Two-stage convolutional neural network for segmentation and detection of carotid web on CT angiography.

BACKGROUND: Carotid web (CaW) is a risk factor for ischemic stroke, mainly in young patients with stroke of undetermined etiology. Its detection is challenging, especially among non-experienced physicians. METHODS: We included patients with CaW from six international trials and registries of patients with acute ischemic stroke. Identification and manual segmentations of CaW were performed by three trained radiologists. We designed a two-stage segmentation strategy based on a convolutional neural network (CNN). At the first stage, the two carotid arteries were segmented using a U-shaped CNN. At the second stage, the segmentation of the CaW was first confined to the vicinity of the carotid arteries. Then, the carotid bifurcation region was localized by the proposed carotid bifurcation localization algorithm followed by another U-shaped CNN. A volume threshold based on the derived CaW manual segmentation statistics was then used to determine whether or not CaW was present. RESULTS: We included 58 patients (median (IQR) age 59 (50-75) years, 60% women). The Dice similarity coefficient and 95th percentile Hausdorff distance between manually segmented CaW and the algorithm segmented CaW were 63.20±19.03% and 1.19±0.9 mm, respectively. Using a volume threshold of 5 mm3, binary classification detection metrics for CaW on a single artery were as follows: accuracy: 92.2% (95% CI 87.93% to 96.55%), precision: 94.83% (95% CI 88.68% to 100.00%), sensitivity: 90.16% (95% CI 82.16% to 96.97%), specificity: 94.55% (95% CI 88.0% to 100.0%), F1 measure: 0.9244 (95% CI 0.8679 to 0.9692), area under the curve: 0.9235 (95%CI 0.8726 to 0.9688). CONCLUSIONS: The proposed two-stage method enables reliable segmentation and detection of CaW from head and neck CT angiography.

Prevalence of depression and anxiety symptoms after stroke in young adults: A systematic review and meta-analysis.

BACKGROUND: Young adults with stroke have distinct professional and social roles making them vulnerable to symptoms of post-stroke depression (PSD) and post-stroke anxiety (PSA). Prior reviews have examined the prevalence of anxiety and depression in stroke populations. However, there are a lack of studies that have focused on these conditions in young adults. OBJECTIVE: We performed a systematic review and meta-analysis of observational studies that reported on symptoms of PSD, PSA and comorbid PSD/PSA in young adults aged 18 to 55 years of age. METHODS: MEDLINE, EMBASE, SCOPUS and PsycINFO were searched for studies reporting the prevalence of symptoms of PSD and/or PSA in young adults with stroke from inception until June 23, 2023. We included studies that evaluated depression and/or anxiety symptoms with screening tools or interviews following ischemic or hemorrhagic stroke. Validated methods were employed to evaluate risk of bias. RESULTS: 4748 patients from twenty eligible studies were included. Among them, 2420 were also evaluated for symptoms of PSA while 847 participants were evaluated for both PSD and PSA symptoms. Sixteen studies were included in the random effects meta-analysis for PSD symptoms, with a pooled prevalence of 31 % (95 % CI 24-38 %). Pooled PSA symptom prevalence was 39 % (95 % CI 30-48 %) and comorbid PSD with PSA symptom prevalence was 25 % (95 % CI 12-39 %). Varying definitions of 'young adult', combinations of stroke subtypes, and methods to assess PSD and PSA contributed to high heterogeneity amongst studies. CONCLUSIONS: We identified high heterogeneity in studies investigating the prevalence of symptoms of PSD and PSA in young adults, emphasizing the importance of standardized approaches in future research to gain insight into the outcomes and prognosis of PSD and PSA symptoms following stroke in young adults. Larger longitudinal epidemiological studies as well as studies on tailored interventions are required to address the mental health needs of this important population. FUNDING: None.

Clinical uncertainty in large vessel occlusion ischemic stroke: does automated perfusion imaging make a difference? An intra-rater and inter-rater agreement study.

