bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 29: Urban versus Non-Urban Hospital Location Impacts on Stroke Outcomes
Authors: Ranta Anna , Thompson Stephanie , Davis Alan , Barber P. Alan , Fink John , Gommans John , Cadilhac Dominique A , Harwood Matire , McNaughton Harry , Abernethy Ginny , Girvan Jackie , Feigin Valery L , Denison Hayley , Corbin Marine , Levack William , Wilson Andrew , Douwes Jeroen
Published: March 2021

Introduction:
Stroke care provision differs between urban and provincial hospitals predominantly due to economy of scale, which is correlated with resources available and degree of specialisation. We assessed the impact of urban versus non-urban hospital location on stroke outcomes.

Methods:
REGIONS Care is a New Zealand (NZ) nationwide prospective observational study that included consecutively admitted stroke patients involving all NZ stroke hospitals between 1 May and 31 October 2018. Patients were followed-up at 3, 6, and 12 months. The primary outcome was favourable modified Rankin Score of 0-2. Results were adjusted for age, stroke severity, pre-morbid level of independence and other potential confounders using multivariate logistic regression.

Results:
Of the 2,379 patients (mean age (SD), 75 (13.7)), 1,963 (82.6%) had ischaemic strokes and 291 (12.3%) haemorrhagic strokes. The odds of achieving a favourable outcome at 3 and 6 months was significantly lower for patients treated in non-urban compared to urban hospitals: aOR 0.72 (95%CI:0.56-0.93; p=0.012) and aOR 0.71 (95%CI:0.52-0.96; p=0.028), respectively. At 12-months this difference was less pronounced (aOR 0.77, 95%CI:0.57-1.04; p=0.089). Similarly, death was significantly more likely at 3 and 6 months, and borderline statistically significant at 12 months: aOR 1.64, 95%CI:1.30-2.29, p=0.001; 1.54, 95%CI:1.12-2.11, p=0.008; and 1.36, 95%CI:0.99-1.87, p=0.06, respectively. Stroke recurrence was similar between urban and non-urban settings at 3 and 6 months, but more likely in the non-urban setting at 12 months (aOR 1.94, 95%CI:1.14-3.29, p=0.014. In the non-urban setting, eligible patients were less likely to receive reperfusion therapy (aOR 0.5, 95%CI:0.28-0.91, p=0.023); acute stroke unit care was less consistently accessed (aOR 0.58, 95%CI:0.48-0.70, p<0.001); and appropriate secondary preventive therapy was less frequently prescribed (aOR 0.50, 95%CI:0.28-0.91, p=0.023).

Conclusion:
This first comprehensive prospective NZ nationwide stroke study showed significant differences in stroke outcomes and access to key acute stroke interventions between urban and non-urban hospitals. This inequity requires urgent intervention from health system funders and providers.
Abstract 40: Hematoma Expansion Shift Analysis to Assess Acute Intracerebral Hemorrhage Treatments
Authors: Yogendrakumar Vignan , Ramsay Tim , MENON Bijoy K , Qureshi Adnan , Saver Jeffrey L , Dowlatshahi Dar
Published: March 2021

Background and Purpose:
In present-day intracerebral hemorrhage (ICH) trials, hematoma expansion (HE) is often analyzed as a binary variable - present or absent. However, dichotomizing intrinsically wide-ranging variables discards substantial information reflective of treatment effect and can reduce the ability to detect relationships between the exposure and outcome of interest. We explored the concept of a “HE shift analysis” as a novel analytic mode for ICH treatment trials using previously published clinical trial data.

Methods:
Using data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial, patients were stratified by treatment status (intensive vs. standard blood pressure lowering with IV nicardipine) and HE shift was evaluated by generating strata based on a) previously established HE definitions, b) quartiles of 24-hour total hematoma volume, and c) quartiles of 24-hour total hematoma volume (THV) change. The relationship between blood pressure treatment and hematoma expansion shift was explored using proportional odds models and adjusted Wilcoxon testing.

Results:
The primary analysis population included 863 patients. In both treatment groups, approximately one-third of patients exhibited no hematoma growth. Using a conventional threshold, significant intraparenchymal expansion (≥33%) was reduced by 5.8% in those assigned to the intensive therapy arm (aOR: 0.77 [95% CI: 0.60-0.99], Figure 1A). The stratified quartiles of 24-hour total hematoma volumes were associated with a 5% shift within the highest and lowest strata in the intensive arm, (aOR: 0.83 [0.66-1.05], Figure 1B). Intensive therapy was associated with a 5.2% reduction from > 3 mL to 0.5-3 mL (aOR: 0.86 [0.68-1.09], Figure 1C).

Conclusions:
A shift analysis model of HE provides additional insights into the biological effects of a given therapy and may be an alternate way to assess hemostatic agents in future hemorrhage trials.
Abstract 52: Changes in Oligodendrocyte Sub-Populations After Neonatal Stroke
Authors: Dingman Andra , Frazier Alexandra , Given Katherine , Wassermann Benjamin , Macklin Wendy B , Herson Paco S
Published: March 2021

Background:
Chronic white matter changes after neonatal stroke have not been well studied. Histologically, we see a robust increase in oligodendrocytes (OLs) in injured striatum 14 days post-middle cerebral artery occlusion (MCAO) in neonatal mice. The contribution of these cells to chronic white matter injury and repair has not been evaluated.

Objective:
Evaluate changes in striatal OL cell gene expression after neonatal MCAO.

