Anterior Circulation Proximal Occlusion Research Articles

Delayed Neurological Improvement After Full Endovascular Reperfusion in Acute Anterior Circulation Ischemic Stroke.

We aimed to determine the prevalence and predictors of delayed neurological improvement (DNI) after complete endovascular reperfusion in anterior circulation acute ischemic stroke (AIS). Retrospective analysis of an online multicenter prospective reperfusion registry of patients with consecutive anterior circulation AIS treated with endovascular thrombectomy (EVT) from January 2018 to June 2019 in tertiary stroke centers of the NORDICTUS (NORD-Spain Network for Research and Innovation in ICTUS) network. We included patients with AIS with a proximal occlusion in whom a modified Thrombolysis in Cerebral Infarction 3 reperfusion pattern was obtained. DNI was defined if, despite absence of early neurological improvement during the first 24 hours, patients achieved functional independence on day 90. Clinical and radiological variables obtained before EVT were analyzed as potential predictors of DNI. Of 1565 patients with consecutive AIS treated with EVT, 1381 had proximal anterior circulation occlusions, 803 (58%) of whom achieved a modified Thrombolysis in Cerebral Infarction 3. Of these, 628 patients fulfilled all selection criteria and were included in the study. Mean age was 73.8 years, 323 (51.4%) were female, and median baseline National Institutes of Health Stroke Scale was 16. Absence of early neurological improvement was observed in 142 (22.6%) patients; 32 of these (22.5%) achieved good long-term outcome and constitute the DNI group. Predictors of DNI in multivariable-adjusted logistic regression were male sex (odds ratio, 6.4 [95% CI, 2.1–22.3] P=0.002), lower pre-EVT National Institutes of Health Stroke Scale score (odds ratio, 1.4 [95% CI, 1.2–1.5], P<0.001), and intravenous thrombolysis (odds ratio, 9.1 [95% CI, 2.7–30.90], P<0.001). One-quarter of patients with anterior circulation AIS who do not clinically improve within the first 24 hours after complete cerebral endovascular recanalization will achieve long-term functional independence, regardless of the poor early clinical course. Male sex, lower initial clinical severity, and use of intravenous thrombolysis before EVT predicted this clinical pattern.

May 2021 Stroke Highlights

May 2021 <i>Stroke</i> Highlights

Brain atrophy predicts mortality after mechanical thrombectomy of proximal anterior circulation occlusion

BackgroundBrain atrophy is associated with an inferior functional outcome in patients undergoing mechanical thrombectomy (MT) for acute ischemic stroke. We hypothesized that brain atrophy determined from pre-interventional non-contrast-enhanced CT scans...

Influence of time to endovascular stroke treatment on outcomes in the early versus extended window paradigms.

The effect of time from stroke onset to thrombectomy in the extended time window remains poorly characterized. We aimed to analyze the relationship between time to treatment and clinical outcomes in the early versus extended time windows. Proximal anterior circulation occlusion patients from a multicentric prospective registry were categorized into early (≤6 h) or extended (>6-24 h) treatment window. Patients with baseline National Institutes of Health Stroke Scale (NIHSS) ≥ 10 and intracranial internal carotid artery or middle cerebral artery-M1-segment occlusion and pre-morbid modified Rankin scale (mRS) 0-1 ("DAWN-like" cohort) served as the population for the primary analysis. The relationship between time to treatment and 90-day mRS, analyzed in ordinal (mRS shift) and dichotomized (good outcome, mRS 0-2) fashion, was compared within and across the extended and early windows. A total of 1603 out of 2008 patients qualified. Despite longer time to treatment (9[7-13.9] vs. 3.4[2.5-4.3] h, p < 0.001), extended-window patients (n = 257) had similar rates of symptomatic intracranial hemorrhage (sICH; 0.8% vs. 1.7%, p = 0.293) and 90-day-mortality (10.5% vs. 9.6%, p = 0.714) with only slightly lower rates of 90-day good outcomes (50.4% vs. 57.6%, p = 0.047) versus early-window patients (n = 709). Time to treatment was associated with 90-day disability in both ordinal (adjusted odd ratio (aOR), ≥ 1-point mRS shift: 0.75; 95%CI [0.66-0.86], p < 0.001) and dichotomized (aOR, mRS 0-2: 0.73; 95%CI [0.62-0.86], p < 0.001) analyses in the early- but not in the extended-window (aOR, mRS shift: 0.96; 95%CI [0.90-1.02], p = 0.15; aOR, mRS0-2: 0.97; 95%CI [0.90-1.04], p = 0.41). Early-window patients had significantly lower 90-day functional disability (aOR, mRS shift: 1.533; 95%CI [1.138-2.065], p = 0.005) and a trend towards higher rates of good outcomes (aOR, mRS 0-2: 1.391; 95%CI [0.972-1.990], p = 0.071). The impact of time to thrombectomy on outcomes appears to be time dependent with a steep influence in the early followed by a less significant plateau in the extended window. However, every effort should be made to shorten treatment times regardless of ischemia duration.

