bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W P63: Comparison of the Efficacy and Safety of the Acute Stroke Patients Receiving Different Dose Intravenous Tissue Plasminogen Activator
Authors: Liao Xiaoling , Wang Yilong , Pan Yuesong , Wang Chunjuan , Zhao Xingquan , Zhao Xingquan , Wang Chunxue , Liu Liping , Wang Yongjun
Published: July 2021

Background and Purpose:
In consideration of the racial differences, distinctly reduced cost of treatment and anticipated lower rates of symptomatic intracranial hemorrhage(SICH) coupled with the comparable efficacy, many Asian centers adopted the low dose intravenous tissue plasminogen activator (tPA). We aimed to examine whether lower dose tPA is comparable to standard dose by comparing the efficacy and safety of different doses of tPA in Chinese acute stroke patients.

Methods:
We analyzed data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China(TIMS-China)- a prospective, multicentric cohort study of intravenous alteplase treatment with patient enrollment from 67 centres across China. Patients who were fully compliant with Chinese product characteristics criteria of alteplase within 4.5 h after symptom onset were included. And these patients were divided into 5 group according to dose regimens of tPA (<0.5, 0.5-0.7, 0.7-0.85 , 0.85-0.95 and >=0.95 mg/kg). The SICH, mortality and 90-day outcome of patients were compared.

Results:
A total of 919 patients were included (<0.5 n=9, 0.5-0.7 n=75, 0.7-0.85 n=131, 0.85-0.95 n=678,and >=0.95 n=26). In consideration of sample size, only 0.5-0.7, 0.7-0.85 and 0.85-0.95 mg/kg group were compared. Median tPA dose were 0.90, 0.79 and 0.64mg/kg.Median Stroke onset to treatment time were 2.79h,2.86h and 2.90h (p=0.941). Median NIHSS score were 11,10 and 10(p=0.252). After adjustment for the baseline variables, there were no significant differences for mortality(5.41% vs 8.66% vs 7.36%, p=0.695) and SICH(0% vs 3.82% vs 1.46%, p=0.106). For excellent recovery outcome defined as modified Ranking Scale(mRS) 0-1 at 3 month, 0.5-0.7 mg/kg group were significantly worse than 0.85-0.95 mg/kg group(OR=0.58,p=0.031). For functional independence outcome defined as mRS 0-2 at 3 month, 0.70-0.85 mg/kg group were significantly worse than 0.85-0.95 mg/kg group(OR=0.66,p=0.036)

Conclusion:
Our study suggests that stoke patients receiving standard dose tPA may have more favorable outcome than those receiving lower dose tPA. For Asian people, 0.9mg/kg is also the most optimal dose for intravenous alteplase treatment.
Abstract W P78: Effect of Weather Patterns on the Admission and Outcome of Intracranial Aneurysms
Authors: Lai Pui Man Rosalind , Dasenbrock Hormuzdiyar , Du Rose
Published: July 2021

Introduction:
There have been speculations that regional weather patterns play a role in the rupture of cerebral aneurysms, although the literature has been scarce and inconsistent. Furthermore, there are no studies analyzing the effect of weather patterns on the outcome of ruptured aneurysms. The purpose of this study was to use a nationwide sample to analyze the effects of temperature, precipitation, daily sunlight and relative humidity on hospital admission rate and outcome of ruptured aneurysms.

Methods:
Patients were identified using the Nationwide Inpatient Sample (2001-2010) by ICD-9 codes for subarachnoid hemorrhage or intracerebral hemorrhage and a procedural code for aneurysm repair. Climate data were obtained from the State of the Climate Report 2010 released by the National Climatic Data Center. Multivariate regression models were used to analyze the effects of average monthly temperature, precipitation, percent possible sunlight and relative morning humidity on monthly hospital admission, in-hospital mortality and non-routine discharges, adjusted for state population in million obtained from US Census 2010. Patients were stratified by sex and age (</>60) to study the effects of weather patterns on the subgroups.

Results:
Over the 10-year period, a total of 16970 hospitalizations were included from 723 hospitals across 41 states. Low daily sunlight and relative humidity were associated with increased admission of ruptured aneurysms (
p<0.001
and
p<0.001)
but had no effect on in-patient mortality or non-routine discharges. Low precipitation was associated with higher mortality (
p=0.005
). When stratified by age, low temperature was associated with reduced admission (
p=0.023
) and increased non-routine discharges (
p=0.009
) in patients age>60. No difference was observed when stratified by sex.

Conclusions:
This is the first nationwide study to suggest that sunlight and relatively humidity are associated with admission of ruptured cerebral aneurysms and that low precipitation is associated with increased mortality. While it has been postulated that external atmospheric factors may cause hormonal and homeostatic changes, these are only speculations and further analyzes are necessary to understand this relationship.
Abstract W P80: Wide Neck Cerebral Bifurcation Aneurysms Treated With Web Device. A Single Center Experience of a New Treatment Modality
Authors: Moret Jacques G , Spelle Laurent , Ikka Leon , Benachour Nidhal , Caroff Jildaz , Caroff Jildaz
Published: July 2021

Introduction:
WEB is a new endosaccular device for treatment of wide neck bifurcation cerebral aneurysms(WNBA). we present a single center experience of 17 cases.

Purpose:
The 17 cases with WNBA were treated in acute or cold situation.

