bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P539: Comparison of Transradial Artery versus Transfemoral Artery Access for Solumbra Technique in Mechanical Thrombectomy
Authors: Nisar Taha , Patel Jimmy , Memon Muhammad Z , Singla Amit , Khandelwal Priyank
Published: March 2021

Introduction:
Solumbra technique involves the simultaneous use of stent-retriever and large-bore aspiration for clot retrieval in mechanical thrombectomy (MT). We aim to compare various time parameters in patients who undergo MT via solumbra technique via transradial artery (TRA) approach vs. transfemoral artery (TRF) approach.

Methods:
We performed a retrospective chart review of patients who underwent MT via solumbra technique for anterior circulation large vessel occlusion at a comprehensive stroke center from 7/2014 to 5/2020. We compared time to recanalization parameters, score of TICI≥2b, and functional independence (3-month mRS≤2) in patients who underwent MT via TRA vs.TRF approach via the solumbra technique. A binary logistic regression analysis was performed, controlling for age, sex, pre-treatment-NIHSS, type of anesthesia (general vs.moderate), laterality, and clot location [proximal (internal carotid or M1 segment of the middle cerebral artery) vs.distal (M2 or M3 segment of the middle cerebral artery)].

Results:
A total of 98 patients met our inclusion criteria. The mean age was 63.59±14.40 years. 18 (18.37%) patients underwent MT through transradial approach. In our cohort, there was a significant association of TRA with shorter angio suite arrival-time to puncture-time (22.12±9.92mins vs.28.83±12.26mins; OR, 0.94; 95% CI, 0.88-1; P 0.026), but not with puncture-time to recanalization-time (84.34±61.34mins vs.63.73±35.29mins; OR, 1.01; 95% CI, 1-1.03; P 0.085), angio suite arrival-time to recanalization-time (103.12±51.29mins vs.93.42±39.08mins; OR, 1.01; 95% CI, 1-1.02; P 0.524), number of passes to recanalization (1.78±1.36 vs.1.68±1.05; OR, 1.03; 95% CI, 0.66-1.63 ; P 0.899), number of patients with TICI≥2b (83.34% vs.91.25%; OR, 0.68; 95% CI, 0.14-3.4; P 0.633), and functional independence (66.67% vs.78.75%; OR, 0.49; 95% CI, 0.13-1.86; P 0.292), when compared to TRF approach for MT using solumbra technique.

Conclusion:
Our study demonstrates a significant association between TRA approach with shorter angio suite arrival-time to puncture-time but not with overall time to recanalization, number of patients with TICI≥2b, and functional independence, when compared to TRF approach for MT using solumbra technique.
Abstract P545: First Pass TICI 2b versus Multiple Passes TICI 3 for Acute Ischemic Stroke Patients: Is First Pass TICI 2b Enough?
Authors: Hassan Ameer E , Dibas Mahmoud , Ghozy Sherief , El-Qushayri Amr Ehab , Dmytriw Adam A , G Tekle Wondwossen , Sarraj Amrou
Published: March 2021

Background and Objective:
Prompt and complete reperfusion with mechanical thrombectomy (MT) is essential to improve outcome in acute ischemic strokes (AIS) with large vessel occlusion (LVO). Recently, first-pass effect (FPE), defined as achieving complete reperfusion with a single pass, has been emphasized as a potentially important MT target. We aimed to compare outcomes between patients who achieve mTICI 2b with first pass to those with multiple devise passes (MDP) mTICI 3.

Methods:
From a single comprehensive stroke center database, we retrospectively grouped LVO pts treated with MT into those who achieved mTICI 2b after a single pass and mTICI 3 after MDP. Clinical outcome (discharge and 90-day mRS), discharge NIHSS and safety (sICH, neurological worsening, mortality) were compared between the two groups.

Results:
Of 186 pts included, 153 (82%) achieved mTICI 3 with MDP, and 33 (18%) had mTICI 2b after a single pass. Mean age (71 vs 69), NIHSS (17 vs 16, p=0.2) were similar between the two groups. Patients with a single pass mTICI 2b had numerically higher IV tPA administration (33% vs 46%, p=.16). There was no difference in other baseline characteristics. There was no significant difference in discharge (21% vs 24.2%, p=0.65) and 90-day mRS 0-2 (24% vs 24%, p=0.5), MDP mTICI 3 and single pass mTICI 2b, respectively. Also, there was no difference in discharge NIHSS score (13.6 vs 16.7, p=0.26), mortality (16.3% vs 18.2%, p=0.8) and sICH rates (7.8% vs 18.2%, p=0.095) or neurological worsening (76.5% vs 69.7%, p=1).

Conclusion:
Our results did not show a significant difference between mTICI 3 with multiple passes and mTICI 2b after a single pass. Future large studies are warranted to explore the possibility of extending the first pass effect to patients who achieve mTICI 2b with a single pass.
Abstract P546: Emergent Carotid Artery Stenting and Intracranial Thrombectomy for Acute Stroke With Tandem Occlusion
Authors: Garg Aayushi , Farooqui Mudassir , Limaye Kaustubh , Dajles Andres , Mendez Ruiz Alan , Zevallos Cynthia , Quispe Orozco Darko , Zaidat Osama O , Ortega Santiago
Published: March 2021

Introduction:
Safety of emergent carotid artery stenting (CAS) during endovascular thrombectomy (EVT) for acute strokes with intracranial large vessel and cervical internal carotid artery tandem occlusion is still unclear. Given the potential risk of symptomatic intracranial hemorrhage (ICH) with anti-thrombotic medications required in the setting of CAS, the decision between CAS versus carotid artery angioplasty (CAA) alone remains controversial. In this study, we aimed to identify the optimal endovascular carotid revascularization approach in this patient population, using a large, nationally representative dataset.