BACKGROUND: Limited research exists regarding the impact of neuroimaging on endovascular thrombectomy (EVT) decisions for late-window cases of large vessel occlusion (LVO) stroke. OBJECTIVE: T0 assess whether perfusion CT imaging: (1) alters the proportion of recommendations for EVT, and (2) enhances the reliability of EVT decision-making compared with non-contrast CT and CT angiography. METHODS: We conducted a survey using 30 patients drawn from an institutional database of 3144 acute stroke cases. These were presented to 29 Canadian physicians with and without perfusion imaging. We used non-overlapping 95% confidence intervals and difference in agreement classification as criteria to suggest a difference between the Gwet AC1 statistics (κG). RESULTS: The percentage of EVT recommendations differed by 1.1% with or without perfusion imaging. Individual decisions changed in 21.4% of cases (11.3% against EVT and 10.1% in favor). Inter-rater agreement (κG) among the 29 raters was similar between non-perfusion and perfusion CT neuroimaging (κG=0.487; 95% CI 0.327 to 0.647 and κG=0.552; 95% CI 0.430 to 0.675). The 95% CIs overlapped with moderate agreement in both. Intra-rater agreement exhibited overlapping 95% CIs for all 28 raters. κG was either substantial or excellent (0.81-1) for 71.4% (20/28) of raters in both groups. CONCLUSIONS: Despite the minimal difference in overall EVT recommendations with either neuroimaging protocol one in five decisions changed with perfusion imaging. Regarding agreement we found that the use of automated CT perfusion images does not significantly impact the reliability of EVT decisions for patients with late-window LVO.

Effect of incomplete reperfusion patterns on clinical outcome: insights from the ESCAPE-NA1 trial.

BACKGROUND: Incomplete reperfusion (IR) after mechanical thrombectomy (MT) can be a consequence of residual occlusion, no-reflow phenomenon, or collateral counterpressure. Data on the impact of these phenomena on clinical outcome are limited. METHODS: Patients from the ESCAPE-NA1 trial with IR (expanded Thrombolysis In Cerebral Infarction (eTICI) 2b) were compared with those with complete or near-complete reperfusion (eTICI 2c-3) on the final angiography run. Final runs were assessed for (a) an MT-accessible occlusion, or (b) a non-MT-accessible occlusion pattern. The primary clinical outcome was modified Rankin Scale (mRS) 0-2 at 90 days. Our imaging outcome was infarction in IR territory on follow-up imaging. Unadjusted and adjusted incidence rate ratios (aIRR) with 95% confidence intervals (95% CI) were obtained. RESULTS: Of 1105 patients, 443 (40.1%) with IR and 506 (46.1%) with complete or near-complete reperfusion were included. An MT-accessible occlusion was identified in 147/443 patients (33.2%) and a non-MT-accessible occlusion in 296/443 (66.8%). As compared with patients with near-complete/complete reperfusion, patients with IR had significantly lower chances of achieving mRS 0-2 at 90 days (aIRR 0.82, 95% CI 0.74 to 0.91). Rates of mRS 0-2 were lower in the MT-accessible occlusion group as compared with the non-MT-accessible occlusion pattern group (aIRR 0.71, 95% CI 0.60 to 0.83, and aIRR 0.89, 95% CI 0.81 to 0.98, respectively). More patients with MT-accessible occlusion patterns developed infarcts in the non-reperfused territory as compared with patients with non-MT occlusion patterns (68.7% vs 46.3%). CONCLUSION: IR was associated with worse clinical outcomes than near-complete/complete reperfusion. Two-thirds of our patients with IR had non-MT-accessible occlusion patterns which were associated with better clinical and imaging outcomes compared with those with MT-accessible occlusion patterns.

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.

Correlation of von Willebrand factor and platelets with acute ischemic stroke etiology and revascularization outcome: an immunohistochemical study.

BACKGROUND: Platelets and von Willebrand factor (vWF) are key components of acute ischemic stroke (AIS) emboli. We aimed to investigate the CD42b (platelets)/vWF expression, its association with stroke etiology and the impact these components may have on the clinical/procedural parameters. METHODS: CD42b/vWF immunostaining was performed on 288 emboli collected as part of the multicenter STRIP Registry. CD42b/VWF expression and distribution were evaluated. Student's t-test and χ2 test were performed as appropriate. RESULTS: The mean CD42b and VWF content in clots was 44.3% and 21.9%, respectively. There was a positive correlation between platelets and vWF (r=0.64, p<0.001**). We found a significantly higher vWF level in the other determined etiology (p=0.016*) and cryptogenic (p=0.049*) groups compared with cardioembolic etiology. No significant difference in CD42b content was found across the etiology subtypes. CD42b/vWF patterns were significantly associated with stroke etiology (p=0.006*). The peripheral pattern was predominant in atherosclerotic clots (36.4%) while the clustering (patchy) pattern was significantly associated with cardioembolic and cryptogenic origin (66.7% and 49.8%, respectively). The clots corresponding to other determined etiology showed mainly a diffuse pattern (28.1%). Two types of platelets were distinguished within the CD42b-positive clusters in all emboli: vWF-positive platelets were observed at the center, surrounded by vWF-negative platelets. Thrombolysis correlated with a high platelet content (p=0.03*). vWF-poor and peripheral CD42b/vWF pattern correlated with first pass effect (p=0.03* and p=0.04*, respectively). CONCLUSIONS: The vWF level and CD42b/vWF distribution pattern in emboli were correlated with AIS etiology and revascularization outcome. Platelet content was associated with response to thrombolysis.

