detection of MBs in subjects with IAs whose presentation is suggestive of SH. If proven in larger cohort, this could eliminate the need for lumbar puncture to screen for SH in subjects with IAs presenting to the emergency department with headaches.
Abstract 146: Time Matters: Adjusted Analysis of the Influence of Direct Transfer to Angio-Suite Protocol in Functional Outcome
Authors: Requena Manuel , Olivé-Gadea Marta , García-Tornel Álvaro , Rodríguez-Villatoro Noelia , Juega Jesús , Deck Matías , Boned Sandra , Muchada Marian , Pagola Jorge , Rodríguez-Luna David , Hernández David , Rubiera Marta , Tomasello Alejandro , Molina Carlos , Ribó Marc
Published: June 2021

Direct transfer to angio suite (DTAS) protocol is a promising measure to improve onset to recanalization time in patients who undergo endovascular treatment. The association of different time windows with prognosis in this population is influenced by several factors. We aim to analyze the influence of DTAS in clinical and functional outcome depending on time from symptom onset to treatment.

Methods:
Retrospective case-control study of 174 consecutive DTAS cases matched with 175 patients initially transferred to CT (DTCT) from February 2016 to April 2019. To obtain comparable groups on admission, cases and controls were matched by occlusion location, age (±2 years), baseline NIHSS score (±2 points) and time from symptoms onset to hospital arrival (±30 minutes). We analyzed the rate of good functional outcome at 3 months (mRS 0-2) and safety variables stratified in less or more than 3 hours from onset to arrive.

Results:
There were no significant differences regarding age, gender or baseline NIHSS score (table 1). Median door-to-groin time was shorter in the DTAS patients (16 (13-21) minutes Vs 70 (41.5-98.5); p<0.01). DTAS patients presented lower NIHSS score at 24 hours 9 (3.5-17) Vs 14 (5-19); p=0.01) and a lower rate of symptomatic hemorrhagic transformation (4.6% versus 10.9%, p<0.03). At 90 days, DTAS patients had a higher rate of good functional outcome (43% versus 29%; OR 1.81, 95% CI, 1.14-2.87; p=0.01). In multivariate analysis adjusted by confounding factors, better outcome in DTAS was observed in patients admitted in the 0-3 hours form onset window (n=156, OR 2.63, 95%CI: 1.31-5.28; p<0.01), but not in patients admitted in the 3-6 hours window (n=193, OR 1.37 955CI:0.72-2.60, p=0.2).

Conclusion:
DTAS seems a feasible and safe strategy to improve functional outcome in patients who undergo endovascular treatment mainly within 3 hours from symptoms onset.
Abstract 153: Novel Machine Learning Proves Stroke Risk is Not Linear
Authors: Orfanoudaki Agni , Nouh Amre M , Chesley Emma , Cadisch Christian , Stein Barry , Alberts Mark , Bertsimas Dimitris
Published: June 2021

Background:
Current stroke risk assessment tools presume the impact of risk factors is linear and cumulative. However, both novel risk factors and their interplay influencing stroke incidence are difficult to reveal using traditional linear models.

Objective:
To improve upon the Revised-Framingham Stroke Risk Score and design an interactive non-linear Stroke Risk Score (NSRS). Our work aimed at increasing the accuracy of event prediction and uncovering new relationships in an interpretable user-friendly fashion.

Methods:
A two phase approach was used to develop our stroke risk score predictor. First, clinical examinations of the Framingham offspring cohort were utilized as the training dataset for the predictive model consisting of 14,196 samples where each clinical examination was considered an independent observation. Optimal Classification Trees (OCT) were used to train a model to predict 10-year stroke risk. Second, this model was validated with 17,527 observations from the Boston Medical Center. The NSRS was developed into an online user friendly application in the form of a questionnaire (http://www.mit.edu/~agniorf/files/questionnaire_Cohort2.html).

Results:
The algorithm suggests a key dichotomy between patients with or without history of cardiovascular disease. While the model agrees with known findings, it also identified 23 unique stroke risk profiles and introduced new non-linear relationships; such as the role of T-wave abnormality on electrocardiography and hematocrit levels in a patient’s risk profile. Our results in both the training and validation populations suggested that the non-linear approach significantly improves upon the existing revised Framingham stroke risk calculator in the c-statistic (training 87.43% (CI 0.85-0.90) vs. 73.74% (CI 0.70-0.76); validation 75.29% (CI 0.74-0.76) vs 65.93% (CI 0.64-0.67), even in multi-ethnicity populations.