Methods:
We utilized the Nationwide Readmissions Database 2016-2017 to identify patients admitted due to acute ischemic stroke who underwent anterior circulation EVT as well as CAS or CAA on the same day. Survey design methods were used to generate national estimates. Logistic regression analysis was used to compare the in-hospital outcomes between patients who underwent CAS versus CAA. Survival analysis was used to estimate the 30-day readmissions.

Results:
We identified 2,042 hospitalizations meeting the study inclusion criteria (mean±SD age: 66.0±12.5 years, female 31.3%). Of these, 1,391 (68.1%) had undergone CAS and 651 (31.9%) CAA alone. Baseline characteristics between the two groups were similar except patients with CAS were more likely to be on anti-thrombotics and were less likely to have received intravenous thrombolysis (tPA) as compared to those with CAA. There was no significant difference in the clinical outcomes including ICH, in-hospital mortality, gastrostomy tube placement, prolonged mechanical ventilation, length of stay, and hospital charges between the two groups in unadjusted analysis and after adjustment for the demographics and tPA use. All-cause 30-day readmission rate was similar between the two groups [hazards ratio (HR) 0.98, 95% confidence interval (CI) 0.64-1.51, p-value 0.924]. Patients with CAS had more readmissions due to ICH (HR 2.72, 95% CI 0.30-24.74) and less readmissions due to ischemic events (HR 0.78, 95% CI 0.12-5.08), although the difference was not statistically significant.

Conclusion:
Emergent CAS-EVT approach appears to be safe with no adverse outcomes compared to CAA alone.
Abstract P559: Sex Differences in Clinical Outcomes After Endovascular Thrombectomy for Large Vessel Occlusion Stroke: A Sub-Analysis of the SELECT Study
Authors: Fifi Johanna T , Nguyen Thanh , Song Sarah , Sharrief Anjail Z , Pujara Deep , Fournier Lauren E , Martin-schild Sheryl B , Sarraj Amrou ,   On behalf of the SELECT Investigators
Published: March 2021

Background:
Women have been shown to have greater disability than men after acute ischemic stroke (AIS) treated by thrombolysis. Whether endovascular thrombectomy (EVT) outcomes differ by sex with AIS from large vessel occlusion (LVO) is controversial. We compared sex differences in EVT outcomes and assessed relationship to post-discharge improvement.

Methods:
In SELECT prospective cohort, EVT treated anterior circulation LVOs (ICA, MCA M1/M2) ≤24 hrs from LKW were stratified by sex. Discharge, 90-day mRS were compared in all patients and a propensity matched cohort. We evaluated mRS improvement (discharge to 90-day) using repeated measure mixed regression with linear approximation of mRS.

Results:
Of 285 patients, 139 (48.8%) were women, and older (mean IQR 69 years (57,81) vs 65 (56,75), p=0.04) with similar NIHSS (17 (11,22) vs 16 (12,20), p=0.44). Women had smaller perfusion lesion 109 (66,151) vs 154 (104,198) cc, p<0.001) and better collaterals on CTA/CTP but similar ischemic core size 8 (0,25) vs 11 (0,38) cc, p=0.22. Discharge functional independence rates, mean (IQR) mRS were similar (women 39% vs men 46%, p=0.14, and mRS: 3 vs 3, p=0.43). 90-day mRS 0-2 did not differ between women and men (50% vs 55%, aOR 0.77, 95% CI 0.39-1.50, p=0.39) and mean (IQR) mRS: 2 (1,4) vs 2 (0,4). Larger predicted mRS score improvement trend seen in men (2.62 vs 2.21, reduction 0.41) than women (2.65 vs 2.46, reduction: 0.19, p=0.21), Fig 2A. In propensity matched 65 pairs, women exhibited worse 90-day mRS 0-2 (46% vs 60%, aOR 0.41, 95% CI 0.16-1.00, p=0.05). mRS improvement from discharge to 90-day was significantly larger in men (2.49 vs 1.88, reduction 0.61 vs women 2.52 vs 2.44, reduction 0.08, p=0.04), despite similar discharge disposition Fig 2B.

Conclusion:
Women had similar discharge outcomes as men following EVT, but improvement at 90 days was significantly worse in women. Further exploration of the influence of post-discharge factors to identify target interventions is warranted.
Abstract P560: Delipid Extracorporeal Lipoprotein Filter System: A New Lipid-Lowering Therapy for Acute Ischemic Stroke Patients
Authors: Jiao Yuqiong , Ye Ting , Han Xiang
Published: March 2021

Objectives:
The purpose of this study was to illustrate a new low-density lipoprotein cholesterol (LDL-C) adsorption system, Delipid Extracorporeal Lipoprotein filter from Plasma (DELP) system, and evaluate its safety and efficacy in acute ischemic stroke patients.

Methods:
This is an observational study of 22 acute ischemic stroke patients who underwent DELP treatment from March to August 2019. The DELP system was composed of a plasma filter JX-DELP, a COM.TEC cell separator and Tubing P1R Plasma Treatment Set. Clinical data and laboratory results including plasma lipids and some safety parameters before and after the apheresis were collected and analyzed.

Results:
The present study included 22 patients (15 males, 7 females, 59.95±13.71 years). The mean LDL-C was significantly reduced from 3.36±0.64 mmol/L to 2.30±0.53 mmol/L (31.5%,
p
<0.001, n=22) during a single DELP treatment, and from 3.59±0.48 mmol/L to 1.85±0.50 mmol/L (48.2%,
p
<0.001, n=13) after two apheresis, respectively. No clinically relevant changes were observed in hematologic safety parameters during DELP treatments.