Results:
Patients ages range from 43 to 71. 4 cases were treated in the acute phase (<24h), 13 were incidental. The size ranges from 5 to 11 mm. 4 cases were basilar aneurysms, 11 were MCA aneurysms and 2 were Acom aneurysms. All patients with an incidental aneurysm were premedicated with Plavix and Aspirin. The acute patients had only Aspirin IV and systemic heparin during the treatment. Except one patient (the first case), all the other had a successful treatment. Up to now we have not had any complication to deplore. The long term anatomical results (according to the Raymond scale) are: 11 patients had 3 to 11 months follow-up. Among those patients 9 were classified A, and 2 B. Discussion: Considering the difficult anatomy of most of the aneurysms, one can say that technically, the delivery of the device is reliable and safe. However the visibility of the WEB is poor and needs VasoCT or a DynaCT to control otherwise the risk of a wrong positioning is too high and should not be taken. Each time we had to change the size of the device during the treatment it was possible, however the larger the device, the more difficult the withdrawal. In all cases, the time of the procedure was short (average of 30') and frequently equal to the imaging process after treatment to be sure of the right positioning of the WEB. Even weird shape of the aneurysm appears to be not too much a problem.

Conclusions:
The WEB brings a new technical solution to WNBA treatment. The tremendous advantage compared to Y stenting and coiling is the possibility to treat in the acute phase. The other advantage is related to the fact that, no device is left in the parent artery. The length of the procedure is incredibly short even if we add the screening post treatment. The preliminary results are promising but need more experience.
Abstract W P92: Preclinical Evaluation of Recombinant T-cell Receptor Ligand RTL1000 as a Therapeutic Agent in Stroke
Authors: Zhu Wenbin , Casper Amanda , Libal Nicole L , Murphy Stephanie J , Bodhankar Sheetal , Offner-Vandenbark Halina , Alkayed Nabil J
Published: July 2021

Objective:
RTL1000, a partial human MHC molecule coupled to a human myelin peptide, reduces infarct size after experimental stroke in HLA-DR2 transgenic mice expressing the human MHC class II allele. In this study, we characterized the therapeutic window of RTL1000. We then determined if RTL1000 efficacy is altered when combined with t-PA, a standard therapy for stroke, and if it affords long-term neurobehavioral functional improvement after stroke in mice.

Methods:
Male DR2 mice underwent 60 min of intraluminal MCA occlusion (MCAO). RTL1000 (100 μg) or vehicle (100 μl) was given S.C. at 4, 6 or 8 h after MCAO, followed by 3 daily S.C. injections. t-PA (10 mg/kg) or vehicle was infused I.V. over 30 min starting at 15 min into ischemia. Brains were collected at either 24 or 96 h of reperfusion. Cortical, striatal and hemispheric infarcts were measured after staining with 2, 3, 5-triphenyltetrazolium chloride. Behavioral testing neuroscore, open field, paw preference and novel object recognition was performed up to 28 days after MCAO.

Results:
RTL1000 significantly reduced infarct size when administered at 4 and 6, but not 8 h after MCAO. Protection was more robust when RTL1000 was given at 4 h, and was limited to cortex when first administration was delayed for 6 h. When administered alone, t-PA reduced infarct size when measured at 24 but not 96 h after MCAO. Importantly, RTL1000 alone reduced infarct size at 96 h after MCAO, and the addition of t-PA did not reduce its ability to protect against ischemic injury. Behavioral testing showed RTL1000 had no effect on acute cognitive impairment on day 7, but improved long term cognitive outcome 28 days after MCAO.

Conclusions:
RTL1000 is protective against ischemic stroke with a therapeutic window of up to 6 h. Protection by RTL1000 is preserved in the presence of t-PA, is long-lasting and improves neurobehavioral functional outcomes after experimental cerebral ischemia.
Abstract 100: Right Insular Infarction is an Independent Predictor of Mortality in Ischemic Stroke
Authors: Hanne Laura , Brunecker Peter , Endres Matthias , Fiebach Jochen B , Ebinger Martin
Published: July 2021

Introduction:
The association between insular infarction and mortality has often been described. However, whether this is simply due to higher lesion volumes is still controversial.

Hypothesis:
We hypothesized that there is an association between insular infarction and mortality independent of lesion volume.

Methods:
We included consecutive stroke patients between 01.09.2008 and 11.11.2012 from the 1000Plus data base with an acute ischemic lesion on diffusion-weighted imaging on day one and a completed 90 days follow-up. Insular location of the infarction was determined using the Stroke Lesion Atlas (SLA). The SLA is an in-house developed spatial database for analyses of imaging studies (Figure). In multivariate regression analyses of mortality and insular infarcts we adjusted for age, lesion volume, atrial fibrillation, NIHSS, capsular infarcts, and left hemispheric infarcts.

Results:
We included 718 patients. Out of 165 patients with insular infarcts 20 patients died; among the 553 patients with lesions outside the Insula 16 patients died (mortality 12% vs. 3%; p<.001). In analyses adjusting for all mentioned confounders insular infarction was not an independent predictor of mortality. After exclusion of NIHSS insular infarcts were independently associated with mortality (OR=3.003, CI 1.41 - 6.38, p=.004). Right insular infarction was an independent mortality predictor adjusted for all confounders including the NIHSS (OR=2.793, CI 1.27 - 6.15, p=.011).

Conclusion:
Right insular involvement is an independent predictor of mortality in ischemic stroke and may be used to improve identification of patients at risk.