Methods:
Mice underwent 60 minutes of MCAO at postnatal day 10 using the filament model and sacrificed 14 days later for fluorescent antibody cell sorting and single cell RNA sequencing. Single cell suspensions from Injured (ipsilateral) and uninjured (contralateral) striata were incubated with antibodies to immature and mature OLs. Cells expressing OL markers were collected and captured using 10x Genomics Chromium with V3.1 chemistry and analyzed in Seurat V3.1.

Results:
We captured a total of 4598 cells, with ~250,000 reads per cell. Our data set was comprised of 2399 oligodendrocytes (915 Contralateral, 1484 Ipsilateral). Feature plots of OL markers demonstrate that the entire lineage is present in our cell population (Fig 1A). Unbiased clustering identified 10 sub-populations of oligodendrocytes (Fig 1B). In ipsilateral striatum there was a significant decrease in the proportion of cells in cluster 8 (p <0.0001, proportions test, Fig 1C), which also express OL progenitor cell (OPC) markers. There was a significant increase in the proportion of cells in clusters 1 and 5. Pathway analysis suggest that both these clusters are comprised of pre-myelinating oligodendrocytes.

Conclusions:
At 14 days after neonatal stroke in mice scSEQ reveals a depletion of an OPC sub-population and an increase in sub-mature clusters of oligodendrocytes in ipsilateral striatum. Ongoing analysis of differential gene expression will reveal new insights into these cells and potential targets to promote white matter repair after neonatal stroke.
Abstract 56: Incidence of Large Vessel Occlusions in Children Who Present Within Extended Thrombectomy Treatment Window
Authors: Barry Megan , Bernard Timothy J , Stence Nicholas V
Published: March 2021

Introduction:
Mechanical thrombectomy (MT) should be considered in children with persistent deficits with large vessel occlusion (LVO), although the recognition and diagnosis of stroke is often delayed. With the recent extension of treatment windows to 24 hours in adult studies, more children may now be MT candidates. The aim of this project was to examine LVO incidence in childhood strokes that present within 24 hours of symptom onset.

Methods:
Patients with clinical and radiographic confirmed stroke from 1995-2018 were identified via internal database search. Patients with last known normal < 24 hours and imaging within the MT time window (24 hours) were included for analysis. A pediatric neuroradiologist independently reviewed imaging to confirm presence/absence of LVO.

Results:
Of 165 patients with childhood stroke, 60 (36.3%) had last known normal <24 hours and vessel imaging within the MT timeframe (table). Fourteen patients (8.5%) had an LVO; nine with internal carotid or M1 and five with M2 occlusions. Median time from symptom onset to imaging was 6.47 hours in LVO patients. Most common stroke etiologies with LVO were unilateral focal cerebral arteriopathy of childhood (5) and other (5). One of the LVO patients underwent MT.

Conclusions:
At our institution, over 1/3
rd
of patients presented within 24 hour of symptom onset with vascular imaging, and nearly 1/4 of those children (8.5% overall) had an LVO amenable to potential MT. While not all children with LVO will be MT candidates, this study shows that significant numbers of children present with LVO within the adult MT treatment window.
Abstract 57: Reduction in Ischemic Stroke With Icosapent Ethyl - Insights From REDUCE-IT
Authors: Bhatt Deepak L , Steg Philippe G , Miller Michael , Brinton Eliot A , Jacobson Terry A , Ketchum Steven , Juliano Rebecca , Jiao Lisa , Doyle Ralph , Granowitz Craig , Tardif Jean-Claude , Gregson John , Gibson C. Michael , Leary Megan C , Ballantyne Christie M
Published: March 2021

Background:
In patients at elevated cardiovascular risk, statins reduce the occurrence of ischemic stroke. However, residual stroke risk persists.

Methods:
REDUCE-IT, a multinational, double-blind trial, randomized 8179 statin-treated patients with controlled low-density lipoprotein cholesterol, elevated triglycerides, and risk for, or evidence of, atherosclerosis to icosapent ethyl (IPE), a purified, stable ethyl ester of eicosapentaenoic acid (4 grams/day), or placebo. IPE reduced the primary composite endpoint (CV death, myocardial infarction (MI), stroke, coronary revascularization, hospitalization for unstable angina) and the key secondary composite endpoint (CV death, MI, stroke) by 25% and 26%, respectively, (each p<0.000001). Total (first and recurrent) ischemic events were reduced by 32% (p<0.000001). We examined additional prespecified and
post hoc
stroke endpoints.

Results:
Event rates for time to first fatal or nonfatal stroke were 2.4% vs. 3.3% for IPE vs. placebo; hazard ratio (HR) (95% CI) = 0.72 (0.55-0.93); P=0.01; the relative risk reduction (RRR) was 28%, absolute risk reduction (ARR) 0.9%, and number needed to treat (NNT) 114. For every 1,000 patients treated for 5 years with IPE, approximately 14 strokes (fatal or nonfatal) were averted; rate ratio (RR) (95%CI) = 0.68 (0.52-0.91); P=0.008 (Figure). Ischemic stroke time to first event rates were 2.0% vs 3.0% for IPE vs placebo a 36% reduction [HR=0.64 (0.49-0.85); P=0.002]. Hemorrhagic stroke occurred at low rates with no significant difference for IPE vs. placebo (0.3% vs 0.2%; P=0.55).