Health-Related Quality of Life Among Patients With Acute Ischemic Stroke and Large Vessel Occlusion in the ESCAPE Trial.

Endovascular thrombectomy (EVT) reduces 90-day disability in patients following acute ischemic stroke due to large vessel occlusion. Patient-reported outcome measures after EVT, such as health-related quality of life and specific functional domains, are less well described. We report outcomes on the EuroQol-5D (EQ-5D) from the ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times) randomized controlled trial at 90 days after stroke. Death was assigned an index value of 0 for EQ-5D. We used quantile regression to evaluate the association between EVT and EQ-5D index scores and logistic regression for the association between EVT and symptom-free status among 90-day survivors for each EQ-5D dimension (self-care, usual activities, mobility, pain/discomfort, and anxiety/depression), assessing for modification by age or sex and adjusting for baseline factors including stroke severity, affected hemisphere, and receipt of alteplase. Lastly, the association between severe disability at 90 days and EQ-5D was evaluated with assessment for modification by EVT, age, and sex. There were 165 patients randomized to EVT and 150 patients randomized to control. Median EQ-5D was significantly higher for those who received EVT compared with best medical management (0.80 versus 0.60; P<0.001). After accounting for the greater number of deaths in the elderly, there was evidence of modification of treatment effect by age, with older age associated with a larger effect size difference in EQ-5D with EVT. Those receiving EVT had higher odds of symptom-free status in self-care, usual activities, mobility for those aged 60 to 79 years, and pain/discomfort for women, but there was no association with anxiety/depression. Severe disability at 90 days was associated with lower EQ-5D in older compared with younger individuals, and the association was not modified by EVT. Patients treated with EVT report substantially improved health-related quality of life, with relatively greater impact in older individuals and observed benefit across multiple dimensions.

Abstract 44: DEVT: Endovascular Treatment Alone versus Intravenous Alteplase Plus Endovascular Treatment in Stroke

Background: In large vessel occlusion strokes, it is unknown whether the potential risks and added costs associated with intravenous alteplase before mechanical thrombectomy remain justifiable. Methods: In 33 stroke centers in China, patients presenting with proximal anterior circulation intracranial occlusion strokes within 4.5 hours from onset and eligible for intravenous thrombolysis underwent 1:1 randomization mechanical thrombectomy alone (primary-thrombectomy group) or standard dose of intravenous alteplase followed by mechanical thrombectomy (bridging-therapy group). The primary endpoint was non-inferiority of functional independence at 90 days (defined as score 0-2 on the modified Rankin scale). Non-inferiority was established with a margin of -0.1. Safety outcomes included the incidence of symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality. Results: The trial was stopped early because of efficacy when 234 of a planned 970 patients had undergone randomization (116 to the primary-thrombectomy and 118 to the bridging-therapy group). The primary endpoint of functional independence at 90 days was achieved by 63(54.3%) patients in the primary-thrombectomy versus 55(46.6%) in the bridging-therapy group (incidence difference, 7.7%; 95% confidence interval, -5.1% to 20.5%), indicating that primary-thrombectomy was non-inferior to bridging-therapy (Z=2.7157, P non-inferiority =0.00330). No significant between-group differences were detected in symptomatic intracerebral hemorrhage (6.1% versus 6.8%) and 90-day mortality (17.2% versus 17.8%). Conclusions: In stroke patients with proximal anterior circulation occlusions within 4.5 hours from onset, mechanical thrombectomy alone was non-inferior to intravenous alteplase followed by mechanical thrombectomy in terms of 90-day functional independence. (Funded by the Natural Science Foundation of China and others; DEVT chictr.org.cn number, ChiCTR-IOR-17013568.)