Endovascular treatment of acute ischemic stroke in patients with pre-morbid disability: a meta-analysis.

BACKGROUND: Trials of endovascular thrombectomy (EVT) for acute stroke have excluded patients with pre-morbid disability. Observational studies may help inform consideration of EVT in this population. We aimed to assess the effectiveness and safety of EVT in patients with pre-morbid disability. METHODS: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched MEDLINE and Embase for studies describing outcomes in patients with pre-morbid disability (modified Rankin Scale (mRS) 2-5), treated with EVT or medical management (MM). Random-effects meta-analysis was used to pool outcomes including 90-day return to baseline mRS, symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. RESULTS: We analyzed 14 studies of patients with pre-morbid disability (mRS 2-5, 1373 EVT and 253 MM). The rate of return to baseline mRS was 30.0% (95% CI 25.3% to 34.7%) in patients treated with EVT. Compared with medical therapy, EVT was associated with a higher likelihood of return to baseline mRS (OR 2.37, 95% CI 1.39 to 4.04) and a trend towards lower mortality (OR 0.68, 95% CI 0.46 to 1.02), with similar odds of sICH (OR 1.01, 95% CI 0.49 to 2.08). In studies comparing patients with versus without pre-morbid disability treated with EVT, similar results were found except that pre-morbid disability, when defined more strictly as mRS 3-5, was associated with mortality (OR 3.49, p<0.001). CONCLUSION: In eligible patients with pre-morbid disability, observational studies suggest that EVT carries a higher chance of return to baseline mRS compared with patients treated with MM or without pre-morbid disability, although with higher mortality than patients without pre-morbid disability. These findings argue against the routine exclusion of such patients from EVT and merit validation with randomized trials.

Prediction of 90 day home time among patients with low baseline ASPECTS undergoing endovascular thrombectomy: results from Alberta's Provincial Stroke Registry (QuICR).

BACKGROUND: The benefit of endovascular thrombectomy (EVT) in stroke patients with a low baseline Alberta Stroke Program Early CT Score (ASPECTS, ≤5) is uncertain. We aim to use random forest regression modeling to predict 90 day home time in patients with low ASPECTS. METHODS: We used the Quality Improvement and Clinical Research (QuICR) provincial stroke registry and administrative data from southern Alberta to identify patients who underwent EVT in our center from July 2015 to November 2020. Baseline ASPECTS on non-contrast CT and CT angiography data were scored by a two physician consensus. The primary outcome was the predicted 90 day home time (the number of nights a patient is back at their premorbid living situation without an increase in level of care within 90 days of the stroke) using random forests regression. Estimates were generated using 200 bootstrapped datasets. Covariate contribution to home time was determined using partial dependence plots. RESULTS: Of 657 EVT patients, 85 (12.9%) had baseline ASPECTS ≤5 (mean age 70.9 years, 44.7% women, 93.9% good-moderate collaterals, 60% M1-middle cerebral artery occlusion). Using partial dependence estimates, mean predicted home times were similar in the low ASPECTS (44.3 days) versus higher ASPECTS (43.1) groups. Factors predicting lower 90 day home time in this population were diabetes mellitus (-8.8 days), hypertension (-5.7 days), and atrial fibrillation (-3.6 days). There was no meaningful difference in predicted 90 day home time by sex, baseline National Institutes of Health Stroke Severity Scale score, occlusion site, tandem lesion, collateral grade or thrombolysis. CONCLUSIONS: Patients with low ASPECTS who are selected for EVT using demographic and clinical profiles similar to higher ASPECTS patients achieved comparable outcomes.

Tmax Volumes Predict Final Infarct Size and Functional Outcome in Ischemic Stroke Patients Receiving Endovascular Treatment.

