Hemorrhagic transformation in acute ischemic stroke: hemorrhagic subtypes and symptomatic intracranial hemorrhage.

BACKGROUND: Few clinical studies perform detailed analyses of subtypes of intracranial hemorrhage (ICH) after mechanical thrombectomy (MT) used to treat acute ischemic stroke. Symptomatic intracranial hemorrhage (sICH) is a formidable complication of MT and is widely used in clinical trials as a safety outcome. However, variable definitions of sICH are used across clinical studies. OBJECTIVE: To radiographically subcategorize post-MT ICH development within this large cohort and examine overlap with sICH. Second, to examine the agreement of this definition of sICH with local site-reported occurrences of sICH to see how sICH rates change with modifications of the definitions used. METHODS: A large cohort of patients treated with MT for acute ischemic stroke (n=1395) was analyzed to (1) radiographically characterize hemorrhagic subtypes of intracranial hemorrhage (ICH) occurring after MT; (2) examine associations of hemorrhagic subtypes with sICH; and (3) compare core laboratory-adjudicated occurrences of sICH with site-reported sICH. RESULTS: The overall rate of ICH was 552/1395 patients (39.6%), and the overall rate of sICH was 47/1395 (3.4%). The most common type of ICH was hemorrhagic infarction type 1 (HI1), which represented 45.3% of all ICH cases- followed by HI2 (31.5%) and subarachnoid hemorrhage (SAH, 29.2%). Parenchymal hematoma 2 (PH2) represented only 3.3% of all ICH cases. Of the PH2 hemorrhages, only 33.3% were determined to be symptomatic. Of sICH cases, the most common ICH subtypes were HI2 (48.9%) and SAH (38.3%). Comparison of sICH rates as determined by core laboratory adjudication versus local site-reported results showed that only 14 patients were identified as having sICH with both definitions, with 47 patients total with sICH according to one definition, but not the other. CONCLUSIONS: Results of this analysis demonstrate the radiographic subtypes of ICH and also highlight the limitations of variable criteria used to define sICH, suggesting that it might be appropriate to revisit how sICH is defined post-MT. TRIAL REGISTRATION NUMBER: Clinical trial NCT03845491.

Placing the balloon-guide catheter in the high cervical segment of the internal carotid artery is associated with improved recanalization.

BACKGROUND: Mechanical thrombectomy (MT) is part of the standard of care for stroke treatment, and improving its efficacy is one of the main objectives of clinical investigation. Of importance is placement of the distal end of balloon-guided catheters (BGC). We aim to determine if this influences outcomes. METHODS: We analyzed data from the ASSIST Registry, an international, multicenter prospective study of 1492 patients. We divided patients treated with BGC according to the placement of the BGC: low cervical (LCG (the lower 2/3 of cervical internal carotid artery (ICA)) or high cervical (HCG (upper 1/3 of cervical ICA, petro-lacerum or higher)). We analyzed characteristics and outcomes overall and stratified on the primary MT technique: Stent-Retriever only (SR Classic), Combined use of aspiration catheter and SR (Combined), and Direct Aspiration (ADAPT). RESULTS: Our study included 704 subjects -323 in the low cervical and 381 in the high cervical groups. Statistical differences were seen in the proportion of females and tandem lesions (both higher for LCG). Placing the BGC in the high cervical segment is associated with better recanalization rates (expanded treatment in cerebral infarction (eTICI) score of 2c-3) at the end of the procedure (P<0.0001) and shorter procedures (P=0.0005). After stratifying on the three primary techniques (SR Classic, Combined, and ADAPT), placing the BGC in the high segment is associated with a better first-pass effect (FPE), less distal emboli, and better clinical outcomes in the SR Classic technique. CONCLUSIONS: Placing the distal end of the BGC at the high cervical segment or higher is associated with better recanalization.

Time From Hospital Arrival Until Endovascular Thrombectomy and Patient-Reported Outcomes in Acute Ischemic Stroke.

