bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 64: Feasibility and safety on intravenous tissue Plasminogen Activator in the Pre-Hospital Acute Neurological Therapy and Optimization of Medical Care in Stroke Patients - Study (PHANTOM-S) Results of the Phantom-S pilot study
Authors: Weber Joachim E , Ebinger Martin , Rozanski Michal , Waldschmidt Carolin , Wendt Matthias , Winter Benjamin , Kellner Philipp , Baumann André M , Eichstaedt Kerstin , Villringer Kersten , Fiebach Jochen B , Endres Matthias , Audebert Heinrich
Published: July 2021

Background:
Beneficial effects of intravenous tissue Plasminogen Activator (tPA) in acute ischemic stroke (AIS) are strongly time-dependent. In PHANTOM-S, we use a specialized stroke ambulance equipped with a CT-scanner and point-of-care laboratory in order to shorten time-to-treatment. We report feasibility and safety of the 3-months pilot phase.

Methods:
The ambulance (staffed by a neurologist, paramedic and technician) is deployed by the dispatch center when the emergency call algorithm yields a suspected acute stroke. The pilot study was restricted to patients able to give informed consent.

Preliminary Results:
Between February 8 and April 30, 2011, the ambulance was deployed 208 times. Specific medical management was provided for 108 patients. 54 patients (50%) had a stroke while 31 (29%) had other neurological and 23 (21%) non-neurological diseases. 24 (48%) (median-NIHSS: 8; mean-age: 75±12) of 50 patients with AIS ambulance diagnosis received tPA (23 in the pre-hospital setting and one patient after admission for CT dysfunction). One of the tPA treated patients had a final non-stroke diagnosis (sepsis). Mean alarm-to-treatment time of pre-hospital tPA application was 58 minutes (62 minutes including the in-hospital tPA-application) compared to 98 minutes in 50 consecutive patients treated with tPA in Charité hospitals in 2010. Two (8%) of the tPA patients suffered a symptomatic intracranial hemorrhage and one patient (4%) died in-hospital. Technical failures comprised one CT dysfunction and two delayed CT-image transmissions

Conclusions:
Pre-hospital acute stroke management including tPA-application is feasible and the results suggest a significant shortening of time-to-treatment without obvious safety concerns. Final data will be presented at the ISC.
Abstract NS 3: Severe Right To Left Shunt Through Pfo In Stroke And Tia Patients Predicted By Intraatrial Septum Morphology
Authors: Shaim Hila , Auriel Eitan , Bornstein Natan M , Hallevi Hen
Published: July 2021

Background:
A patent foramen ovale (PFO) is more common in patients with cryptogenic stroke. The clinical implications of PFO morphology are still not well defined. Until ongoing randomized trials are completed, clinical decisions on performing PFO closure are often based on the extent of right to left shunt and PFO morphology along with clinical symptomatology and imaging data. Quantitative analysis by transesophageal echocardiography (TEE) is helpful in characterizing PFO morphology. The aim of this study was to determine whether there are certain characteristic on TEE, which correlate with PFOs shunt severity defined on trans cranial Doppler (TCD) in patients following stroke or transient ischemic attack.

Methods:
We identified all patients who underwent both TCD and TEE in our medical center.For TCD we used the following classification: 1-10 bubbles- small shunt; 11-20 bubbles - moderate sunt; 21 or more (“curtain effect”) and shunt at rest- high-grade shunt. TEE films of the patients were viewed blinded to the TCD results and the anatomical characteristics of the ventricles, atria, atrial septum and tricuspidal valve for each patient were evaluated and recored.

Results:
101 patients fulfilled the criteria. In the univariate analysis the variables correlating with severe shunt were: right-to-Left bulging of the intra-atrial septum of more than 6 mm, tunnel length less than 9 mm, tunnel width more than 3 mm, smoking status and younger age. In the multivariate analysis only two variables retained independent association with severe shunt: right-to-left bulging of the intra-atrial septum of more than 6 mm and younger age.

Conclusion:
In young patients who experience stroke or TIA, right to left interatrial bulging of more than 6 mm on TEE is a sensitive predictor of large PFO shunt and may increase stroke risk.
Abstract 10: Perfusion Imaging In Patients Randomised To rt-PA or Control In The Third International Stroke Trial (IST-3): Baseline Characteristics And Association With Outcome.
Authors: Wardlaw Joanna , Carpenter Trevor , von Kummer Rudiger , Cohen Geoff , Lindley Richard , Sandercock Peter ,   on behalf of the IST-3 Collaborative Group
Published: July 2021

Aim:
Perfusion imaging (PI) may help identify patients with brain at risk of infarction who may benefit most from rt-PA. It remains unclear which perfusion parameter is most specific or if PI should influence decisions for use of rt-PA. IST-3 aimed to improve use of rt-PA.

Methods:
IST-3 was a randomised trial of iv rt-PA (0.9mg/kg) <6 hours of acute ischaemic stroke (registration
ISRCTN25765518
). Pre-randomisation CT or MR PI was performed in some centres. PI data were processed centrally to produce maps of relative (r) CBF; quantitative (q) CBF, CBV, MTT, Tmax. PI images were read centrally, blind, scoring PI lesion extent by ASPECTS and relative to plain CT/MR lesion size (<80%/100%/>120%). All plain CT or MR imaging was assessed, blind, by an expert panel for early infarct signs (site/size of tissue hypodensity, swelling; hyperdense artery; haemorrhage) and background brain changes (atrophy, leukoaraiosis, prior infarct) with validated scales. We assessed baseline characteristics of patients randomised with/without PI in IST-3 and associations with outcome.

Results:
28 IST-3 centres performed PI on 152 patients: 129 were pre-randomisation, 113 were analysable (97 CT, 16 MR). Baseline features were the same in those with as without PI, respectively: 55% v 53% were aged >80; 52% vs 50% had NIHSS ≥11; 35% v 41% with visible infarct signs. PI lesions were smallest for qCBV, largest for qMTT. PI lesions were larger (all parameters) in patients scanned <3 vs 3-6 hours (with more >120% plain scan lesion), aged >80 vs <80, and with higher NIHSS scores. Large qCBV lesions were associated with SICH, early and late death and poor functional outcome. Large lesions on other PI parameters were associated with poor functional outcome.