OBJECTIVE: The objective of this paper was to explore the utility of time to maximum concentration (Tmax )-based target mismatch on computed tomography perfusion (CTP) in predicting radiological and clinical outcomes in patients with acute ischemic stroke (AIS) with anterior circulation large vessel occlusion (LVO) selected for endovascular treatment (EVT). METHODS: Patients with AIS underwent CTP within 24 hours from onset followed by EVT. Critically hypoperfused tissue and ischemic core volumes were automatically calculated using Tmax thresholds >9.5 seconds and >16 seconds, respectively. The difference between Tmax > 9.5 seconds and Tmax > 16 seconds volumes and the ratio between Tmax > 9.5 seconds and Tmax > 16 seconds volumes were considered ischemic penumbra and Tmax mismatch ratio, respectively. Final infarct volume (FIV) was measured on follow-up non-contrast computed tomography (CT) at 24 hours. Favorable clinical outcome was defined as 90-day modified Rankin Scale 0 to 2. Predictors of FIV and outcome were assessed with multivariable logistic regression. Optimal Tmax volumes for identification of good outcome was defined using receiver operating curves. RESULTS: A total of 393 patients were included, of whom 298 (75.8%) achieved successful recanalization and 258 (65.5%) achieved good outcome. In multivariable analyses, all Tmax parameters were independent predictors of FIV and outcome. Tmax  > 16 seconds volume had the strongest association with FIV (beta coefficient = 0.596 p <0.001) and good outcome (odds ratio [OR] = 0.96 per 1 ml increase, 95% confidence interval [CI] = 0.95-0.97, p < 0.001). Tmax  > 16 seconds volume had the highest discriminative ability for good outcome (area under the curve [AUC] = 0.88, 95% CI = 0.842-0.909). A Tmax  > 16 seconds volume of ≤67 ml best identified subjects with favorable outcome (sensitivity = 0.91 and specificity = 0.73). INTERPRETATION: Tmax target mismatch predicts radiological and clinical outcomes in patients with AIS with LVO receiving EVT within 24 hours from onset. ANN NEUROL 2022;91:878-888.

Quantification of clot spatial heterogeneity and its impact on thrombectomy.

BACKGROUND: Compositional and structural features of retrieved clots by thrombectomy can provide insight into improving the endovascular treatment of ischemic stroke. Currently, histological analysis is limited to quantification of compositions and qualitative description of the clot structure. We hypothesized that heterogeneous clots would be prone to poorer recanalization rates and performed a quantitative analysis to test this hypothesis. METHODS: We collected and did histology on clots retrieved by mechanical thrombectomy from 157 stroke cases (107 achieved first-pass effect (FPE) and 50 did not). Using an in-house algorithm, the scanned images were divided into grids (with sizes of 0.2, 0.3, 0.4, 0.5, and 0.6 mm) and the extent of non-uniformity of RBC distribution was computed using the proposed spatial heterogeneity index (SHI). Finally, we validated the clinical significance of clot heterogeneity using the Mann-Whitney test and an artificial neural network (ANN) model. RESULTS: For cases with FPE, SHI values were smaller (0.033 vs 0.039 for grid size of 0.4 mm, P=0.028) compared with those without. In comparison, the clot composition was not statistically different between those two groups. From the ANN model, clot heterogeneity was the most important factor, followed by fibrin content, thrombectomy techniques, red blood cell content, clot area, platelet content, etiology, and admission of intravenous tissue plasminogen activator (IV-tPA). No statistical difference of clot heterogeneity was found for different etiologies, thrombectomy techniques, and IV-tPA administration. CONCLUSIONS: Clot heterogeneity can affect the clot response to thrombectomy devices and is associated with lower FPE. SHI can be a useful metric to quantify clot heterogeneity.

Management and outcome of patients with acute ischemic stroke and tandem carotid occlusion in the ESCAPE-NA1 trial.