Conclusions:
We concluded that the new LDL-C adsorption system is a promising method for timely and controllable LDL-C administration in acute ischemic stroke patients in view of its high efficacy, simple operation, and safety.
Abstract P565: Influence of Thyroid Disease on Presentation and Outcomes of Moyamoya Disease
Authors: Wang Allan R , Li Yiping , STEINBERG Gary K
Published: March 2021

Introduction:
The presence of thyroid autoantibodies may play a role in the pathogenesis of moyamoya-type angiopathy. However, the influence of thyroid disease on presenting characteristics and treatment outcomes of moyamoya disease (MMD) remains unclear.

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

Results:
264 MMD patients with MMD were identified, 33 (12.5%) of whom presented with concurrent thyroid disease (4 hyperthyroid, 28 hypothyroid, 1 unspecified). Comparing groups with and without thyroid disease, there were no differences in age of presentation (p=0.12), racial composition (p=0.38), or rates of diabetes (p=0.32), hypertension (p=1.0), and hyperlipidemia (p=0.71). There was a higher proportion of females (94% F vs. 74% F, p=0.02) and lower rates of smoking (p=0.04) and alcohol consumption (p=0.04) in the thyroid disease group. Despite lower rates of vascular risk factors, the thyroid disease group exhibited more severe angiographic MMD at presentation, with higher Suzuki grade (p=0.002), higher proportion of bilateral disease (91% vs. 67%, p=0.007), and a trend towards more posterior circulation involvement (39% vs. 24%, p=0.09). MMD patients with concurrent thyroid disease were also more likely to present with carotid occlusion as opposed to large vessel stenosis (39% vs 10%, p=0.03), resulting in increased collateral filling via the extracranial (3.5% vs. 2.8%, p=0.04) and posterior circulations (24% vs. 16%, p=0.002). Patients with thyroid disease trended towards having higher rates of ischemic complications (28% vs. 16.8%, p=0.06) perioperatively; however, there were no differences in rates of post-operative hemorrhage (p=1.0) or transient neurologic events (p=0.85).

Conclusions:
Patients with concurrent moyamoya and thyroid disease present with more advanced angiographic intracranial disease, which may be associated with higher rates of ischemic complications in the perioperative period.
Abstract P589: Pediatric Thrombectomy: Design And Workflow Lessons From Two Experienced Centers
Authors: Lauzier David C , Galardi Maria M , Guilliams Kristin , Goyal Manu S , Amlie-Lefond Catherine , Hallam Danial K , Kansagra Akash P
Published: March 2021

Introduction:
While clinical trials have demonstrated the remarkable efficacy of endovascular thrombectomy (EVT) for treating adult patients suffering from acute ischemic stroke (AIS), benefits reaped from advances in adult stroke care have unfortunately not occurred in parallel with pediatric stroke care. Randomized trials of EVT in childhood stroke are unlikely given the low incidence of stroke in children compared to adults, and despite promising outcomes in small case reports and series, EVT in children remains an off-label procedure lacking established consensus guidelines. Along with a clear need to collect prospective pediatric EVT outcome data, there is a need to enhance pediatric stroke care infrastructure to provide high-quality care to children experiencing stroke.

Methods:
In this work, we review two successful pediatric thrombectomy programs, examining key workflow design features that are likely to be important for other programs that aspire to implement pediatric EVT capability.

Discussion:
While pediatric EVT workflows will vary between centers, we identify several key elements of programmatic success shared between the two reviewed stroke programs that may serve as foundational design considerations for centers aiming to develop their own pediatric EVT programs. These elements include a formalized protocol and workflow, integration with an adult EVT workflow, simplification and automation of workflow steps, pediatric adaptations of stroke imaging, advocacy of pediatric stroke care, and collaboration between providers, among others. These essential features transcend any single hospital environment and may provide an important foundation for other pediatric centers that aim to enhance the care of children with stroke.

Conclusion:
EVT shows promise in reducing stroke-associated morbidity in children. To maximize the efficacy of this intervention, workflow optimizations discussed here should be implemented by centers seeking to develop local pediatric EVT capability.
Abstract P590: Serum Zinc Levels and Incidence of Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study
Authors: Mattern Lindsey , Chen Cheng , McClure Leslie A , Brockman John , Cushman Mary , Judd Suzanne E , He Ka
Published: March 2021

Background and Purpose:
Despite zinc’s role as an anti-oxidant and anti-inflammatory agent, prospective studies relating zinc levels to ischemic stroke risk are lacking. We aimed to examine the association between serum zinc levels and incidence of ischemic stroke in a US population.

Methods:
Using a case-cohort study nested within the REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort, participants were randomly selected from the REGARDS cohort to generate a sub-cohort (
n=
2,346). All incident ischemic stroke cases as of September 2012 (
n
=660) were included, with 62 incident cases overlapping in the sub-cohort. Serum zinc levels were measured at baseline. Barlow-weighted Cox’s proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios (HR) and the corresponding 95% confidence intervals (CI) of ischemic stroke by serum zinc levels.

Results:
The median zinc level for the sub-cohort was 121.19 μg/dL (interquartile range 104.86 to 140.39 μg/dL). Serum zinc levels were inversely associated with incidence of ischemic stroke after adjustment for potential confounders (quartile 4 vs. quartile 1: HR=0.78, 95% CI: 0.61-0.98, p=0.03 for trend). When stratified by pre-specified factors (sex, race, region), only sex showed a significant modification (p=0.03 for interaction). The inverse association was more pronounced among females (quartile 4 vs. quartile 1: HR=0.58, 95% CI: 0.41-0.84, p<0.01 for trend) than males (quartile 4 vs. quartile 1: HR=1.08, 95% CI: 0.78-1.51, p=0.92 for trend).

