Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes after Acute Ischemic Stroke: An Analysis of the DAWN Trial.

OBJECTIVE: We aimed to assess the impact of time to endovascular thrombectomy (EVT) on clinical outcomes in the DAWN trial, while also exploring the potential effect modification of mode of stroke onset on this relationship. METHODS: The association between every 1-h treatment delay with 90-day functional independence (modified Rankin Scale [mRS] score 0-2), symptomatic intracranial hemorrhage, and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs. witnessed vs. unwitnessed). RESULTS: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6 to 12 hours and 12 to 24 hours time window, respectively. Considering all three modes of onset together, there was no statistically significant association between time last seen well to randomization with either functional independence or mortality at 90 days in either the endovascular thrombectomy (mRS 0-2 1-hour delay OR 1.07; 95% CI 0.93-1.24; mRS 6 OR 0.84; 95% CI 0.65-1.03) or medical management (mRS 0-2 1-hour delay OR 0.98; 95% CI 0.80-1.14; mRS 6 1-hour delay OR 0.94; 95% CI 0.79-1.09) groups. Moreover, there was no significant interaction between treatment effect and time (p = 0.439 and p = 0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between time last seen well to successful reperfusion (modified Treatment in Cerebral Infarction ≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p = 0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p = 0.018) negative slope in wake-up patients. There was no association between treatment times and symptomatic intracranial hemorrhage. INTERPRETATION: Mode of onset modifies the effect of time to reperfusion on thrombectomy outcomes, and should be considered when exploring different treatment paradigms in the extended window. ANN NEUROL 2024.

Association Between Body Mass Index and Functional Outcomes in Patients With Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: Evidence of the so-called "obesity paradox," which refers to the protective effect and survival benefit of obesity in patients with spontaneous intracerebral hemorrhage (ICH), remains controversial. This study aims to determine the association between body mass index (BMI) and functional outcomes in patients with ICH and whether it is modified by race/ethnicity. METHODS: Included individuals were derived from the Ethnic/Racial Variations of Intracerebral Hemorrhage study, which prospectively recruited 1,000 non-Hispanic White, 1,000 non-Hispanic Black, and 1,000 Hispanic patients with spontaneous ICH. Only patients with available BMI were included. The primary outcome was 90-day mortality. Secondary outcomes were mortality at discharge, modified Rankin Scale (mRS), Barthel Index, and self-reported health status measures at 90 days. Associations between BMI and ICH outcomes were assessed using univariable and multivariable logistic, ordinal, and linear regression models, as appropriate. Sensitivity analyses after excluding frail patients and by patient race/ethnicity were performed. RESULTS: A total of 2,841 patients with ICH were included. The median age was 60 years (interquartile range 51-73). Most patients were overweight (n = 943; 33.2%) or obese (n = 1,032; 36.3%). After adjusting for covariates, 90-day mortality was significantly lower among overweight and obese patients than their normal weight counterparts (adjusted odds ratio [aOR] = 0.71 [0.52-0.98] and aOR = 0.70 [0.50-0.97], respectively). Compared with patients with BMI <25 kg/m2, those with BMI ≥25 kg/m2 had better 90-day mRS (aOR = 0.80 [CI 0.67-0.95]), EuroQoL Group 5-Dimension (EQ-5D) (aß = 0.05 [0.01-0.08]), and EQ-5D VAS (aß = 3.80 [0.80-6.98]) scores. These differences persisted after excluding withdrawal of care patients. There was an inverse relationship between BMI and 90-day mortality (aOR = 0.97 [0.96-0.99]). Although non-Hispanic White patients had significantly higher 90-day mortality than non-Hispanic Black and Hispanic (26.6% vs 19.5% vs 18.0%, respectively; p < 0.001), no significant interactions were found between BMI and race/ethnicity. No significant interactions between BMI and age or sex for 90-day mortality were found, whereas for 90-day mRS, there was a significant interaction with age (pinteraction = 0.004). CONCLUSION: We demonstrated that a higher BMI is associated with decreased mortality, improved functional outcomes, and better self-reported health status at 90 days, thus supporting the paradoxical role of obesity in patients with ICH. The beneficial effect of high BMI does not seem to be modified by race/ethnicity or sex, whereas age may play a significant role in patient functional outcomes.

Optical Coherence Tomography in the Evaluation of Suspected Carotid Webs.