Figure. Lesion overlap of patients who survived (A) or died (B). Red indicates voxels involved in at least 15% of patients. Deceased patients show a maximum lesion overlap in the right Insula.
Abstract 114: CX3CR1-null Microglia Fail to Transition to an M2 Phenotype after Intracerebral Hemorrhage
Authors: Taylor Roslyn A , Hammond Matthew D , Ai Youxi , Sansing Lauren H
Published: July 2021

Introduction:
Intracerebral hemorrhage (ICH) results in the activation of microglia. Microglia can polarize into either a pro-inflammatory (M1), or a reparative (M2) phenotype; the effect of microglial polarization after ICH is unknown. Microglia express the chemokine receptor CX3CR1, which has been shown to regulate microglial neurotoxicity. CX3CR1
+/GFP
mice have a functional CX3CR1 and are frequently used to identify microglia. We previously reported that mice with CX3CR1-null microglia do not show functional recovery 14 days after ICH. We hypothesize that 1) microglia transition from M1 to M2 phenotypes in the acute to subacute period after ICH and 2) CX3CR1-null microglia fail to make this transition, inhibiting recovery after ICH.

Methods:
ICH was modeled by injecting 20ul of WT blood into the right striatum. Microglia were sorted from male CX3CR1
+/GFP
mice 0.5, 1, 3, 7, and 14 days after ICH in order to specifically study microglia phenotypes. RNA was extracted and qRT-PCR was performed to analyze changes in gene expression. To study microglial CX3CR1 function, C57BL/6 (WT) and CX3CR1
GFP/GFP
(CX3CR1-null) mice were irradiated and reconstituted with WT bone marrow (CD45.1) to generate bone marrow chimeras (CD45.1->WT or CD45.1->CX3CR1-null). Brains were harvested for flow cytometry 14 days after ICH.

Results:
At 12 hours after ICH, microglia have high IL-6 gene expression (M1). However, M2 markers arginase-1, TGF-β and SOCS3 increase over time (Fig. 1), suggesting microglia transition from M1 to M2 over the first 2 weeks after ICH. By flow cytometry, CX3CR1-null microglia had significantly less SIRPα, a receptor involved in phagocytosis of erythrocytes, and CD206, an M2 marker, than WT microglia 14 days after ICH.

Conclusions:
Our data show WT microglia transition from an M1 to an M2 phenotype after ICH. Our results also suggest microglial CX3CR1 is necessary for transition toward an M2 phenotype after ICH and this transition is required for recovery after ICH.
Abstract 12: Do “Drip and Ship” Cases Incur Higher Costs to Warrant CMS MS-DRG Reassignment?
Authors: Mountford William K , Wagner Jeff , Krukas Michelle R , Tayama Darren , Ernst Frank R , Chen Er
Published: July 2021

Background:
Telestroke networks enable acute stroke patients to receive r-tPA at a remote hospital (ie, spoke) emergency department and are subsequently transferred to another hospital (ie, hub) for additional care - commonly referred to as “drip and ship” (D&S). While hub hospitals do not administer r-tPA in D&S cases, they handle all subsequent care for these patients upon arrival. It is hypothesized that current CMS reimbursement rates do not reflect the higher cost to hospitals that receive D&S patients.

Objective:
Compare hospital costs and reimbursement rates for Medicare patients with AIS who received r-tPA, did not receive r-tPA, and were treated and sent to hub hospitals.

Methods:
The study included Medicare-covered patients hospitalized with a primary diagnosis of AIS (ICD-9 codes 433.x1, 434.x1, 436) admitted between 6/9/2007 and 12/30/2012 from 5 hub hospitals in the Premier research database with telestroke implementation ranging from 10/2009 - 12/2011. Treatment arms were defined as r-tPA (billing data), D&S (ICD-9 =V45.88), or none. Costs were reported from the hospital perspective and compared with CMS reimbursements based on MS-DRG assignment. Median costs were compared using the Wilcoxon ranked sum test.

Results:
4122 patients were included in the study, with 84 (2%) receiving r-tPA treatment and 233 (6%) having D&S treatment. Total costs and reimbursement rates are summarized in Table 1.

Conclusions:
Results from the study demonstrate D&S cases were associated with higher costs than untreated cases, despite not administering r-tPA; however, they were reimbursed similarly. Future reassignment of MS-DRG to these cases may be warranted.
Abstract 149: Can Prevention of Risk Factors Pre-Stroke Reduce 30-Day Post-Stroke Mortality?
Authors: Howard Virginia J , Lichtman Judith H , Kleindorfer Dawn O , Kissela Brett M , Anderson Aaron M , Albright Karen C , Rhodes J D , Safford Monika S , Howard George
Published: July 2021

Introduction:
Studies of short-term survival after stroke generally identify patients in the hospital, providing limited insights about the association between pre-stroke risk factors and outcomes. We hypothesized that pre-stroke risk factors will be related to 30-day case fatality.

Methods:
We prospectively studied the association of Framingham Stroke Risk Score (FSRS) factors on 30-day mortality following incident ischemic stroke (IS) among 28,253 stroke-free participants, aged 45+ in REGARDS, a national population based cohort enrolled 2003-2007. Suspect IS events were physician-reviewed. Logistic regression evaluated the association of pre-stroke risk factors with 30-day case-fatality after adjustment for age, race, sex and region of country. The six FSRS factors (hypertension, diabetes, cigarette smoking, atrial fibrillation, left ventricular hypertrophy, heart disease) were considered as predictors of case-fatality (individually, as a composite FSRS, and cumulative number present).

Results:
Of 792 incident IS events, 67 (8.5%) people died within 30-days. Age was strongly associated with case-fatality (p < 0.0001), with a strong association for oldest age groups relative to those <65 years (see table). Race, sex and region were not associated with case fatality. After adjustment for demographic factors, individual risk factors were positively but nonsignificantly associated with higher case fatality. Higher FSRS was associated with higher case fatality (test for trend p = 0.014), with increased fatality for the top two vs. the lowest tertile. Likewise, higher fatality was seen for those with more risk factors (test for trend p = 0.025), with a notable increase for those with 3+ cumulative risk factors.