Conclusions:
Serum zinc concentration was inversely associated with incidence of ischemic stroke, especially among women, indicating that low zinc levels may be a risk factor for ischemic stroke.
Abstract P597: Growing Prevalence of Post-Stroke Sleep-Disordered Breathing
Authors: Brown Devin L , Gibbs River , Shi Xu , Case Erin , Chervin Ronald , Lisabeth Lynda D
Published: March 2021

Introduction:
Sleep-disordered breathing (SDB) is common after stroke and is associated with poor functional and cognitive outcomes, and recurrent stroke. Despite increasing prevalence of SDB in the general population, no data are available about trends in post-stroke SDB. We therefore sought to assess changes in post-stroke SDB prevalence over a 10-year period.

Methods:
Within the Brain Attack Surveillance In Corpus Christi (BASIC) project, a population-based stroke surveillance study in south Texas, participants with acute ischemic stroke were offered assessment of SDB with the ApneaLink Plus device. Medical record abstraction and baseline interviews were conducted and included the Berlin questionnaire to assess SDB status in reference to the prestroke state. SDB testing was performed shortly after stroke presentation (median 12 days (IQR: (6, 21)). Respiratory event index (REI) was calculated as the sum of apneas and hypopneas per hour of overnight recording. SDB was defined as an REI ≥10. SDB assessment procedures remained unchanged throughout (2010-2020). Logistic (SDB) and linear (REI) regression were used to test associations with time (parameterized as years since 2010) adjusted for demographics, and stroke and SDB risk factors including BMI and pre-stroke SDB status.

Results:
Among the 1,197 participants, median age was 65, 53% were male, and 65% were Mexican American. SDB prevalence was 61% in 2010-2011 and 75% in 2018-2019. Median REI was 19 in 2010-2011 and 23 in 2018-2019. A linear association was identified between time and SDB (REI≥10), with an odds ratio of 1.123 (95% CI: 1.062, 1.187) per year, after adjustment. Similarly, a linear association was identified between time and REI, with an average increase of 0.504 (95% CI: 0.148, 0.860) per year, after adjustment. Based on models with interaction terms added, no differences in time trends were found by sex or ethnicity.

Conclusions:
Post-stroke SDB prevalence in this population-based sample has increased over the last 10 years. These data highlight the importance of post-stroke SDB and the pressing need to determine whether its treatment improves outcomes.
Abstract P598: Increased Risk of Acute Stroke in Patients With Severe Course of Covid-19: A Multicenter Study and Meta-Analysis
Authors: Siepmann Timo , Sedghi Annahita , Simon Erik , Winzer Simon , Barlinn Jessica , De With Katja , Mirow Lutz , Wolz Martin , Gruenewald Thomas , Schroettner Percy , von Bonin Simone , Pallesen Lars-Peder , Rosengarten Bernhard , Schubert Joerg , Lohmann Tobias , Machetanz Jochen , Spieth Peter , Koch Thea , Bornstein Stefan , Reichmann Heinz , Puetz Volker , Barlinn Kristian
Published: March 2021

Introduction:
Recent studies linked coronavirus disease 2019 (COVID-19) to thromboembolic complications likely mediated by increased blood coagulability and inflammatory endothelial impairment.

Objective:
We aimed to assess the risk of acute stroke in patients with COVID-19 related to clinical severity of the disease.

Methods:
We conducted an observational multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization. Furthermore, we performed a systematic review using PubMed/MEDLINE, EMBASE, Cochrane Library and bibliographies of identified articles following PRISMA guidelines including data from observational studies of acute stroke in COVID-19 patients. Data was extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RR) and 95% confidence intervals (95%CIs) for acute stroke related to COVID-19 severity using random effects model. Between-study heterogeneity was assessed using Cochran’s Q and I
2
-statistics. PROSPERO identifier
:
CRD42020187194.

Results:
Of 165 patients hospitalized for COVID-19 (49.1% males, median age 67 [57-79], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95%CI: 1.9-8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta-analysis. Among 741 pooled COVID-19 patients overall stroke rate was 2.9% (95%CI: 1.9-4.5). Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR 4.12, 95%CI 1.7-10.25; p=0.002) with no evidence of heterogeneity (I
2
=0%, p=0.82).

Conclusions:
Synthesized analysis of data from our multicenter study and previously published cohorts demonstrate that severity of COVID-19 is associated with an increased risk of acute stroke, underscoring the necessity of neurological monitoring in patients infected with SARS-CoV-2.
Abstract P611: Plasma Pro-Enkephalin a and Ischemic Stroke Risk in the Regards Cohort
Authors: Short Samuel A , Wilkinson Katherine , Long D Leanne , Judd Suzanne E , Schulte Janin , Kissela Brett M , Howard George , Cushman Mary
Published: March 2021

Background:
The opioid precursor peptide pro-enkephalin A (PENK-A) is believed to be a plasma marker of blood brain barrier dysfunction or cardiovascular risk. PENK-A is previously described in acute ischemic stroke, but PENK-A’s impact on stroke development is unknown. The objective of this study was to test the independent association of plasma PENK-A concentration with incident stroke and describe potential differences by race and sex.