Conclusion:
IST-3 is the largest randomised trial of rt-PA in patients with PI. Results will be generalisable to the types of patients included in IST-3. Patients presenting <3 hours have larger PI lesions with more mismatch. Large CBV lesions may predict SICH and poor outcome. Results by rt-PA allocation are awaited.
Abstract 104: The Impact of Ischemic and Structural Brain Tissue Changes on Response to rt-PA: An Analysis of Imaging from 3035 Patients in The Third International Stroke Trial
Authors: Wardlaw Joanna , von Kummer Rudiger , A Farrall Andrew , Cala Lesley , von Heijne Anders , Peeters Andre , Morris Zoe , Bradey Nicholas , Adami Alessandro , Potter Gillian , Lindley Richard , Sandercock Peter ,   on behalf of the IST-3 Collaborative Group
Published: July 2021

Aim:
Early infarct signs predict symptomatic intracranial haemorrhage (SICH) and poor outcome after stroke. Structural brain features increase with age. It is unclear if, or when, any of these imaging signs should influence decisions to use rt-PA. We assessed imaging, SICH, 6-month outcome and rt-PA effects in 3035 patients randomised in IST-3.

Methods:
IST-3 was a randomised trial of iv rt-PA (0.9mg/kg) <6 hours of ischaemic stroke (
ISRCTN25765518
). All pre- and post-randomisation imaging was read centrally, masked, by international experts for early infarct signs (tissue hypodensity site/size, swelling, hyperdense artery) and structural brain changes (atrophy, leukoaraiosis, prior infarct) using validated scales. We tested associations between pre-treatment imaging, SICH, 6-month outcome and rt-PA effects, adjusted for time, NIHSS, age, with logistic regression.

Results:
Of 3035 patients, (1515 rt-PA, 1520 control; baseline imaging CT 2848, 98%, MR 54, 2%), 1616 aged >80; 851 treated <3hr, 1177 3-4.5 and 1007 4.5-6hr; 40% had tissue hypodensity/swelling (ASPECTS <7 in 25%, 8-10 in 75%); 24% had hyperdense artery; 50% had leukoaraiosis, atrophy or prior infarct; 9% were totally normal. On adjusted analyses, no imaging feature alone modified rt-PA effects. SICH increased with prior infarct (OR 1.66, p=0.009), tissue hypodensity (1.51, p=0.04), hyperdense artery (1.51, p=0.04). 6-month independent survival decreased with hypodensity (0.66, p=0.000), swelling (0.59, p=0.000), hyperdense artery (0.59, p=0.000), leukoaraiosis (0.72, p=0.0008) and atrophy (0.74, p=0.01). On elimination modelling, prior infarct predicted 54% of SICH risk; swelling, hyperdense artery, leukoaraiosis each predicted 33% of poor outcome risk.

Conclusion:
Amongst these 3035 patients, neither structural nor early ischaemic imaging features alone modify rt-PA effects, but can inform rt-PA treatment decisions where benefits are likely to be marginal by predicting risk of rt-PA-associated SICH and poor functional outcome. The results are also relevant to older as well as younger patients and to rt-PA given <3 as well as up to 6 hours after stroke.
Abstract 110: Stent-Assisted Coiling of Intracranial Aneurysms: Predictors of Complications, Recanalization, and Outcome in 509 Cases.
Authors: Chalouhi Nohra , Jabbour Pascal , Drueding Ross , Dalyai Richard , Starke Robert M , Tjoumakaris Stavropoula , Dumont Aaron S , Gonzalez L Fernando , Rosenwasser Robert , Randazzo Ciro
Published: July 2021

Introduction:
Self-expanding stents are increasingly used for treatment of complex intracranial aneurysms. We assess the safety and efficacy of intracranial stenting and determine predictors of complications, recanalization, and outcome in the largest series of intracranial aneurysms to date.

Methods:
A total of 509 patients were treated with Neuroform and Enterprise stents between 2005-2011 in our institution. A multivariate logistic regression analysis was conducted to detect predictors of complications, recanalization, and outcome.

Results:
445 (87.4%) patients were treated electively and 64 (12.6%) in the setting of subarachnoid hemorrhage. Mean aneurysm size was 7.7 mm. Stent placement was successful in 97.6% of patients. The Neuroform stent was used in 56.8% and the Enterprise stent in 43.2%. Complete or near-complete aneurysm occlusion was achieved initially in 87.7% of cases. Procedural complications occurred in 5.6% of patients. In multivariate analysis, subarachnoid hemorrhage (p=0.03), delivery of coils prior to stent placement (p=0.002), and carotid terminus/middle cerebral artery aneurysm locations (p=0.01) were independent predictors of procedural complications. Angiographic follow-up was available for 85.1% of patients at a mean of 27 months. The rates of recanalization and retreatment were respectively 11.7% and 6.1%. Previously coiled aneurysms (p=0.02), ruptured aneurysms (p=0.01), larger aneurysms (p<0.001), incompletely occluded aneurysms (p=0.01), and cavernous/vertebrobasilar/posterior communicating/middle cerebral artery aneurysms (p=0.04) were predictors of recanalization. Favorable outcomes were seen in 99.3% of elective patients and 61% of subarachnoid hemorrhage patients. Patient age (p=0.03), Hunt and Hess Grades (p<0.001), and procedural complications (p<0.001) were predictors of outcome. The type of stent was not a predictor of complications, recanalization, or outcome.