BACKGROUND: The optimal treatment and prognosis for stroke patients with tandem cervical carotid occlusion are unclear. We analyzed outcomes and treatment strategies of tandem occlusion patients in the ESCAPE-NA1 trial. METHODS: ESCAPE-NA1 was a multicenter international randomized trial of nerinetide versus placebo in 1105 patients with acute ischemic stroke who underwent endovascular treatment. We defined tandem occlusions as complete occlusion of the cervical internal carotid artery (ICA) on catheter angiography, in addition to a proximal ipsilateral intracranial large vessel occlusion. Baseline characteristics and outcome parameters were compared between patients with tandem occlusions versus those without, and between patients with tandem occlusion who underwent ICA stenting versus those who did not. The influence of tandem occlusions on functional outcome was analyzed using multivariable regression modeling. RESULTS: Among 115/1105 patients (10.4%) with tandem occlusions, 62 (53.9%) received stenting for the cervical ICA occlusion. Of these, 46 (74.2%) were stented after and 16 (25.8%) before the intracranial thrombectomy. A modified Rankin Score (mRS) of 0-2 at 90 days was achieved in 82/115 patients (71.3%) with tandem occlusions compared with 579/981 (59.5%) patients without tandem occlusions. Tandem occlusion did not impact functional outcome in the adjusted analysis (OR 1.5, 95% CI 0.95 to 2.4). Among the subgroup of patients with tandem occlusion, cervical carotid stenting was not associated with different outcomes compared with no stenting (mRS 0-2: 75.8% vs 66.0%, adjusted OR 2.0, 95% CI 0.8 to 5.1). CONCLUSIONS: Tandem cervical carotid occlusion in patients with acute large vessel stroke did not lower the odds of good functional outcome in our study. Functional outcomes were similar irrespective of the management of the cervical ICA occlusion (stenting vs not stenting).

Influence of intravenous alteplase on endovascular treatment decision-making in acute ischemic stroke due to primary medium-vessel occlusion: a case-based survey study.

BACKGROUND: Intravenous alteplase is currently the only evidence-based treatment for medium-vessel occlusion stroke (MeVO; M2/3, A2/3, and P2/3 vessel segment occlusions), but due to its limited efficacy, endovascular treatment (EVT) is increasingly performed in these patients. In this case-based survey study, we examined the influence of intravenous alteplase treatment on physicians' decision-making for EVT in primary MeVO stroke. METHODS: In an international web-based survey among physicians involved in acute stroke care, participants provided their EVT decision for six quasi-identical fictional MeVO case scenarios (three with and without intravenous alteplase administered). Each scenario showed radiological images and clinical information in the form of a short case vignette. We compared EVT decisions ("immediate EVT", "no EVT", or "wait for alteplase effect" [in case scenarios with alteplase treatment only]) for case scenarios with and without alteplase treatment. Clustered multivariable logistic regression was performed to assess the effect of alteplase on treatment decision. RESULTS: The survey was completed by 366 physicians from 44 countries, resulting in 2196 responses included in this study. In alteplase-treated cases, 641/1098 (58.4%) responses favored immediate EVT, (279/1098 [25.4%]) favored no EVT and 178/1098 (16.2%) opted to wait for alteplase effect. In non-alteplase-treated case scenarios, 846/1098 (78.7%) were in favor of and 252/1098 (21.3%) against EVT. Intravenous alteplase was associated with a lower chance of a decision in favor of immediate EVT (adjusted OR 0.38 [95%CI 0.31 to 0.46]). CONCLUSIONS: Intravenous alteplase is an important factor in EVT decision-making for MeVO stroke. However, even in alteplase-treated patients, more than half of the physicians decided to proceed with EVT without waiting for alteplase effect.

Histological evaluation of acute ischemic stroke thrombi may indicate the occurrence of vessel wall injury during mechanical thrombectomy.

BACKGROUND: Several animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine. OBJECTIVE: To investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots. METHODS: As part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells). RESULTS: MT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material.Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1-4] vs 1 [1-3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI. CONCLUSIONS: Histological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device.

Predictors and clinical impact of infarct progression rate in the ESCAPE-NA1 trial.

BACKGROUND: Determining infarct progression rate in acute ischemic stroke (AIS) is important for patient triage, treatment decision-making, and outcome prognostication. OBJECTIVE: To estimate infarct progression rate in patients with AIS with large vessel occlusion (LVO) and determine its predictors and impact on clinical outcome. METHODS: Data are from the ESCAPE-NA1 Trial. Patients with AIS with time from last known well to randomization <6 hours and near-complete reperfusion following endovascular treatment were included. Infarct growth rate (mL/h) was estimated by dividing 24 hour infarct volume (measured by non-contrast CT or diffusion-weighted magnetic resonance imaging) by time from last known well to reperfusion. Multivariable linear regression was used to assess the association of patient baseline variables with log-transformed infarct progression rate. The association of infarct progression rate and good outcome (modified Rankin Scale score 0-2) was determined using multivariable logistic regression. RESULTS: Four hundred and nine patients were included in the study. Median infarct progression rate was 4.74 mL/h (IQR 1.25-14.84). Collateral status (ß: -0.81 (95% CI -1.20 to -0.41)), Alberta Stroke Program Early CT Score (ASPECTS, ß: -0.34 (95% CI -0.46 to -0.23)), blood glucose(ß: 0.09 (95% CI 0.02 to 0.16)), and National Institutes of Health Stroke Scale (NIHS score (ß: 0.07 (95% CI 0.04 to 0.10)) were associated with log-transformed infarct progression rate. Clinical and imaging baseline variables explained 23% of the variance in infarct progression rate. Infarct progression rate was significantly associated with good outcome (aOR per 1 mL/h increase: 0.96 (95% CI 0.95 to 0.98)). CONCLUSION: In this sample of patients presenting within the early time window with LVO and near-complete recanalization, infarct progression rate was significantly associated with good outcome. A significant association between ASPECTS, collateral status, blood glucose, and NIHSS score was observed, but baseline imaging and clinical characteristics explained only a small proportion of the interindividual variance. More research on measurable factors affecting infarct growth is needed.