Conclusions:
In REDUCE-IT, icosapent ethyl significantly reduced the risk of ischemic stroke, with no excess in hemorrhagic stroke, in statin-treated patients with elevated triglycerides and atherosclerosis or diabetes.
Abstract 66: No Evidence of Functional Peri-Infarct Circuit Remapping in Mouse Somatosensory Cortex After Ischemic Stroke
Authors: Zeiger William , Marosi Mate , Saggi Satvir , Noble Natalie , Samad Isa , Portera-Cailliau Carlos
Published: March 2021

Following ischemic stroke, many patients exhibit partial spontaneous recovery, suggesting that the brain has endogenous mechanisms to recover lost functions. Evidence supports a role for peri-infarct cortex in recovery as this area undergoes structural, physiologic, and transcriptomic changes following stroke. It has been hypothesized that these changes promote circuit rewiring, leading spared neurons in the peri-infarct cortex to “remap” and subsume the function previously performed by neurons in the ischemic core. However, direct evidence for remapping at the single neuron level is lacking. To test this, we targeted photothrombotic (PT) strokes to an individual barrel (C1) in the barrel field of mouse primary somatosensory cortex (S1BF). We then performed longitudinal in vivo two-photon (2P) calcium imaging in
Thy1
-GCaMP6s transgenic mice and recorded whisker-evoked responses of individual layer 2/3 neurons in the adjacent D3 barrel. Before stroke, ~30% of active neurons in the D3 barrel respond to stimulation of the D3 whisker and ~8% of neurons respond to the C1 whisker. Based on the remapping hypothesis, we predicted that the percentage of C1 whisker-responsive neurons in the spared D3 barrel would increase after stroke; however, we found that only ~2% of neurons in the D3 barrel responded to C1 whisker stimulation one month after stroke. We also tested the effect of forced-use therapy on recovery by plucking all whiskers, except the C1 whisker corresponding to the infarcted barrel, following stroke. Still, we found that forced-use therapy did not lead to an increased percentage of C1 whisker-responsive neurons, but it did enhance the responses to C1 whisker stimulation in surviving C1-responsive neurons in the peri-infarct cortex. These results suggest that at the circuit level recovery may occur through potentiation of spared homotopic neurons rather than remapping of neurons to perform new functions.
Abstract 8: Retinopathy is Associated With Stroke, Dementia, and Mortality
Authors: Lin Michelle P , Markovic Daniela , Ertekin-Taner Nilufer , Eggenberger Eric R , Stewart Michael W , Brott Thomas G , Meschia James F
Published: March 2021

Introduction:
Retinal microvascular abnormalities have been associated with stroke, but their association with dementia and death is less well described. We tested the hypothesis that retinopathy is associated with stroke, dementia, and age-adjusted mortality.

Methods:
Data were obtained from the US National Health and Nutrition Examination Surveys from 2005 to 2008, with linked mortality through 2015. Severity of retinopathy was defined as no retinopathy, mild nonproliferative retinopathy (NPR), moderate-severe NPR, and proliferative retinopathy. Logistic regression models were performed to evaluate the relationships between retinopathy, stroke, and dementia, respectively. Independent relationships between retinopathy and all-cause mortality were assessed using Cox regression models, before and after adjusting for covariates. All analyses were adjusted for the complex survey design.

Results:
Of 5,543 participants aged ≥18 years with gradable retinal imaging, 696 had retinopathy, 289 had stroke, and 597 had dementia. Mean age of subjects was 56.3 ± 11.7 years. Retinopathy was associated with higher risk of stroke (adj OR 2.39,
P
<0.001) and dementia (adj OR 1.68,
P
=0.005). Over a median duration of 118 months (IQR 111-125), there was a dose-dependent relationship between severity of retinopathy and all-cause mortality (adjusted hazard ratios were 1.0, 1.5, 2.4, 3.4 across retinopathy severity;
P
=0.021). The Figure shows the age-adjusted cumulative mortality curves by retinopathy severity.

Conclusions:
Participants with retinopathy have a greater than 2-fold increase in stroke risk and a 1.7-fold increase in dementia risk. Having more severe retinopathy confers a higher risk of death after adjusting for age and vascular risk factors. The retina may serve as a tissue biomarker in intervention trials for cerebrovascular and neurodegenerative diseases.
Abstract MP1: Safety and Efficacy of IV-tPA for Acute Ischemic Stroke After Transcatheter Aortic Valve Replacement
Authors: Cline Trevor E , Burchette Raoul , Cheng Pamela , Le Duy , Ajani Zahra , Phan Derek , Zadegan Ray , aharonian vicken , Sangha Navdeep S
Published: March 2021

Introduction:
Peri-procedural acute ischemic stroke (AIS) risk after Transcatheter Aortic Valve Replacement (TAVR) is between 3% to 6.7%, and administration of IV-tPA for its management is not well studied. We analyzed patients who had peri-procedural AIS after TAVR and compared those treated with IV-tPA to those who were not.

Methods:
Data were retrospectively abstracted for patients with an AIS after TAVR within a large regional healthcare system. Baseline demographics were analyzed using the Pearson Chi-Square test. Post AIS outcomes (bleeding events, cardiac events, and functional outcomes) were analyzed using the Pearson Chi Square test and Kruskal-Wallis test.

Results:
From 2011 - 2019, 779 patients underwent TAVR, of which 22 (2.6%) had peri- procedural AIS. 8 received tPA and 14 did not. There was no difference in baseline characteristics. See Table 1. During index hospitalization, there were more groin bleeding events in the tPA group (6 {75%} in tPA vs. 0 {0%} in non-tPA p=0.005). More patients in the tPA group had a trend towards a drop in hemoglobin by 2 g/dL and total aggregate bleeding events. There were no differences in symptomatic ICH, other intracranial bleeding, post-procedural Afib/flutter, post-procedural new CHF, and discharge functional outcomes. At 90 days, there were no differences in safety outcomes and median 90-day mRS.