BACKGROUND: Carotid web (CaW) is a subtype of fibromuscular dysplasia that predominantly involves the intimal layer of the arterial wall and is commonly overlooked as a separate causative entity for recurrent strokes. CaW is defined as a shelf-like lesion at the carotid bulb, although different morphological features have been reported. Optical coherence tomography (OCT) has been described in the literature as a useful microscopic and cross-sectional tomographic imaging tool. This study aimed to evaluate the potential utility of OCT in characterizing the wall structure features of patients with suspected CaW. METHODS: Retrospective analysis of patients with suspected CaW who underwent digital subtraction angiography (DSA) coupled with OCT of the carotid bulb from 2018 to 2021 in a single comprehensive stroke center. RESULTS: Sixteen patients were included. The median age was 56 years (IQR 46-61) and 50% were women. OCT corroborated the diagnosis of CaW in 12/16 (75%) cases and ruled it out in 4/16 (25%) patients in whom atherosclerotic disease was demonstrated. Five of the 12 lesions demonstrated a thick fibrotic ridge consistent with CaW but also showed atherosclerotic changes in the vicinity of the carotid bulb (labeled as "CaW+"). In 4/16 (25%) patients, microthrombi adhered to the vessel wall were noted on OCT (inside the CaW pocket or just distal to the web), none of which were observed on CT angiography or DSA. CONCLUSIONS: OCT may have value as a complementary imaging tool in the investigation of patients with suspected CaW and atypical morphological features. Further studies are warranted.

Emergent use of ticagrelor during endovascular reperfusion in large arterial occlusions.

OBJECTIVE: Given many emerging indications for endovascular interventions in ischemic strokes, a safe and effective adjuvant antiplatelet regimen for acute revascularization has become a subject of interest. Ticagrelor is a direct oral P2Y12 inhibitor that may achieve rapid platelet suppression than standard oral therapies. We report our experience of Ticagrelor use in revascularization of acute large arterial steno-occlusive disease, describing procedural post-procedure thrombotic events, major hemorrhages, and other clinical outcomes. METHODS: This was a single-center retrospective case series of large steno-occlusive disease requiring endovascular reperfusion with emergent adjuvant Ticagrelor, defined as 30 min of the procedure from skin puncture to closure of the arteriotomy. Major outcomes investigated were thromboembolism in the target artery, and symptomatic intracranial or extracranial major hemorrhages. Additional analyses were performed with respect to timing of the administration and use of rescue GPIIb/IIIa inhibitors if any. RESULTS: 73 consecutive patients were identified, presenting with severe ischemic stroke (median NIHSS 16) of large artery origin. 67% required stent placement (45% cervical carotid, 22% intracranial artery), 9.5% angioplasty and 23% mechanical thrombectomy only. Two experienced symptomatic in-stent occlusion, and 7 experienced major hemorrhages (9.5%) including 3 fatal symptomatic intracranial hemorrhages (4.1%). Among 19 subjects (26%) who received pretreatment with Ticagrelor, there were fewer GPIIb/IIIa administration, angioplasty and stenting, without yielding benefit in functional outcome or mortality. GPIIb/IIIa was administered as rescue therapy in 45 subjects (62%), which was found associated with increased bleeding compared to patients receiving Ticagrelor only, in whom no bleeding complications were recorded (16% vs. 0%; p = 0.03). CONCLUSION: We report our findings on Ticagrelor as an adjuvant antiplatelet therapy in ischemic stroke of large arterial origin requiring emergent revascularization. Effectiveness, safety, need for additional rescue treatment, and comparison to other commonly used oral antiplatelets should be investigated in future prospective studies.

Higher Procedural Volumes Are Associated with Faster Treatment Times, Better Functional Outcomes, and Lower Mortality in Patients Undergoing Endovascular Treatment for Acute Ischemic Stroke.

OBJECTIVE: We aimed to characterize the association of hospital procedural volumes with outcomes among acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT). METHODS: This was a retrospective, observational cohort study using data prospectively collected from January 1, 2016 to December 31, 2019 in the Get with the Guidelines-Stroke registry. Participants were derived from a cohort of 60,727 AIS patients treated with EVT within 24 hours at 626 hospitals. The primary cohort excluded patients with pretreatment National Institutes of Health Stroke Scale (NIHSS) < 6, onset-to-treatment time > 6 hours, and interhospital transfers. There were 2 secondary cohorts: (1) the EVT metrics cohort excluded patients with missing data on time from door to arterial puncture and (2) the intravenous thrombolysis (IVT) metrics cohort only included patients receiving IVT ≤4.5 hours after onset. RESULTS: The primary cohort (mean ± standard deviation age = 70.7 ± 14.8 years; 51.2% female; median [interquartile range] baseline NIHSS = 18.0 [13-22]; IVT use, 70.2%) comprised 21,209 patients across 595 hospitals. The EVT metrics cohort and IVT metrics cohort comprised 47,262 and 16,889 patients across 408 and 601 hospitals, respectively. Higher procedural volumes were significantly associated with higher odds (expressed as adjusted odds ratio [95% confidence interval] for every 10-case increase in volume) of discharge to home (1.03 [1.02-1.04]), functional independence at discharge (1.02 [1.01-1.04]), and lower rates of in-hospital mortality (0.96 [0.95-0.98]). All secondary measures were also associated with procedural volumes. INTERPRETATION: Among AIS patients primarily presenting to EVT-capable hospitals (excluding those transferred from one facility to another and those suffering in-hospital strokes), EVT at hospitals with higher procedural volumes was associated with faster treatment times, better discharge outcomes, and lower rates of in-hospital mortality. ANN NEUROL 2023.