Conclusions:
Individuals with higher pre-stroke risk factor burden were more likely to have a higher 30-day mortality following infarction. Prevention of risk factors could reduce the incidence of stroke and improve mortality following stroke.
Abstract 163: Delayed Administration of Perlecan Doman V Significantly Increases Neurogenesis and Improves Functional Outcome after Experimental Ischemic Stroke
Authors: Marcelo-McCabe Aileen , de Hoog Leon , Clarkson Andrew , Kahle Michael , Bix Gregory
Published: July 2021

Stroke, a major cause of significant morbidity and death, has limited therapeutic options. To that end, our goal is to develop novel stroke therapies by exploiting the brain’s own neuroreparative potential. We have discovered that perlecan, a prominent brain extracellular matrix proteoglycan, is proteolyzed into the bioactive protein fragment domain V (DV) after experimental and human ischemic stroke. DV is both neuroprotective and pro-angiogenic. Furthermore, functional outcome can be significantly improved in rodents by administering DV 6-24 hours after experimental transient (distal MCA occlusion) or permanent (photothrombosis) stroke. Here we studied in mechanistic detail whether delayed DV administration (initiated 7 days post-stroke) could increase neurogenesis and improve functional outcome after mouse transient MCA occlusion. Delayed DV administration also served to minimize confounding neuroprotective and angiogenic effects which occur with acute DV therapy. After two doses of DV (post-stroke day 7 and 9), stroked 3-month old male C57BL6 mice had significant functional improvement (rotor rod) compared to vehicle treated stroke controls. Brain immunohistochemistry 21 days after stroke demonstrated that DV treated mice had significantly more cells that were positive for BrdU (a marker of cell division), doublecortin (DCX, a marker for immature neurons), and NeuN (another neuronal marker) in the infarct area. Furthermore, stereotactic brain injection (AP + 0.00, ML - 1.2, DV – 2.5) with alpha 2 integrin (a known neuronal DV receptor) function blocking antibody on post-stroke day 3 inhibited DV’s post-stroke neurogenic effects. These results suggest that delayed DV treatment after experimental stroke increases neurogenesis, increases the number of new neurons that reach stroked brain regions and survive there, and improves functional outcome through an alpha 2 integrin dependent mechanism. Importantly, as we are unaware of any other delayed treatment other than FLAME clinical trial (fluoxetine treatment initiated 5-10 days after stroke) that significantly improves functional outcome after stroke, our data further suggest the promise of DV as an effective stroke therapy.
Abstract 172: Does SAMMPRIS Support Stenting Compared to Medical Therapy for Subpopulations of Patients with Intracranial Arterial Stenosis?
Authors: Lutsep Helmi L , Lynn Michael J , Cotsonis George A , Derdeyn Colin P , Turan Tanya N , Fiorella David , Janis L. S , Lane Bethany F , Montgomery Jean , Chimowitz Marc I ,   for the SAMMPRIS Investigators
Published: July 2021

Objectives:
To determine whether SAMMPRIS supported the use of stenting compared to medical therapy alone to prevent recurrent stroke in subpopulations of patients with symptomatic intracranial arterial stenosis.

Methods:
The primary outcome, 30-day stroke and death and later strokes in the territory of the qualifying artery, was compared in those with and without baseline factors in the two treatment arms, percutaneous transluminal angioplasty and stenting (PTAS) plus aggressive medical therapy (AMM) vs. AMM alone. Baseline factors included gender, age (<60 or ≥60 years), race (white or black), diabetes, hypertension, lipid disorder, smoking status, type of qualifying event (QE) (TIA, non-penetrator stroke or penetrator stroke), QE hypoperfusion symptoms (related to either change in position, exertion or recent change in antihypertensive), use of antithrombotic or proton pump inhibitor at baseline, days to enrollment (≤7 or >7), old infarcts in the same territory, percent stenosis (<80% or ≥80%), other artery stenosis and location of the symptomatic artery (internal carotid, middle cerebral, vertebral or basilar; and anterior or posterior). The subgroup analyses were conducted by fitting a Cox proportional hazards regression model that included treatment, treatment by time, the factor, and the treatment by factor interaction (p-value for which is reported).

Results:
A total of 451 patients were enrolled, 227 randomized to AMM and 224 to PTAS. Of all variables evaluated, the observed 2-year event rates were higher with PTAS than with AMM in the vast majority and the interaction with treatment was not statistically significant for any of the factors (Table).

Conclusions:
The SAMMPRIS results do not support the use of PTAS compared to medical treatment in any examined subpopulation of patients with symptomatic intracranial stenosis, including those with QE hypoperfusion symptoms.
Abstract 177: Risk of Thrombolysis-induced Hemorrhagic Transformation in Patients with Acute Ischemic Stroke: A Predictive Model Using Combined MR Perfusion Biomarkers
Authors: Nael Kambiz , Bauer Adam H , Kidwell Chelsea S
Published: July 2021

Purpose:
Hemorrhagic transformation (HT) is a potential devastating complication of thrombolysis in patients with acute ischemic stroke (AIS). The purpose of this study was to evaluate the predictive role of MR perfusion biomarkers including increased microvascular permeability (K2) and decreased cerebral blood volume (CBV) in the infarction core to predict the risk of HT in a cohort of patients with AIS who received thrombolysis.