Methods:
The REGARDS cohort is a population-based cohort of 30,239 black and white adults. Baseline plasma PENK-A was measured in 547 participants who developed stroke and 857 who did not. Participants were followed for a median of 5.6 years (interquartile range 4.4-7.2). PENK-A’s association with incident stroke was examined with multivariable adjusted Cox models.

Results:
Cross-sectionally, PENK-A was higher with female sex, white race, older age, lower body mass index, and antihypertensive medication use. Continuously, higher PENK-A was independently associated with stroke risk (fully adjusted hazard ratio 1.20 per standard deviation higher, 95% confidence interval 1.01-1.42). Restricted cubic spline plots revealed a U-shaped relationship (Figure). Among subgroups, this U-shaped association was most apparent in white men and black women. Adjustment for demographics and established stroke risk factors had minimal impact. PENK-A concentration was not associated with stroke severity or subtype.

Conclusions:
Higher plasma PENK-A concentration was independently associated with incident stroke in REGARDS. This association was U-shaped, and PENK-A may be most relevant to white men and black women. PENK-A’s association with stroke was not impacted by established stroke risk factor suggesting a possible causal role in stroke etiology. Further work is needed to understand the role of PENK-A in stroke pathogenesis.
Abstract P613: Genetic Risk of Vascular Risk Factors and Severity of Leukoaraiosis in Patients With Ischemic Stroke: The MRI-GENIE Study
Authors: Xu Huichun , Gaynor Brady , Ryan Kathleen , McArdle Patrick , Bretzner Martin , Bonkhoff Anna , Donahue Kathleen , Giese Anne-katrin , Schirmer Markus D , Kittner Steven J , Mitchell Braxton D , Rost Natalia S ,   on behalf of the MRI-GENIE Investigators and International Stroke Genetics Consortium
Published: March 2021

Introduction:
Severity of leukoaraiosis detected on T2 MRI scans as white matter hyperintensities (WMH) is associated with infarct growth and poor poststroke outcomes in patients with acute ischemic stroke (AIS). Traditional vascular risk factors (VRF) such as age, hypertension (HTN), type 2 diabetes mellitus (T2D), and cigarette smoking are linked to WMH in large population-based studies, yet casual inferences for WMH in AIS patients are limited. We sought to examine the VRFs for evidence of causal relationships with WMH burden in AIS patients using mendelian randomization principles and polygenic risk score (PRS) methods.

Method:
We examined FLAIR MRIs obtained within 48 hours of AIS onset in 4,362 European Caucasian patients from the MRI-GENetics Interface Exploration (MRI-GENIE) study. WMH volume (WMHv) was measured using a fully automated deep-learning trained algorithm. We considered 13 VRFs: blood pressure (HTN, SBP, DBP, Pulse Pressure), lipid (total cholesterol, HDL, LDL, TG), BMI, T2D, atrial fibrillation, alcohol use and smoking. For each factor, we calculated a weighted PRS for each individual based on the most recent GWAS with various GWAS p-value cutoff. We then used linear regression to estimate associations between each PRS and log transformed WMHv, controlling for age, gender and principal components of genetic ancestries. Strata-specific estimates were combined using inverse-variance weighting based meta-analysis.

Results:
PRS of both SBP and DBP were positively and robustly associated with WMHv in the meta-analysis (p value of the association ranging from <0.001 to 0.046 for various SNP selection strategies (GWAS p-value cutoff ranging from p<1E-5 to p<1E-8)), unlike the PRS of other risk factors, although stratum-specific significance was achieved for some factors.

Conclusion:
Using mendelian randomization, our results lend further evidence that high blood pressure is a causal risk factor for WMH in AIS patients. This result is consistent with previous epidemiological studies of leukoaraiosis in stroke-free populations, and it supports universal control of HTN as common contributor to WMH burden and the overall brain health.
Abstract P626: Periodontal Disease is Independently Associated With Cerebral Small Vessel Disease
Authors: Lowe Forrest , Sen Souvik , Adam Hamdi S , Demmer Ryan , Wasserman Bruce A , Rosamond Wayne D , Moss Kevin , Beck James D , Gottesman Rebecca F
Published: March 2021

Background:
Prior studies have shown the association between periodontal disease, lacunar strokes and cognitive impairment. Using the Atherosclerosis Risk in Communities (ARIC) cohort study we investigated the relationship between periodontal disease (PD) and the development of MRI verified small vessel disease.

Methods:
Using the ARIC database data we extracted data for 1143 (mean age 77 years, 76% white, 24% African-American and 45% male) participants assessed for PD (N=800) versus periodontal health (N=343). These participants were assessed for small vessel disease on 3T MRI as measured by the log of white matter hyperintensity volume (WMHV). WMHV were derived from a semiautomated segmentation of FLAIR images. Student t-test was then used to evaluate the relationship between small vessel disease as the log of WMHV in subjects with PD or periodontal health. Based on WMHV the patients were grouped into quartiles and the association of PD with WMHV were tested using the group in periodontal health and lowest quartile of WMHV as the reference groups. Multinomial logistic regression was used to compute crude and adjusted odds ratio (OR) for the higher quartiles of WMHV compared to the reference quartile.

Results:
There was a significant increase in the presence of small vessel disease measured as log WMHV in the PD cohort as compared to periodontal health cohort with p= 0.023 on Independent Sample t-est. Based on WMHV the subjects were grouped into quartiles 0-6.41, >6.41-11.56, >11.56-21.36 and >21.36 cu mm3). PD was associated with only the highest quartile of WMHV on univariate (crude OR 1.77, 95% CI 1.23-2.56) and multivariable (adjusted OR 1.61, 95% CI 1.06-2.44) analyses. The later was adjusted for age, race, gender, hypertension, diabetes and smoking.