Conclusions:
We constructed a highly predictive, interpretable and user-friendly stroke risk calculator using novel machine-learning uncovering new risk factors, interactions and unique profiles. The clinical implications include prioritization of risk factor modification and personalized care improving targeted intervention for stroke prevention.
Abstract 155: Comparative Effectiveness of Carotid Endarterectomy Compared to Medical Therapy Among Patients With Asymptomatic Carotid Stenosis
Authors: Keyhani Salomeh , Cheng Eric , Hoggatt Katherine , Austin Peter , Hebert Paul , Halm Ethan , Johanning Jason , Naseri Ayman , Chapman Wendy , Bravata Dawn
Published: June 2021

Background:
Carotid endarterectomy (CEA) reduces stroke risk compared to medical therapy alone among patients with asymptomatic carotid stenosis. CEA involves a tradeoff between higher perioperative short-term risks in exchange for a lower long-term risk of stroke. However, overall declines in stroke rates raise concerns that CEA may no longer be a preferred treatment. We examined the effectiveness of CEA compared to medical therapy (MT) among asymptomatic patients in preventing stroke and stroke-death within 5 years of follow-up.

Methods:
We identified Veterans ≥65 years old with carotid stenosis (n=2712 CEA and n=2509 MT patients) who did not have a history of stroke or transient ischemic attack. We propensity score-matched MT patients to CEA patients to control for baseline confounding and used methods to mimic analyses from the Asymptomatic Carotid Stenosis Trial, the last published trial to compare CEA to MT. We accounted for “immortal time” bias by randomizing patients to CEA and MT groups and censoring patients if their actual treatment became inconsistent with the arm in which they were randomized (e.g., patient received CEA, but was randomized to MT). We accounted for the informative censoring by estimating time-dependent inverse probability of censoring weights using measured covariates (demographics and 72 time-varying comorbidities). We computed weighted Kaplan-Meier (KM) curves and estimated the risk of stroke/stroke-death in each group over 5 years of follow-up.

Results:
The observed stroke or death rate (perioperative complications) within 30 days in the CEA arm was 3%. The 5-year risk were similar among patients randomized to CEA 5.5% (95% CI, 4.3%-6.7%) versus MT 7.6% (95% CI,5.9%-9.2%) (risk difference, -2.1%, 95% CI -4%- 0%) with little difference in the KM curves (logrank p=0.2).

Conclusion:
CEA was not superior to MT in a community sample of Veterans after 5 years of follow-up, suggesting that CEA may no longer be the preferred treatment strategy.
Abstract 16: Functional Magnetic Resonance Imaging as a Predictor of Cognitive Impairment in Cerebral Amyloid Angiopathy
Authors: Gokcal Elif , Horn Mitchell J , Fotiadis Panagiotis , Frau-Pascual Aina , Schwab Kristin , Goldstein Joshua N , Jonathan Rosand , Viswanathan Anand , Jonathan Polimeni , Steven M. Greenberg , Gurol Edip
Published: June 2021

Background:
Cerebral Amyloid Angiopathy (CAA) emerged as an important contributor to cognitive impairment (CI) in elderly. Multiple lines of evidence suggest the presence of vascular dysfunction in CAA but its relationship to CI has not been tested. We hypothesized that the degree of vascular dysfunction identified by functional magnetic resonance imaging (fMRI) is a predictor of subsequent development of CI in patients with CAA.

Methods:
Thirty nondemented probable CAA patients diagnosed with Boston criteria were prospectively enrolled. They underwent high-resolution structural MRI and fMRI at baseline and cognitive assessment both at baseline and follow up. Structural MRI markers (microbleed counts, superficial siderosis, enlarged perivascular spaces, cortical microinfarcts) and FreeSurfer based volumetric analyses (cortical thickness, white matter hyperintensity volume) were obtained. An fMRI measure of vascular reactivity to visual stimulation, time-to-peak [TTP] of blood oxygen level-dependent [BOLD] response, was the main physiologic marker of interest. Main outcome measure was the development of CI defined based on structured cognitive assessments.