Comparison of CT Perfusion Software Packages for Thrombectomy Eligibility.

INTRODUCTION: Computed tomography perfusion (CTP) has played an important role in patient selection for mechanical thrombectomy (MT) in acute ischemic stroke. We aimed to investigate the agreement between perfusion parametric maps of 3 software packages - RAPID (RapidAI-IschemaView), Viz CTP(Viz.ai), and e-CTP(Brainomix) - in estimating baseline ischemic core volumes of near completely/completely reperfused patients. METHODS: We retrospectively reviewed a prospectively maintained MT database to identify patients with anterior circulation large vessel occlusion strokes (LVOS) involving the internal carotid artery or middle cerebral artery M1-segment and interpretable CTP maps treated during September 2018 to November 2019. A subset of patients with near-complete/complete reperfusion (expanded thrombolysis in cerebral infarction [eTICI] 2c-3) was used to compare the pre-procedural prediction of final infarct volumes. RESULTS: In this analysis of 242 patients with LVOS, RAPID and Viz CTP relative cerebral blood flow (rCBF) < 30% values had substantial agreement (ρ = 0.767 [95% confidence interval [CI] = 0.71-0.81]) as well as for RAPID and e-CTP (ρ = 0.668 [95% CI = 0.61-0.71]). Excellent agreement was seen for time to maximum of the residue function (Tmax ) > 6 seconds between RAPID and Viz CTP (ρ = 0.811 [95% CI = 0.76-0.84]) and substantial for RAPID and e-CTP (ρ = 0.749 [95% CI = 0.69-0.79]). Final infarct volume (FIV) prediction (n = 136) was substantial in all 3 packages (RAPID ρ = 0.744; Viz CTP ρ = 0.711; and e-CTP ρ = 0.600). CONCLUSION: Perfusion parametric maps of the RAPID, Viz CTP, and e-CTP software have substantial agreement in predicting final infarct volume in near-completely/completely reperfused patients. ANN NEUROL 2023;94:848-855.

Clot composition and recanalization outcomes in mechanical thrombectomy.

BACKGROUND: Mechanical thrombectomy (MT) has become standard for large vessel occlusions, but rates of complete recanalization are suboptimal. Previous reports correlated radiographic signs with clot composition and a better response to specific techniques. Therefore, understanding clot composition may allow improved outcomes. METHODS: Clinical, imaging, and clot data from patients enrolled in the STRIP Registry from September 2016 to September 2020 were analyzed. Samples were fixed in 10% phosphate-buffered formalin and stained with hematoxylin-eosin and Martius Scarlett Blue. Percent composition, richness, and gross appearance were evaluated. Outcome measures included the rate of first-pass effect (FPE, modified Thrombolysis in Cerebral Infarction 2c/3) and the number of passes. RESULTS: A total of 1430 patients of mean±SD age 68.4±13.5 years (median (IQR) baseline National Institutes of Health Stroke Scale score 17.2 (10.5-23), IV-tPA use 36%, stent-retrievers (SR) 27%, contact aspiration (CA) 27%, combined SR+CA 43%) were included. The median (IQR) number of passes was 1 (1-2). FPE was achieved in 39.3% of the cases. There was no association between percent histological composition or clot richness and FPE in the overall population. However, the combined technique resulted in lower FPE rates for red blood cell (RBC)-rich (P<0.0001), platelet-rich (P=0.003), and mixed (P<0.0001) clots. Fibrin-rich and platelet-rich clots required a higher number of passes than RBC-rich and mixed clots (median 2 and 1.5 vs 1, respectively; P=0.02). CA showed a trend towards a higher number of passes with fibrin-rich clots (2 vs 1; P=0.12). By gross appearance, mixed/heterogeneous clots had lower FPE rates than red and white clots. CONCLUSIONS: Despite the lack of correlation between clot histology and FPE, our study adds to the growing evidence supporting the notion that clot composition influences recanalization treatment strategy outcomes.

Falsely normal CT perfusion ischemic core readings are common and often associated with deep infarcts.