MR CLEAN-LATE, a multicenter randomized clinical trial of endovascular treatment of acute ischemic stroke in The Netherlands for late arrivals: study protocol for a randomized controlled trial

BackgroundEndovascular therapy (EVT) for acute ischemic stroke due to proximal occlusion of the anterior intracranial circulation, started within 6 h from symptom onset, has been proven safe and effective. Recently, EVT has been proven effective beyond the 6-h time window in a highly selected population using CT perfusion or MR diffusion. Unfortunately, these imaging modalities are not available in every hospital, and strict selection criteria might exclude patients who could still benefit from EVT. The presence of collaterals on CT angiography (CTA) may offer a more pragmatic imaging criterion that predicts possible benefit from EVT beyond 6 h from time last known well. The aim of this study is to assess the safety and efficacy of EVT for patients treated between 6 and 24 h from time last known well after selection based on the presence of collateral flow.MethodsThe MR CLEAN-LATE trial is a multicenter, randomized, open-label, blinded endpoint trial, aiming to enroll 500 patients. We will investigate the efficacy of EVT between 6 and 24 h from time last known well in acute ischemic stroke due to a proximal intracranial anterior circulation occlusion confirmed by CTA or MRA. Patients with any collateral flow (poor, moderate, or good collaterals) on CTA will be included. The inclusion of poor collateral status will be restricted to a maximum of 100 patients. In line with the current Dutch guidelines, patients who fulfill the characteristics of included patients in DAWN and DEFUSE 3 will be excluded as they are eligible for EVT as standard care. The primary endpoint is functional outcome at 90 days, assessed with the modified Rankin Scale (mRS) score. Treatment effect will be estimated with ordinal logistic regression (shift analysis) on the mRS at 90 days. Secondary endpoints include clinical stroke severity at 24 h and 5–7 days assessed by the NIHSS, symptomatic intracranial hemorrhage, recanalization at 24 h, follow-up infarct size, and mortality at 90 days,DiscussionThis study will provide insight into whether EVT is safe and effective for patients treated between 6 and 24 h from time last known well after selection based on the presence of collateral flow on CTA.Trial registrationNL58246.078.17, ISRCTN19922220, Registered on 11 December 2017

Severe Cerebral Small Vessel Disease Burden Is Associated With Poor Outcomes After Endovascular Thrombectomy in Acute Ischemic Stroke With Large Vessel Occlusion.

BackgroundDespite recent advancements in the treatment of acute ischemic stroke (AIS) with large vessel occlusion (LVO), infarct progression over time and functional outcomes remain variable. This variation in outcomes may be partially attributed to an underlying state of chronic cerebral hypoperfusion and ischemia affecting small cerebral perforating arterioles, venules, and capillaries of the brain; broadly termed cerebral small vessel disease (CSVD). We investigated the association between CSVD burden and the degree of disability following successful recanalization with endovascular thrombectomy (EVT) in patients with AIS presenting with LVO.MethodologyWe conducted a single center retrospective analysis of all patients presenting with AIS LVO between May 2016 and May 2019. Patients who were premorbidly independent and presented within six hours from the last known well (LKW) with a proximal anterior circulation occlusion confirmed on computed tomography (CT) angiography of the head or neck were treated with EVT. Patients presenting after six hours and up to 24 hours from LKW with a target ischemic core to perfusion mismatch profile on CT or magnetic resonance (MR) perfusion, or a clinical imaging mismatch on MR diffusion-weighted imaging, were also treated. Patients with successful revascularization, defined as a thrombolysis in cerebral infarction score 2b or 3, were included and evaluated for CSVD burden. The presence of CSVD was quantified using the Fazekas scale (0-3). All patients were further evaluated for disability at 90 days using the modified Rankin Scale (mRS, range 0-6). An mRS score of ≤2 was defined as a good functional outcome.ResultsOf the 190 patients evaluated, absent (Fazekas grade 0), mild (Fazekas grade 1), moderate (Fazekas grade 2), and severe (Fazekas grade 3) CSVD was present in 33 (17.4%), 84 (44.2%), 35 (18.4%), and 38 (20.0%) patients, respectively. Patients with severe CSVD (Fazekas grade 3) were found to be older, had a higher presenting National Institute of Health Stroke Scale (NIHSS), and had greater proportions of preexisting atrial fibrillation and dementia compared to patients with no CSVD (Fazekas grade 0). Using a multivariate ordinal logistic regression model to adjust for age, presenting NIHSS, thrombus location, LKW to groin puncture time, use of tissue plasminogen activator, ischemic infarct volume, development of a symptomatic intracerebral hemorrhage, and treatment with hemicraniectomy, patients with Fazekas grade 3 were significantly more likely to have poor 90-day functional outcomes compared to patients with Fazekas grade 0 (odds ratio 10.25, 95% confidence interval [3.3-31.84]).ConclusionsBased on our analytical cohort of AIS LVO patients treated with EVT, we found that patients with severe CSVD burden had worse functional outcomes at 90 days and increased mortality. These results provide evidence that the burden of CSVD may be considered an independent risk factor of poor clinical outcome and a predictor of mortality in patients with AIS presenting with LVO, despite successful radiographic recanalization with EVT.