Importance: The time-benefit association of endovascular thrombectomy (EVT) in ischemic stroke with patient-reported outcomes is unknown. Objective: To assess the time-dependent association of EVT with self-reported quality of life in patients with acute ischemic stroke. Design, Setting, and Participants: Data were used from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, which tested the effect of nerinetide on functional outcomes in patients with large vessel occlusion undergoing EVT and enrolled patients from March 1, 2017, to August 12, 2019. The ESCAPE-NA1 trial was an international randomized clinical trial that recruited patients from 7 countries. Patients with EuroQol 5-dimension 5-level (EQ-5D-5L) index values at 90 days and survivors with complete domain scores were included in the current study. Data were analyzed from July to September 2023. Exposure: Hospital arrival to arterial puncture time and other time metrics. Main Outcomes and Measures: EQ-5D-5L index scores were calculated at 90 days using country-specific value sets. The association between time from hospital arrival to EVT arterial-access (door-to-puncture) and EQ-5D-5L index score, quality-adjusted life years, and visual analog scale (EQ-VAS) were evaluated using quantile regression, adjusting for age, sex, stroke severity, stroke imaging, wake-up stroke, alteplase, and nerinetide treatment and accounting for clustering by site. Using logistic regression, the association between door-to-puncture time and reporting no or slight symptoms (compared with moderate, severe, or extreme problems) was determined in each domain (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) or across all domains. Time from stroke onset was also evaluated, and missing data were imputed in sensitivity analyses. Results: Among 1105 patients in the ESCAPE-NA1 trial, there were 1043 patients with EQ-5D-5L index values at 90 days, among whom 147 had died and were given a score of 0, and 1039 patients (mean [SD] age, 69.0 [13.7] years; 527 male [50.7%]) in the final analysis as 4 did not receive EVT. There were 896 survivors with complete domain scores at 90 days. There was a strong association between door-to-puncture time and EQ-5D-5L index score (increase of 0.03; 95% CI, 0.02-0.04 per 15 minutes of earlier treatment), quality-adjusted life years (increase of 0.29; 95% CI, 0.08-0.49 per 15 minutes of earlier treatment), and EQ-VAS (increase of 1.65; 95% CI, 0.56-2.72 per 15 minutes of earlier treatment). Each 15 minutes of faster door-to-puncture time was associated with higher probability of no or slight problems in each of 5 domains and all domains concurrently (range from 1.86%; 95% CI, 1.14-2.58 for pain or discomfort to 3.55%; 95% CI, 2.06-5.04 for all domains concurrently). Door-to-puncture time less than 60 minutes was associated higher odds of no or slight problems in each domain, ranging from odds ratios of 1.49 (95% CI, 1.13-1.95) for pain or discomfort to 2.59 (95% CI, 1.83-3.68) for mobility, with numbers needed to treat ranging from 7 to 17. Results were similar after multiple imputation of missing data and attenuated when evaluating time from stroke onset. Conclusions and Relevance: Results suggest that faster door-to-puncture EVT time was strongly associated with better health-related quality of life across all domains. These results support the beneficial impact of door-to-treatment speed on patient-reported outcomes and should encourage efforts to improve patient-centered care in acute stroke by optimizing in-hospital processes and workflows.

Infarcts Due to Large Vessel Occlusions Continue to Grow Despite Near-Complete Reperfusion After Endovascular Treatment.

