Age and Functional Outcomes in Patients With Large Ischemic Stroke Receiving Endovascular Thrombectomy.

Importance: Randomized clinical trials have demonstrated the efficacy and safety of endovascular thrombectomy for acute ischemic stroke with large infarct. Patients older than 80 years with large infarct are commonly encountered in clinical practice but underrepresented in randomized clinical trials. Objective: To provide an age-based analysis of functional outcomes in endovascular thrombectomy for acute ischemic strokes with large infarct. Design, Setting, and Participants: This retrospective multicenter cohort study included patients from the German Stroke Registry who received endovascular thrombectomy for acute ischemic stroke with large infarct at 1 of 25 German stroke centers between May 2015 and December 2021. Patients with acute ischemic stroke due to anterior circulation large vessel occlusion and large infarct were included. Large infarct was defined as an Alberta Stroke Program Early Computed Tomography Score of 0 to 5. Patients were subdivided by age to evaluate its association with functional outcomes. Exposure: Age. Main Outcomes and Measures: Primary outcomes were independent ambulation (90-day modified Rankin Scale score of 0-3) and mortality (90-day modified Rankin Scale score of 6). Results: A total of 408 patients with large infarct were included (217 women [53.2%]; median [IQR] age, 75 [64-83] years). The rate of independent ambulation decreased from 56.4% in patients aged 60 years and younger (44 of 78 patients) to 15.1% in patients older than 80 years (19 of 126 patients) (P < .001), while mortality increased from 15.4% (12 patients) to 64.3% (81 patients) (P < .001). Being older than 80 years was associated with lower rates of independent ambulation (adjusted odds ratio [aOR], 0.44; 95% CI, 0.23-0.82; P = .01) and higher mortality (aOR, 2.75; 95% CI, 1.61-4.72; P < .001). A final modified Thrombolysis in Cerebral Infarction grade of 2b or 3 was associated with higher rates of independent ambulation (aOR, 4.95; 95% CI, 2.14-11.43; P < .001), independent of age and without significant interaction (aOR, 0.69; 95% CI, 0.35-1.34; P = .27). Conclusions and Relevance: In this cohort study of patients with acute ischemic stroke and large infarct, age was associated with functional outcomes. Patients older than 80 years had poor prognosis with high mortality but with sizeable differences depending on additional baseline and treatment characteristics. While it does not seem justified to apply a fixed upper age limit for endovascular thrombectomy, these results could assist clinicians in making informed treatment decisions in older patients with large ischemic stroke.

Overestimation of the Ischemic Core Is Associated With Higher Core Lesion Volume and Degree of Reperfusion After Thrombectomy.

Background CT perfusion (CTP)-derived baseline ischemic core volume (ICV) can overestimate the true extent of infarction, which may result in exclusion of patients with ischemic stroke from endovascular treatment (EVT). Purpose To determine whether ischemic core overestimation is associated with larger ICV and degree of recanalization. Materials and Methods This retrospective multicenter cohort study included patients with acute ischemic stroke triaged at multimodal CT who underwent EVT between January 2015 and January 2022. The primary outcome was ischemic core overestimation, which was assumed when baseline CTP-derived ICV was larger than the final infarct volume at follow-up imaging. The secondary outcome was functional independence defined as modified Rankin Scale scores of 0-2 90 days after EVT. Successful vessel recanalization was defined as extended Thrombolysis in Cerebral Infarction score of 2b or higher. Categorical variables were compared between patients with ICV of 50 mL or less versus large ICV greater than 50 mL with use of the χ2 test. Adjusted multivariable logistic regression analyses were used to assess the primary and secondary outcomes. Results In total, 721 patients (median age, 76 years [IQR, 64-83 years]; 371 female) were included, of which 162 (22%) demonstrated ischemic core overestimation. Core overestimation occurred more often in patients with ICV greater than 50 mL versus 50 mL or less (48% vs 16%; P < .001) and those with successful versus unsuccessful vessel recanalization (26% vs 13%; P < .001). In an adjusted model, successful recanalization after EVT (odds ratio [OR], 3.14 [95% CI: 1.65, 5.95]; P < .001) and larger ICV (OR, 1.03 [95% CI: 1.02, 1.04]; P < .001) were independently associated with core overestimation, while the time from symptom onset to imaging showed no association (OR, 0.99; P = .96). Core overestimation was independently associated with functional independence (adjusted OR, 2.83 [95% CI: 1.66, 4.81]; P < .001) after successful recanalization. Conclusion Ischemic core overestimation occurred more frequently in patients presenting with large CTP-derived ICV and successful vessel recanalization compared with those with unsuccessful recanalization. © RSNA, 2024 Supplemental material is available for this article.