Conclusions:
This is the largest case series to describe patients who had AIS after TAVR and received tPA. There was no difference between adverse neurological or cardiac outcomes at discharge and 90 days in the tPA group vs. non-tPA group. More tPA patients had groin bleeding, which did not cause any long-term functional impairment. There was a trend toward tPA patients having a lower discharge NIHSS. Overall, tPA appears to be a safe intervention for AIS after TAVR. More evidence is needed to determine its efficacy in TAVR patients.
Abstract MP11: Circulating Plasma Biomarkers Associated With Brain Arteriovenous Malformations
Authors: Wetzel-Strong Sarah E , Weinsheimer Shantel M , Nelson Jeffrey , Pawlikowska Ludmila , Clark Dewi , McCulloch Charles E , Kim Helen , Faughnan Marie E , Marchuk Douglas A ,   Brain Vascular Malformation Consortium HHT Investigator Group
Published: March 2021

Objective:
Circulating plasma protein profiling may aid in the identification of cerebrovascular disease signatures. This study aimed to identify circulating angiogenic and inflammatory biomarkers that may serve as biomarkers to differentiate sporadic brain arteriovenous malformation (bAVM) patients from other conditions with brain AVMs, including hereditary hemorrhagic telangiectasia (HHT) patients.

Methods:
The Quantibody Human Angiogenesis Array 1000 (Raybiotech) is an ELISA multiplex panel that was used to assess the levels of 60 proteins related to angiogenesis and inflammation in heparin plasma samples from 13 sporadic unruptured bAVM patients (69% male, mean age 51 years) and 37 patients with HHT (40% male, mean age 47 years, n=19 (51%) with bAVM). The Quantibody Q-Analyzer tool was used to calculate biomarker concentrations based on the standard curve for each marker and log-transformed marker levels were evaluated for associations between disease states using a multivariable interval regression model adjusted for age, sex, ethnicity and collection site. Statistical significance was based on Bonferroni correction for multiple testing of 60 biomarkers (P< 8.3x10
-
4
).

Results:
Circulating levels of two plasma proteins differed significantly between sporadic bAVM and HHT patients: PDGF-BB (P=2.6x10
-4
, PI= 3.37, 95% CI:1.76-6.46) and CCL5 (P=6.0x10
-6
, PI=3.50, 95% CI=2.04-6.03). When considering markers with a nominal p-value of less than 0.01, MMP1 and angiostatin levels also differed between patients with sporadic bAVM and HHT. Markers with nominal p-values less than 0.05 when comparing sporadic brain AVM and HHT patients also included angiostatin, IL2, VEGF, GRO, CXCL16, ITAC, and TGFB3. Among HHT patients, the circulating levels of UPAR and IL6 were elevated in patients with documented bAVMs when considering markers with nominal p-values less than 0.05.

Conclusions:
This study identified differential expression of two promising plasma biomarkers that differentiate sporadic bAVMs from patients with HHT. Furthermore, this study allowed us to evaluate markers that are associated with the presence of bAVMs in HHT patients, which may offer insight into mechanisms underlying bAVM pathophysiology.
Abstract MP17: Upregulating E2F1 Mitigates Senescence-Associated Phenotypes in Cultured Primary Endothelial Cells
Authors: Maniskas Michael E , Lai Yun-ju , Marrelli Sean P , McCullough Louise D , Moruno-manchon Jose F
Published: March 2021

Vascular contributions to cognitive impairment and dementia (VCID) includes multiple disorders that are identified by cognitive deficits secondary to cerebrovascular pathology. The risk of VCID is higher in people after the age of 70, and, currently, there is no effective treatment. Vascular endothelial cells (VEC) are critical components of the brain vasculature and neurovascular unit and their health is vital to the capacity of the brain vasculature to respond to stressors. However, aged VEC may enter an irreversible replicative-arrest state (senescence), which has been associated with dementia. E2F transcription factor 1 (E2F1) regulates cell cycle progression and DNA damage repair. Importantly, E2F1 deficiency is associated with cell senescence.
We hypothesized
that E2F1 downregulation contributes to senescence in the cerebral endothelium during aging.
We used
cultured primary VEC from young (4-months old, mo) and aged (18-mo) male and female mice for RNA sequencing, plasmid-based gene delivery, high-resolution microscopy, and (4-, 12-, and 18-mo) mice of the bilateral carotid artery stenosis (BCAS) model, which produces chronic cerebral hypoperfusion and recapitulates some of the features seen in patients with VCID.
We found
that overexpression of E2F1 reduced the levels of senescence-associated phenotypes in cultured VEC from young mice that were exposed to oxygen and glucose deprivation (p<0.001), which induces endothelial senescence. Our RNA seq data showed that the expression of
E2f1
was reduced (~40%) in cultured primary VEC from aged mouse brains compared with young cells (p<0.001). E2F1 levels were reduced in the brains of aged mice. Interestingly, we found sex differences in E2F1 levels, with less protein levels (~30%) in males vs females (p<0.05), independently of age. Also, aged BCAS mice (1 month after surgery) had more severe senescence phenotypes, reduced cerebral blood flow, and worse memory deficits compared with control mice (p<0.05). The effect of BCAS was more prominent in aged mice compared with younger (4- and 12-mo) mice.
In conclusion
, our study identifies E2F1 as a potential regulator of endothelial senescence in mice and highlights the contribution of aging as an important factor in losing endothelial resilience.
Abstract MP19: Reimbursement of Mobile Stroke Units in the United States: A Survey by the Prehospital Stroke Treatment Organization (PRESTO)
Authors: Reichenbach Kenneth , Mathiesen Claranne , Thomas Leslie , Hilger Margaret , Grotta James C , Alexandrov Anne W
Published: March 2021

Background:
Mobile Stroke Units (MSU) provide hyperacute diagnosis and treatment in the prehospital setting and are growing in number around the world. However, USA MSU reimbursement limits program proliferation and increases dependency on grants to support program costs. Therefore, we aimed to understand the USA MSU reimbursement paradigm.

