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Background: Clinical trial enrollment and completion is challenging, with nearly half of all trials not being completed or not completed on time. In 2014, the National Institutes of Health StrokeNet in collaboration with stroke epidemiologists from GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study) began providing proposed clinical trials with formal trial feasibility assessments. Herein, we describe the process of prospective feasibility analyses using epidemiological data that can be used to improve enrollment and increase the likelihood a trial is completed. Methods: In 2014, DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trialists, National Institutes of Health StrokeNet, and stroke epidemiologists from GCNKSS collaborated to evaluate the initial inclusion/exclusion criteria for the DEFUSE 3 study. Trial criteria were discussed and an assessment was completed to evaluate the percent of the stroke population that might be eligible for the study. The DEFUSE 3 trial was stopped early with the publication of DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct), and the Wilcoxon rank-sum statistic was used to analyze whether the trial would have been stopped had the proposed changes not been made, following the DEFUSE 3 statistical analysis plan. Results: After initial epidemiological analysis, 2.4% of patients with acute stroke in the GCNKSS population would have been predicted to be eligible for the study. After discussion with primary investigators and modifying 4 key exclusion criteria (upper limit of age increased to 90 years, baseline modified Rankin Scale broadened to 0–2, time since last well expanded to 16 hours, and decreased lower limit of National Institutes of Health Stroke Scale score to Conclusions: Objectively assessing trial inclusion/exclusion criteria using a population-based resource in a collaborative and iterative process including epidemiologists can lead to improved recruitment and can increase the likelihood of successful trial completion.

Background and ObjectivesPerfusion imaging can identify adult patients with salvageable brain tissue who would benefit from thrombectomy in later time windows. The feasibility of obtaining hyperacute perfusion sequences in pediatric stroke is unknown. The aim of this study was to determine whether contrast perfusion imaging delayed time to treatment and to assess perfusion profiles in children with large vessel occlusion stroke.MethodsThe Save ChildS retrospective cohort study (January 2000–December 2018) enrolled children (1 month–18 years) with stroke who underwent thrombectomy from 27 European and U.S. stroke centers. This secondary analysis included patients with anterior circulation occlusion and available imaging for direct review by the neuroimaging core laboratory. Between-group comparisons were performed using the Wilcoxon rank-sum exact test for continuous variables or Fisher exact test for binary variables. Given the small number of patients, evaluation of perfusion imaging parameters was performed descriptively only.ResultsOf 33 patients with available neuroimaging, 15 (45.4%) underwent perfusion (CT perfusion n = 6; MR perfusion n = 9); all were technically adequate. The median time from onset to recanalization did not differ between groups {4 hours (interquartile range [IQR] 4–7.5) perfusion+; 3.4 hours (IQR 2.5–6.5) perfusion-,p= 0.158}. Target mismatch criteria were met by 10/15 (66.7%) patients and did not correlate with reperfusion status or functional outcome. The hypoperfusion intensity ratio (HIR) was favorable in 11/15 patients and correlated with older age but not NIHSS, time to recanalization, or stroke etiology. Favorable HIR was associated with better functional outcome at 6 months (Pediatric Stroke Outcome Measure 1.0 [IQR 0.5–2.0] vs 2.0 [1.5–3.0],p= 0.026) and modified Rankin Scale 1.0 [0–1] vs 2.0 [1.5–3.5],p= 0.048) in this small sample.DiscussionAutomated perfusion imaging is feasible to obtain acutely in children and does not delay time to recanalization. Larger prospective studies are needed to determine biomarkers of favorable outcome in pediatric ischemic stroke and to establish core and penumbral thresholds in children.

Background: Intravenous tPA (tissue-type plasminogen activator) is often administered before endovascular thrombectomy (EVT). Recent studies have questioned whether tPA is necessary given the high rates of arterial recanalization achieved by EVT, but whether tPA impacts venous outflow (VO) is unknown. We investigated whether tPA improves VO profiles on baseline computed tomography (CT) angiography (CTA) images before EVT. Methods: Retrospective multicenter cohort study of patients with acute ischemic stroke due to large vessel occlusion undergoing EVT triage. Included patients underwent CT, CTA, and CT perfusion before EVT. VO profiles were determined by opacification of the vein of Labbé, sphenoparietal sinus, and superficial middle cerebral vein on CTA as 0, not visible; 1, moderate opacification; and 2, full. Pial arterial collaterals were graded on CTA, and tissue-level collaterals were assessed on CT perfusion using the hypoperfusion intensity ratio. Clinical and demographic data were determined from the electronic medical record. Using multivariable regression analysis, we determined the correlation between tPA administration and favorable VO profiles. Results: Seven hundred seventeen patients met inclusion criteria. Three hundred sixty-five patients received tPA (tPA+), while 352 patients were not treated with tPA (tPA−). Fewer tPA+ patients had atrial fibrillation (n=128 [35%] versus n=156 [44%]; P =0.012) and anticoagulants/antiplatelet treatment before acute ischemic stroke due to large vessel occlusion onset (n=130 [36%] versus n=178 [52%]; P P P Conclusions: In patients with acute ischemic stroke due to large vessel occlusion undergoing thrombectomy triage, tPA administration was strongly associated with the presence of favorable VO profiles.

Background and purposeEarly neurological improvement (ENI) after thrombectomy is associated with better long-term outcomes in patients with acute ischaemic stroke due to large vessel occlusion (AIS-LVO). Whether cerebral collaterals influence the likelihood of ENI is poorly described. We hypothesised that favourable collateral perfusion at the arterial, tissue-level and venous outflow (VO) levels is associated with ENI after thrombectomy.Materials and methodsMulticentre retrospective study of patients with AIS-LVO treated by thrombectomy. Tissue-level collaterals (TLC) were measured on cerebral perfusion studies by the hypoperfusion intensity ratio. VO and pial arterial collaterals (PAC) were determined by the Cortical Vein Opacification Score and the modified Tan scale on CT angiography, respectively. ENI was defined as improvement of ≥8 points or a National Institutes of Health Stroke Scale score of 0 hour or 1 24 hours after treatment. Multivariable regression analyses were used to determine the association of collateral biomarkers with ENI and good functional outcomes (modified Rankin Scale 0–2).Results646 patients met inclusion criteria. Favourable PAC (OR: 1.9, CI 1.2 to 3.1; p=0.01), favourable VO (OR: 3.3, CI 2.1 to 5.1; pConclusionFavourable PAC and VO were associated with ENI after thrombectomy. Favourable TLC predicted longer term functional recovery after thrombectomy, but the impact of TLC on ENI is strongly dependent on vessel reperfusion.