Effect of Endovascular Treatment Alone vs Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients With Acute Ischemic Stroke

<h3>Importance</h3> For patients with large vessel occlusion strokes, it is unknown whether endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment (standard treatment) can achieve similar functional outcomes. <h3>Objective</h3> To investigate whether endovascular thrombectomy alone is noninferior to intravenous alteplase followed by endovascular thrombectomy for achieving functional independence at 90 days among patients with large vessel occlusion stroke. <h3>Design, Setting, and Participants</h3> Multicenter, randomized, noninferiority trial conducted at 33 stroke centers in China. Patients (n = 234) were 18 years or older with proximal anterior circulation intracranial occlusion strokes within 4.5 hours from symptoms onset and eligible for intravenous thrombolysis. Enrollment took place from May 20, 2018, to May 2, 2020. Patients were enrolled and followed up for 90 days (final follow-up was July 22, 2020). <h3>Interventions</h3> A total of 116 patients were randomized to the endovascular thrombectomy alone group and 118 patients to combined intravenous thrombolysis and endovascular thrombectomy group. <h3>Main Outcomes and Measures</h3> The primary end point was the proportion of patients achieving functional independence at 90 days (defined as score 0-2 on the modified Rankin Scale; range, 0 [no symptoms] to 6 [death]). The noninferiority margin was −10%. Safety outcomes included the incidence of symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality. <h3>Results</h3> The trial was stopped early because of efficacy when 234 of a planned 970 patients had undergone randomization. All 234 patients who were randomized (mean age, 68 years; 102 women [43.6%]) completed the trial. At the 90-day follow-up, 63 patients (54.3%) in the endovascular thrombectomy alone group vs 55 (46.6%) in the combined treatment group achieved functional independence at the 90-day follow-up (difference, 7.7%, 1-sided 97.5% CI, −5.1% to ∞)<i>P</i>for noninferiority = .003). No significant between-group differences were detected in symptomatic intracerebral hemorrhage (6.1% vs 6.8%; difference, −0.8%; 95% CI, −7.1% to 5.6%) and 90-day mortality (17.2% vs 17.8%; difference, −0.5%; 95% CI, −10.3% to 9.2%). <h3>Conclusions and Relevance</h3> Among patients with ischemic stroke due to proximal anterior circulation occlusion within 4.5 hours from onset, endovascular treatment alone, compared with intravenous alteplase plus endovascular treatment, met the prespecified statistical threshold for noninferiority for the outcome of 90-day functional independence. These findings should be interpreted in the context of the clinical acceptability of the selected noninferiority threshold. <h3>Trial Registration</h3> Chinese Clinical Trial Registry:ChiCTR-IOR-17013568

Association of masseter area and radiodensity with three-month survival after proximal anterior circulation occlusion

BackgroundMasseter area (MA), a surrogate for sarcopenia, appears to be useful when estimating postoperative survival, but there is lack of consensus regarding the potential predictive value of sarcopenia in acute...

Early Recanalization With Alteplase in Stroke Because of Large Vessel Occlusion in the ESCAPE Trial.

Quantitating the effect of intravenous alteplase on the technical outcome of early recanalization of large vessel occlusions aids understanding. We report the prevalence of early recanalization in patients with stroke because of large vessel occlusion treated with and without intravenous alteplase and endovascular thrombectomy, and its association with clinical outcome. Patients with acute ischemic stroke with large vessel occlusion from the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times Trial) were included in this post hoc analysis. Outcomes of interest were the prevalence of early recanalization (1) and good outcome (2), defined as modified Rankin Scale score of 0 to 2 at 90 days. Among 147 patients who did not receive endovascular thrombectomy, early recanalization occurred in 4/30 (13.3%) patients without and 48/117 (41.0%) patients with intravenous alteplase (adjusted risk ratios, 3.2 [95% CI, 1.2-8.1]). Good outcome was achieved by 34/116 (29.3%) of patients who received intravenous alteplase versus 10/29 (34.5%) who did not receive alteplase (adjusted risk ratios, 1.0 [95% CI, 0.6-1.5) and by 20/52 (38.5%) patients with versus 24/93 (25.8%) without early recanalization (adjusted risk ratios, 1.9 [95% CI, 1.2-2.9]). Early recanalization was confirmed as a strong predictor of good outcome in patients who did not undergo endovascular thrombectomy and was improved with intravenous alteplase, yet a majority of patients (59.0%) did not achieve early reperfusion. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01778335.