Methods:
IRB approval was obtained for the conduct of an anonymous national MSU survey. Survey items were developed by MSU leaders experienced with reimbursement models and disseminated to all USA MSU programs. Returned data were entered and analyzed in SPSS using descriptive statistics.

Results:
Of the 20 existing USA MSU programs, 19 (95%) returned surveys. Programs work 26
+
6 (median 30) days per month serving a median 240 sq. mile radius with a median 600 dispatches per year; 47% describe their service area as metropolitan, 16% as rural, with 37% serving both. A median 4 people staff the MSU with 37% including an MD and 16% including an APP as the expert on board; the remaining programs use telemedicine MD coverage. Two programs are classified as “virtual ED” with 1 of these not classified as an EMS vehicle; 1 MSU is classified as an “outpatient clinic” with all other programs classified as EMS vehicles; 21% are certified CT Mobile Laboratories. During the last 12 months, overall the 19 responding programs gave on average 72
+
78 (median 30) alteplase tPA treatments. Of the 15 programs providing billing practices, 47% bill EMS ALS charges; supplemental billing included CT (53%), critical care (5%), telemedicine (53%), tPA (21%), and labs (5%), however, collection was poor. Overall, programs described their financial performance as negative, with only 1 program (outpatient clinic) defining it as positive; 100% rely in part or totally on grants, philanthropy, or institutional support to sustain the program.

Conclusion:
USA billing restrictions challenge MSU financial sustainability limiting reimbursement to traditional EMS ambulance services. Given the importance of early MSU treatment to reduce disability and death, new financial models are needed to ensure the viability of MSU services.
Abstract MP27: Telestroke Capacity and Outcomes for Patients With Stroke
Authors: Wilcock Andrew D , Schwamm Lee H , Zachrison Kori S , Zubizarreta Jose R , Uscher-Pines Lori , Richard Jessica V , Mehrotra Ateev
Published: March 2021

Background:
Telestroke is increasingly used by hospitals, but there has been limited research on its impact on treatment and outcomes.

Methods:
Using a 100% sample of traditional Medicare beneficiaries over a 10-year period, we compared the care patterns and outcomes of acute ischemic stroke admissions that first presented to hospitals with telestroke capacity to matched admissions in control hospitals without telestroke capacity. Matching was based on sociodemographic and clinical characteristics, hospital characteristics, and month and year of admission. Our primary outcomes were receipt of reperfusion treatment through thrombolysis with alteplase or thrombectomy, mortality at 30 days from admission, spending through 90 days from admission, and functional status as measured by days spent in community living after discharge.

Results:
Over the period January 2008 through June 2017, there were 87,338 ischemic stroke admissions cared for at 643 telestroke hospitals of which 76,636 (88%) were matched to an admission at a control hospital. Compared to control admissions, admissions that started in telestroke hospitals had higher rates of reperfusion treatment (6.76% and 5.98%; difference 0.78, 95% CI 0.54 to 1.03, p<.001) and lower mortality (mortality 30 days from admission was 13.12% vs 13.62%; difference 0.50, 95% CI 0.17 to 0.83, p=.003). There were no differences in functional status and spending. Increases in reperfusion treatment were largest in the lowest-volume hospitals, among rural residents, and patients age 85 years and older.

Conclusions:
Patients with ischemic stroke treated at hospitals with telestroke capacity were more likely to receive reperfusion treatment and had lower 30-day mortality.
Abstract MP3: Low Dose versus Standard Dose Alteplase in Acute Lacunar Ischemic Stroke
Authors: Zhou Zien , Delcourt Candice , Xia Chao , Yoshimura Sohei , Carcel Cheryl , Torii-Yoshimura Takako , you shoujiang , Malavera Alejandra , Chen Xiaoying , Hackett Maree , Woodward Mark , Chalmers John , Xu Jianrong , Robinson Thompson G , Parsons Mark W , Demchuk Andrew M , Lindley Richard I , Mair Grant , Wardlaw Joanna M , Anderson Craig S
Published: March 2021

Objective:
To identify any differential efficacy and safety of low- versus standard-dose intravenous alteplase for lacunar versus non-lacunar acute ischemic stroke (AIS) in the alteplase dose-arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).

Methods:
In a cohort of 3297 ENCHANTED participants, we identified those with lacunar or non-lacunar AIS with different levels of confidence (definite/probable/possible) according to pre-specified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin scale [mRS] scores 2-6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration [END] or death) and treatment effects of low- versus standard-dose alteplase across lacunar and non-lacunar AIS with adjustment for baseline covariables.

Results:
Of 2588 participants with available imaging and clinical data, we classified cases as definite or probable lacunar (n=490) or non-lacunar AIS (n=2098) for primary analyses. Regardless of the alteplase dose received, lacunar AIS participants had favorable functional (mRS 2-6, adjusted odds ratio [95% CI] 0.60 [0.47-0.77]) and other clinical or safety outcomes, compared to participants with non-lacunar AIS. Overall, low-dose alteplase (compared to standard) had no differential effect on the functional outcome (mRS 2-6, 1.04 [0.87-1.24]) but reduced the risk of ICH. There were no differential treatment effects of low- versus standard-dose alteplase on all outcomes across lacunar and non-lacunar AIS (all P
interaction
≥0.07).