BACKGROUND: Proper identification of infarct extent is crucial for thrombectomy and prognostication. We sought to study the frequency and topographic aspects of those cases in which CT perfusion (CTP) misses a core lesion that is present on initial non-contrast CT (NCCT). METHODS: A review was carried out of a prospectively collected database of endovascular patients with anterior circulation large vessel occlusion strokes from January 2014 to November 2018. Patients with an e-ASPECTS <10 and adequate CTP maps were included. Total missed ischemic core (TMC) was defined as a CTP core lesion (relative cerebral blood flow <30%) <1 mL with a visualized hypodensity on NCCT. RESULTS: In total, 629 patients were analyzed of which 161 (25.6%) had a TMC. On univariate analysis, TMC was associated with isolated deep middle cerebral artery (MCA) strokes (77.6% vs 56.6%, p<0.001), lower National Institutes of Health Stroke Scale (NIHSS) score (9 (15-20) vs 17 (13-21), p=0.007) and longer times to treatment (452 (288-652) min vs 355 (236-655) min, p=0.03). After adjusting for identifiable confounders, isolated deep MCA stroke was an independent predictor of TMC (OR 2.49 (95% CI 1.63 to 3.8), p<0.001). There were no differences between patients presenting with a TMC and those not with good outcomes (modified Rankin Scale 0-2) (50.8% vs 47.6%, p=0.53) or 90-day mortality (23% vs 17.6%, p=0.17). However, TMC was associated with lower rates of any parenchymal hematomas (5.2% vs 14.6%, p=0.02; aOR 0.11 (95% CI 0.01 to 0.91), p=0.04) and smaller final infarct volumes (20.5 (11.3-42.9) mL vs 47.5 (20.3-85) mL, p<0.001). CONCLUSIONS: CTP may completely fail to detect ischemic core in as many as 25% of cases, especially in isolated deep MCA strokes. Technical refinements of the post-processing algorithms are therefore warranted. TMC infarcts may have a lower risk of reperfusion hemorrhage, potentially due to greater preservation of the neurovascular unit structure in face of delayed recovery of cerebral blood flow.

Comparative analysis between 1-D, 2-D and 3-D carotid web quantification.

BACKGROUND: Carotid webs (CaW) are now recognized as a cause of ischemic stroke in young patients. The thromboembolic potential appears related to the CaW's morphology and consequent impact on local flow dynamics. We aim to evaluate the reliability of different measurement methods for the quantification of CaW and their relationship to symptomatic status, presence of large vessel occlusion stroke (LVOS), clot burden and final infarct volume. METHODS: This was a retrospective analysis of the local comprehensive stroke center CaW database (September 2014-July 2019). CT angiograms (CTAs) were reviewed independently by two raters, blinded to the clinical information and laterality of the stroke/transient ischemic attack. CaW were quantified with 1-D (length), 2-D (area) and 3-D (volume) measurements via Osirix software. Final infarct volume was calculated on MRI. Patients with superimposed CaW thrombus and no repeat imaging were excluded. RESULTS: Forty-eight CaW (37 symptomatic and 11 contralateral/asymptomatic) in 38 patients were included. Mean age (±SD) was 48.7 (±8.5) years, 78.9% were women and 77.1% were black. Inter-rater agreement was 0.921 (p<0.001) for 1-D, 0.930 (p<0.001) for 2-D, and 0.937 (p<0.001) for 3-D CaW measurements. When comparing symptomatic with asymptomatic CaW, mean web length was 3.2 mm versus 2.5 mm (p<0.02), median area was 5.8 versus 5.0 mm2 (p=0.35) and median volume was 15.0 versus 10.6 mm3 (p<0.04), respectively. CaW with a thinner profile (longer intraluminal projection compared with the base) were more likely to be symptomatic (0.67±0.17 vs 0.88±0.37; p=0.01). Average CaW 1-D and final infarct volume had a weak but positive association (Κ=0.230, p<0.05), while no association among web measurements and the presence of LVOS or clot burden was observed. CONCLUSION: CaW dimension quantification (1-D, 2-D and 3-D) is highly reproducible. Linear and volumetric measurements were more strongly associated with symptoms. The impact of CaW size on the presence of LVOS, clot burden and final infarct volume is unclear.

Characterizing Fast and Slow Progressors in Anterior Circulation Large Vessel Occlusion Strokes.

BACKGROUND AND PURPOSE: Infarct growth rate (IGR) in acute ischemic stroke is highly variable. We sought to evaluate impact of symptom-reperfusion time on outcomes in patients undergoing mechanical thrombectomy (MT). METHODS: A prospectively maintained database from January,2012-August,2020 was reviewed. All patients with isolated MCA-M1 occlusion who achieved complete reperfusion(mTICI2C-3), had a witnessed symptom onset and follow-up MRI were included. IGR was calculated as final infarct volume (FIV)(ml)/symptom onset to reperfusion time(hours) and was dichotomized according to the median value into slow-(SP) versus fast-progressors (FP). The primary analysis aimed to evaluate the impact of symptom-reperfusion time on 90-day mRS in SP and FP. Secondary analysis was performed to identify predictors of IGR. RESULTS: A total of 137 patients were eligible for analysis. Mean age was 63 ± 15.4 years and median IGR was 5.13ml/hour. SP(n = 69) had higher median ASPECTS, lower median rCBF<30% lesion volume, higher proportion of favorable collaterals and hypoperfusion intensity ratio (HIR)<0.4, higher minimal mean arterial blood pressure before reperfusion, and lower rates of general anesthesia compared to FP(n = 68). Symptom-reperfusion time was comparable between both groups. SP had higher rates of 90-day mRS0-2(71.9%vs.38.9%,aOR;7.226,95%CI[2.431-21.482],p < 0.001) and lower median FIV. Symptom-reperfusion time was associated with 90-day mRS0-2 in FP (aOR;0.541,95%CI[0.309-0.946],p = 0.03) but not in SP (aOR;0.874,95%CI[0.742-1.056],p = 0.16). On multivariable analysis, high ASPECTS and favorable collaterals in the NCCT/CTA model, and low rCBF<30% and HIR<0.4 in the CTP model were independent predictors of SP. CONCLUSIONS: The impact of symptom-reperfusion time on outcomes significantly varies across slow-versus fast-progressors. ASPECTS, collateral score, rCBF<30%, and HIR define stroke progression profile.