Conclusion:
Stent-assisted coiling of ruptured and unruptured intracranial aneurysms is safe, effective, and provides durable aneurysm closure. Stent delivery prior to coil deployment reduces the risk of procedural complications. The type of stent used does not affect treatment outcome.
Abstract 114: The Predictive Ability of the CTA Spot Sign for Hematoma Expansion is Dependent on Time Since ICH Onset: A Systematic Review and Patient-level Meta-analysis.
Authors: Dowlatshahi Dar , Brouwers Bart , Demchuk Andrew , Hill Michael D , Aviv Richard , Ufholz Lee-Anne , Wang Yongjun , Zhao Xingquan , Wang Yilong , Li Na , Greenberg Steven M , Romero Javier M , Rosand Jonathan , Goldstein Joshua N , Sharma Mukul ,   on behalf of the CTA Spot Sign collaborators.
Published: July 2021

Background:
Hematoma expansion (HE) occurs in up to 40% of patients with intracerebral hemorrhage (ICH), and predicts poor clinical outcome. Contrast extravasation following CT-angiography (CTA), termed “spot sign”, identifies patients at highest risk of HE. However, the prevalence and predictive values of the spot sign varies across studies, possibly due to differences in onset-to-CTA time. We therefore performed a patient-level meta-analysis to define the relationship between onset-to-CTA time and the prevalence & predictive value of spot sign, and the size of HE.

Methods:
We searched the Cochrane Central Register of Controlled Trials, the Cochrane Library Database of Systematic Reviews, MEDLINE and EMBASE for studies of CTA spot sign prevalence and HE. We pooled data on the prevalence and predictive values for significant HE (defined as either 6mL or 33% growth of ICH) for patients with ICH stratified by onset-to-CTA time: <3hours, 3-6 hours, >6hours. We used chi-square analysis to assess the spot sign in each time strata, and two-way ANOVA to compare across time strata.

Results:
We identified ICH spot sign databases derived from 7 countries and 14 centers (n=705). Prevalence of spot sign decreased with increasing onset-to-CTA time (Table; p<0.001). The subset with follow-up scans used for HE analysis (n=582) revealed spot sign sensitivity and PPV were highest in the earliest time strata, whereas specificity and NPV were highest in the latest time strata (Table). Spot positive patients had greatest absolute HE in the earlier CTA time strata (median spot positive growth 6.8mL, 5.6mL, 5.2mL for 6hr respectively; p<0.001; means in Table).

Conclusion:
Prevalence, predictive values and magnitude of effect of the spot sign are dependent on onset-to-CTA timing; these results are relevant to both ICH trial design and acute management.
Abstract 14: Predicting Hemorrhagic Transformation in Ischemic Stroke - Very Low Cerebral Blood Volume versus Permeability Analysis
Authors: Campbell Bruce C , Christensen Søren , Straka Matus , Mlynash Michael , Sharma Gagan , Parsons Mark W , Donnan Geoffrey A , Davis Stephen M , Bammer Roland , Marks Michael P , Lansberg Maarten G , Albers Gregory W ,   on behalf of the DEFUSE 2 Investigators.
Published: July 2021

Background and purpose:
Hemorrhagic transformation is the major complication of reperfusion therapies and carries a high risk of disability and death. Very low cerebral blood volume (VLCBV) and increased blood brain barrier permeability, both markers of severe ischemia, have been proposed as imaging predictors of hemorrhage risk. We aimed to compare the prognostic power of these two approaches using data from the DEFUSE 2 study.

Methods:
Acute ischemic stroke patients had perfusion-diffusion MRI before and within 12 hr after endovascular therapy. Baseline cerebral blood volume (CBV) maps were generated and the volume of VLCBV (CBV<2.5
th
percentile of the normal hemisphere) was calculated. Permeability was assessed using two recirculation parameters: "relative recirculation" (rR): the difference in area encompassed by the observed tissue-concentration curve and a theoretical fit of the first pass bolus; and "percent recovery" (%Recovery): the difference in signal intensity between peak bolus and average post-bolus. Parenchymal hematoma (PH) was defined using ECASS criteria. Reperfusion was defined as >50% reduction in Tmax>6sec lesion volume between baseline and post-procedure MRI. Logistic regression models were compared using Bayesian Information Criterion (BIC).

Results:
In DEFUSE 2, MRI prior to catheter angiography was performed in 110 patients, 59 had tPA pre-treatment and 25 developed PH. In 103 patients with technically adequate acute perfusion MR, preliminary receiver operating characteristic analysis identified >40%rR and <50%Rec as the optimal thresholds to assess the volume of tissue with increased permeability. In logistic regression, PH was associated with increased VLCBV (p=0.02) and rR permeability (p=0.05) but not %Recovery (p=0.17). The VLCBV model had better fit than rR permeability (BIC difference +2.1) and there was no significant interaction between parameters (p=0.33). Reperfusion was strongly associated with PH (p=0.01) and improved fit of the VLCBV model (BIC +7.2).

Conclusions:
VLCBV was a stronger predictor of early PH after reperfusion than permeability parameters in patients treated with endovascular therapy.
Abstract 148: Intensive Lipid Lowering Therapy Using Rosuvastatin Associates with Greater Atherosclerotic Aortic Plaques Regression - A Magnetic Resonance Imaging Study
Authors: Yogo Makiko , Ayaori Makoto , Sato Hiroki , Kihara Teruyoshi , Makoto Sasaki , Iizuka Maki , Takiguchi Shunichi , Uto-Kondo Harumi , Yakushiji Emi , Nakaya Kazuhiro , Komatsu Tomohiro , Momiyama Yukihiko , Nagata Masayoshi , Iguchi Yasuyuki , Ikewaki Katsunori
Published: July 2021