Background: In acute ischemic stroke (AIS) with large vessel occlusion (LVO), core/perfusion mismatch modifies the effect of mechanical thrombectomy (MT) on clinical outcome, MT appears to have greater benefit in patients with significant mismatch. We aimed to study the prevalence of core/perfusion mismatch according to ASPECT score in a large population of LVO-related AIS imaged either with MRI or CT. Methods: Retrospective study including AIS patients with ICA/M1 occlusion and baseline perfusion imaging (MRI or CT) performed within 24hrs from last seen well. To avoid selection bias, patients were selected from (1) the registries of 3 comprehensive centers with systematic use of MRI- or CT-perfusion imaging and including both MT-treated and untreated patients, and (2) one thrombectomy trial where MT decisions were performed blinded to the results of MRI perfusion imaging. Core/perfusion mismatch was defined as mismatch ratio (Tmax>6s volume/ core volume) >1.8 and volume (Tmax>6s - core volume) >15 mL. ASPECT score was rated on diffusion weighted imaging (DWI) or non-contrast CT blinded from the perfusion imaging. Results: Overall, 580 and 350 patients were included in the MRI and CT cohorts. Last-seen-well to imaging time was 4.8hrs (IQR 3.0-8.7) and 3.2hrs (1.3-8.0) in the MRI and CT cohorts, respectively, median ASPECT score was 7 (5-8) and 8 (7-9), and core/perfusion mismatch was present in 393/580 (68%) and 315/350 (90%) patients. In both cohorts, 75% of patients were treated with MT following imaging. In the MRI cohort, mismatch prevalence was 44% (75/170) and 92% (378/410) for DWI-ASPECTS 0-5 and 6-10, respectively. In the CT cohort, mismatch prevalence was 47% (15/32) and 94% (300/318) for ASPECTS 0-5 and 6-10, respectively. Conclusion: About 90% of patients with ASPECTS 6-10 have a core/perfusion mismatch regardless of imaging type. However, patients with ASPECTS ≤5 are heterogeneous in terms of mismatch status. Therefore, perfusion imaging may be particularly useful to select appropriate MT candidates with low ASPECT scores, regardless of imaging type, which has implications for large core trials.

Background: The benefit of mechanical thrombectomy (MT) in acute ischemic stroke (AIS) patients with M2 occlusion is uncertain. Observational studies suggest that perfusion imaging may help select optimal M2 candidates for MT. We aimed to study the prevalence and factors associated with core/perfusion mismatch, as assessed by both CT and MRI, in an unselected population of AIS with M2 occlusion. Methods: Retrospective observational study including AIS patients with M2 occlusion and baseline perfusion imaging (MRI or CT) performed within 24hrs from last seen well. To avoid selection bias, patients were selected from the prospective registries of 3 centers with systematic use of perfusion imaging, including both MT-treated and untreated patients. Core/perfusion mismatch was defined as mismatch ratio (Tmax>6s/ core volume) >1.8 and mismatch volume (Tmax>6s - core volume) >15mL. Results: Overall, 156 and 196 patients were included in the MRI and CT cohorts, respectively. Last-seen-well to imaging time was 5.6hrs (IQR 3.9-9.7) and 3.5hrs (1.5-9.8) in the MRI and CT cohorts, and 103/156 (66%) and 134/196 (68%) had proximal M2 occlusions (the remainder had distal M2 occlusions). Median ASPECT score was 7 (5-8) and 8 (7-9), and core/perfusion mismatch was present in 70/156 (45%) and 167/196 (85%) patients. In both cohorts, mismatch was less frequent in distal M2 occlusions and among patients with lower ASPECTS (Figure). Multivariable analysis showed higher ASPECT scores (OR=3.09, 95%CI=2.11-4.52, P P P =0.002 and OR=32.78, 95%CI 8.36-128.47, P Conclusion: Perfusion imaging may be useful in triaging M2 patients, particularly for those with ASPECT score

Introduction: Reduced left ventricular ejection fraction (EF) is associated with worse outcomes after stroke. CT perfusion (CTP) is widely used in acute stroke evaluation; its reliability in patients with reduced EF is unknown. We hypothesized that patients with reduced EF would have abnormal dose-time curves that may impair standard perfusion maps and reduce their quality. Methods: A retrospective database of all patients presenting to Stanford University for large vessel occlusion (LVO) stroke between 2010-2019 was used. CTPs were post-processed using RAPID software. Concentration-time curve metrics—width of the venous output function (VOF) at half maximum amplitude and VOF peak amplitude—were assessed automatically for each case. A reader blinded to EF visually evaluated the VOF curve for evidence of truncation (yes/no) and graded the quality of the time to maximum (Tmax) map on a scale from 0 (excellent) to 3 (poor), based on the degree of “speckling” present on the map. Continuous parameters were compared using the t-test or Mann-Whitney test and dichotomous parameters with the Fisher’s exact or Chi-square test, where appropriate. Results: 160 patients with sufficient quality baseline CTP and in-hospital echocardiogram were evaluated; 34 had EF Conclusion: Patients with reduced EF have dispersion of the contrast bolus as evidenced by a VOF curve that is wider and has a lower peak. Consequently, the quality of the Tmax map in patients with low EF is reduced, which may render automated CTP results unreliable. Additional studies are needed to determine to what extent poor CTP image quality in patients with low EF affects treatment decisions.

Background A target mismatch profile can identify good clinical response to recanalization after acute ischemic stroke, but does not consider region specificities. Purpose To test whether location-weighted infarction core and mismatch, determined from diffusion and perfusion MRI performed in patients with acute stroke, could improve prediction of good clinical response to mechanical thrombectomy compared with a target mismatch profile. Materials and Methods In this secondary analysis, two prospectively collected independent stroke data sets (2012-2015 and 2017-2019) were analyzed. From the brain before stroke (BBS) study data (data set 1), an eloquent map was computed through voxel-wise associations between the infarction core (based on diffusion MRI on days 1-3 following stroke) and National Institutes of Health Stroke Scale (NIHSS) score. The French acute multimodal imaging to select patients for mechanical thrombectomy (FRAME) data (data set 2) consisted of large vessel occlusion-related acute ischemic stroke successfully recanalized. From acute MRI studies (performed on arrival, prior to thrombectomy) in data set 2, target mismatch and eloquent (vs noneloquent) infarction core and mismatch were computed from the intersection of diffusion- and perfusion-detected lesions with the coregistered eloquent map. Associations of these imaging metrics with early neurologic improvement were tested in multivariable regression models, and areas under the receiver operating characteristic curve (AUCs) were compared. Results Data sets 1 and 2 included 321 (median age, 69 years [IQR, 58-80 years]; 207 men) and 173 (median age, 74 years [IQR, 65-82 years]; 90 women) patients, respectively. Eloquent mismatch was positively and independently associated with good clinical response (odds ratio [OR], 1.14; 95% CI: 1.02, 1.27