Results:
Patients had a mean age of 69.1±7.6 years. During a median follow-up of 23 months, 13 patients (43.3%) developed CI. Patients who developed CI did not differ from the patients without CI in terms of age, sex, risk factors and structural MRI markers (all p>0.2). Patients with CI trended towards fewer years of education (16±2.8 years vs 18±2.8 years, p=0.069). Baseline TTP of BOLD response was significantly higher in patients with incident CI as compared to patients without CI (12.7 ± 5.8 vs 7.8 ± 2.9, p=0.005). In a cox regression analysis, higher TTP was independently associated with future CI risk, after adjusting for age, sex, WMH volumes and education years (hazard ratio: 1.23; 95% CI: 1.06-1.42; p=0.006).

Conclusion:
The severity of baseline vascular dysfunction is associated with future CI in CAA. Unlike markers of parenchymal injury that are typically irreversible, vascular dysfunction might be reversible making our findings potentially relevant to future therapeutic development efforts.
Abstract 172: Bridging Therapy versus Intravenous Thrombolysis in Minor Stroke With Large Vessel Occlusion. A French Multicentric Observational Study (MINOR-STROKE)
Authors: Seners Pierre , Perrin Claire , Turc Guillaume , on behalf of the Minor-Stroke Collaborators .
Published: June 2021

Introduction:
Whether bridging therapy (endovascular therapy [EVT] plus intravenous thrombolysis [IVT]) is superior to IVT alone in minor strokes with large vessel occlusion (LVO) is unknown.

Methods:
MINOR-STROKE was a multicentric retrospective cohort collecting data of IVT-treated minor strokes (NIHSS≤5) with LVO (ICA, M1 or M2; with central reading) treated with or without additional EVT in 45 French stroke units. Patients immediately intended for additional EVT -including those who eventually did not receive EVT- were analyzed in the bridging group, whereas patients initially intended for IVT alone -including those who eventually received rescue EVT- were analyzed in the IVT group. Propensity-score (inverse probability of treatment weighting) was used to reduce baseline between-groups differences. The primary outcome was excellent outcome defined as mRS 0-1 at 3 month.

Results:
Overall, 965 patients were included (237 and 728 in the bridging therapy and IVT groups, respectively). The distribution of all baseline clinical and radiological variables across the 2 groups were similar following propensity-score weighting. Compared with IVT alone, bridging therapy was not associated with better excellent outcome (OR=0.99; 95%CI 0.79-1.24;
P
=0.95), but was associated with higher risks of symptomatic intracranial haemorrhage (OR=2.39; 95%CI 1.51-3.80;
P
<0.001). However, occlusion site was a strong modifier of the effect of bridging therapy on excellent outcome (P
interaction
<0.0001), bridging therapy seeming beneficial in isolated ICA (OR=2.75; 95%CI 1.23 6.13;
P
=0.01) and proximal M1±ICA (OR=3.63; 95%CI 1.94-6.79;
P
<0.0001), neutral for distal M1±ICA (OR=0.96; 95%CI 0.63-1.48;
P
=0.87) but deleterious for M2±ICA (OR=0.54; 95%CI 0.38-0.75;
P
<0.001) occlusions. Bridging therapy was only associated with sICH in patients with M2 occlusions (OR=4.73; 95%CI 2.35-9.49;
P
<0.0001).

Conclusion:
Overall, we observed similar outcomes with bridging therapy or IVT alone in minor strokes with LVO. However, our data suggest benefit of bridging therapy in patients with ICA or proximal M1 occlusion and potential harm through sICH in patients with M2 occlusion. Randomized trials are strongly commended to confirm these results.
Abstract 175: Delayed Effects of Ischemic Stroke on Lung Mechanics and Intrinsic Antioxidant Defenses
Authors: Miller-Rhodes Kathleen J , Prifti Landa , Knowlden Sara , Eliseeva Sophia , Georas Steve , Halterman Marc W
Published: June 2021