Anemia Predicts Poor Clinical Outcome in Mechanical Thrombectomy Patients with Fair or Good Collateral Circulation

Background and Purpose: Anemia predicts poor clinical outcome of ischemic stroke in the general stroke population. We studied whether this applies to those treated with mechanical thrombectomy for proximal anterior circulation occlusion in the setting of differing collateral circulation. Methods: We collected the data of 347 consecutive anterior circulation stroke patients who underwent mechanical thrombectomy after multimodal CT imaging in a single tertiary stroke care center. Patients with occlusion of the internal carotid artery and/or the first segment of the middle cerebral artery were included. We recorded baseline clinical, laboratory, procedural, and imaging variables, and the technical, imaging, and clinical outcomes. Differences between anemic and nonanemic patients were studied with appropriate statistical tests and binary logistic regression analysis. Results: Ninety-four out of the 285 patients eligible for analysis had anemia, and 243 had fair or good collateral circulation (collateral score, CS, >0). Fifty-four percent of the patients experienced good 3-month clinical outcome (modified Rankin Scale ≤2). In pooled analyses of the CS 1–4 and 2–4 ranges, nonanemic patients had good clinical outcome significantly more often (p < 0.001 for both). This effect was not seen in patients with poor collateral circulation (CS = 0). Nonanemic patients had significantly better odds of good clinical outcome (OR = 2.6, 95% CI 1.377–5.030, p = 0.004) in a binary regression model. A 0.1 g/dL increase in hemoglobin improved the odds of good clinical outcome by 2% (OR = 1.02, 95% CI 1.002–1.044, p = 0.03). Conclusions: Low hemoglobin on admission predicts poor clinical outcome in mechanical thrombectomy patients with fair or good collateral circulation.

Quantified ischemic core\u2019s radiological hypodensity and risk of parenchymal hematoma in\u2009>\u20094.5\xa0h-window stroke thrombectomy

We aimed to study the relationship between the ischemic core’s (IC) radiological hypodensity and the risk of parenchymal haematoma after endovascular therapy (EVT) in acute ischemic stroke (AIS) presenting > 4.5 h from onset. We studied AIS patients with a proximal anterior circulation occlusion > 4.5 h from symptoms onset treated with primary EVT. The IC regions of interest (ROI) were manually delineated on pretreatment CT within the affected hemisphere and their specular ROIs on the unaffected side. IC hypodensity ratio was calculated by dividing mean Hounsfield Unit (HU) value from all ROIs in affected/unaffected hemisphere. Primary endpoint: parenchymal hematoma (PH) type hemorrhagic transformation. Secondary: poor long-term clinical outcome. From May 2015 to November 2018, 648 consecutive AIS patients received reperfusion therapies and 107 met all inclusion criteria. PH after EVT was diagnosed in 33 (31%) patients. In bivariate analyses, IC hypodensity ratio (p < 0.001) and minimum HU value (p = 0.008) were associated with PH. A lower IC hypodensity ratio [OR < 0.001 (< 0.001–0.116) p 0.016] predicted PH but not poor clinical outcome in multivariable logistic regression models. A lower IC radiological density predicted a higher risk of PH in > 4.5 h-window AIS patients treated with primary EVT, although it was not independently associated with a worse clinical outcome.

Endovascular Treatment After Stroke Due to Large Vessel Occlusion for Patients Presenting Very Late From Time Last Known Well