Background: Predicting infarct growth rate (IGR) in acute stroke with large vessel occlusion (LVO) is important for treatment decision-making. IGR has typically been studied in patients treated with thrombectomy, which likely has underestimated the prevalence of ‘fast progressors’, as large core patients are less frequently treated. We aimed to study IGR in an unselected LVO population and study the association between Hypoperfusion Intensity Ratio (HIR, a surrogate marker of collaterals) and IGR as assessed by both CT and MRI. Methods: Retrospective study including ICA/M1 stroke patients with witnessed stroke onset and baseline perfusion imaging (MRI or CT) performed within 24hrs from symptoms onset. To avoid selection bias, patients were selected from (1) the registries of 3 centers with systematic use of MRI- or CT-perfusion and including both MT-treated and untreated patients, and (2) one trial where thrombectomy decisions were performed blinded from perfusion MRI results. IGR was defined as core volume/onset-to-imaging time, and fast progressors as IGR≥10mL/hr. HIR was defined as the proportion of Tmax>6s volume with Tmax>10s. Results: Overall, 423 and 215 patients were included in the MRI and CT cohorts. Median IGR was 6.4mL/hr (IQR 2.2-21.3) and 5.2mL/hr (0-25.2) in the MRI and CT cohorts, and median HIR was 0.44 (0.27-0.59) and 0.45 (0.25-0.60). 174 (41%) MRI patients and 86 (40%) CT patients were fast progressors. IGR was increasing with increase of HIR quartiles in both cohorts ( P P P Conclusion: In this unselected LVO population, 40% of patients were fast progressors regardless of imaging modality. HIR was a strong predictor of IGR in both CT and MRI-assessed patients, and may help for patient triage, e.g . for transfer decision from an outside hospital for thrombectomy.

Predictions of functional outcome in neurocritical care (NCC) patients impact care decisions. This study compared the predictive values (PVs) of good and poor functional outcome among health care providers with and without NCC training.Consecutive patients who were intubated for ≥ 72 h with primary neurological illness or neurological complications were prospectively enrolled and followed for 6-month functional outcome. Medical intensive care unit (MICU) attendings, NCC attendings, residents (RES), and nurses (RN) predicted 6-month functional outcome on the modified Rankin scale (mRS). The primary objective was to compare these four groups' PVs of a good (mRS score 0-3) and a poor (mRS score 4-6) outcome prediction.Two hundred eighty-nine patients were enrolled. One hundred seventy-six had mRS scores predicted by a provider from each group and were included in the primary outcome analysis. At 6 months, 54 (31%) patients had good outcome and 122 (69%) had poor outcome. Compared with other providers, NCC attendings expected better outcomes (p 0.001). Consequently, the PV of a poor outcome prediction by NCC attendings was higher (96% [95% confidence interval [CI] 89-99%]) than that by MICU attendings (88% [95% CI 80-93%]), RES (82% [95% CI 74-88%]), and RN (85% [95% CI 77-91%]) (p = 0.047, 0.002, and 0.012, respectively). When patients who had withdrawal of life-sustaining therapy (n = 67) were excluded, NCC attendings remained better at predicting poor outcome (NCC 90% [95% CI 75-97%] vs. MICU 73% [95% CI 59-84%], p = 0.064). The PV of a good outcome prediction was similar among groups (MICU 65% [95% CI 52-76%], NCC 63% [95% CI 51-73%], RES 71% [95% CI 55-84%], and RN 64% [95% CI 50-76%]).Neurointensivists expected better outcomes than other providers and were better at predicting poor functional outcomes. The PV of a good outcome prediction was modest among all providers.

Background: In patients with acute ischemic stroke due to large vessel occlusion (AIS–LVO), development of extensive early ischemic brain edema is associated with poor functional outcomes, despite timely treatment. Robust cortical venous outflow (VO) profiles correlate with favorable tissue perfusion. We hypothesized that favorable VO profiles (VO+) correlate with a reduced early edema progression rate (EPR) and good functional outcomes. Methods: Multicenter, retrospective analysis to investigate AIS–LVO patients treated by mechanical thrombectomy between May 2013 and December 2020. Baseline computed tomography angiography (CTA) was used to determine VO using the cortical vein opacification score (COVES); VO+ was defined as COVES ⩾ 3 and unfavorable as COVES ⩽ 2. EPR was determined as the ratio of net water uptake (NWU) on baseline non-contrast CT and time from symptom onset to admission imaging. Multivariable regression analysis was performed to assess primary (EPR) and secondary outcome (good functional outcomes defined as 0–2 points on the modified Rankin scale). Results: A total of 728 patients were included. Primary outcome analysis showed VO+ (β: –0.03, SE: 0.009, p = 0.002), lower presentation National Institutes of Health Stroke Scale (NIHSS; β: 0.002, SE: 0.001, p = 0.002), and decreased time from onset to admission imaging (β: –0.00002, SE: 0.00004, p Conclusions: Favorable VO profiles were associated with slower infarct edema progression and good long-term functional outcomes as well as better neurological status and ischemic brain alterations at admission.

OBJECTIVE Perfusion imaging identifies anterior circulation stroke patients who respond favorably to endovascular thrombectomy (ET), but its role in basilar artery occlusion (BAO) is unknown. We hypothesized that BAO patients with limited regions of severe hypoperfusion (time to reach maximum concentration in seconds [Tmax] > 10) would have a favorable response to ET compared to patients with more extensive regions involved. METHODS We performed a multicenter retrospective cohort study of BAO patients with perfusion imaging prior to ET. We prespecified a Critical Area Perfusion Score (CAPS; 0-6 points), which quantified severe hypoperfusion (Tmax > 10) in cerebellum (1 point/hemisphere), pons (2 points), and midbrain and/or thalamus (2 points). Patients were dichotomized into favorable (CAPS ≤ 3) and unfavorable (CAPS > 3) groups. The primary outcome was a favorable functional outcome 90 days after ET (modified Rankin Scale = 0-3). RESULTS One hundred three patients were included. CAPS ≤ 3 patients (87%) had a lower median National Institutes of Health Stroke Scale score (NIHSS; 12.5, interquartile range [IQR] = 7-22) compared to CAPS > 3 patients (13%; 23, IQR = 19-36; p = 0.01). Reperfusion was achieved in 84% of all patients, with no difference between CAPS groups (p = 0.42). Sixty-four percent of reperfused CAPS ≤ 3 patients had a favorable outcome compared to 8% of nonreperfused CAPS ≤ 3 patients (odds ratio [OR] = 21.0, 95% confidence interval [CI] = 2.6-170; p 3 patients had a favorable outcome, regardless of reperfusion. In a multivariate regression analysis, CAPS ≤ 3 was a robust independent predictor of favorable outcome after adjustment for reperfusion, age, and pre-ET NIHSS (OR = 39.25, 95% CI = 1.34->999, p = 0.04). INTERPRETATION BAO patients with limited regions of severe hypoperfusion had a favorable response to reperfusion following ET. However, patients with more extensive regions of hypoperfusion in critical brain regions did not benefit from endovascular reperfusion. ANN NEUROL 2021.