Conclusion:
Based on this prospective cohort there is data to suggest that PD may be associated with cerebral small vessel disease. Maintaining proper dental health may decrease future risk for the associated lacunar strokes and vascular cognitive impairment.
Abstract P63: Post-Stroke Cognitive Complaints and Normal MoCA Scores: A Possible Role for Machine Learning-Augmented Cognitive Screening
Authors: Field Thalia S , Zhang Ming , Jang Hyeju , Rebchuk Alexander D , Carenini Giuseppe
Published: March 2021

Background:
The Montreal Cognitive Assessment (MoCA) may be insufficiently sensitive to cognitive impairment in high-functioning stroke survivors. We examined the ability of a machine learning (ML) algorithm to distinguish young stroke survivors with mRS of 0-1 and MoCA >26 vs. age-matched controls.

Methods:
As part of a study comparing performance of the NIH Toolbox Cognitive Battery (NIHTB-CB) in characterizing cognitive deficits in young survivors, we assessed 52 survivors and 53 healthy controls. Voice recordings of subjects describing the Cookie Theft photo were analyzed using a Natural Language Processing algorithm incorporating 335 lexical and acoustic features. We used a stratified five-fold cross validation, performing a feature selection step before training where we selected for inclusion into the model the first k features with the highest absolute correlation with labels in the training fold. Area under the receiver operating curve (AUC) was calculated for each model.

Results:
MoCA was >26 in 83% of controls and 63% of stroke survivors. Using a Gaussian Naive Bayes Classifier, AUC for stroke survivors vs. controls in those with MoCA >26 was 0.74 (95%CI 0.58-0.91). Informative non-acoustic features included lexical and syntactic complexity, info-units (ie. features in the picture) and spatial orientation of info-units. The analysis is ongoing and relation with NIHTB-CB scores will be reported subsequently.

Conclusions:
There is a ceiling effect of the MoCA. Automated ML assessments may serve as efficient screening adjuncts prior to more detailed cognitive assessments in high-functioning stroke survivors with cognitive complaints. Further work is needed.
Abstract P635: Polygenic Risk Scores Augment Stroke Subtyping and Outcome Evaluation
Authors: Li Jiang , Chaudhary Durgesh , Khan Ayesha , Shahjouei Shima ,   Regeneron Genetics Cntr, Griessenauer Christoph , Carey David J , Zand Ramin , Abedi Vida
Published: March 2021

Objective:
To determine whether Polygenic Risk Scores (PRS) derived from MEGASTROKE is associated with ischemic stroke (IS) and its subtypes in an independent tertiary healthcare system and to identify PRS derived from gene-sets of known biological pathways associated with IS and its outcomes (mortality and recurrent stroke).

Methods:
Controls(n=19806/7484, age≥69/79) and cases(n=1184/951 for discovery/replication) of acute IS with European ancestry and clinical risk factors identified by leveraging the Geisinger Electronic Health Record (EHR) and chart review confirmation. All Geisinger MyCode patients with age ≥69/79, without any stroke-related diagnostic codes as low-risk control. Genetic heritability and genetic correlation between Geisinger and MEGASTROKE(EUR) using the summary statistics of GWAS by LDSC. All PRS for any stroke — AS, any ischemic stroke — AIS, large artery stroke — LAS, cardioembolic stroke — CES, and small vessel stroke — SVS constructed by PRSice-2. PRS (top or bottom quantiles) derived from 7350 gene-sets of GO Biological Process was used to stratify the IS.

Results:
A moderate heritability (10-20%) for Geisinger sample as well as the genetic correlation between MEGASTROKE and the Geisinger cohort was identified. Gene sets analyses highlighted the association of PRS with Gene Ontology terms (vascular endothelial growth factor, amyloid precursor protein, and atherosclerosis). The PRS
LAS
, PRS
CES
, and PRS
SVS
explained the most variance of the corresponding subtypes of Geisinger IS suggesting shared etiologies and corroborated Geisinger TOAST subtyping. We further evaluate PRS derived from the gene-sets of which GO terms may best differentiate the survival in IS cases with the corresponding high or low genetic burden. The result from the Cox regression analysis showed simultaneously the effect of several risk factors including PRS on mortality and recurrent stroke probabilities.

Conclusions:
We provide the first evidence that PRSs derived from MEGASTROKE have value in identifying shared etiologies and determining stroke subtypes.
Abstract P643: Incidence of Ischemic Stroke Among Migraineurs on Calcitonin Gene-Related Peptide Inhibitors
Authors: Gomez Juliana , Burish Mark , Savitz Sean I , McCullough Louise D , Ganduglia Cazaban Cecilia
Published: March 2021

Introduction:
Migraine is common and often disabling. Recent research has focused on a new class of treatments targeting the pain-signaling molecule calcitonin-gene-related peptide (CGRP). CGRP inhibitors are the first preventive therapies designed specifically for migraine. However, CGRP also induces vasodilation, and plays a role in cerebral blood flow autoregulation. The clinical cerebrovascular effects of long-term blockade of CGRP are not yet known.

Methods:
We analyzed a retrospective cohort of migraine patients from a large administrative dataset in the United States (OPTUM) that covers patients with commercial insurance and Medicare Advantage, during 2018 and 2019, using ICD-10 codes for all types of migraines. Migraine patients were divided into two groups based on their use of CGRP inhibitors (erenumab, fremanezumab, galcanezumab). We determined the incidence of stroke during 2018 and 2019 among both groups. For the group of migraine patients who used CGRP inhibitors, we focused on the incidence of stroke after these medications were initiated.