Whether intensive lipid-lowering therapy yields greater regression of atherosclerotic plaques remains inconclusive. We therefore performed a prospective, randomized trial comparing standard (achieving LDL-C levels recommended by the Japanese guideline) and intensive (achieving further 30% lower levels than the former) rosuvastatin therapy for 1 year with primary outcome of aortic plaques evaluated by MRI. Sixty dyslipidemic patients, who were eligible for statins therapy, were randomized to standard or intensive group, and dose of rosuvastatin were titrated to achieve the respective target LDL-C. Average doses of rosuvastatin throughout the study were 2.9±3.1 and 6.5±5.1 mg/day in standard and intensive group, respectively. Although both treatments significantly reduced serum LDL-C and hsCRP levels, reduction of LDL-C levels was greater in intensive group than in standard group (-46 vs. -34%). Intensive therapy improved endothelial function as evaluated by FMD in brachial artery compared to standard therapy (95 vs. 22%). MRI study revealed that both thoracic and abdominal plaques were significantly regressed in both groups with greater regression in thoracic plaques in intensive group compared to standard group (-9.1 vs. -3.2%) (Figure A). Correlation analysis revealed no significant association of plaque regression with the doses of rosuvastatin and the changes in serum lipids/FMD. In contrast, thoracic plaque regression correlated with hsCRP reduction (Figure B). Multivariate analysis demonstrated that this association still remain significant even after adjustment of the doses at flow-up, serum lipids and FMD. In conclusions, the present study demonstrated that intensive lipid-lowering using rosuvastatin led to additive plaques regression compared to standard therapy. Therefore, rosuvastatin may provide long term benefit in patients with increased risk through its LDL-C lowering and anti-inflammatory effects.
Abstract 155: No Increased Stroke Risk with Lower Blood Pressures in Hemodynamic Cerebral Ischemia
Authors: Powers William J , Clarke William R , Grubb Robert L , Videen Tom O , Adams Harold P , Derdeyn Colin P ,   for the COSS Investigators
Published: July 2021

Patients with symptomatic carotid artery occlusion and hemodynamic cerebral ischemia manifested by increased oxygen extraction fraction (OEF) are at 20-25% risk for ipsilateral stroke within 2 years. Disagreement exists whether strict blood pressure control is the best medical management for these patients or if higher blood pressures are needed to preserve cerebral perfusion. To address this issue, we analyzed data from the non-surgical group of the Carotid Occlusion Surgery Study (COSS), a randomized, controlled trial performed to determine whether EC-IC bypass could reduce subsequent ipsilateral ischemic stroke at two years in participants with recently symptomatic internal carotid artery occlusion and increased OEF. Of the 98 patients in the non-surgical group, 95 had 1-19 blood pressures recorded at follow-up visits. Average systolic and diastolic blood pressures were calculated from these data. Cox regression analyses were used to estimate the relative hazard of a post-randomization ipsilateral stroke in the tercile of subjects with the lowest average blood pressures ( </= 124 mm Hg systolic or 73 mm Hg diastolic) compared to the remainder. Lower blood pressures were associated with reduced, not increased, stroke risk. If the samples analyzed were from populations in which the true hazards were the same, hazard ratios of this magnitude or less would be expected less than 10% of the time. We cannot conclude from these data that strict blood pressure control is beneficial in patients with symptomatic carotid occlusion and increased OEF. However, since we found no evidence that that blood pressures below 124/73 were associated with increased stroke risk, we recommend treatment of blood pressure in these patients according to JNC VII guidelines to targets of < 140/90 or <130/80 for those with concomitant diabetes mellitus or kidney disease.
Abstract 162: The Challenges of Decision-making Regarding Futility in a Randomized Trial: The IMS III Experience
Authors: Yeatts Sharon D , Martin Renee’ H , Foster Lydia D , Woolson Robert F , Broderick Joseph P , Palesch Yuko Y
Published: July 2021

INTRODUCTION:
IMS 3 Trial is a multicenter randomized study to compare the effectiveness of the bridging (IV tPA + intra-arterial) therapy to the IV tPA only treatment in patients with acute ischemic stroke presenting within 3 hours of symptom onset. The trial intended to enroll 900 subjects to ensure adequate statistical power to detect an absolute 10% difference in the % of subjects with good outcome, defined as mRS score of 0-2 at 3 months. In April 2012, after 656 subjects were randomized, further enrollment was terminated by the NINDS upon recommendation by the DSMB. The decision was based on the pre-specified criterion for futility using conditional power of <20%. We describe the process in which the IMS 3 Trial was deemed futile by the DSMB.

METHOD:
Conditional power was defined as the likelihood of finding statistical significance at the end of the study given the accumulated data to date and with the assumption that a minimum hypothesized difference of 10% truly exists between the two groups. Hence, it is akin to ordinary statistical power.

RESULTS:
The futility boundary was crossed at the Trial’s 4
th
interim analysis. The details of the evolution of the study that led to the futility determination are presented, including the interaction between the unblinded study statisticians and the DSMB in the complex deliberation of the data analysis results.

CONCLUSION:
Even in spite of pre-specifying the parameters of interim analysis, interim looks at the data pose challenges in the interpretation and decision-making. It therefore underscores the importance of taking utmost care in the design of the study, including specification of objective stopping guidelines.
Abstract 166: Clinical Outcome Strongly Associated with the Degree of Endovascular Reperfusion Achieved in Target Mismatch
Authors: Inoue Manabu , Lansberg Maarten G , Mlynash Michael , Straka Matus , Kemp Stephanie M , Tipirneni Aaryani , Bammer Roland , Marks Michael P , Albers Gregory W ,   The DEFUSE 2 investigators
Published: July 2021

Background and Purpose:
The aim of this study was to investigate the relationship between the degree of early reperfusion achieved following endovascular therapy and clinical outcomes. We hypothesized that this relationship would differ in Target mismatch (TMM) vs. No Target mismatch (No TMM) patients.

Methods:
This is a DEFUSE 2 substudy. The volume of hypoperfusion on PWI (Tmax >6 sec) was assessed before and within 12 hours after endovascular therapy. The degree of reperfusion was defined as the relative difference between the baseline and the follow-up PWI lesion volumes. Patients were grouped into quartiles according to the degree of reperfusion that they achieved. We assessed the association between the degree of reperfusion and clinical outcomes in patients with and without Target Mismatch. Favorable clinical response (FCR) was defined as an improvement in the NIHSS of 8 or more points between baseline and day 30 or an NIHSS score <1 at day 30. Good functional outcome (GFO) was defined as a modified Rankin Scale <2 at day 90.