Methods:
In this retrospective study, patients were included if they: had AIS, received thrombolysis, had pre-treatment MRI (including diffusion and perfusion) and had follow-up MRI for evaluation of HT within 7 days. MR perfusion data were processed employing a Bayesian probabilistic method. Using coregistered images, voxel-based K2 and rCBV values were obtained in the region of infarction (defined by ADC < 600 10
–6
mm
2
/s) and compared in patients with and without HT. Receiver operating characteristic (ROC) analysis was performed to determine the optimal parameter/s and threshold for predicting HT.

Results:
Forty-eight patients met study criteria: mean (SD) age was 67.5 ± 15, median baseline NIHSS was 9 (IQR: 5-24) and mean infarct volume of 34 ± 18 ml (range 11-78 ml). Thirty percent of patients (14/48) had HT. The mean K2 value was significantly (
p< .
0001) higher in patients with HT (0.24 ± 0.17) versus patients without HT (0.08 ± 0.03). Mean rCBV was significantly (
p=0
.0001) lower in patients with HT (0.21 ± 0.02) compared to patients without HT (1.28 ± 0.66). ROC analysis showed a threshold and corresponding sensitivity/specificity of 0.104, 94%/84% for K2 and 0.38, 94/97% for rCBV. The combination of K2 and rCBV resulted in a higher discriminative power with an AUC of 0.97, sensitivity of 94% and specificity of 100%. In a multivariable logistic regression model that included NIHSS and infarct volume, the combined K2-rCBV classifier was an independent predictor of HT.

Conclusion:
Combined increased permeability and decreased CBV derived from MR perfusion have improved sensitivity and specificity, compared to either measure alone, for prediction of HT following thrombolysis. A larger clinical study is required to validate our results in an independent cohort.
Abstract 197: Time Dependency and Relationship to Reperfusion Grade in Acute Ischemic Stroke
Authors: Prabhakaran Shyam , Castonguay Alicia C , Gupta Rishi , Chung-Huan J. Sun Chung-Huan , Coleman Martin Coleman , Holloway William , Mueller-Kronast Nils , English Joey , Linfante Italo , Dabus Guilherme , Malisch Tim , Marden Franklin , Bozorgchami Hormozd , Xavier Andrew , Rai Ansaar , Froehler Michael , Badruddin Aamir , Abraham Michael , Janardhan Vallabh , Shaltoni Hashem , Yoo Albert , Abou-Chebl Alex , Chen Peng , Britz Gavin , Kaushal Ritesh , Nanda Ashish , Nogueira Raul , Nguyen Thanh , Zaidat Osama O
Published: July 2021

Background:
Time to reperfusion following endovascular treatment (ET) strongly predicts outcomes after acute ischemic stroke (AIS). However, the impact of time may vary depending on the grade of reperfusion. We sought to assess time-outcome relationship within grades of reperfusion in the North American Solitaire Acute Stroke (NASA) registry.

Methods:
The investigator-initiated NASA registry recruited 24 clinical sites within North America to submit demographic, clinical, site-adjudicated angiographic, and clinical outcome data on consecutive patients treated with the Solitaire Flow Restoration device. We identified patients treated with anterior circulation ischemic stroke treated within 8 hours. The modified Thrombolysis in Cerebral Ischemia (TICI) was used wherein TICI 2 was divided in TICI 2a (< 50% reperfusion) and TICI 2b (> 50% reperfusion). We assessed the impact of time to reperfusion (onset to procedure completion time) on good outcome (modified Rankin Scale 0-2 at 3 months) in those who achieved at least TICI 2a reperfusion, independent of other relevant covariates using logistic regression analysis. We further assessed this relationship within strata of reperfusion grade.

Results:
Among 265 eligible patients, 209 (78.9%) had complete data (mean age 68.4 years, median NIHSS score 18). Reperfusion grade was as follows: TICI 3: 35.4%; TICI 2b: 39.7%, TICI 2a: 14.8%; TICI 0-1: 10.0%. Independent predictors of outcome at 3 months among those achieving TICI 2-3 reperfusion were: initial NIHSS score, intravenous tissue plasminogen activator use, symptomatic hemorrhage, and time to reperfusion. For each 30 minutes, the adjusted OR for time to reperfusion was 0.874 (95% CI 0.797-958). There was a significant interaction between final TICI grade and 30-minute time to reperfusion intervals (P=0.001) such that the effect of time was strongest in TICI 2a patients.

Conclusions:
Time to reperfusion is a strong predictor of outcome following ET for AIS with 13% decreased odds of good outcome per 30-minute delay in achieving TICI 2-3 reperfusion. However, the effect varied by TICI grade such that its greatest effect was in those achieving TICI 2a reperfusion.
Abstract 200: Early Time to Presentation in Acute Ischemic Stroke Predicts Delay to IA Therapy in Acute Stroke
Authors: Mehta Brijesh , Gupta Rishi , Yoo Albert , Buell Hope , Adamski Kelly , Hak Susana , Kuo Sophia , Bose Arani , Sit Siu Po
Published: July 2021

Purpose:
Recent reports from the IMS 3 trial showed the importance of early reperfusion to functional recovery after mechanical thrombectomy. The purpose of this study was to determine the cause(s) for delaying the start of IA intervention in the Penumbra trials.

Methods:
A pooled analysis of 1028 patients was conducted in the prospective (Pivotal N=124, PICS N=261, START N=133) and retrospective/registry (POST N=108, RetroSTART N=191, Speed 054 N=71) Penumbra trials. All obtained treatment at <8 hours from stroke symptom onset. Tested covariates (patient demographics, admission NIHSS scores, time of presentation from onset, day of the week presented to the hospital, IV tPA, and pre-treatment infarct size) were considered in the multivariable model.