BACKGROUND AND PURPOSE: Infarcts in acute ischemic stroke (AIS) patients may continue to grow even after reperfusion, due to mechanisms such as microvascular obstruction and reperfusion injury. We investigated whether and how much infarcts grow in AIS patients after near-complete (expanded Thrombolysis in Cerebral Infarction [eTICI] 2c/3) reperfusion following endovascular treatment (EVT), and to assess the association of post-reperfusion infarct growth with clinical outcomes. METHODS: Data are from a single-center retrospective observational cohort study that included AIS patients undergoing EVT with near-complete reperfusion who received diffusion-weighted magnetic resonance imaging (MRI) within 2 hours post-EVT and 24 hours after EVT. Association of infarct growth between 2 and 24 hours post-EVT and 24-hour National Institutes of Health Stroke Scale (NIHSS) as well as 90-day modified Rankin Scale score was assessed using multivariable logistic regression. RESULTS: Ninety-four of 155 (60.6%) patients achieved eTICI 2c/3 and were included in the analysis. Eighty of these 94 (85.1%) patients showed infarct growth between 2 and 24 hours post-reperfusion. Infarct growth ≥5 mL was seen in 39/94 (41.5%) patients, and infarct growth ≥10 mL was seen in 20/94 (21.3%) patients. Median infarct growth between 2 and 24 hours post-reperfusion was 4.5 mL (interquartile range: 0.4-9.2 mL). Post-reperfusion infarct growth was associated with the 24-hour NIHSS in multivariable analysis (odds ratio: 1.16 [95% confidence interval 1.09-1.24], P<0.01). CONCLUSION: Infarcts continue to grow after EVT, even if near-complete reperfusion is achieved. Investigating the underlying mechanisms may inform future therapeutic approaches for mitigating the process and help improve patient outcome.

Association between CT Perfusion Parameters and Hemorrhagic Transformation after Endovascular Treatment in Acute Ischemic Stroke: Results from the ESCAPE-NA1 Trial.

BACKGROUND AND PURPOSE: Hemorrhagic transformation can occur as a complication of endovascular treatment for acute ischemic stroke. This study aimed to determine whether ischemia depth as measured by admission CTP metrics can predict the development of hemorrhagic transformation at 24 hours. MATERIALS AND METHODS: Patients with baseline CTP and 24-hour follow-up imaging from the ESCAPE-NA1 trial were included. RAPID software was used to generate CTP volume maps for relative CBF, CBV, and time-to-maximum at different thresholds. Hemorrhage on 24-hour imaging was classified according to the Heidelberg system, and volumes were calculated. Univariable and multivariable regression analyses assessed the association between CTP lesion volumes and hemorrhage/hemorrhage subtypes. RESULTS: Among 408 patients with baseline CTP, 142 (35%) had hemorrhagic transformation at 24-hour follow-up, with 89 (63%) classified as hemorrhagic infarction (HI1/HI2), and 53 (37%), as parenchymal hematoma (PH1/PH2). Patients with HI or PH had larger volumes of low relative CBF and CBV at each threshold compared with those without hemorrhage. After we adjustied for baseline and treatment variables, only increased relative CBF <30% lesion volume was associated with any hemorrhage (adjusted OR, 1.14; 95% CI, 1.02-1.27 per 10 mL), as well as parenchymal hematoma (adjusted OR, 1.23; 95% CI, 1.06-1.43 per 10 mL). No significant associations were observed for hemorrhagic infarction. CONCLUSIONS: Larger "core" volumes of relative CBF <30% were associated with an increased risk of PH following endovascular treatment. This particular metric, in conjunction with other clinical and imaging variables, may, therefore, help estimate the risk of post-endovascular treatment hemorrhagic complications.

Influence of Infarct Morphology and Patterns on Cognitive Outcomes After Endovascular Thrombectomy.

