bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P506: Machine Learning Models Improve Prediction of Large Vessel Occlusion and Mechanical Thrombectomy Candidacy in Acute Ischemic Stroke
Authors: Thomas Shon , De La Pena Paula , Butler Liam , Akbilgic Oguz , Heiferman Daniel , Garg Ravi , Gill Rick , Serrone Joesph
Published: March 2021

Background and Purpose:
Early identification of large vessel occlusions (LVO) and timely recanalization are paramount in improved clinical outcomes in acute ischemic stroke. Multiple simple stroke scales have good sensitivity, but compromise specificity for predicting LVO. No scale has been shown to predict mechanical thrombectomy (MT) candidacy. Machine learning techniques are being used for predictive modeling in many aspects of stroke care and may have potential in predicting LVO presence and MT candidacy.

Methods:
287 acute ischemic stroke patients from July 2018 to July 2019 at Loyola University Medical Center were included. 36 clinical and demographic variables were analyzed using machine learning and statistical algorithms, including logistic regression, extreme gradient boosting, random forest, and decision trees to build models predictive of LVO and MT. The best performing model was compared with prior stroke scales.

Results:
Random forest based model resulted in the highest classification performance to predict both LVO and MT outcomes with an area under the curve (AUC) of 0.90±0.07 and 0.94±0.04, respectively. When the predictors were reduced to 7, random forest maintained a high AUC for predicting LVO (0.89). When reduced to 10 predictors, the random forest model predicted MT with an AUC = 0.93. Random forest models had excellent sensitivity and specificity of 0.86 and 0.89 for LVO and 0.89 and 0.95 for MT, respectively. The negative predictive value was 0.94 for LVO and 0.98 for MT while the positive predictive value was 0.77 for LVO and 0.79 for MT. With equal sensitivity, the random forest model was favorable to all previous stroke scales.

Conclusion:
Machine learning utilizing clinical and demographic variables predicts LVO and patient candidacy for MT with a high degree of accuracy. Further validation of this strategy for triage of stroke patients requires prospective and external validation.
Abstract P51: Temporal Changes In Nitric Oxide Synthase Isoform Expression And Function In Spontaneously Hypertensive Stroke Prone Rats
Authors: Ewees Mohamed G , Moore Jordan , Zweier Jay L , Hannawi Yousef
Published: March 2021

Introduction:
Nitric oxide (NO) has been implicated in the pathogenesis of cerebral small vessel disease (cSVD). NO is produced by three NO synthase (NOS) isoforms including endothelial (eNOS), neuronal (nNOS), and inducible (iNOS). While eNOS has been implicated in cSVD pathologies that occur in Spontaneously Hypertensive Stroke Prone Rats (SHRSP), cSVD model, the mechanistic role and temporal changes of NOS isoform expression including eNOS in relation to cSVD development in SHRSP remains unknown. We aimed to characterize the temporal changes of NOS isoforms expression in SHRSP from the asymptomatic stage until the development of cSVD lesions.

Methods:
20 SHRSP and 20 Wistar Kyoto (WKY) male rats were studied. Systolic blood pressure (SBP) was measured weekly using tail-cuff plethysmography. Half of the groups were euthanized at 7 weeks of age and the remaining rats were followed until 24 weeks of age. Routine histology and immunohistochemistry were performed for eNOS, nNOS, iNOS, superoxide radicals (DHE), NO (DAF) and Iba1 for microglia activation.

Results:
At 7 weeks, SBP was not significantly different between the groups (WKY 106.6±5.4 vs SHRSP 120.8±5.4, P=0.06). SHRSP developed hypertension between 9-11 weeks and maintained it throughout the experiment (SBP (21 weeks): WKY 134.8±5.4 vs 168.9±5.4, P<0.0001). Brain histology was largely negative for cSVD lesions at 7 weeks. At 24 weeks, histology showed areas of demyelination, microbleed formation, arteriosclerosis and hemosiderin deposits in SHRSP. At 7 weeks, compared to WKY, eNOS and nNOS expression were 50% and 30% lower in SHRSP (P=0.0038 and 0.0211, respectively). iNOS expression was 93% higher in SHRSP (P=0.0068). Superoxide levels were 133% higher in SHRSP (P<0.0001) and NO was 40% lower in SHRSP (P<0.0008). At 24 weeks, all of these differences became larger. Iba-1 expression was 25% higher at 7 weeks and became 97% higher in SHRSP at 24 weeks (P<0.0001).

Conclusions:
SHRSP show significant differences in NOS isoform expression with loss of NO and gain of superoxide production early in life prior to development of cSVD lesions. Superoxide overproduction and related oxidant stress may lead to NOS dysfunction and uncoupling which may trigger cSVD onset and point towards potential future therapies.
Abstract P514: Clinically Approximated Hypoperfused Tissue in Large Vessel Occlusion Stroke
Authors: Desai Shashvat , Ortega Santiago , Sheth Sunil , Farooqui Mudassir , Lopez Rivera Victor , Zevallos Cynthia , Abdelkhaliq Rania , Jovin Tudor G , Jadhav Ashutosh
Published: March 2021

Introduction:
Patient selection for thrombectomy of acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) in the delayed time window (>6 hours) is dependent on delineation of clinical-core mismatch or radiological target mismatch using perfusion imaging. Selection paradigms not involving advanced imaging and software processing may reduce time to treatment and broaden eligibility. We aim to develop a conversion factor to approximately determine the volume of hypoperfused tissue using the NIHSS score [CAT volume (clinically approximated tissue)] and explore its ability to identify patients eligible for thrombectomy in the late time window.