Assessment of Discrepancies Between Follow-up Infarct Volume and 90-Day Outcomes Among Patients With Ischemic Stroke Who Received Endovascular Therapy.

Importance: Some patients have poor outcomes despite small infarcts after endovascular therapy (EVT), while others with large infarcts do well. Understanding why these discrepancies occur may help to optimize EVT outcomes. Objective: To validate exploratory findings from the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial regarding pretreatment, treatment-related, and posttreatment factors associated with discrepancies between follow-up infarct volume (FIV) and 90-day functional outcome. Design, Setting, and Participants: This cohort study is a post hoc analysis of the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, a double-blind, randomized, placebo-controlled, international, multicenter trial conducted from March 2017 to August 2019. Patients who participated in ESCAPE-NA1 and had available 90-day modified Rankin Scale (mRS) scores and 24-hour to 48-hour posttreatment follow-up parenchymal imaging were included. Exposures: Small FIV (volume ≤25th percentile) and large FIV (volume ≥75th percentile) on 24-hour computed tomography/magnetic resonance imaging. Baseline factors, outcomes, treatments, and poststroke serious adverse events (SAEs) were compared between discrepant cases (ie, patients with 90-day mRS score ≥3 despite small FIV or those with mRS scores ≤2 despite large FIV) and nondiscrepant cases. Main Outcomes and Measures: Area under the curve (AUC) and goodness of fit of prespecified logistic models, including pretreatment (eg, age, cancer, vascular risk factors) and treatment-related and posttreatment (eg, SAEs) factors, were compared with stepwise regression-derived models for ability to identify small FIV with higher mRS score and large FIV with lower mRS score. Results: Among 1091 patients (median [IQR] age, 70.8 [60.8-79.8] years; 549 [49.7%] women; median [IQR] FIV, 24.9 mL [6.6-92.2 mL]), 42 of 287 patients (14.6%) with FIV of 7 mL or less (ie, ≤25th percentile) had an mRS score of at least 3; 65 of 275 patients (23.6%) with FIV of 92 mL or greater (ie, ≥75th percentile) had an mRS score of 2 or less. Prespecified models of pretreatment factors (ie, age, cancer, vascular risk factors) associated with low FIV and higher mRS score performed similarly to models selected by stepwise regression (AUC, 0.92 [95% CI, 0.89-0.95] vs 0.93 [95% CI, 0.90-0.95]; P = .42). SAEs, specifically infarct in new territory, recurrent stroke, pneumonia, and congestive heart failure, were associated with low FIV and higher mRS scores; stepwise models also identified 24-hour hemoglobin as treatment-related/posttreatment factor (AUC, 0.92 [95% CI, 0.90-0.95] vs 0.94 [95% CI, 0.91-0.96]; P = .14). Younger age was associated with high FIV and lower mRS score; stepwise models identified absence of diabetes and higher baseline hemoglobin as additional pretreatment factors (AUC, 0.76 [95% CI, 0.70-0.82] vs 0.77 [95% CI, 0.71-0.83]; P = .82). Absence of SAEs, especially stroke progression, symptomatic intracerebral hemorrhage, and pneumonia, was associated with high FIV and lower mRS score2; stepwise models also identified 24-hour hemoglobin level, glucose, and diastolic blood pressure as posttreatment factors associated with discrepant cases (AUC, 0.80 [95% CI, 0.74-0.87] vs 0.79 [95% CI, 0.72-0.86]; P = .92). Conclusions and Relevance: In this study, discrepancies between functional outcome and post-EVT infarct volume were associated with differences in pretreatment factors, such as age and comorbidities, and posttreatment complications related to index stroke evolution, secondary prevention, and quality of stroke unit care. Besides preventing such complications, optimization of blood pressure, glucose levels, and hemoglobin levels are potentially modifiable factors meriting further study.