Results:
Among the patients reviewed, 888 met study criteria. Mean age was 66.1±15.0 and 52.3% were female (464/888). Average NIHSS at admission was 17.5 ± 6.2 and 46.0% were administered IV-tPA prior to mechanical thrombectomy. Mean pre-treatment ASPECTS score was 7.5± 2.1.

The average time from symptom onset to hospital presentation was 129.1±100.7 minutes and the average time from presentation to procedure start was 134.9±75.2 minutes. There is a significant, inverse relationship between onset to hospital and onset to groin puncture (R=-0.350, p<0.0001). Patients who presented late to the hospital were often treated earlier. Similarly, patients who experienced delays prior to arrival at the hospital were more likely to have a larger infarct core as indicated by a significantly lower ASPECTS score (p=0.028). In a multivariate analysis, a shorter symptom onset to presentation significantly predicts in-hospital delays (p<0.0001). Admission NIHSS scores, target vessel location, day of the week presentation, or IV lytic treatment were not significant contributing factors to the delay in endovascular treatment.

Conclusion:
In this pooled cohort of Penumbra cases, delay to IA therapy was predicted by an early presentation to the hospital and a smaller infarct core. Our findings suggest that there is a need to conduct an intensive review of in-hospital triaging procedures for endovascular therapy.
Abstract 213: Cerebral Microbleeds in 1278 Lacunar Stroke Patients: The Secondary Prevention of Small Subcortical Strokes (SPS3) Trial
Authors: Shoamanesh Ashkan , Pearce Lesly A , Bazan Carlos , Catanese Luciana , McClure Leslie A , Marti-Fabregas Joan , Kase Carlos S , Hart Robert G , Benavente Oscar R
Published: July 2021

Background:
Cerebral microbleeds (CMBs) are radiographic markers of cerebral small vessel disease (CSVD) reported to independently predict recurrent stroke and mortality. However, characterization of CMBs in a large population of pure CSVD is lacking. We aimed to characterize CMBs in a well-defined population of lacunar stroke patients, and assess the relationship between CMBs and recurrent stroke and death. Methods: SPS3 was a randomized trial investigating optimal blood pressure target and antiplatelet regimen in 3020 patients with recent, symptomatic, MRI-confirmed lacunar stroke. CMBs were rated as per the Brain Observer MicroBleed Scale in all participants who had an interpretable axial T2*- GRE sequence available as part of their baseline MRI (n=1278, intra-rater reliability for + CMB 91% agreement, Kappa = 0.82). Results: CMBs were present in 30% of 1278 patients (mean age 63 y, 65% male, 75% history of hypertension). CMBs were lobar in 21%, deep in 44%, and mixed in 35% of cases. Of patients with CMBs, most (57%) had 1-2 CMBs, 31% had 3-10, and 12% >10. Male gender (OR 1.7, 95% CI 1.3-2.3), history of hypertension (1.6, 1.2-2.3), increased systolic blood pressure (1.2 per 20 mmHg, 1.1-1.4), non-diabetic (1.4, 1.1-1.9), multiple lacunar infarcts (1.9, 1.5-2.5) and moderate (1.7, 1.2-2.3) or severe (4.2, 3.0-5.9) white matter hyperintensities on MRI were independently associated with the odds of having CMBs in multivariable logistic regression. During a mean follow-up of 3.3 y, overall stroke recurrence was 2.5% per patient-y. In comparison to patients without CMBs, those with CMBs had a two-fold increased risk of stroke (HR 2.1, 1.4-3.1), after adjusting for assigned treatments and risk factors, whereas those with >10 CMBs had a four-fold increased risk (HR 4.0, 1.8-8.7). CMBs were not a risk factor for death (HR 1.2, 0.8-2.0). There were no interactions between CMBs and treatment assignments. Conclusions: In this largest reported cohort of lacunar stroke investigating CMBs, CMBs were highly prevalent and an independent predictor of stroke recurrence. Accordingly, patients with lacunar stroke and CMBs likely represent a more aggressive form of CSVD in need of efficacious therapeutic strategies. Further research is warranted in this field.
Abstract 25: Carotid Plaque Thickness, Stenosis, Ulceration, Age And Male Sex Optimally Predict Carotid Intraplaque Hemorrhage
Authors: McNally Joseph S , McLaughlin Michael , Hinckley Peter , Treiman Scott , Treiman Gerald , Parker Dennis
Published: July 2021

Background and Purpose:
MRI-detected intraplaque hemorrhage (IPH) is associated with acute and future stroke. IPH can be detected with a high sensitivity, specificity and accuracy using heavily T1-weighted sequences such as the magnetization-prepared rapid acquisition gradient echo (MPRAGE) sequence. This sequence is not always available in screening of potential carotid sources of stroke. The purpose of this study was to determine the discriminatory power of clinical and imaging markers in predicting carotid IPH.

Methods:
In this retrospective cross sectional study, patients undergoing stroke workup were imaged with magnetic resonance imaging (MRI) and IPH detection. A total of 726 carotid plaques were imaged. Carotid imaging characteristics were recorded, including percent diameter and mm stenosis, plaque thickness, ulceration, intraluminal thrombus and IPH. Clinical confounders were recorded and a multivariable logistic regression model was fitted. Backward-elimination was used to determine essential predictors of IPH with a threshold two-sided p<.10. Receiver operating characteristic (ROC) analysis was performed to determine discriminatory value.