Ischemia-reperfusion injury causes central and peripheral inflammatory changes for which there are no viable therapeutic options. Following ischemic stroke, danger signals are released into the periphery, which activate circulating immune and endothelial cells and therefore contribute to collateral tissue damage. Our lab and others have shown the lung is particularly susceptible to injury and inflammation following ischemic stroke. However, the mechanistic basis for this susceptibility is unknown. We hypothesized that focal ischemic stroke induces lung injury and inflammation by reducing endogenous antioxidants, such as superoxide dismutase 3 (SOD3), within the lung. To test this hypothesis, we performed middle cerebral artery occlusion (MCAO: 60-minutes) or sham surgery on C57BL/6 mice before initiating reperfusion for 3-days (n=8/group), after which brain and lung were collected for analysis. In a separate cohort of C57BL/6 mice (n=5/group), we used the FlexiVent system and Inficon’s Gas Chromatography to assess lung mechanics and gas exchange, respectively. In the lung of mice that received MCAO, we observed a significant reduction in SOD3 (Sham vs. MCAO, Mean±SD: 1.772±0.32AU vs 0.94±0.24AU; p=0.04) and VCAM-1 (1.00±0.17AU vs. 0.30±0.12AU; p=0.0028) levels. This was accompanied by an increase in 4-HNE protein adducts (0.45±0.06AU vs 1.94±0.5AU; p=0.019) in the lung following stroke, indicating greater oxidative injury. In our functional analyses, we found that stroke induced a significant decrease in lung compliance (0.04±0.02mL/cmH
2
O vs 0.03±0.001 mL/cmH
2
O, p=0.04) and an increase in elastance (25.28±1.26cmH
2
O/mL vs 29.2±0.90cmH
2
O/mL, p=0.03) while simultaneously changing resistance at the airways (0.31±0.08cmH
2
O.s/mL vs 0.19±0.01cmH
2
O.s/mL, p=0.008) and distal alveolar spaces (0.58±0.04 cmH
2
O.s/mL vs 0.75±0.04cmH
2
O.s/mL, p=0.01). However, ischemic stroke did not change lung gas exchange (0.77±0.12AU vs 0.74±0.06AU; n.s.); this finding was corroborated by the lack of any robust structural changes in the lung following injury (11.83±0.93um vs 13.54±2.79um). Taken together, these findings highlight ischemic stroke drives changes in lung mechanics by altering the inflammatory and redox environment within the lung.
Abstract 176: Platelet Cyclophilin D Mediates Neutrophil Recruitment and Ischemic Stroke Outcomes in Mice
Authors: Denorme Frederik , Manne Bhanukanth , Kosaka Yasuhiro , Majersik Jennifer , Kile Benjamin , Rondina Matthew , Campbell Robert
Published: June 2021

Rationale:
Besides their role in thrombosis, platelets also mediate inflammation through platelet-neutrophil aggregates (PNA). Recently, cyclophilin D (CypD)-mediated platelet necrosis emerged as a potential mediator of detrimental PNA during thrombosis. However, the role of platelet CypD in ischemic stroke has never been examined.

Objective:
Here, we investigate the contribution of platelet CypD following ischemic stroke.

Methods:
We generated mice lacking CypD specifically in platelets (KO). Both wild-type (WT) and KO mice were subjected to a 1h transient middle cerebral artery occlusion (tMCAO) stroke model. Twenty-four hours after occlusion, neurological and motor function, and stroke infarct size were determined. We also examined if the CypD pathway was altered in human platelets after ischemic stroke.

Results:
Loss of platelet CypD significantly improved neurological (p<0.001) and motor (p<0.005) functions compared to WT mice after tMCAO. Furthermore, platelet CypD deficient significantly reduced ischemic stroke infarct volume (39.1±15.7mm
3
vs. 78.6±27.7mm
3
, n=15; p<0.0001). Smaller infarcts in KO mice was not due to difference in blood flow during the ischemia stage. Twenty-four hours after stroke, a greater than 2-fold reduction in neutrophils was observed in the brains from KO mice (p<0.0001). In addition, we observed significantly fewer circulating and cerebral PNA (p<0.01). Depletion of neutrophils significantly (p<0.05) reduced infarct size and neurological damage following ischemic stroke in WT mice, however, no additional protective effect was observed in KO mice, suggesting necrotic PNAs are critical during ischemic stroke. RNA-sequencing on platelets isolated from ischemic stroke patients (n=8) and healthy aged, gender matched controls (n=7) revealed significant increases in several targets involved in CypD-mediated necrosis, including MCUR1, TMEM16F and calpain2 (p<0.005).