BACKGROUND: To assess the association of qualitative and quantitative infarct characteristics and 3 cognitive outcome tests, namely the Montreal Cognitive Assessment (MOCA) for mild cognitive impairment, the Boston Naming Test for visual confrontation naming, and the Sunnybrook Neglect Assessment Procedure for neglect, in large vessel occlusion stroke. METHODS: Secondary observational cohort study using data from the randomized-controlled ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke), in which patients with large vessel occlusion undergoing endovascular treatment were randomized to receive either intravenous Nerinetide or placebo. MOCA, Sunnybrook Neglect Assessment Procedure, and 15-item Boston Naming Test were obtained at 90 days. Total infarct volume, gray matter, and white matter infarct volumes were manually measured on 24-hour follow-up imaging. Infarcts were also visually classified as either involving the gray matter only or both the gray and white matter and scattered versus territorial. Associations of infarct variables and cognitive outcomes were analyzed using multivariable ordinal or binary logistic regression models. RESULTS: Of 1105 patients enrolled in ESCAPE-NA1, 1026 patients with visible infarcts on 24-hour follow-up imaging were included. MOCA and Sunnybrook Neglect Assessment Procedure were available for 706 (68.8%) patients and the 15-item Boston Naming Test was available for 682 (66.5%) patients. Total infarct volume was associated with worse MOCA scores (adjusted common odds ratio per 10 mL increase, 1.05 [95% CI, 1.04-1.06]). After adjusting for baseline variables and total infarct volume, mixed gray and white matter involvement (versus gray matter-only adjusted common odds ratio, 1.92 [95% CI, 1.37-2.69]), white matter infarct volume (adjusted common odds ratio per 10 mL increase 1.36 [95% CI, 1.18-1.58]) and territorial (versus scattered) infarct pattern (adjusted common odds ratio, 1.65 [95% CI, 1.15-2.38]) were associated with worse MOCA scores. Results for Sunnybrook Neglect Assessment Procedure and 15-item Boston Naming Test were similar, except for the territorial infarct pattern, which did not reach statistical significance in multivariable analysis. CONCLUSIONS: Besides total infarct volume, infarcts that involve the white matter and that show a territorial distribution were associated with worse cognitive outcomes, even after adjusting for total infarct volume.

Portable cerebral blood flow monitor to detect large vessel occlusion in patients with suspected stroke.

BACKGROUND: Early detection of large vessel occlusion (LVO) facilitates triage to an appropriate stroke center to reduce treatment times and improve outcomes. Prehospital stroke scales are not sufficiently sensitive, so we investigated the ability of the portable Openwater optical blood flow monitor to detect LVO. METHODS: Patients were prospectively enrolled at two comprehensive stroke centers during stroke alert evaluation within 24 hours of onset with National Institutes of Health Stroke Scale (NIHSS) score ≥2. A 70 s bedside optical blood flow scan generated cerebral blood flow waveforms based on relative changes in speckle contrast. Anterior circulation LVO was determined by CT angiography. A deep learning model trained on all patient data using fivefold cross-validation and learned discriminative representations from the raw speckle contrast waveform data. Receiver operating characteristic (ROC) analysis compared the Openwater diagnostic performance (ie, LVO detection) with prehospital stroke scales. RESULTS: Among 135 patients, 52 (39%) had an anterior circulation LVO. The median NIHSS score was 8 (IQR 4-14). The Openwater instrument had 79% sensitivity and 84% specificity for the detection of LVO. The rapid arterial occlusion evaluation (RACE) scale had 60% sensitivity and 81% specificity and the Los Angeles motor scale (LAMS) had 50% sensitivity and 81% specificity. The binary Openwater classification (high-likelihood vs low-likelihood) had an area under the ROC (AUROC) of 0.82 (95% CI 0.75 to 0.88), which outperformed RACE (AUC 0.70; 95% CI 0.62 to 0.78; P=0.04) and LAMS (AUC 0.65; 95% CI 0.57 to 0.73; P=0.002). CONCLUSIONS: The Openwater optical blood flow monitor outperformed prehospital stroke scales for the detection of LVO in patients undergoing acute stroke evaluation in the emergency department. These encouraging findings need to be validated in an independent test set and the prehospital environment.

Cost-Effectiveness of Late Endovascular Thrombectomy vs. Best Medical Management in a Clinical Trial Setting and Real-World Setting.