Results:
We identified 646,404 migraine patients; 18, 692 (2.9%) of them had used a CGRP inhibitor. Among the users of CGRP inhibitors, 86% were females, and 58% of patients were in the 41 to 65-year-old range. The average time of follow-up was 197 days after initiation of the medication. A total of 1.3 % of patients who used CGRP inhibitors had an ischemic stroke during the follow-up period versus 2.4% of patients who did not use CGRP inhibitors. The lower rate of stroke in the CGRP antibody group was found in both sexes and all age groups.

Conclusions:
These preliminary results suggest that CGRP inhibitors are not associated with a higher frequency of stroke in the initial months of use. This could be related to the avoidance of these medications in patients with known cardiovascular risk factors. Further analyses will be completed on vascular risk factor incidence in these populations as well as multiple regression. Prospective, long term studies are needed to confirm these results.
Abstract P65: Arterial Stiffness Relationship With Periventricular and Deep White Matter Hyperintensities in a Middle-Aged Population
Authors: Hannawi Yousef , Yanek Lisa R , Kral Brian G , Vaidya Dhananjay , Becker Lewis C , Becker Diane M , Nyquist Paul A
Published: March 2021

Introduction and hypothesis:
Periventricular white matter (PVWM) is perfused by perforators originating from the proximal large caliber cerebral arteries with direct transmission of systemic hemodynamic changes as compared to the deep white matter (DWM) that is perfused by distal perforators with dampened transmission. We hypothesized that PVWM hyperintensities (PVWMH) are more strongly associated with the systemic vascular properties representing arterial stiffness (AS) due to vascular aging and hypertension compared to DWM hyperintensities (DWMH).

Methods:
Apparently healthy first degree relatives of subjects with coronary artery disease who had brain MRI as participants in GeneSTAR were selected. PVWMH and DWMH volumes were computed by an automated analysis software. Arterial stiffness indicators included peak systolic blood pressure during treadmill test, pulse pressure (PP), brachial artery (BA) diameter, carotid distensibility index, and diastolic dysfunction estimated by filling and systolic emptying rates (SER) on sestamibi cardiac scan. Statistical analysis was completed using unadjusted and age-adjusted linear regression models in the cohort that was divided into 4 quartiles based on age distribution (1
st
: 29-43, 2
nd
: 44-51, 3
rd
: 52-59, 4
th
: 60-74).

Results:
782 participants were included (age 51.05±10.6 years, 58.4% female, 39% African American, PVWMH volume 1977.01±5195.81 ml and DWMH volume 625.93±1108.37 ml). In the unadjusted analysis, PVWMH showed association with PP in the 1
st
and 3
rd
age quartiles (p= 0.02 and 0.03, respectively) and SER in the 2
nd
and 4
th
age quartiles (p=0.04 and 0.03). This relationship remained significant in the adjusted analysis for SER (p=0.047, and 0.032, respectively) and in the 1
st
age quartile for PP (P=0.02). DWMH relationship with BA diameter was significant in the 2
nd
age quartile in the unadjusted and adjusted models (P=0.011, and 0.02, respectively). DWMH was also associated with ratio of cardiac filling/SER (P=0.039 and 0.047) in the 1
st
age quartile.

Conclusions:
In this exploratory analysis, AS measures show different relationships to PVWMH and DWMH across age groups in middle-aged population suggesting a potential mechanistic role of AS in WMH pathology.
Abstract P66: Prediction of Early Post-Stroke Major Neurocognitive Disorder Using Support Vector Machines
Authors: Aamodt Eva Birgitte , Schellhorn Till , Apostolova Liana , Svaldi Diana O , Stage Eddie , Logan Paige E , Sanjay Apoorva B , Saltvedt Ingvild , Beyer Mona K.
Published: March 2021

Neurocognitive disorder (NCD) appears in 10% of survivors of a first-ever stroke and in 30% after a recurrent one. We aimed to classify clinical- and imaging factors related to the development of major NCD 3 months post stroke, so as to examine whether early development (<1 yr) is mainly of a neurodegenerative or vascular origin. Based on previous literature we hypothesized that early post-stroke major NCD would mainly be of neurodegenerative origin. 227 stroke survivors (age = 71.69 (11.25), NIHSS = 3.79 (4.75), females (43,61%)) were included from the ‘Norwegian COgnitive Impairment After STroke’ study. Clinical- and MRI data at baseline, and neuropsychological data at baseline and 3 months was used. Cortical thicknesses were automatically measured using Freesurfer and white matter hyperintensity (WMH) volumes were semi-automatically measured using FSL Bianca. Stroke lesion volumes were semi-automatically measured using ITK-snap. Support Vector Machine (SVM) classification was used in order to investigate the prognostic value of the neuroimaging findings and the clinical factors. Model performance was measured using Area Under Receiving Operating Characteristics (ROC) and -Curve (AUC). The best model correctly predicted major NCD in 88% of the patients and was driven by 19 features, with the top five features being stroke volume, WMH volume, left hemisphere occipital- and temporal thickness, and right hemisphere cingulate thickness.

In conclusion, clinical- and MRI findings may be used in prediction of cognitive outcome for stroke patients. Various meta-studies of post-stroke major NCD prediction show levels ranging from .48 to .91, showing that the current model is performing well. Early development of major NCD seems dependent not on neurodegenerative causes alone, but also on vascular factors, as well as aspects of the stroke itself. This highlights the complexity of post-stroke NCD and thus also its prediction.