Association between clot composition and stroke origin in mechanical thrombectomy patients: analysis of the Stroke Thromboembolism Registry of Imaging and Pathology.

BACKGROUND: We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients to study the association between histological composition and stroke etiology METHODS: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using martius scarlet blue (MSB) staining, and quantification for red blood cells (RBCs), white blood cells (WBCs), fibrin and platelets was performed using Orbit Image Software. A Wilcoxon test was used for continuous variables and χ2 test for categorical variables. RESULTS: 1350 patients were included in this study. The overall rate of Thrombolysis In Cerebral Infarction (TICI) 2c/3 was 68%. 501 patients received tissue plasminogen activator (tPA) (37%). 267 patients (20%) had a large artery atherosclerosis (LAA) source, 662 (49%) a cardioembolic (CE) source, 301 (22%) were cryptogenic, and the remainder had other identifiable sources including hypercoagulable state or dissection. LAA thrombi had a higher mean RBC density (46±23% vs 42±22%, p=0.01) and a lower platelet density (24±18% vs 27±18%, p=0.03) than CE thrombi. Clots from dissection patients had the highest mean RBC density (50±24%) while clots from patients with a hypercoagulable state had the lowest mean RBC density (26±21%). CONCLUSIONS: Our study found statistically significant but clinically insignificant differences between clots of CE and LAA etiologies. Future studies should emphasize molecular, proteomic and immunohistochemical characteristics to determine links between clot composition and etiology.

Current and future usefulness and potential of virtual simulation in improving outcomes and reducing complications in endovascular treatment of unruptured intracranial aneurysms.

BACKGROUND: Simulation training has been used in the aviation industry and surgical specialties for many years, but integration into neurointerventional practice is lagging behind. OBJECTIVE: To investigate how neurointerventionalists perceive the usefulness and limitations of simulation tools for the treatment of unruptured intracranial aneurysms (UIAs), and to identify simulation applications that were perceived to be most valuable for endovascular UIA treatment. METHODS: A web-based international multidisciplinary survey was conducted among neurointerventionalists. Participants were asked for their perceptions on the usefulness of current simulation tools and the potential impact of future simulation tools in endovascular UIA treatment. They identified simulation applications that could add most value to endovascular UIA treatment and help to specifically reduce endovascular UIA treatment complications. RESULTS: 233 neurointerventionalists from 38 countries completed the survey, most of whom (157/233 (67.4%)) had access to a simulator as a trainee, but only 15.3% used it frequently. Most participants (117/233 (50.2%)) considered currently available simulation tools relatively useful for endovascular UIA treatment, with greater value for trainees than for staff. Simulation of new devices (147/233 (63.1%)) and virtual practice runs in individual patient anatomy (119/233 (51.1%)) were considered most valuable for reducing endovascular UIA treatment complications. CONCLUSION: Although neurointerventionalists perceived currently available simulation tools relatively useful, they did not use them regularly during their training. A priori testing of new devices and practice runs in individual patient anatomy in a virtual environment were thought to have the greatest potential for reducing endovascular UIA treatment complications.

A System for Continuous Pre- to Post-reperfusion Intra-carotid Cold Infusion for Selective Brain Hypothermia in Rodent StrokeModels.

Intra-carotid cold infusion (ICCI) appears as a promising method for hypothermia-mediated brain protection from ischemic stroke. Recent clinical pilot studies indicate easy implementation of ICCI into endovascular acute ischemic stroke treatment. Current rodent ICCI-in-stroke models limit ICCI to the post-reperfusion phase. To establish a method for continuous ICCI over the duration of intra-ischemia to post-reperfusion in rodent stroke models, a novel system was developed. Eighteen male Sprague-Dawley rats were included. Intraluminal filament method was used for transient middle cerebral artery occlusion (MCAO). Normal saline (~ 0 °C) was delivered (≤ 2.0 mL/min) into the internal carotid artery via a customized infusion system without interruption during MCAO (intra-ischemia) to after filament withdrawal (post-reperfusion). Bilateral cortical and striatal temperatures were monitored. Hypothermia goals were a temperature reduction in the ischemic hemisphere by 2 °C prior to reperfusion and thereafter maintenance of regional brain hypothermia at ~ 32 °C limiting the administered ICCI volume to ½ of each rat's total blood volume. During ischemia, maximum brain cooling rate was achieved with ICCI at 0.5 mL/min. It took 2 min to reduce ischemic striatal temperature by 2.3 ± 0.3 °C. After reperfusion, brain cooling was continued at 2 mL/min ICCI first (over 42 s) and maintained at 32.1 ± 0.3 °C at 0.7 mL/min ICCI over a duration of 15 ± 0.8 min. ICCI (total 12.6 ± 0.6 mL) was uninterrupted over the duration of the studied phases. First system that allows continuous ICCI during the phases of intra-ischemia to post-reperfusion in small animals for selective brain cooling and for investigations of other neuroprotective infusions.