Aim Previous studies evaluating the relationship between sex and post-resuscitation care and outcomes following out-of-hospital cardiac arrest (OHCA) are conflicting. We investigated the association between sex and outcomes as well as neurodiagnostic testing in a prospective multicenter international registry of patients admitted to intensive care units following OHCA. Methods OHCA survivors enrolled in the International Cardiac Arrest Registry (INTCAR) from 2012 to 2017 were included. We assessed the independent association between sex and survival to hospital discharge, good neurologic outcome (Cerebral Performance Category 1 or 2), neurodiagnostic testing, and withdrawal of life-sustaining therapy (WLST). Results Of 2407 eligible patients, 809 (33.6%) were women. Baseline characteristics differed by sex, with less bystander CPR and initial shockable rhythms among women. Women were less likely to survive to hospital discharge, however significance abated following adjusted analysis (30.1% vs 42.7%, adjusted OR 0.85, 95% CI 0.67–1.08). Women were less likely to have good neurologic outcome at discharge (21.4% vs 34.0%, adjusted OR 0.74, 95% CI 0.57–0.96) and at six months post-arrest (16.7% vs 29.4%, adjusted OR 0.73, 95% CI 0.54–0.98) that persisted after adjustment. Neuroimaging (75.5% vs 74.3%, p = 0.54) and other neurophysiologic testing (78.8% vs 78.6%, p = 0.91) was similar across sex. Women were more likely to undergo WLST (55.6% vs 42.8%, adjusted OR 1.35, 95% CI 1.09–1.66). Conclusions Women with cardiac arrest have lower odds of good neurologic outcomes and higher odds of WLST, despite comparable rates of neurodiagnostic testing and after controlling for baseline differences in clinical characteristics and cardiac arrest features.

BACKGROUND AND PURPOSE Arterial clot localization affects collateral flow to ischemic brain in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). We determined the association between vessel occlusion locations, tissue-level collaterals (TLC), and venous outflow (VO) profiles and their impact on good functional outcomes. METHODS We conducted a multicenter retrospective cohort study of consecutive AIS-LVO patients who underwent thrombectomy triage. Baseline computed tomographic angiography (CTA) was used to localize vessel occlusion, which was dichotomized into proximal vessel occlusion (PVO; internal carotid artery and proximal first segment of the middle cerebral artery [M1]) and distal vessel occlusion (DVO; distal M1 and M2), and to assess collateral scores. TLC were assessed on computed tomographic perfusion data using the hypoperfusion intensity ratio. VO was determined on baseline CTA by the cortical vein opacification score. Primary outcomes were favorable VO and TLC; secondary outcome was the modified Rankin Scale after 90 days. RESULTS A total of 649 patients met inclusion criteria. Of these, 376 patients (58%) had a PVO and 273 patients (42%) had a DVO. Multivariate ordinal logistic regression showed that DVO predicted favorable TLC (odds ratio [OR] = 1.77, 95% confidence interval [CI] = 1.24-2.52, p = 0.002) and favorable VO (OR = 7.2, 95% CI = 5.2-11.9, p < 0.001). DVO (OR = 3.4, 95% CI = 2.1-5.6, p < 0.001), favorable VO (OR = 6.4, 95% CI = 3.8-10.6, p < 0.001), and favorable TLC (OR = 3.2, 95% CI = 2-5.3, p < 0.001), but not CTA collaterals (OR = 1.07, 95% CI = 0.60-1.91, p = 0.813), were predictors of good functional outcome. CONCLUSIONS DVO in AIS-LVO patients correlates with favorable TLC and VO profiles, which are associated with good functional outcome.

Background Ischemic lesion net water uptake (NWU) at noncontrast head CT enables quantification of cerebral edema in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Purpose To assess whether favorable venous outflow (VO) profiles at CT angiography are associated with reduced NWU and good functional outcomes in patients with AIS due to LVO. Materials and Methods This multicenter retrospective cohort study evaluated consecutive patients with AIS due to LVO who underwent thrombectomy triage between January 2013 and December 2019. Arterial collateral vessel status (Tan scale) and venous output were measured at CT angiography. Venous outflow was graded with use of the cortical vein opacification score, which quantifies opacification of the vein of Labbé, sphenoparietal sinus, and superficial middle cerebral vein. Favorable VO was regarded as a score of 3-6 and unfavorable VO as a score of 0-2. NWU was determined at follow-up noncontrast CT. Multivariable regression analyses were performed to determine the association between favorable VO profiles and NWU after treatment and good functional outcome (modified Rankin Scale, ≤2). Results A total of 580 patients were included. Of the 580 patients, 231 had favorable VO (104 women; median age, 73 years [interquartile range {IQR}, 62-81 years]) and 349 had unfavorable VO (190 women; median age, 77 years [IQR, 66-84 years]). Compared with patients with unfavorable VO, those with favorable VO exhibited lower baseline National Institutes of Health Stroke Scale score (median, 12.5 [IQR, 7-17] vs 17 [IQR, 13-21]), higher Alberta Stroke Program Early CT Score (median, 9 [IQR, 7-10] vs 7 [IQR, 6-8]), and less NWU after treatment (median, 7% [IQR, 4.6%-11.5%] vs 17.9% [IQR, 12.3%-22.2%]). In a multivariable regression analysis, NWU mean difference between patients with unfavorable VO and those with favorable VO was 6.1% (95% CI: 4.9, 7.3

Baseline variables could be used to guide the administration of additional intravenous alteplase (IVT) before mechanical thrombectomy (MT). The aim of this study was to determine how baseline imaging and demographic parameters modify the effect of IVT on clinical outcomes in patients with ischemic stroke due to large vessel occlusion.Multicenter retrospective cohort study of ischemic stroke patients triaged by multimodal-CT undergoing MT treatment after direct admission to an MT-eligible center. Inverse-probability weighting analysis (IPW) was used to assess the treatment effect of IVT adjusted for baseline variables. Multivariable logistic regression analysis with IPW-weighting and interaction terms for IVT was performed to predict functional independence (mRS 0-2 at 90-days).720 patients were included, of which 366 (51%) received IVT. In IPW, the treatment effect of IVT on outcome (mRS 0-2) distinctively varied according to the ASPECTS subgroup (ASPECTS 9-10: +15%, ASPECTS 6-8: +7%, ASPECTS6: -11%). In multivariable logistic regression analysis, IVT was independently associated with functional independence (aOR: 1.57, 95% CI: 1.16-2.14, p = 0.003) and the interaction term was significant for ASPECTS and IVT revealing that IVT was only significantly associated with better outcomes in patients with higher ASPECTS. No other significant baseline variable interaction terms were identified.ASPECTS was the only baseline variable that showed a significant interaction with IVT for outcome prediction. Use of IVT prior to MT in patients with an ASPECTS of6 was not associated with a treatment benefit and should be considered carefully. ANN NEUROL 2022;92:588-595.

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 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.