Results:
Out of 104 patients enrolled, 87 had interpretable perfusion images at baseline and follow-up PWI. Of these, 69 had TMM. The median degree of reperfusion did not differ in TMM patients (69%) vs. No TMM patients (57%) (p=0.22). The degree of reperfusion correlated with FCR (p<0.001) and GFO (p<0.05) in TMM patients (see figure) but not in the No TMM patients. The rate of FCR was significantly higher in TMM patients who achieved complete reperfusion vs. incomplete reperfusion (94% vs. 46%, OR 18.7; 95% CI 2.3-151.3). Similarly, TMM patients who achieved complete reperfusion had a high rate of GFO (76% vs. 42%, OR 4.4; 95% CI 1.3-15.4).

Conclusion:
The degree of reperfusion documented on PWI following endovascular therapy corresponds closely with the rate of favorable clinical outcomes in TMM patients; there was no association in No TMM.
Abstract 167: Collateral Flow and ASPECTS of Infarct Evolution Dominate Time to Reperfusion in Outcomes of TREVO2
Authors: Liebeskind David S , Sanossian Nerses , Jovin Tudor G , Lutsep Helmi L , Gupta Rishi , Walker Gary A , Albers Gregory W , Smith Wade S , Nogueira Raul G ,   for the TREVO2 Investigators
Published: July 2021

Background:
Definitive reperfusion, or revascularization associated with good clinical outcomes, is likely dependent on key imaging variables. ASPECTS score on imaging before and after revascularization may chronicle the extent of ischemic injury in acute stroke. We hypothesized that ASPECTS and other key imaging variables would be associated with clinical outcome after endovascular therapy in the TREVO2 trial.

Methods:
TREVO2 utilized independent core labs for CT/MRI and angiography central review. Retrospective review of ASPECTS by expert consensus on baseline and 24 hour imaging was conducted in anterior circulation cases, blinded to all other data. Univariate and multivariate analyses determined the impact of key imaging variables (baseline ASPECTS, ASPECTS ≥ 8, collaterals, time to TICI 2a reperfusion or greater, final TICI, 24-hour ASPECTS) on good clinical outcome (mRS 0-2) and mortality at day 90.

Results:
166/177 cases in TREVO2 were anterior circulation occlusions. Baseline ASPECTS was ≤ 7 in 83/166 (50%) cases. Baseline ASPECTS score ≤ 7 was unrelated to age, gender, or any other clinical parameter other than NIHSS score (median 19 (17-23) vs. 17 (13-20) for ASPECTS > 7, p<0.001) and clot location (more ICA than M2 occlusions, p=0.044). Baseline ASPECTS ≤ 7 was also unrelated to post-device TICI or post-procedure SICH. Baseline ASPECTS ≤ 7 was associated with asymptomatic hemorrhage at 24 hours (63.9% vs. 37.3%, p=0.001), 90-day mortality (35.4% vs. 19.3%, p=0.024), and less frequent good clinical outcome (21.5% vs. 42.0%, p=0.007). Univariate imaging predictors of good clinical outcome at day 90 included baseline ASPECTS (OR 1.82, p<0.001), baseline ASPECTS ≥ 8 (OR 2.64, p=0.006), collateral grade (OR 1.85, p=0.003), post-procedure TICI (OR 2.11, p<0.001), 24-hour ASPECTS (OR 1.67, p<0.001) and 24-hour ASPECTS ≥ 8 (OR 4.38, p<0.001). Time to TICI 2a or greater was not predictive. Multivariate analyses showed that 24-hour ASPECTS (OR 1.70, p<0.001) and post-procedure TICI (OR 2.49, p=0.003) best predicted good outcome.

Conclusions:
Better ASPECTS (≥ 8), collaterals, and reperfusion are strongly associated with good clinical outcome whereas the large proportion (50%) of TREVO2 cases with baseline ASPECTS ≤ 7 likely influenced mortality.
Abstract 178: Persistent Occlusion After Intravenous Thrombolysis Is Not Associated with Symptomatic Intracerebral Hemorrhage.
Authors: Novotna Jana , Kadlecova Pavla , Kobayashi Adam , Brozman Miroslav , Svigelj Viktor , Fekete Klara , Korv Janika , Demarin Vida , Jatuzis Dalius , Mikulik Robert
Published: July 2021

Introduction:
There is no conclusive evidence if the association between status of brain artery and risk of intracerebral hemorhage after intravenous thrombolysis (IVT) exists. Therefore, we explored if the hyperdense cerebral artery sign (HCAS) on CT or CT-angiography (CTA)-evidenced occlusion at baseline and follow-up after intravenous thrombolysis (IVT) is associated with symptomatic intracerebral hemorrhage (SICH).

Methods:
The study population was the Safe Implementation of Treatments in Stroke-EAST (SITS-EAST) database with all stroke patients between February 2003 and December 2011 receiving IVT up to 4.5 hours after symptom onset. SICH was distinguished as per NINDS, ECASS II and SITS-MOST definitions. Arterial patency at baseline and on follow-up was assessed by the presence of HCAS on CT or by CTA. Logistic regression was used to adjust for differences in the following baseline variables: NIHSS baseline, age, sex, onset to treatment time, weight, early ischemic changes on CT, systolic blood pressure, glucose, actilyse dose, treatment with anticoagulation or antiplatelets, stroke subtype by ICD classification, history of hypertension, diabetes mellitus, atrial fibrillation, congestive heart failure, and previous stroke.

Results:
Of 8878 cases, baseline CT scans revealed HCAS in 1553 (19%) of 8375 patients and CTA-evidenced occlusion in 1606 (57%) of 2809 cases. On follow-up CT after IVT, HCAS persisted in 477 (36%) of 1327 cases and CTA-evidenced occlusion persisted in 185 (45%) of 411 cases. After adjustment, SICH per the NINDS definition was independently predicted at baseline both by the presence of HCAS (OR 1.57, 95%CI 1.20 to 2.05) and occlusion on CTA (OR 2.87, 95%CI 1.69 to 4.87). Also SICH per the ECASS II definition was independently predicted by the presence of occlusion on CTA (OR 2.61, 95%CI 1.34 to 5.05). In contrast, at follow-up neither persistent HCAS nor persistent CTA-evidenced occlusion was associated with SICH per any definition.