Thrombectomy patients with minor stroke: factors of early neurological deterioration.

BACKGROUND: A sizeable proportion of stroke patients with large vessel occlusion present with minor neurological deficits. Whether mechanical thrombectomy (MT) is beneficial in these patients is controversial. We aimed to investigate factors of early neurological deterioration (END) in thrombectomy patients with minor stroke and hypothesized that END is linked to unfavorable functional outcomes. METHODS: Multicenter cohort study screening all patients prospectively enrolled in the German Stroke Registry-Endovascular Treatment (n=13 082) between 2015 and 2021. Patients who underwent MT for anterior circulation vessel occlusion with baseline National Institutes of Health Stroke Scale (NIHSS) score of <6 were included. END was defined as an increase in NIHSS score of ≥4 within the first 24 hours after MT. Multivariable regression analyses were performed to investigate factors associated with END and its association with unfavorable functional outcomes 90 days after treatment (modified Rankin Scale (mRS) score ≥2). RESULTS: Among 817 patients included, 24% exhibited END and 48% had unfavorable functional outcomes. Prestroke mRS (adjusted odds ratio (aOR) [95% CI] 1.42 [1.13 to 1.78]), baseline NIHSS (aOR [95% CI] 0.83 [0.73 to 0.94]), time from admission to groin puncture (aOR [95% CI] 1.04 [1.02 to 1.07]), general anesthesia (aOR [95% CI] 1.68 [1.08 to 2.63]), number of passes (aOR [95% CI] 1.15 [1.03 to 1.29]), adverse events during treatment (aOR [95% CI] 1.89 [1.19 to 3.01]), successful recanalization (aOR [95% CI] 0.29 [0.17 to 0.50]), and intracranial hemorrhage on follow-up imaging (aOR [95% CI] 3.40 [1.90 to 6.07]) were independently associated with END. END was independently linked to unfavorable functional outcomes (aOR [95% CI] 7.51 [4.57 to 12.34]). CONCLUSIONS: Almost a quarter of thrombectomy patients with minor stroke developed END. These patients had twice the odds of experiencing unfavorable functional outcomes.

Predictors of Futile Recanalization in Ischemic Stroke Patients with low baseline NIHSS.

BACKGROUND: There is yet no randomized controlled evidence that mechanical thrombectomy (MT) is superior to best medical treatment in patients with large vessel occlusion but minor stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] <6). Prior studies of patients with admission NIHSS scores >6 observed unfavorable functional outcomes despite successful recanalization, commonly termed as futile recanalization (FR), in up to 50% of cases. AIM: The aim of this study is to determine the prevalence of FR in patients with minor stroke and identify associated patient-specific risk factors. METHODS: Our multicenter cohort study screened all patients prospectively enrolled in the German Stroke Registry Endovascular Treatment from 2015 to 2021 (n=13082). Included were patients who underwent MT for anterior circulation vessel occlusion with a baseline NIHSS score of <6 and successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] score of 2b-3). FR was defined by a modified Rankin Scale (mRS) score of 2-6 at 90 days. Multivariable logistic regression analysis was conducted to explore factors associated with FR. RESULTS: A total of 674 patients met the inclusion criteria. FR occurred in 268 (40%) patients. Multivariable logistic regression analysis indicates that higher age (adjusted odds ratio: 1.04 [95% confidence interval: 1.02-1.06]), pre-stroke mRS 1 (aOR: 2.70 [1.51-4.84]), transfer from admission hospital to comprehensive stroke center (aOR: 1.67 [1.08-2.56]), longer time from symptom onset/last seen well to admission (aOR: 1.02 [1.00-1.04]), MT under general anesthesia (aOR: 1.78 [1.13-2.82]), higher NIHSS after 24 hours (aOR: 1.09 [1.05-1.14]), and symptomatic intracranial hemorrhage (aOR: 16.88 [2.03-140.14]) increased the odds of FR. There was no significant difference in primary outcome between achieving mTICI 2b or 3. CONCLUSIONS: Unfavorable functional outcomes despite successful vessel recanalization were frequent in acute ischemic stroke patients with low NIHSS scores on admission. We provide patient-specific risk factors that indicate an increased risk of FR and should be considered when treating patients with minor stroke. DATA ACCESS STATEMENT: The data that support the findings of our study are available on reasonable request after approval of the GSR steering committee.

How much of the variance in functional outcome related to intracerebral hemorrhage volume is already apparent in neurological status at admission?