Conclusions:
We found no clear evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard-dose for definite/probable lacunar AIS.
Abstract MP40:
Klotho
-vS Heterozygosity is Associated With Lower Risk of Lobar Intracerebral Hemorrhage
Authors: Acosta Julian N , Szejko Natalia , Both Cameron , Leasure Audrey C , Woo Daniel , Langefeld Carl D , Biffi Alessandro , Anderson Christopher D , Rosand Jonathan , Gill Thomas M , Sansing Lauren H , Sheth Kevin N , Falcone Guido J
Published: March 2021

Introduction:
Klotho is a transmembrane protein highly expressed in the kidneys and choroid plexus. Klotho modulates insulin sensitivity and suppresses oxidative stress. Two missense variants in the
Klotho
gene (
KL
) form the functional haplotype
KL-VS
. Heterozygosity for
KL-VS
(
KL-VS-Het+
) increases serum levels of Klotho and attenuates the excess risk of Alzheimer’s Disease conferred by
APOE
epsilon 4. We tested the hypothesis that
KL-VS-Het+
lowers the risk of spontaneous intracerebral hemorrhage (ICH) and the excess in this risk conferred by the
APOE
epsilon variants.

Methods:
We conducted a genetic association study that combined publicly available data from 3 case-control studies of ICH in Europeans. We identified the two genetic variants that define
KL-VS
(rs9536314 and rs9527025) and the two genetic variants that define the
APOE
epsilon alleles (rs429358 and rs7412). We tested for association between
KL-VS-Het+
and ICH risk via study-specific logistic regression followed by fixed-effects, inverse-variance weighted meta-analysis using I
2
to quantify heterogeneity. Given the known biological differences between lobar and non-lobar ICH, we conducted stratified analyses based on location. Additionally, we evaluated the role of
KL-VS-Het+
in carriers of
APOE
epsilon 2 and 4 variants.

Results:
A total of 1066 ICH cases (464 lobar and 602 non-lobar) and 1073 controls were included in the study (mean age 69 [SD 14], female sex 919 [47%]).
KL-VS-Het+,
present in 554 (26%) participants, was associated with a lower risk of ICH (OR 0.81, 95%CI 0.67-0.99; p=0.04) without heterogeneity across studies (I
2
=0%). Stratified analyses indicated that
KL-VS-Het+
was associated with a lower risk of lobar ICH (OR 0.68, 95%CI 0.52-0.88; p=0.004) but not of non-lobar ICH (OR 0.92, 95%CI 0.73-1.16; p=0.48). In secondary analyses,
KL-VS-Het+
was associated with a lower risk of ICH in carriers of
APOE
epsilon 2 (OR 0.52, 95%CI 0.28-0.96; p=0.037; I
2
=0%) but not epsilon 4 (OR 0.82, 95%CI 0.5-1.33; p=0.42).

Conclusion:
KL-VS
-Het+ is associated with a lower risk of ICH. This protective association was stronger in lobar hemorrhages and in carriers of
APOE
epsilon 2. Further research should evaluate these associations in non-Europeans and identify the mediating molecular pathways.
Abstract MP47: Clinicoradiological Outcomes of Surgical Revascularization for Moyamoya Disease With Minimum 10-Year Follow-Up
Authors: Li Yiping , Wang Allan R , STEINBERG Gary K
Published: March 2021

Introduction:
The long-term progression of disease and recurrence rate of symptomatic events after surgical revascularization for moyamoya disease (MMD) are unknown.

Method:
Patients with MMD operated on between 1991 and 2009 were prospectively enrolled into the departmental database.

Results:
230 revascularization (87% combined direct and indirect and 13% indirect alone) procedures were performed on 129 patients for the treatment of MMD with a long-term bypass patency rate of 98%. Unilateral presentation was identified in 39 (30.2%) compared to 90 (69.8%) with bilateral MMD. Posterior circulation (PC) involvement was identified in 34 (26.4%) patients. Over a median follow-up period of 13 years (range 10-26 years), 15 (38.5%) patients experienced radiographic progression of unilateral disease and 14 (10.9%) experienced PC radiographic progression. Delayed surgical revascularization of the untreated contralateral anterior circulation was performed on 11 (28.2%) patients due to symptomatic progression of disease. Progression of PC disease occurred only in patients with PC involvement upon presentation. Aside from those with unilateral progression, fourteen additional patients (10.9%) experienced delayed cerebrovascular accidents (CVAs), 8 of which were ischemic and 6 were hemorrhagic strokes. Twelve delayed CVAs occurred in a previously revascularized hemisphere while one occurred in an un-diseased hemisphere from a micro pseudoaneurysm. Repeat revascularization was performed in 6 patients while 4 were managed conservatively and 4 were deceased. Relative to baseline presenting mRS, 92.2% of patients were improved or unchanged at 10 year follow-up. On multivariate regression, progression of the PC predicted the development of delayed CVA (Odds ratio 8.1, 95% CI 1.1-59.2) while pre-operative stroke (Odds ratio 3.4, 95% CI 1.2-9.8) presentation and progression of disease was predictive of 10-year outcome (Odds ratio 4.0, 95% CI 1.5-10.6).

Conclusion:
Good functional outcomes over a median follow-up period of 13 years support the strategy of revascularization for MMD patients. Disease progression of the posterior circulation is common and may reduce pial-pial collaterals resulting in delayed CVAs.
Abstract MP50: Effect of Linoleic Acid on Ischemic Stroke: A Mendelian Randomization Study
Authors: Wu David , Huang Huijun , Qian Yu , Mao Yingying
Published: March 2021

Background and Purpose:
Linoleic acid (LA) is an essential fatty acid involved in eicosanoid synthesis. Epidemiological studies have suggested an inverse association between circulating LA levels and ischemic stroke (IS), however, it is unclear whether the observed association is causal or due to confounding or reverse causation. We conducted a Mendelian randomization (MR) to evaluate the potential causal relationship between circulating LA levels and risk of IS.