Imaging criteria across pivotal randomized controlled trials for late window thrombectomy patient selection.

BACKGROUND: The DAWN and DEFUSE-3 trials showed the benefit of endovascular treatment (EVT) in acute ischemic stroke patients presenting beyond 6 hours from last known well (LKW) and selected by perfusion imaging criteria. The ESCAPE NA1-trial selected patients based on non-contrast CT (NCCT) Alberta Stroke Program Early CT Score (ASPECTS) and multiphase CT angiography (CTA) collateral status. This study compares baseline characteristics, workflow, and outcomes in the EVT arms of DAWN and DEFUSE-3 with late-window patients from the EVT-only arm of ESCAPE-NA1. METHODS: Aggregate data on baseline characteristics, workflow, reperfusion quality, final infarct volume, and clinical outcomes (modified Rankin Score [mRS] at 90 days) in subjects enrolled in the DAWN and DEFUSE-3 EVT arms were compared with similar data from the ESCAPE-NA1 control arm (EVT-only arm) presenting beyond 6 hours from LKW using descriptive statistics. RESULTS: Baseline characteristics among late-window patients in the ESCAPE NA1 trial were similar to those in the DAWN and DEFUSE-3 EVT arms. Median time from LKW-to-puncture in subjects enrolled in the ESCAPE NA1 trial was 9 hrs (IQR: 7.5-11 hours) when compared with DAWN (n=107; 12.8 hours, IQR: 10.6-16.7 hours) and DEFUSE-3 (n=92; 11.5 hours, IQR: 9.2-12.8 hours). Median post-treatment infarct-volume was largest in the ESCAPE NA1-patients (47 mL [IQR: 19-146] vs median 8 mL [IQR: 0-48] in the DAWN group and 35 mL [IQR: 18-82] in DEFUSE-3), while % mRS 0-2 at 90 days were similar across the three trials (ESCAPE NA1: 50/111 [45%], DAWN: 52/107 [49%], DEFUSE-3: 41/92 [45%]). CONCLUSION: Patients enrolled beyond 6 hours from LKW in the ESCAPE-NA1 trial based on NCCT-ASPECTS and mCTA had similar clinical outcomes when compared with patients selected by perfusion imaging in the DAWN and DEFUSE-3 trials.

Therapeutic Hypothermia in Patients with Malignant Ischemic Stroke and Hemicraniectomy-A Systematic Review and Meta-analysis.

BACKGROUND: Therapeutic hypothermia (TH) offers cerebral protection following ischemic stroke and may improve outcomes in conjunction with decompressive hemicraniectomy (DHC). We aimed to assess the effectiveness of TH in patients with malignant ischemic stroke and DHC. METHODS: We performed a meta-analysis in patients with malignant ischemic stroke undergoing DHC comparing TH versus normothermia in studies published up to August 2019. Included studies had ≥10 adults with acute ischemic stroke. Primary outcome was functional independence, and secondary outcomes included complications. Effect size was pooled and described by relative risk (RR) ratios and 95% confidence intervals (CIs). RESULTS: Five studies (n = 269 patients; n = 130 TH, n = 139 controls) were included, 4 of which were prospective (n = 2 randomized controlled trials). Median achieved body temperature of TH was 33.6°C (range 33°C-35°C). Median modified Rankin Scale at the study completion was similar between TH and controls (RR 1.08, 95% CI 0.56-2.07, P = 0.8). Three studies reported individual patient modified Rankin Scale outcomes demonstrated a shift toward worse outcomes with TH (unadjusted common odds ratio 1.74; 95% CI 1.05-2.88, P = 0.01). Overall complications were similar between groups (RR 1.20, 95% CI 0.70-2.05, random effects P = 0.5). A suggestion of higher mortality was seen in TH (RR 1.50, 95% CI 0.97-2.32, P = 0.07). CONCLUSIONS: Clinical and functional outcomes were not overall different between patients undergoing systemic TH and controls following DHC despite the shift toward worse outcomes with TH observed in some studies.