Endovascular treatment (EVT) after ischemic stroke due to emergent large vessel occlusion is usually constrained by a specific window of less than 16 to 24 hours from the time the patient was last known well (LKW). Patients with slow progression and tenacious collateral circulation may persist beyond 16 hours. To estimate the prevalence of salvageable tissues 16 hours or more from LKW after ischemic stroke due to emergent large vessel occlusion and investigate the effectiveness of EVT in delayed large vessel occlusion. In this case-control study, from a total of 8032 patients with stroke or transient ischemic attack who were admitted between January 1, 2012, and December 31, 2018, to a single referral university hospital, 150 patients were retrospectively identified who had an acute ischemic stroke with internal carotid artery or middle cerebral artery occlusion, had a baseline National Institutes of Health Stroke Scale score of 6 or more, and arrived 16 hours or more from time LKW. The decision for EVT was made by a treating physician according to the institutional protocol. Baseline ischemic core, collateral circulation status, and computed tomographic or magnetic resonance perfusion parameters were retrospectively quantified. Follow-up images, evaluated a median of 93 hours (interquartile range, 66-120 hours) after arrival, were used to assess the final infarct and hemorrhagic transformation. The main outcome was the modified Rankin Scale score at 90 days. For 150 patients (81 men [54%]; mean [SD] age at onset, 70.1 [13.0] years; median National Institutes of Health Stroke Scale score, 12 [interquartile range, 8-18]), the median ischemic core volume was 11.5 mL (interquartile range, 0-39.1 mL), the median penumbra volume (>6 seconds) was 55.0 mL (interquartile range, 15-128 mL), and the median mismatch ratio was 4.0 (interquartile range, 0.9-18.3). By the imaging inclusion criteria for EVT trials, there were 50 DAWN (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-up and Late Presenting Strokes Undergoing Neurointervention With Trevo)-eligible patients (33%), 58 DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke)-eligible patients (39%), and 57 ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times)-eligible patients (38%). Endovascular treatment was performed for 24 patients (16%). In propensity score-matched analyses, EVT was associated with better odds of a 90-day modified Rankin Scale score of 0 to 2 (adjusted odds ratio, 11.08 [95% CI, 1.88-108.60]) and a 90-day modified Rankin Scale score shift (common adjusted odds ratio, 5.17 [95% CI, 1.80-15.62]). Type 2 parenchymal hemorrhage was seen in 3 of 24 patients (13%) who received EVT and in 4 of 126 patients (3%) who received medical management (adjusted odds ratio, 4.06 [95% CI, 0.63-26.30]). In a subgroup of 109 patients who were 24 hours from time LKW, EVT was associated with a favorable mRS shift (common adjusted odds ratio, 10.54 [95% CI, 2.18-59.34]). This study suggests that patients with anterior circulation large vessel occlusion presenting very late (>16 hours to 10 days) from the time they were LKW may benefit from EVT.

Isolated Sulcal Effacement and Response to Intravenous Thrombolysis in Acute Ischemic Stroke

Background and PurposeIsolated Sulcal Effacement (ISE) is focal cortical swelling without obscuration of cortical gray-white junction. The available information on its role in acute stroke patients treated with intravenous (IV) tissue plasminogen activator (tPA) is limited. MethodsISE along with ASPECT and rLMC collateral score were determined in pre-treatment CT/CT angiography of 195 consecutive acute stroke patients treated with IV tPA “only”. In addition, ISE-ASPECT score was created. Role of ISE on responsiveness to IV tPA, thrombolysis-associated hemorrhage and functional outcome were studied in 102 patients with CT-angiography-confirmed anterior system proximal vessel occlusion. ResultsISE was observed in 12 patients (6.2% of all and 11.4% of those with occlusion of the carotid terminus, M1, or proximal M2) corresponding to excellent specificity (100%) but fair sensitivity (12%) for diagnosis of anterior cerebral circulation proximal artery occlusion. ISE ASPECT score was significantly correlated with rLMC score (p=0.023). Presence of ISE was linked to younger age, female gender, lower NIHSS, along with higher ASPECT and rLMC scores. Albeit not persisted after adjustment for collateral status and NIHSS, dramatic response to IV tPA along with excellent (23% vs. 8%, p<0.05), good (21% vs. 6%, p<0.05) and acceptable (19% vs. 4%, p<0.05) functional outcome were significantly higher in patients with ISE. ConclusionsAs a plain CT marker of sufficient collateral status and increased cerebral blood volume, ISE indicates a better response to IV tPA. However, it should be noted that this relatively rare CT finding is highly specific for cerebral large vessel occlusions amenable neurothrombectomy.

Structural integrity of white matter tracts as a predictor of acute ischemic stroke outcome.

Clinical assessment scores in acute ischemic stroke are only moderately correlated with lesion volume since lesion location is an important confounding factor. Many studies have investigated gray matter indicators of stroke severity, but the understanding of white matter tract involvement is limited in the early phase after stroke. This study aimed to measure and model the involvement of white matter tracts with respect to 24-h post-stroke National Institutes of Health Stroke Scale (NIHSS). A total of 96 patients (50 females, mean age 66.4 ± 14.0 years, median NIHSS 5, interquartile range: 2-9.5) with follow-up fluid-attenuated inversion recovery magnetic resonance imaging data sets acquired one to seven days after acute ischemic stroke onset due to proximal anterior circulation occlusion were included. Lesions were semi-automatically segmented and non-linearly registered to a common reference atlas. The lesion overlap and tract integrity were determined for each white matter tract in the AALCAT atlas and used to model NIHSS outcomes using a supervised linear-kernel support vector regression method, which was evaluated using leave-one-patient-out cross validation. The support vector regression model using the tract integrity and tract lesion overlap measurements predicted the 24-h NIHSS score with a high correlation value of r = 0.7. Using the tract overlap and tract integrity feature improved the modeling accuracy of NIHSS significantly by 6% (p < 0.05) compared to using overlap measures only. White matter tract integrity and lesion load are important predictors for clinical outcome after an acute ischemic stroke as measured by the NIHSS and should be integrated for predictive modeling.