Methods:
We performed a retrospective analysis of anterior circulation LVO strokes at three comprehensive stroke centers. Demographic, clinical (NIHSS score, TLKW-time last known well) and imaging [computed tomography with perfusion (CTP) processed using RAPID, IschemaView] information was analyzed. A conversion factor, which is a multiple of the NIHSS score (one multiple for NIHSS score <10 and another for NIHSS score ≥10), was derived to calculate CAT volumes. Accuracy (sensitivity and specificity) of CAT-based thrombectomy eligibility criteria (similar to DEFUSE-3 criteria but using CAT volume instead of Tmax >6 seconds volume) was tested using DEFUSE-3 criteria eligibility as a gold standard.

Result:
Of the 309 LVO strokes [mean age of 70 ±14, 46% male, median NIHSS 16 (12-20)] included in this study, 38% of patients arrived beyond 6 hours of TLKW. Conversion factors derived (derivation cohort-center A:187) based on median (50
th
percentile) values of Tmax >6s volume for NIHSS <10 subgroup was 15 and for NIHSS ≥10 subgroup was 6. Subsequently calculated CAT volume-based eligibility criteria yielded a sensitivity of 100% and specificity of 92% in detecting DEFUSE-3 eligible patients (AUC-0.92 CI-0.82-1) in the validation cohort (center B and C:122).

Conclusions:
Clinical severity of stroke (NIHSS score) may be used to calculate the volume of hypoperfused tissue during LVO stroke. Clinically approximated hypoperfused tissue (CAT) volumes for NIHSS score <10 (using a factor of 15) and ≥10 (using a factor of 6) subgroups can accurately identify DEFUSE-3 eligible patients.
Abstract P527: Temporal Trend of Mechanical Thrombectomy Utilization in Treatment of Perioperative Ischemic Stroke Following Elective Inpatient Surgery in the United States
Authors: Shah Shreyansh , Fuller Matthew , Ohnuma Tetsu , James Michael L , Bartz Raquel , Raghunathan Karthik , Krishnamoorthy Vijay
Published: March 2021

Background:
Perioperative ischemic stroke (PIS) significantly increases morbidity and mortality in patients undergoing elective surgery. Mechanical thrombectomy (MT) can improve outcomes of ischemic stroke, but the frequency and trend of its utilization for treatment of PIS is not studied.

Methods:
In this retrospective observational study using the Premier Healthcare Database, we identified adults who underwent elective inpatient surgery from 2008 to 2018. Patients with PIS were identified using the established International Classification of Diseases (ICD) ninth revision codes or equivalent ICD, tenth revision codes. Cases that underwent MT were further identified using established ICD9 and ICD10 procedure codes. Descriptive statistics were used to compare patient and center level characteristics between patients who received MT versus did not after PIS.

Results:
Of 6,349,668 patients with elective inpatient surgery, 12,507 (0.2%) had PIS. The mean age (and standard deviation) of these patients was 69.5 (11.7) years, and 48.8% were female. MT was used in 1.7% of all patients with PIS and its use increased from 0.0% in 3
rd
quarter, 2008 to 4.4% in 4
th
quarter, 2018. There was a significant increase in the use of MT after 3
rd
quarter, 2015 when MT use was incorporated in acute stroke treatment guidelines (1.14% before 3
rd
quarter, 2015 versus 3.07% after; p<0.0001). Amongst patients with PIS, patients who received mechanical thrombectomy were more likely to have their surgery performed at a teaching institute (67.3% versus 53.9%).

Conclusion:
Although there was a significant increase in rates of utilization of MT, rates of utilization remain low, especially in non-teaching hospitals. This highlights improvements in the management of perioperative ischemic strokes and further opportunities to improve outcomes.
Abstract P53: Long-Term Mortality Among Ischemic Stroke Patients With Pre-Existing Mild Cognitive Impairment or Dementia
Authors: Vahidy Farhaan S , Potter Thomas , Meeks Jennifer , Pan Alan , Khan Osman , Misra Vivek , Masdeu Joseph , Seshadri Sudha
Published: March 2021

Introduction:
The contribution of preexisting mild cognitive impairment (MCI) or dementia (MCID) towards long term mortality in Ischemic Stroke (IS) patients is under studied.

Methods:
We conducted a propensity score (PS) matched analysis of pooled data from 39 healthcare organizations to evaluate the association between MCID and post stroke mortality (PSM) through a 5-year period. Using ICD-10 codes for MCI, Alzheimer disease, vascular/other dementias, and MCID specific medications; we flagged preexisting MCID diagnoses up till 1 month prior to the index IS event (MCID group). The non-MCID group had no documented MCID diagnoses till after 1 month of the index event. Groups were PS matched on demographic (age, sex, race, ethnicity) and comorbidity variables. Risk Ratios (RR) and 95% confidence intervals (CI) were calculated.

Results:
Among 544,700 IS patients, 124,892 (22.9%) had preexisting MCID. MCID patients (vs. non-MCID) were older (mean age: 67.8 vs. 64.8 years), had higher proportion (%) of females (52.8 vs. 49.4) and Blacks (21.1 vs. 17.1). A higher proportion (%) of MCID patients had hypertension (77.3 vs. 36.0), diabetes (36.9 vs. 17.4), ischemic heart disease (31.6 vs 13.5), chronic kidney disease (21.4 vs. 7.8) and liver disease (9.5 vs. 3.1). Optimal co-variate balance was achieved post PS match (figure). In the unmatched sample, 8.6% of MCID and 6.0% of non-MCID patients experienced PSM by the 1-year time point; representing 56.2% and 64.2% of the total 5-year PSM, respectively. Matched and unmatched RR (CI) for PSM at 3 month and 1,3,5-year are reported (figure). An increasing risk of PSM was observed across the four time-points which was significantly higher for years 1,3, and 5 in the matched sample.

Conclusion:
A 24% long term increased risk of PSM was observed in a large national sample of IS patients with preexisting MCID. Majority of PSM burden is experienced by 1 year. MCID screening and exploring mechanisms of MCID-linked PSM is critical among IS patients.
Abstract P534: Relationship Between rCBF and Pial Collateral Recruitment in Experimental Acute Ischemic Stroke
Authors: Saadat Niloufar , Christoforidis Greg , Niekrasz Marek , Roth Steven , Carroll Timothy
Published: March 2021

Purpose:
The purpose of this study was to assess the relationship between relative cerebral blood flow (rCBF) by MRI and leptomeningeal collateral recruitment in an experimental acute ischemic stroke model.