Carotid web: an under-recognized and misdiagnosed ischemic stroke etiology.

BACKGROUND: Carotid web (CaW) constitutes a possible cause of ischemic stroke, particularly large vessel occlusion syndromes. We aim to evaluate misdiagnosis rates and diagnosis trends for CaW. METHODS: Based on CT angiography (CTA), we prospectively identified a cohort of patients with symptomatic CaW treated at two comprehensive stroke centers (CSC) from 2014 to 2020 to assess misdiagnosis. Official CTA reports from the CSCs and referring hospitals were then reviewed for mention of CaW. For diagnosis trends, we retrospectively analyzed a CSC electronic medical record, identifying patients with CaW mentioned in an official CTA report from 2011 to 2020. RESULTS: For misdiagnosis, 56 patients with symptomatic CaW were identified in the CSCs; 16 (28%) had bilateral CaW, totaling 72 CaWs. Only one CaW (5.5%) was reported at referring facilities, from 14 patients/18 CaWs imaged with CTA. Conversely, 43 (69%) CaWs were reported from 49 patients/62 CaWs at the CSC (p<0.01). For diagnosis trends, from 2011 to 2020, 242 patients at a CSC accounted for 266 CTA reports mentioning CaW. The majority of these reports (n=206, 77%) were associated with stroke/transient ischemic attack (TIA) ICD-9/ICD-10 codes. The rate of CaW diagnosis adjusted per 1000 patients with stroke/TIA increased over time, 2015 being the most significant point of change ('joinpoint'; p=0.01). The analysis of CaW mentions normalized per 1000 CTA reports also showed increasing rates of diagnosis over time (joinpoint:2014; p<0.02). CONCLUSION: CaW was predominantly identified in patients with strokes/TIAs rather than asymptomatic patients. CaW was commonly overlooked in facilities with lower levels of cerebrovascular certification. Recognition of CaW at a CSC has significantly increased over time, independent of overall imaging and stroke patient volume.

Endovascular reperfusion outcomes in patients with a stroke and low ASPECTS is highly dependent on baseline infarct volumes.

BACKGROUND: Patients with large vessel occlusion stroke (LVOS) and a low Alberta Stroke Program Early CT Score (ASPECTS) are often not offered endovascular therapy (ET) as they are thought to have a poor prognosis. OBJECTIVE: To compare the outcomes of patients with low and high ASPECTS undergoing ET based on baseline infarct volumes. METHODS: Review of a prospectively collected endovascular database at a tertiary care center between September 2010 and March 2020. All patients with anterior circulation LVOS and interpretable baseline CT perfusion (CTP) were included. Subjects were divided into groups with low ASPECTS (0-5) and high ASPECTS (6-10) and subsequently into limited and large CTP-core volumes (cerebral blood flow 30% >70 cc). The primary outcome measure was the difference in rates of 90-day good outcome as defined by a modified Rankin Scale (mRS) score of 0 to 2 across groups. RESULTS: 1248 patients fit the inclusion criteria. 125 patients had low ASPECTS, of whom 16 (12.8%) had a large core (LC), whereas 1123 patients presented with high ASPECTS, including 29 (2.6%) patients with a LC. In the category with a low ASPECTS, there was a trend towards lower rates of functional independence (90-day modified Rankin Scale (mRS) score 0-2) in the LC group (18.8% vs 38.9%, p=0.12), which became significant after adjusting for potential confounders in multivariable analysis (aOR=0.12, 95% CI 0.016 to 0.912, p=0.04). Likewise, LC was associated with significantly lower rates of functional independence (31% vs 51.9%, p=0.03; aOR=0.293, 95% CI 0.095 to 0.909, p=0.04) among patients with high ASPECTS. CONCLUSIONS: Outcomes may vary significantly in the same ASPECTS category depending on infarct volume. Patients with ASPECTS ≤5 but baseline infarct volumes ≤70 cc may achieve independence in nearly 40% of the cases and thus should not be excluded from treatment.