Abstract TP91: Unfavorable Baseline Hypoperfusion Intensity Ratio is Associated With Infarct Growth and Poor Outcome in Patients With Distal MCA Occlusions

Background: A low hypoperfusion intensity ratio (HIR) predicts good collateral vessel status and correlates with infarct growth and functional outcome in early window patients with proximal large vessel anterior circulation occlusions. Its performance in predicting clinical and radiologic outcome has not been assessed in patients with more distal occlusions. In this retrospective analysis of the CT Perfusion to Predict Response to Recanalization in Ischemic Stroke (CRISP) study, we hypothesized that a favorable baseline HIR would predict less infarct growth in patients with distal middle cerebral artery (MCA) occlusions. Methodology: Patients with occlusions of an M2 or M3 branch of the MCA on catheter angiography were included; all patients underwent mechanical thrombectomy with TICI2B/3 reperfusion. Baseline ischemic core volume and HIR (Tmax &gt;10s / Tmax &gt;6s) were assessed with RAPID software; late follow-up infarct volumes (&gt;36 hours from initial CT perfusion) were manually determined from DWI MRI. Excellent functional outcome was defined as a modified Rankin score of 0-1. Results: Fourteen patients with baseline perfusion and late follow-up imaging were included; nine patients presented with M2 occlusions, and 5 with M3 occlusions. The mean baseline HIR of 0.48 was used to dichotomize patients into favorable or unfavorable baseline profiles. Patients with a favorable baseline HIR had significantly smaller baseline ischemic core volumes (0 mL [IQR 0-3.3] vs. 14.0 mL [IQR 8.7-22.1], p=0.01), smaller final infarct volumes (16.1 mL [IQR 12.7-41.2] vs. 71.4 mL [IQR 43.8-113.5], p=0.01) and less infarct growth (16.1 mL [IQR 9.4-31.9] vs. 49.0 mL [IQR 31.1-100.8], p=0.03). Excellent functional outcome was achieved in 6/6 (100%) of those with favorable baseline HIR, versus 3/8 (37.5%) with unfavorable baseline profile (p=0.03). Conclusion: In patients with distal MCA occlusions, poor collateral status at baseline as demonstrated by a high HIR score is associated with more infarct growth and worse clinical outcomes. HIR may be helpful for guiding thrombectomy decisions in patients with distal occlusions and warrants further prospective study in this population.

Abstract TP303: Improved Metrics and Outcomes Post Implementation of an ELVO Taskforce

Objective: To assess whether the implementation of a standardized protocol for the rapid diagnosis, transfer, and management of emergent large vessel occlusions (ELVO) improves treatment times and reduces disability in patients that undergo mechanical thrombectomy. Methods: Retrospective review was conducted on all patients who underwent thrombectomy within 6 hours of last known well (LKW) from May 22, 2016 to May 1, 2019. Patients with proximal anterior circulation occlusion confirmed on CTA and admission NIHSS of ≥6 were included. Comparisons were made to assess differences in workflow metrics and outcomes pre- and post-ELVO taskforce implementation. 90-day modified Rankin Scale scores (mRS) and patient information was collected from the Houston Methodist Hospital Outcomes Based Prospective Endpoints in Stroke (HOPES) registry. Results: A total of 287 patients met inclusion criteria. 116 were excluded for low NIHSS, out-of-window presentation, undocumented metrics, or lost to follow up. 102 patients presented prior to protocol implementation, with 48 (71.81y [SD±13.51]; 50% M) arriving directly to our CSC and 54 (68.56y [SD±16.85]; 46% M) arriving via inter-facility transfer from a PSC. 69 patients presented post-implementation, 32 (69.78y [SD±16.33]; 53% M) directly and 37 (70.57y [SD±13.96]; 62% M) were transferred. In those presenting directly to the CSC, a statistically significant reduction in the mean door to CT time was observed post-implementation, 12.25 to 5.03 minutes (7.22, 95% CI [1.50, 12.93] p=0.007). In those who were transferred, we found a significant reduction in the mean door-in to door-out time, 138.06 to 128.00 minutes (10.06, 95% CI [7.90, 28.02] p=0.028). A trend towards improved functional outcomes was observed in both cohorts post-protocol implementation. Admission NIHSS, use of lytics, and LKW were found not to be confounders. Conclusion: Based on our review of patients who underwent mechanical thrombectomy, implementation of a standardized protocol for the management of ELVO patients both improved treatment times and showed a trend toward greater functional independence at 90 days. This protocol can be easily replicated to help improve stroke care and potentially reduce disability for patients presenting with ELVO.