BACKGROUND: Hematoma volume is a major pathophysiological hallmark of acute intracerebral hemorrhage (ICH). We investigated how the variance in functional outcome induced by the ICH volume is explained by neurological deficits at admission using a mediation model. METHODS: Patients with acute ICH treated in three tertiary stroke centers between January 2010 and April 2019 were retrospectively analyzed. Mediation analysis was performed to investigate the effect of ICH volume (0.8 ml (5% quantile) versus 130.6 ml (95% quantile)) on the risk of unfavorable functional outcome at discharge defined as modified Rankin Score (mRS) ≥ 3 with mediation through National Institutes of Health Stroke Scale (NIHSS) at admission. Multivariable regression was conducted to identify factors related to neurological improvement and deterioration. RESULTS: Three hundred thirty-eight patients were analyzed. One hundred twenty-one patients (36%) achieved mRS ≤ 3 at discharge. Mediation analysis showed that NIHSS on admission explained 30% [13%; 58%] of the ICH volume-induced variance in functional outcome at smaller ICH volume levels, and 14% [4%; 46%] at larger ICH volume levels. Higher ICH volume at admission and brainstem or intraventricular location of ICH were associated with neurological deterioration, while younger age, normotension, lower ICH volumes, and lobar location of ICH were predictors for neurological improvement. CONCLUSION: NIHSS at admission reflects 14% of the functional outcome at discharge for larger hematoma volumes and 30% for smaller hematoma volumes. These results underscore the importance of effects not reflected in NIHSS admission for the outcome of ICH patients such as secondary brain injury and early rehabilitation.

Thrombectomy in ischemic stroke patients with large core but minor ischemic changes on non-enhanced computed tomography.

PURPOSE: The Alberta Stroke Program Early CT Score (ASPECTS) is regularly used to guide patient selection for mechanical thrombectomy (MT). Similarly, penumbral imaging based on computed tomography perfusion (CTP) may serve as neuroimaging tool to guide treatment. Yet, patients with a large ischemic core on CTP may show only minor ischemic changes resulting in a high ASPECTS. AIM: We hypothesized twofold: (1) the treatment effect of vessel recanalization in patients with core volume > 50 mL but ASPECTS ⩾ 6 is not different compared to high ASPECTS patients with core volume < 50 mL, and (2) recanalization is associated with core overestimation. METHODS: We conducted an observational study analyzing ischemic stroke patients consecutively treated with MT after triage by multimodal CT. Functional endpoint was the rate of functional independence at Day 90 defined as modified Rankin Scale (mRS) 0-2. Imaging endpoint was core overestimation, which was considered when CTP-derived core was larger than the final infarct volume assessed on follow-up imaging. Recanalization was evaluated with the extended Thrombolysis in Cerebral Infarction (eTICI) scale. Multivariable logistic regression analysis and propensity score matching (PSM) were used to assess the association of recanalization (eTICI ⩾ 2b) with functional outcome and core overestimation. RESULTS: Of 630 patients with ASPECTS ⩾ 6, 91 patients (14.4%) had a large ischemic core. Following 1:1 PSM, the treatment effect of recanalization was not different in patients with large core and ASPECTS ⩾ 6 (+ 25.8%, 95% CI: 16.3-35.4, p < 0.001) compared to patients with ASPECTS ⩾ 6 and core volume < 50 mL (+ 14.9%, 95% CI: 5.7-24.1, p = 0.002). Recanalization (aOR: 3.46, 95% CI: 1.85-6.47, p < 0.001) and higher core volume (aOR: 1.03, 95% CI: 1.02-1.04, p < 0.001) were significantly associated with core overestimation. CONCLUSION: In patients with ASPECTS ⩾ 6, core volumes did not significantly modify outcomes following recanalization. Reperfusion and higher core volume were significantly associated with core overestimation which may explain the treatment effect of MT for patients with a large ischemic core but minor ischemic changes on non-enhanced CT. DATA ACCESS STATEMENT: The data analyzed in this study will be available and shared on reasonable request from any qualified researcher for the purpose of replicating the results after clearance by the local ethics committee.

Prediction of tissue outcome in acute ischemic stroke based on single-phase CT angiography at admission.