Methods:
This study was approved by the local IACUC. Eight mongrel canines (20-30kg) underwent endovascular middle cerebral artery occlusion (MCAO). Anesthetics were chosen not to interfere with cerebrovascular reactivity. Physiologic parameters were maintained within normal ranges. Pial collateral recruitment was angiographically assessed using a previously published 11-point scale. After the MCAO, subjects underwent DSC and DTI MRI (3T Achieva, Philips Healthcare, Best, Netherlands) in order to derive rCBF and infarct volume by diffusion restriction on mean diffusivity maps. DSC images were imported into Visage software (Visage Imaging; Richmond Australia). The region of interest was drawn on the penumbra and infarct core and corresponding contralateral side. Infarct volume was calculated by using a quantitative voxel-wise threshold by setting a threshold of 1.5 SD relative to normal values based on an ROI drawn to cover the entire contralateral normal hemisphere exclusive of the ventricles.

Results:
The pial collateral recruitment was strongly correlated with the rCBF on the penumbral region (r
2
= 0.7823, P-value= 0.003), and with the infarct volume measured two hours following occlusion (r
2
= 0.933376, P value= 0.00009.). There was a poor correlation between the pial collateral recruitment and the rCBF ratio on the core region (R
2
=0.4447, p-value= 0.07.)

Conclusion:
Preliminary data from this study suggests rCBF from the penumbral regions in experimental MCAO has a closer association with pial collateral recruitment relative to rCBF in the core infarct zone. This information has the potential to affect the interpretation of angiographic studies in acute ischemic stroke and underscores the importance of assessing regional differences in rCBF.
Abstract P537: Patients With Similar Core Infarcts Presenting in Delayed Windows Have Worse Long-Term Outcomes Compared With Early Time Windows
Authors: Shahrivari Mahan , Salazar Sergio , Abdelkhaleq Rania , Lopez-Rivera Victor , Jeevarajan Jerome , Savitz Sean I , Sheth Sunil
Published: March 2021

Introduction:
Endovascular therapy (ET) in acute ischemic stroke (AIS) care has established clear improvements in clinical outcome. However, a large percentage of treated patients still do poorly, and the rate of good outcome remains relatively low, even in patients who achieve substantial reperfusion. While the importance of time and rapid reperfusion have been well described in AIS, the recent prominence of imaging-alone based selection criteria has brought the relevance of time into question. We hypothesize that ischemic time even in patients with comparable infarct cores at presentation still plays an important role in modifying outcome in patients with AIS and large vessel occlusion (LVO) treated with ET.

Method:
From our prospectively collected institutional registry across 4 comprehensive stroke centers, we identified consecutive patients with LVO AIS treated with ET from 1/2017 to 1/2020. Patients were included if they had anterior circulation LVO, successful reperfusion TICI 2b/3, and witnessed time of symptom onset. Propensity score analysis used among patients matched by age, NIHSS, occlusion location, ASPECTS, TICI score and infarct core to evaluate if time from onset to arrival affect the likelihood of mRS 0-2 at 90 days. Data are presented as median [IQR] or mean±SD.

Results:
Among 242 patients that met inclusion criteria, mean age was 67±13.8, 50% were female, median NIHSS was 16 [10], and mean time from symptom onset to arrival (SOA) was 4.17±0.19 (hrs.min). The most common locations of the occlusion included M1 47.1%, ICA 20.2 %, M2 13.2% and A1 1.2%. In univariable analysis, fewer patients in the late time window (SOA > 6 hrs) achieved 90d mRS 0-2 compared to patients in the early window, but this difference was not statistically significant (66%% vs 34%%, early vs. late, P=0.1, Fisher’s exact). Propensity score analysis showed that among matched patients, later SOA was associated with decreased likelihood of mRS 0-2 at 90 days (coef: -0.22 [0.37-0.60], P=0.007).

Conclusion:
In patients with successful endovascular reperfusion, those presenting in later time windows had worse outcomes compared to those presenting earlier, even after accounting for differences in presentation infarct core.
Abstract P55: Retinal Microvascular Parameters Predict Retinal Amyloid Burden and Co-Jointly Predict Verbal Memory
Authors: Dumitrascu Oana M , Rosenberry Ryan , Khansari Maziyar , Shi Yonggang , Torbati Tania , Sherman Dale , Sherzai Ayesha Z , Sheyn Julia , Johnson Kenneth , Czeszynki Alan , Verdooner Steven , Frautschy Sally , Koronyo-Hamaoui Maya , Black Keith , Koronyo Yosef , Lyden Patrick D , Cheng Susan
Published: March 2021

Introduction:
Retinal vascular features predict cognitive performance and retinal imaging is a non-invasive tool to study brain health. Patients with Alzheimer’s disease (AD)-related cognitive disorders exhibit both retinal vascular abnormalities and intraretinal accumulation of amyloid-beta (Aβ) plaque. Curcumin-enhanced retinal fluorescence imaging (CRFI) was recently translated as a safe imaging tool for retinal Aβ plaque quantification. In this study, we sought to determine whether and which retinal arterial and venous parameters are predictive of retinal Aβ burden and cognitive Z-scores.

Methods:
We used scanning laser ophthalmoscopy with RetiaTM (Centervue, Inc) to obtain CRFI in a cohort of patients with cognitive decline. Retinal blood vessels were segmented in a predefined circumpapillary region of interest. For each centerline, vessel tortuosity index (VTI), vessel inflection index (VII), and branching angle (VBA) were quantified, independently for arteries and veins. Additionally, we automatically quantified retinal amyloid count in the supero-temporal quadrant and its subregions: posterior pole (PP), proximal mid-periphery (PMP), and distal mid-periphery (DMP). All quantifications were done blinded to the subjects’ clinical characteristics. Linear regression models were used to assess the correlations between retinal vascular and amyloid parameters.