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

BACKGROUND: The effect of time from stroke onset to thrombectomy in the extended time window remains poorly characterized. AIM: We aimed to analyze the relationship between time to treatment and clinical outcomes in the early versus extended time windows. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The Prognostic Value of Quantitative EEG in Patients Undergoing Mechanical Thrombectomy for Acute Ischemic Stroke.

PURPOSE: Previous work has shown that quantitative EEG measures correlate with the severity of ischemic stroke. This has not been systematically validated in patients with acute ischemic stroke who have undergone mechanical thrombectomy. METHODS: Data were collected from 73 patients who underwent mechanical thrombectomy and had a standard head set EEG performed during their hospital admission. For each patient, the global delta-alpha ratio (DAR) and its difference between the two hemispheres were calculated. Associations between the global and interhemispheric DAR difference with the patients' National Institutes of Health Stroke and Modified Rankin Scale scores at discharge and 3 months after thrombectomy were assessed. RESULTS: The interhemispheric DAR difference correlated with the National Institutes of Health Stroke scores at discharge (Spearman R = 0.41, P = 0.0008), National Institutes of Health Stroke scores at 3 months (Spearman R = 0.60, P = 0.02) and Modified Rankin Scale scores at 3 months (Spearman R = 0.27, P = 0.01). In contrast, the global DAR did not correlate significantly with any of these clinical outcomes when evaluated as continuous variables. In a multivariate logistic regression model, both the interhemispheric DAR difference (ß = 0.25, P = 0.03) and the infarct volume (ß = 0.02, P = 0.03) were independently predictive of good versus poor functional outcome (Modified Rankin Scale score ≤2 vs. >2) at 3 months. CONCLUSIONS: The quantitative EEG measure of interhemispheric slow relative to fast frequencies power asymmetry correlated with the discharge and 3-month National Institutes of Health Stroke and Modified Rankin Scale scores and provided added value to infarct volume in predicting functional outcome at 3 months. These data support the prognostic value of quantitative EEG in ischemic stroke patients who have undergone mechanical thrombectomy.

Clinical effectiveness of endovascular stroke treatment in the early and extended time windows.

BACKGROUND: The clinical efficacy of mechanical thrombectomy has been unequivocally demonstrated in multiple randomized clinical trials. However, these studies were performed in carefully selected centers and utilized strict inclusion criteria. AIM: We aimed to assess the clinical effectiveness of mechanical thrombectomy in a prospective registry. METHODS: A total of 2008 patients from 76 sites across 12 countries were enrolled in a prospective open-label mechanical thrombectomy registry. Patients were categorized into the corresponding cohorts of the SWIFT-Prime, DAWN, and DEFUSE 3 trials according to the basic demographic and clinical criteria without considering specific parenchymal imaging findings. Baseline and outcome variables were compared across the corresponding groups. RESULTS: As compared to the treated patients in the actual trials, registry-derived patients tended to be younger and had lower baseline ASPECTS. In addition, time to treatment was earlier and the use of intravenous tissue plasminogen activator (IV-tPA) and general anesthesia were higher in DAWN- and DEFUSE-3 registry derived patients versus their corresponding trials. Reperfusion rates were higher in the registry patients. The rates of 90-day good outcome (mRS0-2) in registry-derived patients were comparable to those of the patients treated in the corresponding randomized clinical trials (SWIFT-Prime, 64.5% vs. 60.2%; DAWN, 50.4% vs. 48.6%; Beyond-DAWN: 52.4% vs. 48.6%; DEFUSE 3, 52% vs. 44.6%, respectively; all P > 0.05). Registry-derived patients had significant less disability than the corresponding randomized clinical trial controls (ordinal modified Rankin Scale (mRS) shift odds ratio (OR), P < 0.05 for all). CONCLUSION: Our study provides favorable generalizability data for the safety and efficacy of thrombectomy in the "real-world" setting and supports that patients may be safely treated outside the constraints of randomized clinical trials.

Age-adjusted infarct volume cut-off points improve stroke outcome prognostication beyond modeling with age and infarct volume.