Conclusion:
Our results demonstrate necrotic platelets interact with neutrophils to exacerbate brain injury following ischemic stroke. As inhibiting platelet necrosis does not compromise hemostasis, targeting platelet CypD may be a potential therapeutic strategy to limit brain damage after ischemic stroke.
Abstract 178: Cholesterol Limits Macrophage Activation in Response to Intracerebral Hemorrhage-Relevant Signals
Authors: DeLong Jonathan H , Velazquez Sofia , Landreneau Margaret J , Sansing Lauren H
Published: June 2021

Introduction:
In response to intracerebral hemorrhage (ICH), monocytes are recruited to the brain parenchyma, where they differentiate into macrophages and contribute to a pathological inflammatory response. However, by day 3 after ICH, brain macrophages have adopted a more reparative phenotype and are important for clearance of apoptotic cells and recovery. The signals that control this inflammatory to reparative differentiation are incompletely understood, but cholesterol has been found to limit macrophage activation in multiple systems. The brain has the highest cholesterol content of any organ and we hypothesized that cholesterol uptake by macrophages limits inflammation and promotes the development of reparative macrophages following ICH.

Methods and Results:
Murine bone marrow-derived macrophages were stimulated with a cocktail of thrombin, S100A8, and IL-1b in order to mimic the Danger-Associated Molecular Patterns present in the brain after ICH (ICH-DAMP), LPS, or vehicle for 14-18 hours. Cytokine production was quantified by cytometric bead array and activation markers by flow cytometry. ICH-DAMP was found to upregulate CCL2, IL-6 and TNF, recapitulating the inflammatory phenotype seen in the first days after ICH. However, when cells were stimulated in the presence of cholesterol, production of CCL2, IL-6, and TNF were limited. Dectin-1 has inhibitory properties in some sterile injury models. ICH-DAMP was found to limit expression of dectin-1, and cholesterol reversed this inhibition. Exposure to exogenous cholesterol also upregulated the cholesterol transporter ABCA1, allowing cells to efflux excess cholesterol. The drug Valspodar was therefore used to block cholesterol efflux and was found to further limit ICH-DAMP-mediated upregulation of CCL2.

Conclusion:
These results suggest that the cholesterol in the brain may limit macrophage activation in response to the stimuli present during intracerebral hemorrhage.
Abstract 182: Changing Risk Factor Profile Among Middle-aged Adults Hospitalized For Stroke, United States 2007-2016
Authors: Tong Xin , Yang Quanhe , George Mary G , Gillespie Cathleen , Merritt Robert
Published: June 2021

Introduction:
Previous studies reported increasing trends in stroke hospitalizations among adults 35-64 years.

Methods:
We used data from the National Inpatient Sample to identify stroke hospitalizations (principal ICD-9-CM/ICD-10-CM codes) among adults aged 35-64 years from 2007 through 2016. Four major risk factors (RFs) (hypertension, diabetes, lipid disorder, and tobacco use) were identified using secondary codes for each hospitalization. We used relative percent change (RPC) to assess the changes in prevalence between 2007-08 and 2015-16. Orthogonal polynomial coefficients were calculated by the method of Fisher and Yates for linear trend testing.

Results:
Approximately 2.4 million stroke hospitalizations occurred during 2007-2016. The prevalence of having all 4 RFs among stroke hospitalizations nearly doubled, from 3.6% in 2007-08 to 7.0% in 2015-16 (p <0.001 for trend, Table), prevalence of any 3 RFs increased from 21.4% in 2007-08 to 29.3% in 2015-16 (RPC 37%, p<0.001). There was a small but significant decrease in the prevalence of only 2 RFs (RPC of -2%, p=0.004). Stroke hospitalizations with only 1 RF decreased by 15-39% (p<0.001), and the prevalence of not having any RFs decreased by 37% (p<0.001). The most prevalent RF triad was hypertension, diabetes, and lipid disorder (11.8% in 2007-08, and 16.9% in 2015-16, RPC of 44%), and the most common RF dyad was hypertension and lipid disorder (RPC of 1%).

Conclusions:
Our findings have important implications for younger adults. Regardless of stroke etiology, younger adults are increasingly at higher risk for stroke from preventable and treatable traditional RFs. This growing public health problem will require clinicians, healthcare systems, and public health efforts to implement more effective prevention strategies to address the rising prevalence of multiple co-existing RFs among this population.