Introduction: In acute ischemic stroke, prediction of the tissue outcome after reperfusion can be used to identify patients that might benefit from mechanical thrombectomy (MT). The aim of this work was to develop a deep learning model that can predict the follow-up infarct location and extent exclusively based on acute single-phase computed tomography angiography (CTA) datasets. In comparison to CT perfusion (CTP), CTA imaging is more widely available, less prone to artifacts, and the established standard of care in acute stroke imaging protocols. Furthermore, recent RCTs have shown that also patients with large established infarctions benefit from MT, which might not have been selected for MT based on CTP core/penumbra mismatch analysis. Methods: All patients with acute large vessel occlusion of the anterior circulation treated at our institution between 12/2015 and 12/2020 were screened (N = 404) and 238 patients undergoing MT with successful reperfusion were included for final analysis. Ground truth infarct lesions were segmented on 24 h follow-up CT scans. Pre-processed CTA images were used as input for a U-Net-based convolutional neural network trained for lesion prediction, enhanced with a spatial and channel-wise squeeze-and-excitation block. Post-processing was applied to remove small predicted lesion components. The model was evaluated using a 5-fold cross-validation and a separate test set with Dice similarity coefficient (DSC) as the primary metric and average volume error as the secondary metric. Results: The mean ± standard deviation test set DSC over all folds after post-processing was 0.35 ± 0.2 and the mean test set average volume error was 11.5 mL. The performance was relatively uniform across models with the best model according to the DSC achieved a score of 0.37 ± 0.2 after post-processing and the best model in terms of average volume error yielded 3.9 mL. Conclusion: 24 h follow-up infarct prediction using acute CTA imaging exclusively is feasible with DSC measures comparable to results of CTP-based algorithms reported in other studies. The proposed method might pave the way to a wider acceptance, feasibility, and applicability of follow-up infarct prediction based on artificial intelligence.

Association of clinical outcome and imaging endpoints in extensive ischemic stroke-comparing measures of cerebral edema.

OBJECTIVES: Ischemic edema is associated with worse clinical outcomes, especially in large infarcts. Computed tomography (CT)-based densitometry allows direct quantification of absolute edema volume (EV), which challenges indirect biomarkers like midline shift (MLS). We compared EV and MLS as imaging biomarkers of ischemic edema and predictors of malignant infarction (MI) and very poor clinical outcome (VPCO) in early follow-up CT of patients with large infarcts. MATERIALS AND METHODS: Patients with anterior circulation stroke, large vessel occlusion, and Alberta Stroke Program Early CT Score (ASPECTS) ≤ 5 were included. VPCO was defined as modified Rankin scale (mRS) ≥ 5 at discharge. MLS and EV were quantified at admission and in follow-up CT 24 h after admission. Correlation was analyzed between MLS, EV, and total infarct volume (TIV). Multivariable logistic regression and receiver operating characteristics curve analyses were performed to compare MLS and EV as predictors of MI and VPCO. RESULTS: Seventy patients (median TIV 110 mL) were analyzed. EV showed strong correlation to TIV (r = 0.91, p < 0.001) and good diagnostic accuracy to classify MI (EV AUC 0.74 [95%CI 0.61-0.88] vs. MLS AUC 0.82 [95%CI 0.71-0.94]; p = 0.48) and VPCO (EV AUC 0.72 [95%CI 0.60-0.84] vs. MLS AUC 0.69 [95%CI 0.57-0.81]; p = 0.5) with no significant difference compared to MLS, which did not correlate with TIV < 110 mL (r = 0.17, p = 0.33). CONCLUSION: EV might serve as an imaging biomarker of ischemic edema in future studies, as it is applicable to infarcts of all volumes and predicts MI and VPCO in patients with large infarcts with the same accuracy as MLS. CLINICAL RELEVANCE STATEMENT: Utilization of edema volume instead of midline shift as an edema parameter would allow differentiation of patients with large and small infarcts based on the extent of edema, with possible advantages in the prediction of treatment effects, complications, and outcome. KEY POINTS: • CT densitometry-based absolute edema volume challenges midline shift as current gold standard measure of ischemic edema. • Edema volume predicts malignant infarction and poor clinical outcome in patients with large infarcts with similar accuracy compared to MLS irrespective of the lesion extent. • Edema volume might serve as a reliable quantitative imaging biomarker of ischemic edema in acute stroke triage independent of lesion size.

Thrombectomy in Patients With Ischemic Stroke Without Salvageable Tissue on CT Perfusion.