Methods:
Summary statistics for IS were obtained from the MEGASTROKE consortium, including 34,217 IS cases and 404,630 controls of European ancestry. Seventeen single nucleotide polymorphisms (SNPs) associated with circulating LA levels were used as instrumental variables (IVs) in the MR analysis, with another two SNP sets used in sensitivity analyses. We used the inverse-variance weighted method to evaluate the potential causal associations of circulating LA levels with IS, complemented with other MR approaches including weighted-median, weighted-mode, MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression.

Results:
Each 1-standard deviation increase of genetically-predicted LA levels was inversely associated with a 2% (95% confidence interval [CI], 1%-3%) reduction in IS incidence. Subgroup analyses showed significant causal associations for large artery stroke (OR, 0.95; 95% CI, 0.92-0.98;
P
=3.45х10
-4
), but not for cardioembolic stroke (OR, 0.98; 95% CI, 0.96-1.00;
P
=0.05) and small vessel stroke (OR, 1.02; 95% CI, 0.99-1.05;
P
=0.11). Sensitivity analyses using two additional SNP sets as IVs produced consistent findings.

Conclusions:
Our study provides evidence for an inverse causal association of circulating LA levels with risk of IS, particularly large artery stroke. Further studies are warranted to clarify the underlying mechanism of LA in the prevention of IS.
Abstract MP6: Thrombolysis for Acute Wake-Up And Unclear Onset Strokes With Alteplase at 0.6mg /kg in Clinical Practice: THAWS2 Study
Authors: Yoshimura Sohei , Koga Masatoshi , Okada Takashi , Inoue Manabu , Miwa Kaori , Fukuda-doi Mayumi , Kondo Rei , Inoue Takeshi , Ichijo Masahiko , Ohtaki Masafumi , Nagakane Yoshinari , Itabashi Ryo , Sakai Nobuyuki , Aoki Junya , Shiokawa Yoshiaki , Yagita Yoshiki , Iwama Toru , Yakushiji Yusuke , Kusumi Masayoshi , Kamiyama Kenji , Doijiri Ryosuke , Igarashi Shuichi , Kanzawa Takao , Matsumoto Shoji , Ito Yasuhiro , Yoshimura Shinichi , Ohsaki Masato , Ihara Masafumi , Toyoda Kazunori
Published: March 2021

Background and Purpose:
IV alteplase at 0.6 mg/kg for acute wake-up and unclear onset strokes was recommended in Japanese stroke guidelines in March 2019. We determined the safety and effectiveness of this newly recommended thrombolysis in clinical practice.

Methods:
This is a multicenter observational study, enrolling acute ischemic stroke patients with a time last-known-well >4.5 h who have a mismatch between DWI and FLAIR treated with intravenous alteplase. The safety outcomes are intracranial hemorrhage (ICH) with neurological deterioration within 36 h after thrombolysis, all cause deaths within 90 days, and adverse events. The efficacy outcomes are functionally independence defined as a mRS score of 0-1 at 90 days, and NIHSS change at 24h from baseline.

Results:
Between 2019 March and 2020 March, 63 patients (33 females; age, 74±11y; premorbid functionally independence, 50 (82%); median NIHSS on admission, 11) were enrolled at 14 hospitals. Of them, 40 patients (63%) recognized stroke symptoms at wake-up time, and median time between last-known-well and admission was 6.5 h. Baseline MRA showed any vessel occlusion in 52 patients (88%). IV alteplase was disrupted in one patient. Two patients (3%) had symptomatic ICH (≥4 increase in NIHSS) within 36 h. NIHSS change was -5.1±8.1. Twenty-one patients (36%) had functionally independence at discharge and there was no death during acute hospitalization. Of the overall 63 patients, 22 also underwent mechanical thrombectomy (36%, 72±9y, median NIHSS 16), showing no symptomatic ICH, mean NIHSS change of -8.9±7.5, and 8 patients (42%) had functionally independence at discharge.

Conclusions:
In clinical practice, IV alteplase for wake-up and unclear onset stroke patients with DWI-FLAIR mismatch seemed to be safe and effective compared with previous randomized control trials. Mechanical thrombectomy could be combined with alteplase safely and effectively.
Abstract MP8: Long Term Angiographic and Clinical Outcomes From 1,000 Aneurysms Treated With the Pipeline Embolization Device
Authors: Lylyk Ivan , Lylyk Pedro N , Lundquist Javier , Scrivano Esteban , Perez Nicolas , viso rene g , Carlos Bleise D , Ciardi Celina , Granillo Gaston , Murad Sampaio Daniel , Nella Castro Rodolfo , Caballero Laura , Cirio Juan Jose ,   Instituto Medico Eneri- Clinica La Sagrada Familia, Lylyk Pedro
Published: March 2021

Background and Purpose:
Prospective studies have established the safety and efficacy of the Pipeline
TM
Embolization Device (PED) for the treatment of intracranial aneurysms (IA). Here, we report long-term outcomes from The Pipeline Embolization Devices for the Treatment of Intracranial Aneurysms (PEDESTRIAN) Registry.

Methods:
This was a retrospective review of prospectively collected data from the PEDESTRIAN registry. Between March 2006 and July 2019, consecutive patients with complex IA were treated with PED at one center in Argentina. Patients with unfavorable anatomy and/or recurrence following previous treatment were included, and those with acute subarachnoid hemorrhage (SAH) were excluded. The primary angiographic endpoint was complete occlusion and long-term stability. Clinical and angiographic follow-up was performed at 3-6 months, 12 months, and yearly thereafter.