Results:
29 subjects (55% female, mean age 64±6 years) were included in the analysis: 11 had normal cognition, 16 mild cognitive impairment and 2 probable AD. Venous VTI was the only vascular parameter significantly different across levels of Clinical Dementia Rate scores and between cognitively normal and impaired. Venous VBA was a significant predictor of DMP amyloid count (p=0.03). Arterial VII significantly predicted PP amyloid count (p=0.02). VBA predicted Wechsler Adult Intelligence Scale Z-score (p=0.08). The combined VTI-PMP amyloid index significantly predicted Wechsler Memory Scale, California Verbal Learning Test and SF-36 mental component score Z-scores (p<0.05).

Conclusion:
Retinal venous tortuosity discriminates across cognitive scores and in combination with PMP amyloid count may predict verbal memory and related quality-of-life scores.
Abstract P561: Efficacy of Beveled Tip Aspiration Catheter in Mechanical Thrombectomy for Acute Ischemic Stroke
Authors: Vargas Machaj Jan , Blalock Jonathan , Venkatraman Anand , Anagnostakou Vania , King Robert , Ewing Joseph A , Gounis Matthew , Turner Raymond , Chaudry Imran , Turk Aquilla
Published: March 2021

Introduction:
The ADAPT technique uses large bore aspiration catheters for mechanical thrombectomy. Several aspiration catheters are now available. We report a bench-top exploration of a beveled-tip catheter, and our experience in treating large vessel occlusions using next-generation aspiration catheters.

Methods:
Twenty experiments were conducted with either a Sofia Plus or a Zoom71 using a vascular phantom in which a clot model was introduced. Rate of ingestion, complete recanalization after a single attempt, and pressure at the catheter tip for both devices were recorded. A retrospective analysis from a prospectively-maintained database was performed. Patient demographics, periprocedural metrics, discharge and 90-day modified Rankin Scales were collected. Patients were divided into two groups based on which aspiration catheter was used.

Results:
In our bench-top experiment, complete ingestion of the clot occurred in 90% of beveled tip and 20% of control device experiments (p=0.006). Our clinical data demonstrated no significant difference in age, gender, IV tPA administration, admission NIHSS, baseline mRS, or LVO location between the beveled tip and flat tip groups. With the beveled tip, TICI 2C or better recanalization was more frequent (93.2% vs 74.2%, p-value 0.017), stent retriever usage was lower (9.1% versus 29%, p-value 0.024), and patients had lower mRS on discharge (median 3 vs 4, p less than 0.001) and at 90 days (median 2 vs 4, p=0.008).

Conclusion:
The beveled tip design leads to more frequent clot ingestion in a bench top model, which may translate into a more efficacious thrombectomy device with improved outcomes.
Abstract P562: The Safety Of Mechanical Thrombectomy In Nonagenarians In A Majority Hispanic Population
Authors: Salhadar Nura , TEKLE WONDWOSSEN , Sarraj Amrou , Hassan Ameer E
Published: March 2021

Background and objective:
Elderly patients were underrepresented in RCTs that proved the efficacy and safety of mechanical thrombectomy (MT) in acute ischemic strokes (AIS) due to large vessel occlusion (LVO). Additionally, the impact of race and socio-economics in AIS outcomes is well-reported. We sought to assess MT clinical outcomes in Hispanic Octogenarians and Nonagenarians that reside in underserved border communities.

Methods:
A retrospective cohort study from a prospectively collected comprehensive stroke center database was conducted. The primary outcome was discharge (mRS 0-2). Secondary outcomes were NIHSS improvement ≥4 points at discharge, sICH, mortality and length of stay (LOS). A two-tailed t-test assessed statistical significance between the two groups.

Results:
Of 202 included patients, 172 (85%) were octogenarians and 30 nonagenarians (17%). Nonagenarians had higher rates of females (80% vs 59%; p<0.05), similar rates of Hispanics (57% vs. 63%, p-xx) and a trend towards higher NIHS (20 vs. 17, P=0.09). Other baseline characteristics were similar (Table 1). Time last known well to arrival to MT center and to recanalization were longer in octogenarians, all other time metrics did not differ. Nonagenarians had numerically lower favorable outcomes at discharge (7% vs. 16%, p=0.11) as compared to octogenarians. Rates of clinical improvement on NIHSS were similar (27% vs. 23%, p=0.74). Mortality (23% vs. 28%, p=0.63) and sICH (7% vs 4%, p=0.46), octogenarians and nonagenarians, respectively. Octogenarians trended towards longer LOS (10 vs 6 days, p=0.05).

Conclusions:
Both groups had lower favorable good outcome rates than MT outcomes reported in RCTs. Nonagenarians had numerically lower favorable outcomes but mortality and sICH were similar. Further studies are warranted to further assess the impact of age and socioeconomics on MT outcomes.
Abstract P566: Identifying Sex-Specific Differences in the Carotid Revascularization Literature: Findings From a Scoping Review
Authors: Yogendrakumar Vignan , Shamy Michel C , Dewar Brian , Fergusson Dean , Dowlatshahi Dar , Hamel Candyce , Gocan Sophia , Fedyk Mark , Mas Jean-Louis , Howard Virginia J , Rothwell Peter , Bereznyakova Olena
Published: March 2021

Background and Purpose:
No systematic review of the literature has dedicated itself to looking at the management of symptomatic carotid stenosis in women. In this scoping review, we aimed to identify all randomized controlled trials (RCTs) that reported sex-specific outcomes for patients who underwent carotid revascularization, and determine whether sufficient information is reported within these studies to assess women’s short and long-term outcomes.

Methods:
We systematically searched Medline, Embase, Pubmed, and Cochrane libraries for RCTs published between 1991 and 2020 that included women and compared either endarterectomy with stenting, or any revascularization (endarterectomy or stenting) with medical therapy in patients with symptomatic high grade (greater than 50%) carotid stenosis.