BACKGROUND: Age and infarct volume are among the most powerful predictors of outcome after large vessel occlusion acute strokes (LVOS). OBJECTIVE: To study the impact of age-adjusted final infarct volume (FIV) on functional outcomes. METHODS: Review of a prospectively collected thrombectomy database at a tertiary care center between September 2010 and February 2018. Consecutive patients with anterior circulation LVOS who achieved full reperfusion (modified Thrombolysis in Cerebral Infarction 3) were categorized into four age groups: (G1) <60 years, (G2) 60-69, (G3) 70-79, (G4) ≥80 years. The Youden Index was used to identify the optimal FIV cut-off point for good outcome (modified Rankin Scale score 0-2) discrimination in each group and the overall population. The predictive ability of these specific thresholds was evaluated using binary logistic regressions and compared with the non-age-adjusted cut-off point. RESULTS: 516 patients were analyzed (G1: n=171, G2: n=130, G3: n=103, G4: n=112). Patients with poor outcome had a larger FIV in each group (p<0.01 for all). The target FIV cut-off point decreased with increased age: G1: 45.7 mL (sensitivity 56%, specificity 80%); G2: 30.4 mL (sensitivity 63%, specificity 75%); G3: 20.2 mL (sensitivity 76%, specificity 65%); G4: 16.9 mL (sensitivity 68%, specificity 70%). The non-age-adjusted cut-off point was 19.2 mL (sensitivity 70%, specificity 59%).In multivariate analysis, adjusting for confounders including age and FIV, achieving a FIV less than the age-adjusted threshold was an independent predictor of good outcome (aOR=2.72, 95% CI 1.41 to 5.24, p<0.001). In contrast, a similar model including the non-age-adjusted target cut-off point failed to reveal an association with good outcome (aOR=1.72, 95% CI 0.93 to 3.19, p<0.085). Furthermore, the latter model had a weaker outcome predictive ability as assessed by the Akaike information criterion (409 vs 403). CONCLUSIONS: Age-adjusted infarct volume represents a strong outcome discriminator beyond age and infarct volume in isolation and might help to refine patient selection and improve outcome prognostication in stroke thrombectomy.

Stent-retriever alone vs. aspiration and stent-retriever combination in large vessel occlusion stroke: A matched analysis.

BACKGROUND: Three randomized clinical trials have reported similar safety and efficacy for contact aspiration and stent-retriever thrombectomy. AIM: We aimed to determine whether the combined technique (stent-retriever + contact aspiration) was superior to stent-retriever alone as first-line thrombectomy strategy in a patient cohort where balloon guide catheter was universally used. METHODS: A prospectively maintained mechanical thrombectomy database from January 2018 to December 2019 was reviewed. Patients were included if they had anterior circulation proximal occlusion ischemic stroke (intracranial ICA or MCA-M1/M2 segments) and underwent stent-retriever alone thrombectomy or stent-retriever + contact aspiration as first-line therapy. The primary outcome was the first-pass effect (mTICI2c-3). Secondary outcomes included modified first-pass effect (mTICI2b-3), successful reperfusion (mTICI2b-3) prior to and after any rescue strategy, and 90-day functional independence (mRS ≤ 2). Safety outcomes included rate of parenchymal hematoma type-2 and 90-day mortality. Sensitivity analyses were performed after dividing the overall cohort according to first-line modality into two matched groups. RESULTS: A total of 420 patients were included in the analysis (mean age 64.4 years; median baseline NIHSS 16 (11-21)). As compared to first-line stent-retriever alone, first-line stent-retriever + contact aspiration resulted in similar rates of first-pass effect (53% vs. 51%, adjusted odds ratio (aOR) 1.122, 95%CI (0.745-1.691), p = 0.58), modified first-pass effect (63% vs. 60.4%, aOR1.250, 95%CI (0.782-2.00), p = 0.35), final successful reperfusion (97.6% vs. 98%, p = 0.75), and higher chances of successful reperfusion prior to any rescue strategy (81.8% vs. 72.5%, aOR 2.033, 95%CI (1.209-3.419), p = 0.007). Functional outcome and safety measures were comparable between both groups. Likewise, the matched analysis (148 patient-pairs) demonstrated comparable results for all clinical and angiographic outcomes except for significantly higher rates of successful reperfusion prior to any rescue strategies with the first-line stent-retriever + contact aspiration treatment (81.8% vs. 73.6%, aOR 1.881, 95%CI (1.039-3.405), p = 0.037). CONCLUSIONS: Our findings reinforce the findings of ASTER-2 trial in that the first-line thrombectomy with a combined technique did not result in increased rates of first-pass reperfusion or better clinical outcomes. However, the addition of contact aspiration after initial stent-retriever failure might be beneficial in achieving earlier reperfusion.

No Racial Disparity in Outcome Measures After Endovascular Treatment for Stroke in the Elderly.