Results:
A total of 835 patients (mean age 55.9±14.7 years; 80% [671/835] female) with 1,000 aneurysms were included. The majority (64.6%) of aneurysms were small (≤10mm), 25.6% were large (11-24mm), and 9.8% were giant (≥25mm). A total of 1,214 PEDs were deployed, with a single device deployed in 84.2% of aneurysms. Follow-up angiography was available for 85.1% of patients with 776 aneurysms at mean 24.6±25.0 months. Complete Raymond Roy I occlusion was demonstrated in 75.8% (588/776) of aneurysms at 12-months, 92.9% (300/323) at 2-4 years, and 96.4% (159/165) at >5 years. During the post-procedural period, mRS remained stable or improved in 96.2% of patients, with stability or improvement in 99.1% of patients in the longer term. The overall major morbidity and neurological mortality rate was 5.8% (44/835), and the all-cause mortality rate was 4.6% (38/835).

Conclusions:
Endovascular treatment of IA with PED is safe and effective, with rates of complete occlusion, complications, and mortality comparable to previous prospective studies. Serial angiographic follow-up showed high and increasing occlusion rates, with stable occlusion of all cases at 13 years.
Abstract P103: Value of Chest Computed Tomographic Scan Added to Acute Stroke Neuroimaging Protocol for Identifying Coronavirus Disease 2019: A Critical Assessment of a Prospective Protocol
Authors: Ishfaq Muhammad F , Bhagavan Sachin , Ishfaq Ammad , Kumar Mukaish , Pulimamidi Shruthi , French Brandi R , Siddiq Farhan , Gomez Camilo r , Qureshi Adnan I
Published: March 2021

Background:
Coronavirus Disease 2019 (COVID-19) is associated with an increased risk for acute ischemic stroke but screening for COVID-19 based on clinical criteria or laboratory testing may be difficult in acute stroke evaluation. Chest computed tomographic (CT) scan may be another time-sensitive option for identification. of COVID-19 in such patients.

Objective:
We report our experience of incorporating chest CT scan in the initial neuroimaging protocol for evaluation of acute stroke patients.

Methods:
All acute stroke patients underwent chest CT scan concurrent to CT head, CT angiogram of head and neck and CT perfusion for 4 months. We identified patients who had chest CT scan findings that were suggestive of COVID-19 including bilateral, multilobar ground glass opacification with a peripheral or posterior distribution, and/or consolidation (mainly in the lower lobes). All patients subsequently underwent polymerase chain reaction (PCR) testing of nasopharyngeal swab with contact isolation until COVID-19 could be excluded.

Results:
A total of 224 consecutive patients (mean age 62.12 years±SD; 15.3) underwent acute stroke evaluation with a concurrent chest CT scan. The chest CT identified findings suggestive of COVID-19 in 11 (4.9%) patients. Subsequent PCR testing did not confirm the diagnosis of COVID-19 in any of the patient. Another 99 patients (44%) without any findings suggestive of COVID-19 on chest CT scan underwent PCR testing. PCR testing did not confirm the diagnosis of COVID-19 in any of the patients. Four patients (4.3%) with chest CT scan findings suggestive of COVID-19 were found to have an ischemic stroke while 7 patients (5.9%) with chest CT scan findings suggestive of COVID-19 did not have any ischemic stroke (stroke mimic).

Conclusions:
We found a very low yield for identifying COVID-19 in acute stroke patients by performing chest CT scan concurrent to standard acute stroke neuroimaging protocol.
Abstract P106: Population-Based Drug Repurposing to Treat Thrombosis in COVID-19 Patients
Authors: Kim Yejin , Chen Luyao , Jiang Xiaoqian , Savitz Sean I
Published: March 2021

Introduction:
Patients with coronavirus disease 2019 (COVID-19) have an increased risk of thrombosis. Our objective is to obtain population-level treatment effects of drugs on treating thrombosis in COVID-19.

Methods:
We conducted a retrospective analysis of Optum electronic health records (EHRs) with 34,043 hospitalized COVID-19 patients. We identified case-patient with thrombosis (stroke, deep vein thrombosis, pulmonary embolism, and myocardial infarction) using PheWas codes. The propensity score matching was used to select comparable control patients who survived without any thrombosis based on demographics and admission status (temperature and SpO
2
level). We computed the average treatment effect (ATT) for medication using advanced inverse propensity score weighting based on pre-treatment conditions (i.e., comorbidities in the last 6 months and medications in the last 2 months before hospitalization).

Results:
We identified 2,446 case-patients with thrombosis and 5,020 comparable control patients. There were a total of 540 drugs that were administered in at least 80 patients. We calculated the 540 drugs’ ATT coefficient. As a result, 23 drugs had a positive ATT coefficient with a
p
-value of less than 0.05. After filtering out commonly prescribed symptomatic drugs (e.g., Acetaminophen, Guaifenesin, and Ondansetron), we highlight the following drugs with statistically significant treatment effects: Atorvastatin (ATT=0.34), Ceftriaxone (ATT=0.26), Levothyroxine (ATT=0.26), Albuterol (ATT=0.25), Azithromycin (ATT=0.23), Enoxaparin (ATT=0.20), and Metformin (ATT=0.20).

Conclusions:
In this preliminary work, we identified anti-thrombotic drugs (Enoxaparin) but also anti-inflammatory drugs (Atorvastatin, Metformin) and possibly antibiotics that have a significant treatment effect in COVID-19 patients that could reduce risk of thrombosis. We also observed that several anti-thrombotic drugs (Apixaban and Ticagrelor) had negative treatment effects, which was partly due to an imbalance in pre-treatment conditions. Our future work is to incorporate more extensive data (such as lab tests and vital signs) into the propensity scores to better capture the severity of admission status.