Results:
From 1,537 references examined, 27 eligible studies were identified. Sex-specific outcomes were reported in 13 studies. Baseline patient characteristics of enrolled women were reported in 2 of those 13 studies. Common outcomes reported included stroke and death, however there was significant heterogeneity in the reporting of both periprocedural and long-term outcomes. Sex-specific differences relating to the degree of stenosis and time from index event to treatment were limited to studies comparing endarterectomy to medical therapy. Adverse events were not reported by sex.

Conclusions:
Half of the previously published RCTs and systematic reviews report sex-specific outcomes. Detailed analysis on the benefits of carotid artery intervention for women with symptomatic stenosis is limited . Further analysis with individual patient data and a network meta-analysis is the necessary next step to better assess the treatment effects of carotid management in women.
Abstract P568: Incidence and Progression of Posterior Circulation Involvement in Moyamoya Disease
Authors: Li Yiping , Wang Allan R , STEINBERG Gary K
Published: March 2021

Introduction:
The incidence and natural history of posterior circulation moyamoya disease (PCMMD) is not well-characterized.

Methods:
Consecutive patients with moyamoya disease prospectively treated at our institution from 2015-2018 were reviewed.

Results:
262 consecutive patients with moyamoya disease undergoing 370 revascularization procedures were enrolled. Concurrent PCMMD was identified in 68 (26%) patients – all of which were confined to the anterior circulation. There were no differences in age, sex, race, or rates of diabetes, hypertension, smoking, or symptoms upon presentation between patients with or without PCMMD. Patients with PCMMD were more likely to present with bilateral disease (p<0.001), higher Suzuki grade (p=0.001), more extensive collateral angiopathy (p<0.001), and pial-pial collaterals from the PCA territory (p=0.03). Patients with PCMMD were more likely to suffer from ischemic peri-operative complications in both the anterior (p=0.03) and posterior (p<0.001) circulation territories after anterior circulation revascularization. No differences were observed for hemorrhagic complications (p=1.0). Over a mean follow-up of 1.91±1.5 years, 19 (7.3%) developed new or progressive PCMMD. Patients with PCMMD progression had an Asian predilection and were less likely to present with sentinel symptoms such as headaches (p=0.05 and 0.01 respectively). Patients with bilateral disease (p=0.02), higher Suzuki (p<0.001) and collateral angiopathy grades (p=0.002), and more extensive external carotid artery supply (p=0.03) were also more likely to experience PCMMD progression. There was no association between PCMMD progression and delayed neurological events or functional outcomes, but patients with concurrent PCMMD upon presentation were associated with poor functional outcome (mRS >2) at last follow-up (p=0.02).

Conclusions:
Posterior circulation disease involvement often presents in the later stages of moyamoya and is associated with higher rates of ischemic peri-operative complications and poor functional outcomes likely due to reduced collateral flow. Progression of PCMMD is not uncommon. Future studies are needed to assess the impact of PCMMD progression on long-term outcomes.
Abstract P573: The Interplay Between Mineral and Skeletal Metabolism Biomarkers and Intracranial Internal Carotid Artery Calcifications in Stroke Patients
Authors: Arsava Ethem M , Oge Dogan Dinc , Gultekin-Zaim Ozge Berna , Gumeler Ekim , Kim Jeong-Min , Park Kwang-Yeol , Oguz Kader K , Topcuoglu Mehmet A
Published: March 2021

Background:
Intracranial internal carotid artery calcifications (IICAC), considered a phenomenon within the spectrum of atherosclerosis and vascular aging, are frequently encountered in ischemic stroke patients. While intimal IICAC directly contributes to ischemic stroke pathophysiology, the medial counterpart is generally deemed as a risk factor for vascular end-points. Apart from aging and cardiovascular risk factors, the underlying pathophysiology that contributes to development of IICAC is not well understood; herein we studied the interplay between mineral and skeletal metabolism biomarkers, and IICAC presence and pattern.

Methods:
In a prospective series of 194 ischemic stroke patients (mean±SD age: 69±14 yr), blood samples were collected to determine calcium, phosphorus, magnesium, osteocalcin, parathyroid hormone, and vitamin D levels within 72 hours of symptom onset. IICAC presence and type was determined on admission CT-angiography source images; a medial or intimal type of IICAC category was assigned according to Kockelkoren criteria.

Results:
A total of 45 (23%) patients had no calcifications, while 95 (49%) had an intimal pattern and 54 (28%) had non-intimal (or medial) pattern. Apart from the well-known factors related with IICAC, such as age, lower glomerular filtration rate (GFR), history of hypertension, diabetes mellitus, coronary artery disease and atrial fibrillation, we identified admission magnesium levels to be associated with IICAC presence and pattern (no calcification: 1.96±0.18 mEq/L, intimal calcification 1.93±0.19 mEq/L, medial calcification: 1.81±0.28 mEq/L; p=0.006). None of the other biomarkers had any significant relationship to IICAC. In multivariate models, a lower magnesium level was significantly associated with medial calcification (each 0.1 mEq/L drop increased the odds by 1.2 (95% CI 1.0-1.4; p=0.046)), in addition to older age, history of diabetes mellitus and lower GFR.