Background and Purpose: The DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) randomized clinical trial demonstrated the efficacy of endovascular therapy in treating ischemic stroke 6 to 16 hours after onset, resulting in better functional outcomes than standard medical therapy alone. The objective of this secondary analysis is to analyze the effect of late-window endovascular treatment of ischemic stroke on quality of life (QoL) outcomes. Methods: Patients (n=182) who presented between 6 and 16 hours after they were last known to be well with acute anterior circulation ischemic stroke were randomized to endovascular thrombectomy plus standard medical therapy or standard medical therapy alone and followed-up through 90 days poststroke. QoL at day 90 was assessed with the QoL in Neurological Disorders measurement tool. Results: Of the 146 subjects alive at day 90, 136 (95%) filled out QoL in Neurological Disorders short forms. Patients treated with endovascular therapy had better QoL scores in each domain: mobility, social participation, cognitive function, and depression ( P 2 =0.82), a moderate proportion in social participation (Rs 2 =0.62), and a low proportion in cognition (Rs 2 =0.31) and depression (Rs 2 =0.19). Conclusions: Patients treated with endovascular therapy 6 to 16 hours after stroke have better QoL than patients treated with medical therapy alone, including better mobility, more social participation, superior cognition, and less depression. The modified Rankin Scale fails to capture patients’ outcomes in cognition and depression, which should therefore be assessed with dedicated QoL tools. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02586415.

Background and Purpose: Contrast-enhanced noninvasive angiography and perfusion imaging are recommended to identify eligible patients for endovascular therapy (EVT) in extended time windows (>6 hours or wake-up). If eligible, additional intraarterial contrast exposure will occur during EVT. We aimed to study the renal safety in the DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) population, selected with contrast-enhanced multimodal Imaging and randomized to EVT versus medical management. Methods: In the randomized DEFUSE 3 trial population, we compared changes in serum creatinine between baseline (before randomization) and 24 hours later. The primary outcome was the relative change in creatinine level between baseline and 24 hours in the EVT versus medical arm. The secondary outcome was a comparison between computed tomography (CT) versus magnetic resonance imaging selection in the EVT arm. The safety outcome was a comparison of the proportion of patients with criteria for contrast-associated kidney injury in the EVT versus medical arm and a comparison between CT versus magnetic resonance imaging selection in the EVT arm. Results: In the DEFUSE 3 population (n=182, age 69±13, 51% female), mean creatinine decreased from a baseline of 0.98±0.33 mg/dL to 0.88±0.28 mg/dL at 24 hours ( P P =0.294. Absolute decrease −0.08±0.18 in EVT versus −0.12±0.18 in medical, P =0.135; Among patients treated with EVT, there was no difference in 24-hour creatinine level changes between patients who were selected with CT angiography/CT perfusion (−0.08±0.18) versus magnetic resonance imaging (−0.07±0.19), P =0.808 or 6.8% reduction versus 4.8%, P =0.696. In the EVT arm, contrast-associated kidney injury was encountered in 4 out of 91 (4.4%) versus 2/90 (2.2%) in the medical arm P =0.682. In the EVT arm, contrast-associated kidney injury was evenly distributed between magnetic resonance imaging (1/22, 4.6%) versus CT 3 out of 69 (4.4%), P =1.0. Conclusions: Perfusion imaging before EVT was not associated with evidence of decline in renal function. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

Background and Purpose: Mechanical thrombectomy (MT) is the recommended treatment for acute ischemic stroke caused by anterior circulation large vessel occlusion. However, despite a high rate of reperfusion, the clinical response to successful MT remains highly variable in the early time window where optimal imaging selection criteria have not been established. We hypothesize that the baseline perfusion imaging profile may help forecast the clinical response to MT in this setting. Methods: We conducted a prospective multicenter cohort study of patients with large vessel occlusion–related acute ischemic stroke treated by MT within 6 hours. Treatment decisions and the modified Rankin Scale evaluation at 3 months were performed blinded to the results of baseline perfusion imaging. Study groups were defined a posteriori based on predefined imaging profiles: target mismatch (TMM; core volume 1.2 and mismatch volume >10 mL) versus no TMM or mismatch (MM; mismatch ratio >1.2 and volume >10 mL) versus no MM. Functional recovery (modified Rankin Scale, 0–2) at 3 months was compared based on imaging profile at baseline and whether reperfusion (modified Thrombolysis in Cerebral Infarction 2bc3) was achieved. Results: Two hundred eighteen patients (mean age, 71±15 years; median National Institutes of Health Stroke Scale score, 17 [interquartile range, 12–21]) were enrolled. Perfusion imaging profiles were 71% TMM and 82% MM. The rate of functional recovery was 54% overall. Both TMM and MM profiles were independently associated with a higher rate on functional recovery at 3 months Adjusted odds ratios were 3.3 (95% CI, 1.4–7.9) for TMM and 5.9 (95% CI, 1.8–19.6) for MM. Reperfusion (modified Thrombolysis in Cerebral Infarction 2bc3) was achieved in 86% and was more frequent in TMM and MM patients. Reperfusion was associated with a higher rate of functional recovery in MM and TMM patients but not among those with no MM. Conclusions: In this cohort study, about 80% of the patients with a large vessel occlusion–related acute ischemic stroke had evidence of penumbra, regardless of infarction volume. Perfusion imaging profiles predict the clinical response to MT.

Malignant cerebral edema (MCE) is a well-known complication in patients with acute ischemic stroke with core infarcts ≥ 80 mL caused by large-vessel occlusions. MCE can also develop in patients with smaller infarcts with moderate -to-large volume of tissue at risk who do not achieve successful revascularization with endovascular thrombectomy (ET). Features that predict the development of MCE in this population are not well-described. We aim to identify predictors of MCE and 90-day functional outcome in stroke patients with an anterior circulation large vessel occlusion (LVO) and a 6 s volume ≥ 80 mL, and a mismatch ratio ≥ 1.8. MCE was defined as ≥ 5 mm of midline shift on follow-up imaging, obtained 6–48 h after the pre-ET perfusion scan. Thirty-six patients met inclusion criteria. Unadjusted analysis demonstrated that younger age, higher systolic blood pressure, larger core volume, and higher hypoperfusion intensity ratio (HIR) were associated with MCE (all p

Background and purpose Intracranial pressure (ICP) monitoring is recommended in severe traumatic brain injury (sTBI), yet invasive monitoring has risks, and many patients do not develop elevated ICP. Tools to identify patients at risk for ICP elevation are limited. We aimed to identify early radiologic biomarkers of ICP elevation. Methods In this retrospective study, we analyzed a prospectively enrolled cohort of patients with a sTBI at an academic level 1 trauma center. Inclusion criteria were nonpenetrating TBI, age ≥16 years, Glasgow Coma Scale (GCS) score ≤8, and presence of an ICP monitor. Two independent reviewers manually evaluated 30 prespecified features on serial head computed tomography (CTs). Patient characteristics and radiologic features were correlated with elevated ICP. The primary outcome was clinically relevant ICP elevation, defined as ICP ≥ 20 mm Hg on at least 5 or more hourly recordings during postinjury days 0-7 with concurrent administration of an ICP-lowering treatment. Results Among 111 sTBI patients, the median GCS was 6 (interquartile range 3-8), and 45% had elevated ICP. Features associated with elevated ICP were younger age (every 10-year decrease, odds ratio [OR] 1.4), modified Fisher scale (mFS) score at 0-4 hours postinjury (every 1 point, OR 1.8), and combined volume of contusional hemorrhage and peri-hematoma edema (10 ml, OR 1.2) at 4-18 hours postinjury. Conclusions Younger age, mFS score, and volume of contusion are associated with ICP elevation in patients with a sTBI. Imaging features may stratify patients by their risk of subsequent ICP elevation.