Conclusions:
In stroke patients receiving IVT, presence of clot at admission was an independent predictor of SICH. Persistent occlusion after IVT was not, however, associated with SICH.
Abstract 179: Patient Selection for Endovascular Stroke Therapy: Can MRA substitute for PWI?
Authors: Mishra Nishant K. , Albers Gregory W , Marks Michael , Liggins John , Hamilton Scott , Straka Matus , Kemp Stephanie , Mlynash Michael , Bammer Roland , Lansberg Maarten ,   The DEFUSE 2 Investigators
Published: July 2021

Background:
The DEFUSE 2 study demonstrated that in acute ischemic stroke patients, the perfusion-diffusion mismatch profile, termed Target Mismatch (TMM), is associated with favorable clinical outcomes following endovascular reperfusion; no association was present for patients without TMM. Perfusion imaging,however, may not be feasible in various clinical settings. We examined whether a combination of magnetic resonance angiography (MRA) and DWI could be used as an alternative to PWI/DWI.

Methods:
We assessed agreement between the MRA/DWI mismatch and TMM profiles. MRA/DWI Mismatch was defined as an ICA or MCA-M1 occlusion with a DWI volume <25 ml, or a distal MCA occlusion with a DWI volume <15 ml. The TMM was defined as a PWI (Tmax >6 sec) / DWI >1.8, DWI <70 ml and PWI (Tmax >10 sec) <100 mL. Favorable Clinical Response was defined as an improvement of ≥8 points on the NIHSS between day 0 and day 30, or an NIHSS score of ≤1 at day 30. The response to reperfusion was assessed in patients with MRA/DWI mismatch and no MRA/DWI mismatch, and similarly, in patients with TMM and no TMM.

Results:
In DEFUSE 2, 58 of 94 patients had MRA/DWI mismatch (61.7%) and 76 had TMM (80.9%). The MRA/DWI mismatch model correctly identified 71% of the TMM patients (54/76). It had a high positive predictive value for identifying TMM (54/58; 93.1%), but relatively low sensitivity (54/76; 71%). There was a differential response to reperfusion according to a patient’s TMM status (p=0.03), but not according to their MRA/DWI mismatch status (p=0.5; see figure).

Conclusions:
The MRA/DWI mismatch model has high specificity for identifying TMM but lacks sensitivity.Consequently, patient selection based on MRA/DWI criteria may exclude a substantial proportion of patients from treatment who have the potential to respond favorably to reperfusion.
Abstract 19: Reducing Time to Intra-Arterial Therapy in Acute Ischemic Stroke
Authors: Mehta Brijesh P , Leslie-Mazwi Thabele M , Chandra Ronil V , Bell Donnie L , Rabinov James D , Ogilvy Christopher S , Hirsch Joshua A , Goldstein Joshua N , Rost Natalia S , Schwamm Lee H , Yoo Albert J
Published: July 2021

Background:
Time to recanalization is known to predict clinical outcome in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). Unlike for IV tPA, there is no established goal time to intra-arterial therapy (IAT), resulting in potential delays and worse outcomes. We assessed the effect of a quality improvement (QI) initiative on reducing door-to-angio suite arrival times modeled after similar efforts in the AHA Target Stroke program.

Methods:
We examined two cohorts: pre- and post-implementation of a protocol for early alert of the neurointerventional radiology (NIR) team based on patient presentation within the treatment window (anterior circulation 8 hours, posterior circulation 24 hours) and clinical suspicion for LVO (NIHSS >10). We compared time from patient arrival to completion of imaging and arrival into the angio suite by Wilcoxon and multivariable linear regression.

Results:
Seventy one patients (48 pre- vs. 23 post-QI) with mean age of 68 years (36 (51%) male; median NIHSS 16, IQR 14-20) were included. Of these, 37 (52%) presented during work hours (weekdays 6am to 6pm). Post-QI, the NIR team was alerted early in 83% of cases. Overall QI impact was a reduction in absolute median door-to-suite time of 48 minutes (124 vs. 76 min, p<0.0001) (Figure). Among time sub-intervals, the time from last imaging acquisition to suite arrival has decreased significantly (median 55 vs. 30 min, p=0.004) post-QI. Use of the early alert protocol and patient arrival during work hours were the only independent predictors of shorter door-to-suite times.

Conclusions:
Early notification of the NIR team resulted in a major reduction in time from door-to-angio suite arrival of ~50 minutes. This time savings was achieved through parallel work flow of the multidisciplinary teams during AIS evaluation. As the certification of Comprehensive Stroke Centers commences, such QI initiatives aimed at improving rapid delivery of time-sensitive therapies will be critical.
Abstract 196: Multicenter Experience of Acute Ischemic Strokes in Patients on Dabigatran Etexilate
Authors: Sangha Navdeep S , Nguyen Claude , Fong Albert , Johnson Mark S , Song Shlee S , Pandurengan Renga , Lyden Patrick D , Grotta James C , Liebeskind David S
Published: July 2021

Objective:
Dabigatran etexilate (DE) is an FDA-approved reversible direct thrombin inhibitor to prevent acute ischemic strokes (AIS) in patients with non-valvular atrial fibrillation. There is increasing literature on the management of patients on coumadin who present with AIS, however there is a paucity of the same in reference to newer oral anticoagulants such as DE. We studied patients on DE who presented with AIS to better understand their clinical and laboratory characteristics.

Methods:
We retrospectively collected data on patients who had AIS and were on DE from 3 large stroke centers in California and Texas from December 2010 to August 2012. Data included baseline demographics, coagulation parameters, creatinine, GFR, use of IV rt-PA or intra-arterial thrombectomy (IAT), and duration of being off of DE prior to AIS. Descriptive statistics were used to evaluate the dataset.