Results:
Significant predictors of carotid IPH included plaque thickness (Odds ratio, OR=2.20, p<.001), mm stenosis (OR=0.46, p<.001), ulceration (OR=4.25, p=.020), age (OR=1.11, p=.001) and male sex (OR=3.23, p=.077). Percent diameter stenosis (OR=31.0, p=.001) could be used nearly interchangeably with mm stenosis. The final model discriminatory value was excellent (Area under the curve, AUC=0.932). This was significantly higher than models using only plaque thickness (AUC=0.881), only mm stenosis (AUC=0.830) or only ulceration (AUC=0.715) p<.001.

Conclusions:
Optimal discrimination of carotid IPH required information on plaque thickness, mm stenosis, ulceration, age and male sex. When these factors are recorded, IPH can be predicted with a high discriminatory power.
Abstract 50: Shape of the TPA Time - Benefit Curve: Insights From The National US Get With The Guidelines - Stroke Population
Authors: Saver Jeffrey L , Fonarow Gregg C , Smith Eric E , Reeves Mathew J , Navalkele Digvijaya , Grotta James C , Grau-Sepulveda Maria V , Hernandez Adrian F , Peterson Eric D , Schwamm Lee
Published: July 2021

Background:
Randomized trials demonstrated benefit of IV tissue plasminogen activator (tPA) is strongly time-dependent, but were underpowered to specify the shape of the time - benefit curve. Large registries can provide insight into how quickly benefits of tPA decay with time.

Methods:
We analyzed the relationship between onset to treatment (OTT) and 4 outcomes, discharge to home, discharge free of disability (mRS 0-1), discharge ambulatory status, and mortality, in acute ischemic stroke patients treated with tPA within 4.5h in 1456 GWTG-Stroke hospitals from Jan 2009 to Sept 2013.

Results:
Among the 65,384 tPA-treated patients, median age was 72, 50.5% were female, median OTT was 141 mins (IQR 110-173), and 11.3% (7368) had OTT 0-90m, 71.1% (46,457) had OTT 91-180m, and 17.6% (11,559) had OTT 181-270m. A slight curvilinear relationship was observed between OTT and discharge to home and discharge free of disability, with inflection at 150 minutes (Figure). Discharge free of disability showed rapid decline between 15-150m (11 fewer patients per 1000 treated per 15m delay) and slower decline from 151-270m (5 fewer per 1000 treated per 15m delay). In contrast, a linear relationship with OTT throughout the 15-270 minute window was observed for independent ambulation at discharge (8 fewer per 1000 treated per 15m delay) and in-hospital mortality (2 fewer per 1000 treated per 15m delay). Considering all mRS disability scale transitions, benefit declined more rapidly in the first and second hours (25 and 33 worse outcomes per 1000 treated per 15m delay) compared to 3-4.5 hours (11 worse outcomes per 1000 treated per 15m delay).

Conclusions:
Rates of excellent, disability-free outcome and of discharge to home after IV tPA decay more rapidly in the first 2.5 hours after stroke onset, while independent ambulation and mortality decline in a linear fashion throughout the 4.5 hour window. Speedier start of tPA treatment within the first 2.5 hours after onset maximizes treatment benefit.
Abstract 51: Access to Primary Stroke Centers for Older Adults and Implications for Travel Times, and Mortality
Authors: Bekelis Kimon , Wong Kendrew , Marth Nancy , Zhou Weiping , Skinner Jonathan
Published: July 2021

Background:
Regionalization of care to primary stroke centers (PSC) may improve outcomes for stroke patients. We evaluated the current access of Medicare stroke patients to PSC, and its potential impact on mortality.

Methods:
We performed a retrospective cohort study of a 100% sample of Medicare fee-for-service claims data for patients admitted with stroke in 2008-2009, with one-year follow-up through 2010. Population weighted centroids were created, helicopter pad locations were identified, and driving distances were calculated based on real road network data. Driving and flying speeds, dispatch, scene, and pre-hospital times were estimated using validated models, adjusted for population density. The association of 30-day mortality with travel times, and treatment at a PSC was investigated using multivariable regression models.

Results:
During the study period, 510,822 patients (mean age 79.6 years, 59.7% females) had a stroke. There was significant regional variation in our cohort, (Figure) with 8.6% of stroke patients having ground access to a PSC within 30 minutes, 14.9% from 30 to 45 minutes, 11.1% from 45 to 60 minutes, 43.9% from 1 to 4.5 hours, and 21.5% over 4.5 hours. The latter group could be limited to 0.1% of stroke patients, if existing helicopter services were used optimally. 164,485 (32.2%) patients received treatment in a PSC, and had modestly decreased mortality (OR, 0.97; 95% CI, 0.95-0.99). For this group, actual travel time to the PSC was not associated with mortality for patients within one hour of the PSC. On the contrary, travel times from 1 to 4.5 hours (OR, 1.15; 95% CI, 1.08-1.22), and over 4.5 hours (OR, 1.41; 95% CI, 1.29-1.54) were associated with increased mortality.

Conclusions:
There is significant regional variation in access to PSC for elderly stroke patients, with a potential impact on outcomes. Optimal use of helicopter services may address these disparities.