Introduction: Depression is common after stroke, and is a debilitating factor undermining recovery in approximately one third of stroke survivors. It is essential to understand the underlying mechanisms to develop better treatments. Such insight may come from identifying plasma proteins correlated with post-stroke depression. Previous work investigated inflammatory proteins. Methods: We recruited 85 subjects 5 months to 9 years after ischemic stroke, age >40, and able to perform cognitive testing. Mood was assessed with the Stroke Impact Scale (SIS3), transformed to a 100-point scale. Plasma was analyzed by O-link proteomics for 1011 proteins. Multivariable regression models were constructed to estimate SIS3 using proteomics and clinical data. Models were subject to bootstrapping for robustness, and cross-validation to ensure results were reported on subjects blinded during model training. Pearson correlation analysis identified linear associations between individual proteins and SIS3 scores. We also report differences in key proteins in subjects dichotomized into non-depressed (SIS3>63) or depressed (SIS3≤63) groups. Results: Proteomics results alone predicted SIS3 in multivariable models, and the best model also used age and time since stroke. A total of 180 proteins correlated significantly with SIS3. Plasma levels of IL-6 (p=0.0325), EGF (p Conclusions: We report that machine learning models can predict post-stroke mood from comprehensive plasma proteomics, and that age and time since stroke improves those models. Our findings also support other reports of elevated IL-6 in subjects with depression. We also identified proteins of interest including HPGDS (produces Prostaglandin D), EGF, or TRIM5 (upstream of NFkB) in post-stroke depression. Future studies are needed to replicate these findings, and studies in preclinical models may help uncover mechanistic relationships that could lead to new therapies.

Introduction: Cognitive impairment is common following stroke and is associated with poor functional outcomes. We examined how cognitive domain and depression scores predict long-term functional disability following stroke. Methods: Data were analyzed from 70 participants with chronic ischemic stroke as part of the StrokeCog study. The battery yielded a global composite score and composite scores of memory, processing speed, working memory, language, and spatial ability. The Stroke Impact Scale was used to assess depression (SIS-Depression) and 3 functional disability measures: subjective memory and thinking (SIS-Cognition), activities of daily living (SIS-ADL), and participation in work, social, and leisure activities (SIS-Participation). A correlation network was constructed using a t-SNE algorithm to examine relationships amongst variables. Partial least squares analyses (PLS) were used to determine whether cognitive domains and depression predicted functional disability, with depression, cognitive composites, age, stroke severity (NIHSS), and fatigue (FACIT) as predictor variables. Results: Both the t-SNE plot and PLS indicated that functional disability is more closely related to depression than to cognitive composite scores. PLS analyses demonstrated that depression was the most significant predictor of SIS-Cognition, SIS-Participation, and SIS-ADL, accounting for 37%, 60%, and 47% of the variances, respectively. Processing speed accounted for an additional 11% of variance in SIS-Cognition. Spatial ability accounted for an additional 12% of variance in SIS-Participation and an additional 12% of variance in SIS-ADL. There were no other significant predictors. Conclusions: Depression was significantly associated with all 3 of the long-term functional outcomes we examined. Neuropsychological performance (namely processing speed and spatial ability) was also associated with functional disability, but to a lesser degree than depression, even for self-reported cognition. These findings are of interest given that depression is a common but treatable sequela of stroke.

Introduction: Acute ischemic stroke due to basilar artery occlusion (AIS-BAO) results in significant morbidity and mortality. Endovascular thrombectomy (ET) has not been shown to improve outcomes in AIS-BAO patients in randomized trials, which may be due to insufficient selection before ET. We determined whether the Critical Area Perfusion Score (CAPS) and posterior circulation ASPECTS (PC-ASPECTS) predict a favorable response to ET. Methods: We performed a multicenter retrospective study of AIS-BAO patients with perfusion imaging prior to ET. PC-ASPECTS was determined on NCCT by evaluating the cerebellum (1 point/hemisphere), pons (2 points), midbrain (2 points), thalamus (1 point/hemisphere), and posterior cerebral artery (1 point/hemisphere) territories, and points were subtracted for hypodensity in these regions. CAPS was quantified severe hypoperfusion (Tmax >10s) in cerebellum (1 point/hemisphere), pons (2 points), midbrain and/or thalamus (2 points). The primary outcome was a favorable outcome 90-days after ET (modified Rankin Scale [mRS] 0-3). Results: 89 patients were included. CAPS (AUC=0.70 [95% CI: 0.59-0.80]; p=0.002) and PC-ASPECTS (AUC=0.63 [95% CI: 0.52-0.75]; p=0.034) both predicted favorable outcomes in a receiver operating curve analysis, but there was no difference between the two (p=0.434). After dichotomization, patients with favorable CAPS (≤3) and PC-ASPECTS (≥7) were more likely to achieve a good functional outcome after successful reperfusion after ET (Figure). However, an unfavorable CAPS (>3) was associated with poor outcomes despite successful thrombectomy in all patients, whereas 22% of patients with unfavorable PC-ASPECTS ( Conclusions: CAPS and PC-ASPECTS both identify AIS-BAO patients who are likely to have a favorable clinical response to ET. CAPS, but not PC-ASPECTS, appears to accurately identify a subgroup in whom ET may be futile.

Introduction: Infection after stroke is more common with large strokes and thus peripheral markers of inflammation are not well defined in stroke survivors with smaller strokes. We sought here to define the prevalence of infection, low grade fever (T≥38°C), and white blood cell count over 11x10 3 /mL (WBC>11) in the first week after stroke in subjects with smaller stroke sizes, and to ask how inflammation in the acute period affects cognitive outcomes in this population. Methods: We performed systematic chart review of hospitalization after ischemic stroke (up to 7 days) in 65 subjects enrolled in the StrokeCog study who returned for testing 5-13 months later (median stroke volume 6 mL, [IQR 0.5, 16.6]). We assessed infection (CDC consensus criteria), highest WBC, and presence of T≥38°C. Mann-Whitney U test and general linear models were used to assess whether WBC in the first week predicted outcomes at follow-up: MoCA, Stroke Impact Scale Depression (SIS3), a global cognitive score, and composite scores of memory, motor functioning, processing speed, language, and spatial ability. Models were adjusted when appropriate for age, sex, and stroke size or NIHSS at admission. Results: Infection and T≥38°C were each present in 8%, and WBC>11 in 18% of participants within 7 days of stroke. Since only high WBC was present in a substantial proportion of subjects, we compared outcomes in high (>11) vs. normal (≤11) WBC. Subjects with high WBC had larger strokes (13cc [6.6, 38.6] vs. 3.2[0.4, 10.6], p= 0.027) and worse admission NIHSS (10[4,13)] vs 2[1,5], p =0.003). In addition, WBC>11 in the first week was associated with worse mood and lower scores in memory, language, and global cognition months later. After adjustment, WBC remained significantly predictive of mood ( p =.039) and global cognition ( p =0.003); language remained significant if adjusted for stroke size ( p =0.010) but not NIHSS ( p =0.19). Conclusions: Infection and T≥38°C are uncommon during acute hospitalization of ischemic stroke survivors who can return to complete comprehensive testing batteries 5-13 months later. WBC>11 within the first week after stroke may be a marker of later inflammation and predicts more chronic depression and worse cognitive outcomes in this population.