Results:
Twenty-seven patients were identified, 16 (40.7%) were women, and the mean age was 70.6 (±13.7) years. Medication dosage was known for 17 patients:14 (82%) were taking 150 mg BID, 2 (11.8%) took 75 mg BID, and 1 (5.8%) took 75 mg daily. The median aPTT and INR were 37.1s (23.6s- >200s) and 1.1 (0.89-1.95) respectively. The median creatinine was 1.1 (0.7-1.6) and median GFR was 64ml/min/1.73m
2
(32-97). Sixteen (49.7%) of patients were actively taking DE prior to their acute event. One patient stopped it 48 hours, another 72 hours, and one 2 week prior to the AIS. Eleven (40.0%) of patients were concomitantly taking either aspirin or Plavix. Three were treated with IVtPA, two of which were taken for (IAT). None had hemorrhagic transformation. One patient had only IAT.

Conclusions:
To our knowledge this is the largest cohort of patients in the post-marketing phase of DE with acute ischemic strokes. The majority of the patients presented while actively taking DE, and more than half had normal INRs and aPTTs. As the use of DE and other novel oral anticoagulants increases, it will become imperative to create guidelines on how to manage these patients in the setting of AIS.
Abstract 198: PFO and Recurrent Stroke: Predictors Differ In Patients With “Probable Pathogenic” Versus Other PFOs
Authors: Thaler David E , Ruthazer Robin , Di Angelantonio Emanuele , Di Tullio Marco R , Donovan Jennifer S , Elkind Mitchell S , Griffith John , Homma Shunichi , Jaigobin Cheryl , Mas Jean-Louis , Mattle Heinrich P , Michel Patrik , Mono Marie-Luise , Nedeltchev Krassen , Papetti Federica , Serena Joaquín , Weimar Christian , Kent David M
Published: July 2021

Background
The “RoPE Score” is a predictive model created to stratify patients by the likelihood that a patent foramen ovale (PFO) is incidental or pathogenic using clinical variables. We hypothesized that the predictors of recurrent stroke differ between patients with pathogenic and incidental PFOs.

Methods
Patients in the Risk of Paradoxical Embolism (RoPE) database with cryptogenic stroke (CS) and PFO were classified as having a probable pathogenic PFO (RoPE Score of >6, estimated PFO attributable fraction 72-99%, n=646) and others (RoPE Score of <6 points estimated PFO attributable fraction 0-72%, n=678). We tested 15 clinical, 5 radiological, and 3 echo variables for associations with stroke recurrence using Cox survival models with component database as a stratification factor. An interaction with RoPE score was checked for the variables that were significant.

Results
Follow-up was available for 91%, 80%, and 58% at 1, 2, and 3 years. Overall, a higher recurrence risk was associated with an index TIA, not being on a statin at baseline, and having a prior radiological stroke. For the low RoPE score group, older age, male sex, high cholesterol and antiplatelet (vs warfarin) treatment predicted recurrence. For those with high RoPE scores, predictors were prior (clinical) stroke/TIA and 2 echo features: septal hypermobility and a small shunt (<10 bubbles).

Conclusions
Predictors of recurrence differ when PFO relatedness is classified by the RoPE Score. The hypothesis that patients with CS and PFO form a heterogenous group with different stroke mechanisms is supported. Conventional stroke risk factors were strong predictors among patients with lower RoPE scores. Echocardiographic features - including a counterintuitive association between smaller shunts and increased recurrence risk - were uniquely predictive in the high RoPE score group (likely pathogenic PFO).
Abstract 20: Acute Stroke Care and Thrombolysis at Critical Access Hospitals in Illinois
Authors: Prabhakaran Shyam , Hamann Robin , O’Neill Kathleen , Gardner Michelle , Jones Peggy
Published: July 2021

Background:
Critical access hospitals (CAH) are the first point of stroke care in many rural regions of the United States (US). The Illinois Critical Access Hospital Network (ICAHN), a network of 51 CAH in Illinois, began a quality improvement program to address acute stroke care in 2009. We evaluated the performance on several metrics in acute stroke care at CAH between 2009 and 2011.

Methods:
Currently, 28 of 51 CAHs in Illinois currently participate in the American Heart Association’s Get With The Guidelines - Stroke (GWTG-S) registry for quality improvement. The GWTG-S registry captured elements including demographics, diagnosis, times of arrival, imaging completion, and intravenous tissue plasminogen activator (IV tPA) administration, and final discharge disposition. We analyzed the change in percent of stroke patients receiving tPA, door-to-needle (DTN) time, and proportion of total stroke patients admitted versus transferred to another facility over the 3 years. Fisher’s exact and Mann-Whitney tests were used as appropriate.

Results:
In the baseline assessment (2009), there were 111 strokes from 8 sites which grew to 12 sites and 305 strokes in year 1 (2010) and 14 sites and 328 strokes in year 3 (2011). The rate of tPA use for ischemic stroke was 2.2% in 2009, 4.0% in 2010, and 6.2% in 2011 (P=0.20). EMS arrival (41.1%), EMS pre-notification (82.6%), door-to-CT times (median 35 minutes; 34.6% < 25 minutes), and DTN times (average 93 minutes; 13.3% DTN time < 60 minutes) were not different over time. The rate of transfer from CAH to another hospital (51.3%) was constant. Every patient that received tPA except 1 (96.9%) was transferred (drip-ship) for post-tPA care.

Conclusions:
Improving acute stroke care at CAHs is feasible and represents a significant opportunity to increase tPA utilization in rural areas. As stroke systems develop, it is vital that CAHs be included in quality improvement efforts. The ICAHN stroke collaborative provided the opportunity to coordinate resources, share best practices, participate in targeted educational programming, and utilize data for performance improvement through the funded GWTG-S registry.
Abstract 202: Cost-effectiveness Of Carotid Stenting In Canada
Authors: Almekhlafi Mohammed , Clement Fiona , Hill Michael D
Published: July 2021

BACKGROUND
To estimate the cost-effectiveness of carotid stenting (CAS) compared to endarterectomy (CEA) in symptomatic patients.