Conclusion:
Hypomagnesemia is one of the factors well-known to be associated with vascular calcifications in the body. Our findings, extend this relationship to the intracranial vascular bed. No similar association was observed for other biomarkers related to mineral and skeletal metabolism. (Funding: TUBITAK grant 218S753)
Abstract P576: Plasma Bacterial Lipopolysaccharide Associates With Carotid Atherosclerosis, a Cause of Large Vessel Stroke
Authors: Hakoupian Marisa , Ferino Eva , Jickling Glen , Amini Hajar , Stamova Boryana , Ander Bradley , Carmona-Mora Paulina , Sharp Frank R , Zhan Xinhua
Published: March 2021

Introduction:
Inflammation and infection are associated with cerebrovascular diseases including stroke due to carotid atherosclerotic plaques. C-reactive protein (CRP), an acute-phase protein, is upregulated in the plasma of patients with carotid atherosclerotic plaques. However, little is known about whether bacterial molecules trigger inflammation or play a role in patients with carotid atherosclerotic plaques. Recently, it has been recognized that inflammation associated with atherosclerosis and morbidity and mortality in cardiovascular diseases may be due to lipopolysaccharide (LPS) that is found in the outer wall of all Gram-negative bacteria. These findings prompted this study to explore whether plasma levels of LPS and LPS-binding protein (LBP) are elevated and correlated with CRP levels in patients with asymptomatic carotid plaques (ACP). We also compared LBP levels in patients with ACP to large vessel (LV) strokes due to carotid plaques and to matched controls.

Methods:
Patients (n = 30) with ACP, LV stroke due to carotid atherosclerosis and age-, sex- matched healthy controls gave consent and had their blood drawn. Plasma was processed for LPS, LBP and CRP detection using separate ELISA for each.

Results:
Plasma LBP level in ACP (22.7 ± 2.92 μg/ml) was similar to LV stroke (21.6 ± 1.56 μg/ml,
p
= 0.74, ACP vs LV) but greater than controls (13.6 ± 1.43 μg/ml,
p
= 0.011, ACP vs controls). In ACP patients, plasma LPS level (159.5 ± 30.5 μg/ml) was greater than controls (42.6 ± 11.7 μg/ml,
p
= 0.001); plasma CRP levels (20.2 ± 6.2 μg/ml) was higher than controls (5.3 ± 2.1 μg/ml,
p
= 0.011). There was a positive correlation between LPS levels and LBP levels (r = 0.86,
p
< 0.00001), LPS levels and CRP levels (r = 0.82,
p
= 0.00001), and LBP levels and CRP levels (r = 0.89,
p
< 0.00001) in ACP cases.

Conclusions:
Plasma LPS, LBP and CRP associate with asymptomatic carotid plaques suggesting a pro-inflammatory state exists in patients with asymptomatic carotid plaques, a cause of large vessel stroke. LPS is postulated to directly upregulate both CRP and LBP. Elevated LBP in large vessel stroke patients suggests a Gram-negative bacteria associated post-stroke inflammatory state.
Abstract P578: A Comparison of Clinical Features Between Posterior Reversible Encephalopathy Syndrome and Reversible Cerebral Vasoconstriction Syndrome
Authors: Toljan Karlo , Scarsella Monica , Purohit Meghan , Wisco Dolora R , Uchino Ken
Published: March 2021

Introduction:
Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) might represent a pathophysiological spectrum. They are commonly diagnosed separately, based on prominent clinical features. We aimed to compare clinical and radiographic findings of PRES and RCVS.

Methods:
We performed a retrospective study of adult patients admitted to a tertiary medical center from February 2008 until February 2018 and were diagnosed with PRES or RCVS. Patient demographics, risk factors, clinical features, imaging, and outcomes were compared. Appropriate statistical tests were used to compare the variables and significant findings are reported.

Results:
There were 281 PRES and 98 RCVS cases meeting diagnostic criteria. Seizures, encephalopathy, and hypertension were more common with PRES, whereas headache was more common with RCVS (p <0.001). Hypertension and transplant recipient or immunocompromised status were associated with PRES (p <0.001), as did diabetes mellitus (p <0.05). Marijuana use, smoking, and obesity were associated with RCVS (p <0.05). ). Intraparenchymal or subarachnoid hemorrhage was found in 51 PRES cases and 34 RCVS cases. Arterial stenosis was present in 19 % of PRES cases. Brain FLAIR MRI hyperintensity that was reversible on follow-up was present in 26% of RCVS cases.

Conclusion:
PRES and RCVS share common clinical characteristics and might represent a pathophysiological spectrum, though distinct clinical features were noted in our retrospective analysis.
Abstract P59: Peak Width of Skeletonized Mean Diffusivity Outperforms Other Diffusion Tensor Imaging Metrics as Biomarker for Cognition in Memory-Clinic Subjects With Cerebral Amyloid Angiopathy
Authors: Zanon Zotin Maria Clara , Schoemaker Dorothee , Perosa Valentina , Bretzner Martin , Sveikata Lukas , Van Veluw Susanne , Charidimou Andreas , Etherton Mark R , Gurol Edip M , Greenberg Steven , Duering Marco , Raposo Nicolas , Viswanathan Anand
Published: March 2021

Introduction:
Peak width of skeletonized mean diffusivity (PSMD) is a novel fully automated diffusion tensor imaging (DTI) marker that has been consistently associated with cognition in cerebral small vessel disease (SVD) cohorts, including cerebral amyloid angiopathy (CAA). We hypothesized that PSMD would be more strongly associated with cognitive performance compared to other conventional DTI metrics in our CAA sample.

Methods:
We recruited non-demented subjects with probable-CAA from a single-center memory-clinic cohort. We analyzed structural MRIs to compute a validated CAA burden score (0-6 points scale, based on the following MRI features: lobar microbleeds, superficial siderosis, perivascular spaces in centrum semiovale, and white matter hyperintensities). PSMD was obtained using a freely available script (
www.psmd-marker.com
). We used the same skeleton-mask to compute: mean of skeletonized mean diffusivity (mean MD) and mean of skeletonized fractional anisotropy (mean FA). We used linear regression analyses to explore relationships with CAA burden score and cognitive composite scores (processing speed, executive function, memory, and language - z-scores adjusted for age, sex and education level).