Figure 1: ROC curve of SVM model, with an AUC of .88.
Abstract P664: Radon Exposure and Cerebrovascular Disease - A Systematic Review and Meta-Analysis of Observational Studies in Occupational and General Populations
Authors: Lu Liping , Zhang Yijia , Chen Cheng , Field R. William , Kahe Ka
Published: March 2021

Background:
Radon is the second leading cause of lung cancer and one of the top ten causes of cancer mortality in the United States. However, research findings examining the causal relationship between radon exposure and cerebrovascular disease (CeVD) are inconsistent.

Hypothesis:
Although it is biologically plausible that radon in the blood stream and vascular tissue may cause vascular damage resulting in CeVD, the discrepancy in the previous research highlights a need to systematically review the existing literature. We hypothesized that there was an association between radon exposure and risk of CeVD.

Methods:
We searched Pubmed, Embase and Google Scholar for original studies on the association between radon and CeVD in both occupational and general populations. We systematically reviewed the literature and quantitatively summarized the available data using weighed random-effect models.

Results:
A total of 17 studies were identified in the systematic review, including 14 occupational studies among uranium workers. Of the 14 occupational studies, four studies were eligible for the meta-analysis (99,730 participants and 2,745 deaths). The pooled relative risk of CeVD mortality per 100 working level month (WLM) was 1.10 (95% confidence interval [CI]=0.92, 1.31). Three studies conducted in the general population consistently demonstrated a statistically significant association between cumulative residential radon exposure and the prevalence or mortality of CeVD.

Conclusion:
The existing literature revealed an association between radon exposure and CeVD risk in general population, but not in occupationally-exposed miners. While competing risk of lung cancer and healthy worker effect need to be evaluated in the occupational studies, more scientifically rigorous case-control or cohort studies in the general population are warranted.
Abstract P666: Covid-19 Geographic Distribution and Stroke Code Activation Within San Diego County
Authors: Perrinez Emily , Calara Robin , Schoenheit-Scott Paige , Kenner Brininger Amelia , Olson-Mack Lindsay L , Reeling Carol A , Davis Cecile , Sundby Christine , Rockwell Jean M , Burley Jessica , Libby Kathyrn J , Couts Linda , Januszewicz Lourdes , Kenny Luisa J , Nabulsi Mohammed , McGurk Penny , Koenig Kristi L , Kalafut Mary A , Hemmen Thomas
Published: March 2021

Introduction:
In the early months of the COVID-19 pandemic, decreased numbers of stroke code activations were reported nationwide. In San Diego County, a diverse region that borders Mexico with over 4500 square miles and population 3.3 million, trends in COVID-19 cases varied geographically. We saw an overall decrease in stroke cases across our systems and aimed to better understand if high COVID infection rates in subregions affected stroke code activations.

Methods:
Stroke code activation data from 15 Stroke Receiving Centers were matched with COVID-19 case rates by patient home zip code. Patients arriving via emergency medical services (EMS) or private transportation were included. Patients with home zip codes outside of San Diego County were excluded. Data represented the cumulative rate of stroke codes and COVID-19 cases per 100,000 population per zip code for the period of March 1 through June 30, 2020.

Results:
We counted 1,927 stroke code activations across 106 zip codes in San Diego County. The average stroke code activation rate was 58.4 per 100,000 (range: 0-310.6) The median stroke code activation rate was 55.95 (IQR=32.1-73.1) per 100,000 population. The median COVID rate per zip code was 244.9 (IQR=177-448.4) per 100,000 population. There were 958 (49.7%) non-stroke diagnoses, 576 (29.9%) AIS, 272 (14.1%) TIA, 104 (5.4%) ICH and 17 (.9%) SAH. We did not identify a correlation between stroke code activation rates and COVID rates across zip codes (r=.17, p=.09, 95% CI(-.02, .35)).

Conclusions:
Across a large and diverse single-county region, no correlation was found between COVID positivity rate per zip code and stroke code activations. We found no decreases in stroke code activations in areas with high COVID rates.
Abstract P672: Black White Disparity in Multiple Risk Factors is Increased in Older Young Adults
Authors: Mehndiratta Prachi , Ryan Kathleen , Morawo Adeolu , Chaturvedi Seemant , Cronin Carolyn A , Phipps Michael S , Wozniak Marcella A , Cole John W , Dutta Tara , Kittner Steven J
Published: March 2021

Background:
Stroke in young adults constitutes 15-18% of all ischemic strokes. Vascular risk factors contribute to stroke risk in young adults particularly older young adults. Few studies have addressed Black White differences in risk, stratified by age. We evaluated the prevalence of risk factors in the younger young (less than 40 years) vs. the older young adults (40 and above).

Methods:
A population based case control study with 1034 cases and 1091 controls, ages 15-49 was used to investigate the relationship between risk factors (DM, HTN, Smoking and Obesity) and stroke. Groups were defined by the number of risk factors (RF) among cases and controls : no risk factors (ref group), one RF, two RF, three RF and four RF. Prevalence of risk factors was determined in the entire population and stratified by age, sex and race. Logistic regression was used to determine odds of stroke based on the number of risk factors compared to the reference group.

Results:
The percent of cases with three or more risk factors was compared in different subgroups: ages 15-39 vs. 40-49 was 8.4 vs. 21.6, women vs. men was 15.6 vs. 18.6 and White vs. Black was 12.3 vs. 22.7. Among cases 40 years and older, Blacks were 3 times more likely than Whites (5.9 vs. 2) to have four or more risk factors.Across all age, race and sex subgroups, the odds of having a stroke increased exponentially with an increase in the number of risk factors.

Conclusion:
Blacks are more likely to have multiple risk factors than Whites. This difference is accentuated in those 40 years and older. Targeting young adults with multiple risk factors for preventive interventions would address a root case of excess stroke risk especially among Blacks.