Funding:
NIH (P01-AG19783, and U01-AG046830-01).
Abstract 70: Gender Moderates the Associations between Caregiving and Health Status in Stroke Caregivers
Authors: Chung Misook L , Bakas Tamilyn , Plue Laura D , Williams Linda S
Published: July 2021

Background:
Women who are caregivers report more burden than men in similar caregiving situations. Caregiving is associated with poor health outcomes but there is lack of evidence about whether gender moderates the association. The purpose of this study was to examine whether gender moderates the association between caregiving and health status based on relationship of caregiver with stroke patients (spouse vs. non-spouse) and caregiver being of the same or opposite gender as patient

Method:
Caregivers (N=277, 74% female, mean age 53 years) of stroke survivors completed questionnaires after the initial 2 months of post-stroke management. Difficulty and time spent with caregiving tasks were assessed using the Oberst Caregiving Burden Scale. Perception of life changes due to caregiving was assessed using the Bakas Caregiving Outcome Scale. Health status was assessed using a visual analog scale of the Euro Quality of Life questionnaire. Hierarchical multiple regressions were used with an interaction variable (gender x caregiving).

Results:
Longer time caregiving, difficulty of caregiving tasks, and negative changes in life were significantly associated with poor health status. Significant gender moderation was found only for spousal caregivers and for caregivers who were the opposite gender from patients. For female spousal caregivers, there were strong associations between difficulty of caregiving tasks and health status, and between perception of life changes and health status, but not for male spousal caregivers (Figure1). Similar results were found for caregivers who were the opposite gender from patients.

Conclusion:
Gender in caregiver and patient, and relationship with stroke patients may be beneficial to identify caregivers at high risk of poor health. Further research is needed to examine the dynamics that influence caregiving relationships to be able to individualize interventions responsive to gender and relationship of caregiver to patient.
Abstract 83: Effect of Dietary Cholesterol and Egg Consumption On Mortality And Cardiovascular Risk in the REGARDS Study
Authors: Spence J David , Judd Suzanne , Howard Virginia , Safford Monika , Howard George
Published: July 2021

Background and purpose:
It has long been recommended that patients at risk of cardiovascular events limit their intake of dietary cholesterol to <200 mg/day. One large egg yolk contains more than 200mg of cholesterol, and also contains 250mg of phosphatidylcholine, which is converted by intestinal bacterial to trimethylamine. In the face of increasingly widespread belief that consumption of dietary cholesterol and eggs is harmless, we analyzed the effects of these dietary constituents on mortality and cardiovascular outcomes in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study population.

Methods:
A longitudinal cohort study of 30,239 community-dwelling black and white individuals aged 45+ years, recruited between January 2003 and October 2007 from the 48 contiguous states. The study oversampled black participants (44%), and residents of the southeastern “stroke belt” (56%). We analyzed total mortality and atherosclerotic events (ischemic stroke, myocardial infarction and revascularization) after 4.9 (SD 1.7) years of followup. Hazard ratios were computed for egg consumption and cholesterol consumption by quartiles, adjusted for race, age, sex, income, education, region, dyslipidemia, exercise, hypertension, diabetes, smoking, atrial fibrillation and caloric intake.

Results:
As shown in the table, there was a dose-related increase in all-cause mortality and atherosclerotic events with both cholesterol intake and egg consumption.

Conclusions:
Recommendations to limit the intake of cholesterol remain good advice for patients at risk of cardiovascular events. As one large egg yolk contains more than the daily recommended intake of cholesterol, egg yolk consumption should also be limited.
Abstract 86: Accuracy of Emergency Medical Services Dispatcher and Provider Recognition of Stroke in Clinical Practice
Authors: Jia Judy , Abboud Michael , Pajerowski William , Guo Michelle , David Guy , Messe Steven R , Band Roger , Carr Brendan G , Mullen Michael T
Published: July 2021

Objective:
It is imperative that prehospital providers accurately recognize stroke. We assessed the sensitivity of stroke recognition by emergency medical services (EMS) in clinical practice in a major US city, and assessed variables associated with failure to recognize stroke.

Methods:
Data from the Philadelphia EMS system was linked with data from a single comprehensive stroke center to identify patients diagnosed with transient ischemic attack, ischemic stroke, or intracerebral hemorrhage by EMS dispatchers, EMS providers, or at hospital discharge between September 2009 and October 2012. Sensitivity and positive predictive value (PPV) were calculated. Multivariable logistic regression was used to identify variables associated with EMS recognition of stroke.

Results:
There were a total of 709 cases, 400 of which were cerebrovascular events (38% infarct, 10% ICH, and 8% TIA). Of these cases, 80 (20%) were not recognized by EMS dispatcher or EMS provider, 90 (23%) were recognized by dispatcher alone, 87 (22%) by EMS provider alone, and 143 (36%) by both. EMS providers recognized stroke with a sensitivity of 58%, PPV 69%. Dispatchers or EMS providers recognized stroke with a sensitivity of 80%, PPV 51%. In a multivariable model, EMS providers were more likely to miss a stroke when NIHSS was low (compared to NIHSS 10+, NIHSS 5-9 OR=1.6, 95% CI 0.9-3.0 & NIHSS<5 OR=4.6, 95% CI 2.7-7.9), when motor signs were absent (OR=2.4, 95% CI 1.5-3.9), and when symptom duration was > 270 minutes (OR=2.4, 95% CI 1.5-3.8). Medics correctly recognized 81% of stroke patients with NIHSS>4 and symptom duration <270 minutes, and dispatcher or EMS providers correctly recognized 90% of these patients.

Conclusions:
EMS recognized stroke with limited sensitivity, resulting in a high proportion of missed stroke cases. When added to the EMS provider impression, dispatcher impression meaningfully improves the sensitivity for recognizing stroke. Maximizing sensitivity is critical to prehospital interventions which may improve overall stroke care, such as transportation to designated stroke centers or EMS prenotification of receiving hospitals.