Introduction: Stroke increases the risk of cognitive and motor impairment long after the subacute recovery period. Clinicians often rely on patients to self-report symptoms, though this may not always align with objective findings. The aim of this study was to determine the associations between self-report and objective methods of evaluation when examining cognitive and motor functioning in stroke survivors. Methods: Seventy ischemic stroke participants over age 45 completed the Hopkins Verbal Learning Test-Revised (HVLT) and the Finger Tapping Test (FTT) 5-13 months post-stroke as part of the StrokeCog study. Performance of at least one standard deviation below the normative mean was considered abnormal. Self-report ratings in memory and thinking, hand function, and depression were assessed with the Stroke Impact Scale (SIS) as well as fatigue (FACIT) and stroke severity (NIHSS). Logistic regression was used to assess associations with HVLT and FTT performance as dependent factors. Results: Thirty-nine percent of participants demonstrated abnormal memory performance on the HVLT. The normal and abnormal memory groups did not differ in self-reported memory (p = 0.242) or depression (p = 0.232). A trend towards less stroke severity among patients with normal (median (IQR) NIHSS 2 (1-8)) vs. impaired memory exists (NIHSS 6 (2-12.5); p = 0.08). Less fatigue (OR (95% CI) 1.05 [1.001-1.11]) and female sex (OR 3.80 [1.09-13.21]) were independently associated with normal memory. Fifty-two percent of participants demonstrated abnormal motor performance on the FTT. The normal and abnormal motor groups did not differ in self-reported hand function (p = 0.285). Male sex (OR 19.6 [3.8-100]) and lower depression (OR 1.12 [1.05 - 1.20]) were independently associated with normal motor function. Conclusion: Self-report did not align with objective assessments of memory and fine motor functioning in stroke survivors. Fatigue and male sex were associated with memory impairment while depression and female sex were associated with motor impairment. This highlights the role of fatigue and depression in long-term stroke outcomes and the importance of using both objective and subjective methods when evaluating cognitive and motor impairment.

Background: With the advent of extended window endovascular therapy (EVT) for acute ischemic stroke (AIS), interhospital transfer is increasingly frequent. However, not all patients who are transferred undergo EVT. To use resources judiciously, stroke centers need to identify which patients are most likely to benefit from EVT prior to transfer. Methods: We performed a retrospective study of AIS patients transferred for potential EVT at our neurovascular center between 2015 and 2018. We noted whether pre-acceptance imaging was available for visual review on LifeImage, RAPID perfusion software, or Telestroke PACS. The primary outcome was EVT on arrival. Results: 530 AIS patients were included. 270 underwent EVT (50.9%); 156 (29.4%) had pre-acceptance imaging reviewed; 275 (51.9%) received IVtPA. Of all patients who were transferred, performance of pre-transfer CTA was significantly associated with EVT (57% vs 40%, p Conclusions: Pre-acceptance visual review of imaging by accepting team, in particular via perfusion software, was significantly associated with likelihood of EVT in patients who did not receive IVtPA and/or who did not recanalize by time of arrival. Performance of CTA at outside hospital prior to transfer (regardless of imaging review) was associated with likelihood of EVT. Type of imaging performed and ability for accepting team to review imaging prior to transfer acceptance may help improve interhospital transfer resource utilization.

Background Stroke increases the risk of cognitive impairment even several years after the stroke event. The exact mechanisms of post-stroke cognitive decline are unclear, but the immunological response to stroke might play a role. The aims of the StrokeCog study are to examine the associations between immunological responses and long-term post-stroke cognitive trajectories in individuals with ischemic stroke. Methods StrokeCog is a single-center, prospective, observational, cohort study. Starting 6–12 months after stroke, comprehensive neuropsychological assessment, plasma and serum, and psychosocial variables will be collected at up to 4 annual visits. Single cell sequencing of peripheral blood monocytes and plasma proteomics will be conducted. The primary outcome will be the change in global and domain-specific neuropsychological performance across annual evaluations. To explain the differences in cognitive change amongst participants, we will examine the relationships between comprehensive immunological measures and these cognitive trajectories. It is anticipated that 210 participants will be enrolled during the first 3 years of this 4-year study. Accounting for attrition, an anticipated final sample size of 158 participants with an average of 3 annual study visits will be available at the completion of the study. Power analyses indicate that this sample size will provide 90% power to detect an average cognitive change of at least 0.23 standard deviations in either direction. Discussion StrokeCog will provide novel insight into the relationships between immune events and cognitive change late after stroke.

Background Thrombectomy for acute ischemic stroke treatment leads to improved outcomes, but many patients do not achieve a good outcome despite successful reperfusion. We determined predictors of poor outcome after successful thrombectomy (TICI 2b–3) with an emphasis on modifiable factors. Methods Patients from the randomized DEFUSE 3 trial who underwent thrombectomy with TICI 2b–3 revascularization were included. Primary outcome was a poor outcome at 90 days (modified Rankin Scale score 3–6). Results 70 patients were included. Poor outcome patients were older (73.5 vs 66.5 years; P=0.01), more likely to be female (68% vs 39%; P=0.02), had higher NIHSS scores (20 vs 13; P Conclusions In late time windows, both mild and severe reperfusion hemorrhage were associated with poor outcomes. Older age, higher NIHSS, and increased time from imaging to arterial puncture were also associated with poor outcomes despite successful revascularization. Trial registration https://clinicaltrials.gov/ct2/show/NCT02586415

This study sought to analyze blood pressure trends in children with Down syndrome at multiple centers. A multicenter, retrospective, cross-sectional study was performed. All patients were P P