BACKGROUND AND PURPOSE: To assess cost-effectiveness of late time-window endovascular treatment (EVT) in a clinical trial setting and a "real-world" setting. METHODS: Data are from the randomized ESCAPE trial and a prospective cohort study (ESCAPE-LATE). Anterior circulation large vessel occlusion patients presenting > 6 hours from last-known-well were included, whereby collateral status was an inclusion criterion for ESCAPE but not ESCAPE-LATE. A Markov state transition model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) for EVT in addition to best medical care vs. best medical care only in a clinical trial setting (comparing ESCAPE-EVT to ESCAPE control arm patients) and a "real-world" setting (comparing ESCAPE-LATE to ESCAPE control arm patients). We performed an unadjusted analysis, using 90-day modified Rankin Scale(mRS) scores as model input and analysis adjusted for baseline factors. Acceptability of EVT was calculated using upper/lower willingness-to-pay thresholds of 100,000 USD/50,000 USD/QALY. RESULTS: Two-hundred and forty-nine patients were included (ESCAPE-LATE:n = 200, ESCAPE EVT-arm:n = 29, ESCAPE control-arm:n = 20). Late EVT in addition to best medical care was cost effective in the unadjusted analysis both in the clinical trial and real-world setting, with acceptability 96.6%-99.0%. After adjusting for differences in baseline variables between the groups, late EVT was marginally cost effective in the clinical trial setting (acceptability:49.9%-61.6%), but not the "real-world" setting (acceptability:32.9%-42.6%). CONCLUSION: EVT for LVO-patients presenting beyond 6 hours was cost effective in the clinical trial setting and "real-world" setting, although this was largely related to baseline patient differences favoring the "real-world" EVT group. After adjusting for these, EVT benefit was reduced in the trial setting, and absent in the real-world setting.

Modeling diffusion-weighted imaging lesion expansion between 2 and 24 h after endovascular thrombectomy in acute ischemic stroke.

PURPOSE: Diffusion-weighted imaging (DWI) lesion expansion after endovascular thrombectomy (EVT) is not well characterized. We used serial diffusion-weighted magnetic resonance imaging (MRI) to measure lesion expansion between 2 and 24 h after EVT. METHODS: In this single-center observational analysis of patients with acute ischemic stroke due to large vessel occlusion, DWI was performed post-EVT (< 2 h after closure) and 24-h later. DWI lesion expansion was evaluated using multivariate generalized linear mixed modeling with various clinical moderators. RESULTS: We included 151 patients, of which 133 (88%) had DWI lesion expansion, defined as a positive change in lesion volume between 2 and 24 h. In an unadjusted analysis, median baseline DWI lesion volume immediately post-EVT was 15.0 mL (IQR: 6.6-36.8) and median DWI lesion volume 24 h post-EVT was 20.8 mL (IQR: 9.4-66.6), representing a median change of 6.1 mL (IQR: 1.5-17.7), or a 39% increase. There were no significant associations among univariable models of lesion expansion. Adjusted models of DWI lesion expansion demonstrated that relative lesion expansion (defined as final/initial DWI lesion volume) was consistent across eTICI scores (0-2a, 0.52%; 2b, 0.49%; 2c-3, 0.42%, p = 0.69). For every 1 mL increase in lesion volume, there was 2% odds of an increase in 90-day mRS (OR: 1.021, 95%CI [1.009, 1.034], p < 0.001). CONCLUSION: We observed substantial lesion expansion post-EVT whereby relative lesion expansion was consistent across eTICI categories, and greater absolute lesion expansion was associated with worse clinical outcome. Our findings suggest that alternate endpoints for cerebroprotectant trials may be feasible.

Technique and impact on first pass effect primary results of the ASSIST global registry.