Results:
We included 43 subjects (mean age 74.4 ± 5.9 years; 48.8% female; PSMD median [IQR]: 4.05 [3.58 - 4.80] x 10
-4
mm
2
/s). In linear regression models adjusting for age, DTI metrics were significantly associated with CAA burden score (mean FA:
β
= -0.563, Adj. R
2
: 0.27;
p
< 0.001; mean MD:
β
= 0.581; Adj. R
2
: 0.32;
p
< 0.001; PSMD:
β
= 0.364, Adj. R
2
: 0.12;
p
= 0.018). PSMD was significantly associated with cognitive performance, specifically in the domains of executive function (
β
= -0.568; Adj. R
2
: 0.25;
p
< 0.001) and processing speed (
β
= -0.447; Adj. R
2
: 0.19;
p
= 0.004). Other DTI metrics were not significantly associated with cognitive scores.

Conclusion:
In this CAA sample, all DTI metrics were associated with CAA burden scores, however, only PSMD was significantly associated with cognition, in domains that are commonly affected in vascular cognitive impairment. Our results warrant confirmation in larger samples, but support PSMD as biomarker for cognition in CAA, outperforming other conventional DTI metrics.
Abstract P595: Incidentally-Discovered Asymptomatic Ischemic Lesions Identified Using Natural Language Processing Are Strong Risk Factors for Dementia
Authors: Kent David M , Leung Lester Y , Zhou Yichen , Luetmer Patrick H , Kallmes David F , Fu Sunyang , Zheng Chengyi , Liu Hongfang , Chen Wansu
Published: March 2021

Background:
White matter disease (WMD) and silent brain infarction (SBI) are known to be risk markers for dementia. Nevertheless, the effects of incidentally-discovered WMD and SBI on routinely-obtained neuroimages is unknown.

Methods:
In the retrospective cohort study, Kaiser Permanente-Southern California (KPSC) health plan enrollees aged ≥ 50 years old with a brain cross-sectional image (CT or MRI) between 2009-2019 and without a prior history of ischemic stroke, transient ischemic attack, or dementia were identified. Natural language processing (NLP) was used to identify patients with SBI and WMD on the first qualifying neuroimaging report. Cox proportional hazards regression model was applied to estimate the effects of WMD and SBI on dementia, controlling for major cardiovascular risk factors.

Results:
Among 262,875 individuals receiving brain neuroimaging, 13,154 (5.0%) and 78,330 (29.8%) had SBI and WMD, respectively. The table below summarizes the crude dementia incidence rates. The crude hazard ratio (HR) was 3.69 (95% CI 3.58-3.80) for WMD and 2.80 (95% CI 2.68-2.93) for SBI. In the multivariable model controlling for all major cardiovascular risk factors, the effect of WMD on dementia risk was found to be stronger in younger compared to older patients and for CT- compared to MRI-discovered lesions. With CT, the adjusted HR was 3.08 (95% CI 2.84-3.34) for those < age 70 and 1.90 (95% CI 1.83-1.97) for those ≥ age 70. With MRI, the adjusted HR was 2.58 (95% CI 2.31-2.87) for those < age 70 and 1.59 (95% CI 1.45-1.75) for those ≥ age 70. The adjusted HR associated with a finding of SBI was 2.01 (95% CI 1.78-2.32) for patients age <70 and 1.26 (95% CI 1.20-1.32) for patients age ≥70, and was not modified by imaging modality.

Conclusion:
Incidentally-discovered WMD and SBI are common in patients ≥ age 50 and are associated with substantial increase in the risk of subsequent dementia. The findings may represent an opportunity for dementia prevention.
Abstract P596: How Common Are Microembolic Signals After Cerebrovascular Events and Are They Related to Recurrent Admissions?
Authors: SABAYAN Behnam , Mahinrad Simin , Sedaghat Sanaz , Liotta Eric M , Sorond Farzaneh A
Published: March 2021

Introduction:
Microembolic signals (MES) identified by transcranial Doppler (TCD) reflect an ongoing embolic phenomenon with implications for the recurrence of cerebrovascular events and complications. In this study, we investigated the prevalence of MES detected after stroke or transient ischemic attack (TIA) and studied their relationship with future re-admissions.

Method:
This clinical cohort study is comprised of 961 consecutive patients (mean age 65 years, 59% male) admitted to Northwestern Memorial Hospital with the diagnosis of acute stroke (n: 872) or TIA (n: 89) and underwent TCD evaluation. TCD is performed within the first 48 hours of admission as a routine component of stroke etiology evaluation at our institution. After discharge, patients were followed for an average of 18 months for any hospital readmissions. Cox regression models were used to estimate risk of re-admissions in relation to MES.

Results:
MES were detected in 99 (10%, 95% CI; 8-12%) patients. During the follow up period, 356 patients had emergency room re-admissions. Compared to patients without MES, those with MES were younger (
p
=0.007) and had longer index hospital stay (
p
=0.008). Patients with MES, as compared to patients without MES, had 1.56-fold (hazard ratio 95% CI=1.15, 2.13;
p
=0.005) higher risk of readmission. This association was independent of age, sex, race, smoking, history of hyperlipidemia, diabetes, atrial fibrillation, history of pulmonary emboli, deep vein thrombosis, hypertension, coronary artery disease and heart failure.

Conclusion:
We show that MES are present in one tenth of patients admitted with stroke or TIA, and they are associated with higher risk of re-admission. These data highlight the importance of embolic signals in stroke complication risk stratification and suggest the need for prospective clinical trials targeting MES in secondary stroke risk and complication prevention.
Abstract P607: Interplay Between Post-Myocardial Infarction Left Ventricular Systolic Dysfunction and Atrial Fibrillation: Prognostic Implications for Post-Myocardial Infarction Acute Ischaemic Stroke
Authors: Sia Ching Hui , Tan Benjamin YQ , Zheng Huili , Ho Andrew , Foo David , Foo Ling-Li , Lim Patrick Zhan-Yun , Liew Boon Wah , Ahmad Aftab , Chan Bernard P , Chang Hui Meng , Kong Keng He , Young Sherry , Tang Kok Foo , Chua Terrance , Hausenloy Derek J , Tiong-Cheng Yeo , Tan Huay Cheem , Venketasubramanian Narayanaswamy , Yeo Leonard , Chan Mark Y
Published: March 2021

Introduction:
Acute myocardial infarction (MI) and acute ischaemic stroke (AIS) are leading causes of morbidity and mortality. There is scarce data examining the interplay between post-MI left ventricular systolic dysfunction (LVSD), with or without atrial fibrillation (AF), and subsequent AIS, especially in patients with milder degrees of LVSD (ejection fraction 40-49%). Evidence of an association would be helpful in developing new strategies of reducing AIS after MI. As such, we sought to study this relationship in a real-world population-based registry.