BACKGROUND AND PURPOSE: Despite the lower rates of good outcomes and higher mortality in elderly patients, age does not modify the treatment effect of mechanical thrombectomy for large vessel occlusion strokes. We aimed to study whether racial background influences the outcome after mechanical thrombectomy in the elderly population. METHODS: We reviewed a prospectively maintained database of patients with acute ischemic stroke treated with mechanical thrombectomy from October 2010 through June 2020 to identify all consecutive patients with age ≥80 years and anterior circulation large vessel occlusion strokes. The patients were categorized according to their race as Black and White. Univariable and multivariable analyses were performed to define the predictors of 90-day modified Rankin Scale and mortality in the overall population and in each race separately. RESULTS: Among 2241 mechanical thrombectomy, a total of 344 patients (median [interquartile range]; age 85 [82-88] years, baseline National Institutes of Health Stroke Scale score of 19 [15-23], Alberta Stroke Program Early CT Score 9 [7-9], 69.5% females) were eligible for the analysis. White patients (n=251; 73%) had significantly lower median body mass index (25.37 versus 26.89, P=0.04) and less frequent hypertension (78.9% versus 90.3%, P=0.01) but more atrial fibrillation (64.5% versus 44.1%, P=0.001) compared with African Americans (n=93; 27%). Other clinical, imaging, and procedural characteristics were comparable between groups. The rates of symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score of 0 to 2, and mortality were comparable among both groups. On multivariable analysis, race was neither a predictor of 90-day modified Rankin Scale score of 0 to 2 (White race: odds ratio, 0.899 [95% CI, 0.409-1.974], P=0.79) nor 90-day mortality (White race: odds ratio, 1.368; [95% CI, 0.715-2.618], P=0.34). CONCLUSIONS: In elderly patients undergoing mechanical thrombectomy for acute ischemic stroke, there was no racial difference in terms of outcome.

Automated Large Artery Occlusion Detection in Stroke: A Single-Center Validation Study of an Artificial Intelligence Algorithm.

INTRODUCTION: Expediting notification of lesions in acute ischemic stroke (AIS) is critical. Limited availability of experts to assess such lesions and delays in large vessel occlusion (LVO) recognition can negatively affect outcomes. Artificial intelligence (AI) may aid LVO recognition and treatment. This study aims to evaluate the performance of an AI-based algorithm for LVO detection in AIS. METHODS: Retrospective analysis of a database of AIS patients admitted in a single center between 2014 and 2019. Vascular neurologists graded computed tomography angiographies (CTAs) for presence and site of LVO. Studies were analyzed by the Viz-LVO Algorithm® version 1.4 - neural network programmed to detect occlusions from the internal carotid artery terminus (ICA-T) to the Sylvian fissure. Comparisons between human versus AI-based readings were done by test characteristic analysis and Cohen's kappa. Primary analysis included ICA-T and/or middle cerebral artery (MCA)-M1 LVOs versus non-LVOs/more distal occlusions. Secondary analysis included MCA-M2 occlusions. RESULTS: 610 CTAs were analyzed. The AI algorithm rejected 2.5% of the CTAs due to poor quality, which were excluded from the analysis. Viz-LVO identified ICA-T and MCA-M1 LVOs with a sensitivity of 87.6%, specificity of 88.5%, and accuracy of 87.9% (AUC 0.88, 95% CI: 0.85-0.92, p < 0.001). Cohen's kappa was 0.74. In the secondary analysis, the algorithm yielded a sensitivity of 80.3%, specificity of 88.5%, and accuracy of 82.7%. The mean run time of the algorithm was 2.78 ± 0.5 min. CONCLUSION: Automated AI reading allows for fast and accurate identification of LVO strokes with timely notification to emergency teams, enabling quick decision-making for reperfusion therapies or transfer to specialized centers if needed.

Impact of Intravenous Alteplase Door-to-Needle Times on 2-Year Mortality in Patients With Acute Ischemic Stroke.

Objective: We sought to determine whether administration of Intravenous Thrombolysis (IVT) to patients with Acute Ischemic Stroke (AIS) within 60 min from hospital arrival is associated with lower 2-year mortality. Methods: This retrospective study was conducted among patients receiving IVT in hospitals participating in the Georgia Coverdell Acute Stroke Registry (GCASR) from January 1, 2008 through June 30, 2018. Two-year mortality data was obtained by linking the 2008-2018 Georgia Discharge Data System data and the 2008-2020 Georgia death records. We analyzed the study population in two groups based on the time from hospital arrival to initiation of IVT expressed as Door to Needle time (DTN) in a dichotomized (DTN ≤ 60 vs. > 60 min) fashion. Results: The median age of patients was 68 years, 49.4% were females, and the median NIHSS was 9. DTN ≤60 min was associated with lower 30-day [odds ratio (OR), 0.62; 95% CI, 0.52-0.73; P < 0.0001], 1-year (OR, 0.71; 95% CI, 0.61-0.83; P < 0.0001) and 2-year (OR, 0.76; 95% CI, 0.65-0.88; P = 0.001) mortality as well as lower rates of sICH at 36 h (OR, 0.57; 95% CI, 0.43-0.75; P = 0.0001), higher rates of ambulation at discharge (OR, 1.38; 95% CI, 1.25-1.53; P < 0.0001) and discharge to home (OR, 1.36; 95% CI, 1.23-1.52; P < 0.0001). Conclusion: Faster DTN in patients with AIS was associated with lower 2-year mortality across all age, gender and race subgroups. These findings reinforce the need for intensifying quality improvement measures to reduce DTN in AIS patients.