BACKGROUND: Patients treated with mechanical thrombectomy (MT) for acute ischemic strokes from large vessel occlusion (LVO) have better outcomes with effective reperfusion. However, it is unknown which technique leads to better technical and clinical success. We aimed to determine which technique yields the most effective first pass reperfusion during MT. METHODS: In a prospective, multicenter global registry we enrolled patients treated with operator preferred MT technique at 71 hospitals from January 2019 to January 2022. Three techniques were assessed: SR Classic with stent retriever (SR) and balloon guide catheter (BGC); SR Combination which employed SR with contact aspiration with or without BGC; and direct aspiration (DA) with or without BGC. The primary outcome was achieving an expanded Thrombolysis In Cerebral Infarction (eTICI) score of 2c or 3 on the first pass, with the primary technique as adjudicated by core lab. The primary clinical outcome measure was a 90-day modified Rankin Scale (mRS) score of 0-2. RESULTS: A total of 1492 patients were enrolled. Patients treated with SR Classic or SR Combination were more likely to achieve first pass eTICI 2c or 3 reperfusion (P=0.01). There was no significant difference in mRS 0-2 (P=0.46) or safety endpoints. CONCLUSIONS: The use of SR Classic or SR Combination was more likely to achieve first pass eTICI 2c or 3 reperfusion. There were no significant differences in clinical outcomes and safety endpoints.

Infarct Evolution on MR-DWI After Thrombectomy in Acute Stroke Patients Randomized to Nerinetide or Placebo: The REPERFUSE-NA1 Study

BACKGROUND AND OBJECTIVES: The neuroprotectant nerinetide has shown promise in reducing infarct volumes in primate models of ischemia reperfusion. We hypothesized that early secondary infarct growth after endovascular therapy (EVT) (1) may be a suitable surrogate biomarker for testing neuroprotective compounds, (2) is feasible to assess in the acute setting using sequential MRI, and (3) can be modified by treatment with nerinetide. METHODS: REPERFUSE-NA1 was a prospective, multisite MRI substudy of the randomized controlled trial ESCAPE-NA1 (ClinicalTrials.gov NCT02930018) that involved patients with acute disabling large vessel occlusive stroke undergoing EVT within 12 hours of onset who were randomized to receive intravenous nerinetide or placebo. Patients enrolled in REPERFUSE-NA1 underwent sequential MRI <5 hours post-EVT (day 1) and at 24 hours (day 2). The primary outcome was total diffusion-weighted MRI infarct growth early after EVT, defined as the lesion volume difference between day 2 and day 1. The secondary outcome was region-specific infarct growth in different brain tissue compartments. Statistical analyses were performed using the Mann-Whitney U test and multiple linear regression. RESULTS: Sixty-seven of 71 patients included had MRI of sufficient quality. The median infarct volume post-EVT was 12.98 mL (IQR, 5.93-28.08) in the nerinetide group and 10.80 mL (IQR, 3.11-24.45) in the control group (p = 0.59). Patients receiving nerinetide showed a median early secondary infarct growth of 5.92 mL (IQR, 1.09-21.30) compared with 10.80 mL (interquartile range [IQR], 2.54-21.81) in patients with placebo (p = 0.30). Intravenous alteplase modified the effect of nerinetide on region-specific infarct growth in white matter and basal ganglia compartments. In patients with no alteplase, the infarct growth rate was reduced by 120% (standard error [SE], 60%) in the white matter (p = 0.03) and by 340% (SE, 140%) in the basal ganglia (p = 0.02) in the nerinetide group compared with placebo after adjusting for confounders. DISCUSSION: This study highlights the potential of using MR imaging as a biomarker to estimate the effect of a neuroprotective agent in acute stroke treatment. Patients with acute large vessel occlusive stroke exhibited appreciable early infarct growth both in the gray matter and the white matter after undergoing EVT. Acknowledging relatively small overall infarct volumes in this study, treatment with nerinetide was associated with slightly reduced percentage infarct growth in the white matter and basal ganglia compared with placebo in patients not receiving intravenous alteplase and had no effect on the total early secondary infarct growth. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT02930018. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with acute large vessel ischemic stroke undergoing EVT, nerinetide did not significantly decrease early post-EVT infarct growth compared with placebo.

Symptomatic Non-stenotic Carotid Disease in Embolic Stroke of Undetermined Source : Analysis of the ESCAPE-NA1 Trial.