METHODS
A cost-utility analysis from the Canadian health system perspective was performed using a Markov analytic model. Clinical estimates were based on a recent meta-analysis. Procedural costs for CAS and CEA were derived from a local cohort. The costs for hospitalization and rehabilitation for minor and major strokes were based on the Burden of Ischemic Stroke (BURST) study. Utility scores were based on SAPPHIRE trial. A Monte Carlo simulation using a hypothetical cohort of 10,000 and sensitivity analyses were performed to investigate the model assumptions and uncertainties.

RESULTS
CAS was more expensive (incremental cost of $6106.84) and had a lower effectiveness (- 0.12 QALYs). The model was sensitive to the risk of annual death. At a threshold odds ratio (OR) of 0.85, CAS was associated with an incremental cost-effectiveness ratio (ICER) of $32,839.04. Using estimates from SAPPHIRE trial, CAS dominated CEA. When estimates from CREST or EVA-3S trials were used, CEA dominated CAS. Only after simultaneously reducing CAS costs and risks of periprocedural and annual minor strokes, CAS had a favorable ICER. This was achieved at a threshold CAS procedural cost of $4350, a threshold OR of periprocedural minor stroke of 1, and a threshold OR of annual minor stroke of 1.15or less; resulting in an ICER of $577.5. The figure shows CAS cost-effectiveness plane.

CONCLUSIONS
In this analysis, CAS was associated with higher costs and lower effectiveness compared to CEA in symptomatic carotid stenosis patients. The results were driven by the costs of periprocedural major and minor stroke. The costs associated with MI did not impact the results. For CAS to be more effective, it needs to be performed in patients with longer survival, in patients at a high surgical-risk, or at a lower procedural costs plus lower rates of periprocedural and annual minor strokes.
Abstract 209: Final Results of the Surprise Study:Long-term Monitoring For Atrial Fibrillation (AF) in Cryptogenic Stroke
Authors: Christensen Louisa M , Krieger Derk , Højberg Søren , Pedersen Ole D , Karlsen Finn M , Jacobsen Michael D , Worch René , Nielsen Henrik , Ægidius Karen , Rosenbaum Sverre , Marstrand Jakob , Biering-Sørensen Tor , Willer Lasse , Christensen Hanne
Published: July 2021

Background
The true frequency of AF in patients with cryptogenic stroke or TIA is not well defined. The aim was to estimate the frequency and burden of AF in patients with apparent cryptogenic minor stroke or TIA by long term monitoring providing complete data on arrhythmia occurrence.

Methods
Patients with minor stroke or DWI-positive TIA were included if stroke causation remained unknown during standardized work up including 24 hours telemetry. A Reveal XT®, an atrial fibrillation sensitive loop-recorder, was implanted subcutaneously allowing continuous monitoring for up to 3 years. Arrhythmia episodes were adjudicated by senior consultant cardiologist. Endpoints include episodes of AF, time and burden of AF. A total of 84 patients were included and had a minimum of three months of monitoring before final analysis. Five patients were explanted due to local infections or discomfort. (fig.2)

Results
In 13 patients (15.5 %) AF was documented by long term monitoring. The mean burden of AF was 2 hours pr day monitored, varying from less than a minute to 17 hours pr day monitored. (median 20 minutes pr day monitored) Kaplan Meier (fig.1) presents time from stroke onset to first AF event, mean time was 106,0 days (SD 47,9 days) Time from stroke onset to implantation was at a median of 56 days. (Mean 80 days, SD 74,9). Logistic regression analysis including all elements of CHADS2VAS found increasing risk of AF with an OR = 1.096 (p=0.015) with increasing age in years. CHADS
2
VAS score was 4.14 in the AF group vs. 3.24 (p=0.03).

Conclusion
Paroxysmal AF is frequent and brief in patients with cryptogenic stroke. Long term monitoring resulted in change of treatment in one out of 6 patients in this cohort.
Abstract 38: Reactive Oxygen Species Contribute To Aneurysmal Rupture in Mice
Authors: Shimada Kenji , Tada Yoshiteru , Wada Kosuke , Kudo Mari , Murakami Shoko , Makino Hiroshi , Liang Elena I , Kitazato Keiko T , Nagahiro Shinji , Hashimoto Tomoki
Published: July 2021

Background and Purpose:
Inflammation and apoptosis are recognized as key factors for aneurysmal rupture. Reactive oxygen species (ROS) mediates both inflammation and apoptosis in vascular walls. Therefore, we hypothesized that ROS produced by xanthine oxidase and NADPH oxidase contributes to aneurysmal rupture. Recently we have demonstrated the feasibility of using a mouse model of intracranial aneurysms to test pharmacological therapies for the prevention of aneurysmal rupture. We tested the hypothesis by using this newly established mouse model.

Methods:
Intracranial aneurysms were induced in male mice using a combination of a single injection of elastase into the cerebrospinal fluid and the deoxycorticosterone acetate (DOCA) salt hypertension. Six days after aneurysm induction, we started 2-week treatment with vehicle (n=27), a superoxide scavenger (tempol; n=13), a xanthine oxidase inhibitor (oxypurinol; n=15), and a NADPH oxidase inhibitor (apocynin; n=16). Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysms with subarachnoid hemorrhage. Dihydroethidium staining and in situ zymography were performed to detect superoxide production and gelatinase activity, respectively.

Results:
A superoxide scavenger (tempol) significantly reduced rupture rate (vehicle vs. tempol: 74% vs. 27%, P < 0.05) (Figure1). It reduced superoxide production and gelatinase activity in aneurysmal walls (Figure2). Furthermore, the xanthine oxidase inhibitor (oxypurinol), and the NADPH oxidase inhibitor (apocynin) reduced the rupture rate (vehicle vs. oxypurinol: 74% vs. 30%, P< 0.05, vehicle vs. apocynin: 74% vs. 33%, P < 0.05).

Conclusion:
Our results indicate that superoxide produced by xanthine oxidase and NADPH oxidase contributes to aneurysmal rupture, by activating matrix metalloproteinases.