Methods:
This study involved linking national-level data from the Singapore Myocardial Infarction Registry with the Singapore Stroke Registry from 1st January 2007 to 31st December 2018. Both data sets have similar definitions for patient demographics. The ejection fraction (EF) and AF status were recorded during the MI episode. The outcome studied was the first instance of AIS that developed after the MI episode. We also studied the relationship between EF, AF and the severity of AIS as measured by the NIH Stroke Scale (NIHSS).

Results:
There were 64,512 patients available for analysis. The median age was 65.7 (IQR 56.1-76.5) and 69.5% were male. The median duration post-MI to develop AIS was 16.9 (IQR 1.6-46.1) months. There was an independent association between LVSD and the outcome of AIS (adjusted HR 1.18, 95% CI 1.10-1.27); this was evident even in mild forms of LVSD (adjusted HR 1.16, 95% CI 1.06-1.27). AF was not a statistically significant predictor of AIS in post-MI patients with LVSD. Amongst patients without AF, post-MI LVSD was associated with a more severe stroke and higher NIHSS.

Conclusion:
Post-MI LVSD is associated with the occurrence of subsequent AIS. Although this relationship was independent of AF status, patients with LVSD but no AF had suffered a more severe AIS. These findings support the need to develop effectives therapies to prevent AIS post-MI, especially among those with LVSD.
Abstract P610: Ten-Year International Temporal Variations in Age-Standardized Stroke-Related Mortality in Men and Women
Authors: Ouellet Suzie , Alturki Ahmed , Marafi Mariam , Wein Theodore , Vieira Lucy , Huynh Thao
Published: March 2021

Background:
Stroke is one of the leading causes of mortality worldwide. During the last decade, there have been several improvements in stroke-related care such as raising public awareness for early presentation, lifestyle modification, thrombolytic therapy and endovascular therapy. We aimed to evaluate the potential changes in global stroke-related mortality following these innovations.

Methods:
We completed a systematic review of all population-based cohort studies published during the last two decades (2000-2020). We retained all studies which reported age-adjusted and sex-specific stroke-related mortality. We grouped the countries into: developed countries with predominant White population* (Canada, United States of America, Western Europe, Australia, New Zealand), Eastern Europe, Latin America, and Asia. For each of the region, we compared the median stroke-related mortality during the decade 2010 to the stroke-related mortality of the 2000 decade.

Results:
Of 210 articles screened, there were eight studies that reported population-based age-standardized and sex-specific stroke-related mortality in 47 countries. We presented the international secular variations in sex-specific stroke-related mortality in Figure 1. We noted significant temporal decreases in age-standardized stroke-related mortality for both men and women in all regions except for Eastern European women and Asian men. Globally, the stroke-related mortality decreased from 40.0 to 31.7 and from 31.6 to 22.8 per 100,000 for men and women, respectively The reductions of stroke-related deaths approximated 22% and 29%, for men and women, respectively.

Conclusion:
Despite its temporal decrease in most regions, the lack of reduction in stroke-related mortality of Eastern European women and Asian men are noteworthy. Future research is needed to decrease the stroke-related mortality in these high-risk populations. *: As defined by the International Monetary Fund
Abstract P623: Lipid-Lowering Therapy and Intracerebral Hemorrhage Risk: Comparative Meta-Analysis of Statins and PCSK9 Inhibitors
Authors: Sanz Cuesta Borja E , Saver Jeffrey L
Published: March 2021

Background:
Statins were shown to increase intracerebral hemorrhage rates in patients with a first cerebrovascular event in 2006 (SPARCL), likely due to off-target antithrombotic effects, but continued to sometimes be used in elevated ICH risk patients due to absence of alternative agents. Recently, the PCSK9 inhibitors (PCK9is) have become available as potent lipid-lowering class that may not share the hemorrhagic propensity of statins.

Methods:
Systematic comparative meta-analysis assessing ICH rates across all completed statin and PCSK9i RCTs, following PRISMA guidelines. In addition to ICH rates across all trials, causal relation was probed by evaluating for dose-response relationships by agent (low vs high agent dose) and by degree of brain injury at inception (none vs ischemic stroke vs ICH).

Results:
The systematic review identified 33 statin RCTs (203,305 patients) and 4 PCSK9i RCTs (53,253 patients). Across all patient types and all agent doses, statins were associated with increased ICH: relative risk (RR) 1.15, p=0.04; PCSK9is were not (p=0.59). In the agent dose analysis (Table), higher dose statins (7 trials, 62,204 patients) were associated with magnified ICH risk: RR 1.53, p=0.002; higher dose PCSK9is (2 trials, 31,153 patients) were not (p=0.99). In the brain injury dose analysis (Table), for statins, h/o ischemic stroke was associated with a magnified risk of ICH: RR 1.40, p=0.03; and h/o initial ICH was associated with an extremely high effect estimate of risk of recurrent ICH: RR 4.06. For PCSK9is, h/o ischemic stroke was not associated with ICH (p=0.97).

Conclusion:
Statins increase the risk of intracerebral hemorrhage, and the risk is magnified in an agent dose- and brain injury dose-dependent manner; PCSK9is do not ICH risk. PCSK9is may be a preferred lipid-lowering agent class in patients with elevated ICH risk, including patients with intracerebral hemorrhage or multiple covert cerebral microbleeds.