A Cost-Utility Analysis of Endovascular Thrombectomy in a Real-World Setting.

Endovascular thrombectomy (EVT) is efficacious for ischemic stroke caused by proximal intracranial large-vessel occlusion involving the anterior cerebral circulation. However, evidence of its cost-effectiveness, especially in a real-world setting, is limited. We assessed whether EVT ± tissue plasminogen activator (tPA) was cost-effective when compared with standard care ± tPA at our center. We identified patients treated with EVT ± tPA after the Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing computed tomography to recanalization times trial from our prospective stroke registry from February 1, 2013 to January 31, 2017. Patients admitted before February 2013 and treated with standard care ± tPA constitute the controls. The sample size was 88. Cost-effectiveness was assessed using the net monetary benefit (NMB). Differences in average costs and quality-adjusted life years (QALYs) were estimated using the augmented inverse probability weighted estimator. We accounted for sampling and methodological uncertainty in sensitivity analyses. Patients treated with EVT ± tPA had a net gain of 2.89 [95% confidence interval (CI): 0.93-4.99] QALYs at an additional cost of $22,200 (95% CI: -28,902-78,244) per patient compared with the standard care ± tPA group. The NMB was $122,300 (95% CI: -4777-253,133) with a 0.85 probability of being cost-effective. The expected savings to the healthcare system would amount to $321,334 per year. EVT ± tPA had higher costs and higher QALYs compared with the control, and is likely to be cost-effective at a willingness-to-pay threshold of $50,000 per QALY.

Fast Automatic Detection of Large Vessel Occlusions on CT Angiography.

Background and Purpose- Accurate and rapid detection of anterior circulation large vessel occlusion (LVO) is of paramount importance in patients with acute stroke due to the potentially rapid infarction of at-risk tissue and the limited therapeutic window for endovascular clot retrieval. Hence, the optimal threshold of a new, fully automated software-based approach for LVO detection was determined, and its diagnostic performance evaluated in a large cohort study. Methods- For this retrospective study, data were pooled from: 2 stroke trials, DEFUSE 2 (n=62; 07/08-09/11) and DEFUSE 3 (n=213; 05/17-05/18); a cohort of endovascular clot retrieval candidates (n=82; August 2, 2014-August 30, 2015) and normals (n=111; June 6, 2017-January 28, 2019) from a single quaternary center; and code stroke patients (n=501; January 1, 2017-December 31, 2018) from a single regional hospital. All CTAs were assessed by the automated algorithm. Consensus reads by 2 neuroradiologists served as the reference standard. ROC analysis was used to assess diagnostic performance of the algorithm for detection of (1) anterior circulation LVOs involving the intracranial internal carotid artery or M1 segment middle cerebral artery (M1-MCA); (2) anterior circulation LVOs and proximal M2 segment MCA (M2-MCA) occlusions; and (3) individual segment occlusions. Results- CTAs from 926 patients (median age 70 years, interquartile range: 58-80; 422 females) were analyzed. Three hundred ninety-five patients had an anterior circulation LVO or M2-MCA occlusion (National Institutes of Health Stroke Scale 14 [median], interquartile range: 9-19). Sensitivity and specificity were 97% and 74%, respectively, for LVO detection, and 95% and 79%, respectively, when M2 occlusions were included. On analysis by occlusion site, sensitivities were 90% (M2-MCA), 97% (M1-MCA), and 97% (intracranial internal carotid artery) with corresponding area-under-the-ROC-curves of 0.874 (M2), 0.962 (M1), and 0.997 (intracranial internal carotid artery). Conclusions- Intracranial anterior circulation LVOs and proximal M2 occlusions can be rapidly and reliably detected by an automated detection tool, which may facilitate intra- and inter-instutional workflows and emergent imaging triage in the care of patients with stroke.