Background and Purpose— Clinical deficits from ischemic stroke are more severe in women, but the pathophysiological basis of this sex difference is unknown. Sex differences in core and penumbral volumes and their relation to outcome were assessed in this substudy of the DEFUSE 3 clinical trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). Methods— DEFUSE 3 randomized patients to thrombectomy or medical management who presented 6 to 16 hours from last known well with proximal middle cerebral artery or internal carotid artery occlusion and had target core and perfusion mismatch volumes on computed tomography or magnetic resonance imaging. Using univariate and adjusted regression models, the effect of sex was assessed on prerandomization measures of core, perfusion, and mismatch volumes and hypoperfusion intensity ratio, and on core volume growth using 24-hour scans. Results— All patients were included in the analysis (n=182) with 90 men and 92 women. There was no sex difference in the site of baseline arterial occlusion. Adjusted by age, baseline National Institutes of Health Stroke Scale, baseline modified Rankin Scale score, time to randomization, and imaging modality, women had smaller core, hypoperfusion, and penumbral volumes than men. Median (interquartile range) volumes for core were 8.0 mL (1.9–18.4) in women versus 12.6 mL (2.7–29.6) in men, for T max >6 seconds 89.0 mL (63.8–131.7) versus 133.9 mL (87.0–175.4), and for mismatch 82.1mL (53.8–112.8) versus 108.2 (64.1–149.2). The hypoperfusion intensity ratio was lower in women, 0.31 (0.15–0.46) versus 0.39 (0.26–0.57), P =0.006, indicating better collateral circulation, which was consistent with the observed slower ischemic core growth than men within the medical group ( P =0.003). Conclusions— In the large vessel ischemic stroke cohort selected for DEFUSE 3, women had imaging evidence of better collateral circulation, smaller baseline core volumes, and slower ischemic core growth. These observations suggest sex differences in hemodynamic and temporal features of anterior circulation large artery occlusions. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

ObjectiveTo describe and assess the effectiveness of a neurology resident quality improvement curriculum focused on development of practical skills and project experience.MethodsWe designed and implemented a quality improvement curriculum composed of (1) a workshop series and (2) monthly resident-led Morbidity, Mortality, & Improvement conferences focused on case analysis and project development. Surveys were administered precurriculum and 18 months postcurriculum to assess the effect on self-assessed confidence with quality improvement skills, attitudes, and project participation. Scholarship in the form of posters, presentations, and manuscripts was tracked during the course of the study.ResultsPrecurriculum, 83% of neurology residents felt that instruction in quality improvement was important, but most rated their confidence level with various skills as low. Following implementation of the curriculum, residents were significantly more confident in analyzing a patient case (odds ratio, 95% confidence interval) (2.4, 1.9–3.1), proposing system changes (3.1, 2.3–3.9), writing a problem statement (9.9, 6.2–13.5), studying a process (3.1, 2.3–3.8), identifying resources (3.1, 2.3–3.8), identifying appropriate measures (2.5, 1.9–3.0), collaborating with other providers to make improvements (4.9, 3.5–6.4), and making changes in a system (3.1, 2.3–3.8). Project participation increased from the precurriculum baseline (7/18, 39%) to the postcurriculum period (17/22, 77%; p = 0.023). One hundred percent of residents surveyed rated the curriculum positively.ConclusionsOur multifaceted curriculum was associated with increased resident confidence with quality improvement skills and increased participation in improvement projects. With adequate faculty mentorship, this curriculum represents a novel template for preparing neurology residents for meeting the expectations of improvement in practice and offers scholarship opportunities.

Cerebral perfusion imaging may be used to identify the ischemic core in acute ischemic stroke (AIS) patients with a large vessel occlusion of the anterior circulation; however, perfusion parameters that predict the ischemic core in AIS patients with a basilar artery occlusion (BAO) are poorly described. We determined which cerebral perfusion parameters best predict the ischemic core after successful endovascular thrombectomy (EVT) in BAO patients.We performed multicenter retrospective study of BAO patients with perfusion imaging before EVT and a DWI after successful EVT. The ischemic core was defined as regions on CTP, which were co-registered to the final DWI infarct. Various time-to-maximum (Tmax) and cerebral blood flow (CBF) thresholds were compared to final infarct volume to determine the best predictor of the final infarct.28 patients were included in the analysis for this study. Tmax8s (rPre-EVT CT perfusion imaging is useful to predict the final ischemic infarct volume in BAO patients. Tmax8s and Tmax10s were the strongest predictors of the post-EVT final infarct volume.

Background and Purpose— Imaging is frequently used to select acute stroke patients for intra-arterial therapy. Quantitative cerebral blood flow can be measured noninvasively with arterial spin labeling magnetic resonance imaging. Cerebral blood flow levels in the contralateral (unaffected) hemisphere may affect capacity for collateral flow and patient outcome. The goal of this study was to determine whether higher contralateral cerebral blood flow (cCBF) in acute stroke identifies patients with better 90-day functional outcome. Methods— Patients were part of the prospective, multicenter iCAS study (Imaging Collaterals in Acute Stroke) between 2013 and 2017. Consecutive patients were enrolled after being diagnosed with anterior circulation acute ischemic stroke. Inclusion criteria were ischemic anterior circulation stroke, baseline National Institutes of Health Stroke Scale score ≥1, prestroke modified Rankin Scale score ≤2, onset-to-imaging time Results— Seventy-seven patients (41 women) met the inclusion criteria with median (interquartile range) age of 66 (55–76) yrs, onset-to-imaging time of 4.8 (3.6–7.7) hours, and baseline National Institutes of Health Stroke Scale score of 13 (9–20). Median cCBF was 38.9 (31.2–44.5) mL per 100 g/min. Higher cCBF predicted good outcome at day 90 (odds ratio, 4.6 [95% CI, 1.4–14.7]; P =0.01), after controlling for baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging lesion volume, and intra-arterial therapy. Conclusions— Higher quantitative cCBF at baseline is a significant predictor of good neurological outcome at day 90. cCBF levels may inform decisions regarding stroke triage, treatment of acute stroke, and general outcome prognosis. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02225730.

Background and Purpose: Determining the mechanism of large vessel occlusion related acute ischemic stroke is of major importance to initiate a tailored secondary prevention strategy. We investigated using the atherosclerosis, small vessel disease, cardiac source, other cause, dissection (ASCOD) classification the distribution of the causes of large vessel occlusion related acute ischemic stroke treated by mechanical thrombectomy. Methods: This was a predefined substudy of the FRAME (French Acute Multimodal Imaging to Select Patient for Mechanical Thrombectomy). Each patient underwent a systematic etiological workup including brain and vascular imaging, electrocardiogram monitoring lasting at least 24 hours and routine blood tests. Stroke mechanisms were systematically evaluated using the atherosclerosis, small vessel disease, cardiac source, other cause, dissection grading system at 3 months. We defined single potential cause by one cause graded 1 in a single domain, possible cause as a cause graded 1 or 2 regardless of overlap, and no identified cause without grade 1 nor 2 causes. Results: A total of 215 patients (mean age 70±14; 50% male) were included. A single potential cause was identified in 148 (69%). Cardio-embolism (53%) was the most frequent, followed by atherosclerosis (9%), dissection (5%) and other causes (1%). Atrial fibrillation accounted for 88% of C1. Overlap between grade 1 causes was uncommon (3%). Possible causes were identified in 168 patients (83%) and 16 (7%) had no cause identified after the initial evaluation. Conclusions: Cardio-embolism, especially atrial fibrillation, was the major cause of large vessel occlusion related acute ischemic stroke. This finding emphasizes the yield of paroxysmal atrial fibrillation detection in those patients. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03045146.