PURPOSE: Non-stenotic (< 50%) carotid disease may play an important etiological role in ischemic stroke classified as embolic stroke of undetermined source (ESUS). We aimed to assess the prevalence of non-stenotic carotid disease and its association with ipsilateral ischemic stroke. METHODS: Data are from ESCAPE-NA1, a randomized controlled trial investigating the neuroprotectant nerinetide in patients with acute ischemic stroke and large vessel occlusion (LVO). The degree of stenosis of the extracranial internal carotid artery (ICA) and high-risk plaque features were assessed on baseline computed tomography (CT) angiography. We evaluated the association of non-stenotic carotid disease and ipsilateral stroke by age-adjusted and sex-adjusted logistic regression and calculated the attributable risk of ipsilateral stroke caused by non-stenotic carotid disease. RESULTS: After excluding patients with non-assessable imaging, symptomatic > 50% carotid stenosis and extracranial dissection, 799/1105 (72.1%) patients enrolled in ESCAPE-NA1 remained for this analysis. Of these, 127 (15.9%) were classified as ESUS. Non-stenotic carotid disease occurred in 34/127 ESUS patients (26.8%) and was associated with the presence of ipsilateral ischemic stroke (odds ratio, OR 1.6, 95% confidence interval, CI 1.0-2.6, p = 0.049). The risk of ipsilateral ischemic stroke attributable to non-stenotic carotid disease in ESUS was estimated to be 19.7% (95% CI -5.7% to 39%), the population attributable risk was calculated as 4.3%. Imaging features such as plaque thickness, plaque irregularity or plaque ulceration were not different between non-stenotic carotids with vs. without ipsilateral stroke. CONCLUSION: Non-stenotic carotid disease frequently occurs in patients classified as ESUS and is associated with ipsilateral ischemic stroke. Our findings support the role of non-stenotic carotid disease as stroke etiology in ESUS, but further prospective research is needed to prove a causal relationship.

Predicting outcome in acute stroke with large vessel occlusion-application and validation of MR PREDICTS in the ESCAPE-NA1 population.

BACKGROUND: Predicting outcome after endovascular treatment for acute ischemic stroke is challenging. We aim to investigate differences between predicted and observed outcomes in patients with acute ischemic stroke treated with endovascular treatment and to evaluate the performance of a validated outcome prediction score. PATIENTS AND METHODS: MR PREDICTS is an outcome prediction tool based on a logistic regression model designed to predict the treatment benefit of endovascular treatment based on the MR CLEAN and HERMES populations. ESCAPE-NA1 is a randomized trial of nerinetide vs. placebo in patients with acute stroke and large vessel occlusion. We applied MR PREDICTS to patients in the control arm of ESCAPE-NA1. Model performance was assessed by calculating its discriminative ability and calibration. RESULTS: Overall, 556/1105 patients (50.3%) in the ESCAPE-NA1-trial were randomized to the control arm, 435/556 (78.2%) were treated within 6 h of symptom onset. Good outcome (modified Rankin scale 0-2) at 3 months was achieved in 275/435 patients (63.2%), the predicted probability of good outcome was 52.5%. Baseline characteristics were similar in the study and model derivation cohort except for age (ESCAPE-NA1: mean: 70 y vs. HERMES: 66 y), hypertension (72% vs. 57%), and collaterals (good collaterals, 15% vs. 44%). Compared to HERMES we observed higher rates of successful reperfusion (TICI 2b-3, ESCAPE-NA1: 87% vs. HERMES: 71%) and faster times from symptom onset to reperfusion (median: 201 min vs. 286 min). Model performance was good, indicated by a c-statistic of 0.76 (95%confidence interval: 0.71-0.81). CONCLUSION: Outcome-prediction using models created from HERMES data, based on information available in the emergency department underestimated the actual outcome in patients with acute ischemic stroke and large vessel occlusion receiving endovascular treatment despite overall good model performance, which might be explained by differences in quality of and time to reperfusion. These findings underline the importance of timely and successful reperfusion for functional outcomes in acute stroke patients.