BACKGROUND: Computed tomography perfusion (CTP) imaging is regularly used to guide patient selection for mechanical thrombectomy (MT). However, the effect of MT in patients without salvageable tissue on CTP has not been investigated. The purpose of this study was to assess the effect of MT in patients with stroke without perfusion mismatch profiles. METHODS: This observational study analyzed patients with ischemic stroke consecutively treated between March 1, 2015, and January 31, 2022, triaged by multimodal-computed tomography undergoing MT. CTP lesion-core mismatch profiles were defined using a mismatch volume/ratio of ≥10 mL/1.2, respectively. The primary end point was the rate of functional independence at 90 days, defined as the modified Rankin Scale score of 0 to 2. Recanalization was evaluated with the modified Thrombolysis in Cerebral Infarction scale. The effect of baseline variables on functional outcome was assessed using multivariable logistic regression analysis. Outcomes of patients with and without CTP-mismatch profiles were compared using 1:1 propensity score matching. RESULTS: Of 724 patients who met the inclusion criteria of this retrospective observational study, 110 (15%) patients had no CTP mismatch and were analyzed. The median age was 74 (interquartile range, 62-80) years and 53% were women. Successful recanalization (modified Thrombolysis in Cerebral Infarction score, ≥2b) was achieved in 66% (73) and associated with functional independence at 90 days (adjusted odds ratio, 7.33 [95% CI, 1.22-43.70]; P=0.03). A significant interaction was observed between recanalization and age, as well as the extent of infarction, indicating MT to be most effective in patients <70 years and with a baseline Alberta Stroke Program Early Computed Tomography Score range between 3 and 7. These findings remained stable after propensity score matching, analyzing 152 matched pairs with similar rates of functional independence between patients with and without CTP-mismatch profiles (17% versus 23%; P=0.42). CONCLUSIONS: In patients without CTP-mismatch profiles defined according to the EXTEND (Extending the Time for Thrombolysis in Emergency Neurological Deficits) criteria, recanalization was associated with improved functional outcomes. This effect was associated with baseline Alberta Stroke Program Early Computed Tomography Score and age, but not with the time from onset to imaging.

Quantification of ischemic brain edema after mechanical thrombectomy using dual-energy computed tomography in patients with ischemic stroke.

Net water uptake (NWU) is a quantitative imaging biomarker used to assess cerebral edema resulting from ischemia via Computed Tomography (CT)-densitometry. It serves as a strong predictor of clinical outcome. Nevertheless, NWU measurements on follow-up CT scans after mechanical thrombectomy (MT) can be affected by contrast staining. To improve the accuracy of edema estimation, virtual non-contrast images (VNC-I) from dual-energy CT scans (DECT) were compared to conventional polychromatic CT images (CP-I) in this study. We examined NWU measurements derived from VNC-I and CP-I to assess their agreement and predictive value in clinical outcome. 88 consecutive patients who received DECT as follow-up after MT were included. NWU was quantified on CP-I (cNWU) and VNC-I (vNWU). The clinical endpoint was functional independence at discharge. cNWU and vNWU were highly correlated (r = 0.71, p < 0.0001). The median difference between cNWU and vNWU was 8.7% (IQR: 4.5-14.1%), associated with successful vessel recanalization (mTICI2b-3) (ß: 11.6%, 95% CI 2.9-23.0%, p = 0.04), and age (ß: 4.2%, 95% CI 1.3-7.0%, p = 0.005). The diagnostic accuracy to classify outcome between cNWU and vNWU was similar (AUC:0.78 versus 0.77). Although there was an 8.7% median difference, indicating potential edema underestimation on CP-I, it did not have short-term clinical implications.

Prognostic value of recanalization attempts in endovascular therapy for M2 segment middle cerebral artery occlusions.

BACKGROUND: There is growing evidence suggesting efficacy of endovascular therapy for M2 occlusions of the middle cerebral artery. More than one recanalization attempt is often required to achieve successful reperfusion in M2 occlusions, associated with general concerns about the safety of multiple maneuvers in these medium vessel occlusions. AIM: The aim of this study was to investigate the association between the number of recanalization attempts and functional outcomes in M2 occlusions in comparison with large vessel occlusions (LVO). METHODS: Retrospective multicenter cohort study of patients who underwent endovascular therapy for primary M2 occlusions. Patients were enrolled in the German Stroke Registry at 1 of 25 comprehensive stroke centers between 2015 and 2021. The study cohort was subdivided into patients with unsuccessful reperfusion (mTICI 0-2a) and successful reperfusion (mTICI 2b-3) at first, second, third, fourth, or ⩾fifth recanalization attempt. Primary outcome was 90-day functional independence defined as modified Rankin Scale score of 0-2. Safety outcome was the occurrence of symptomatic intracranial hemorrhage. Internal carotid artery or M1 occlusions were defined as LVO and served as comparison group. RESULTS: A total of 1078 patients with M2 occlusion were included. Successful reperfusion was observed in 87.1% and 90-day functional independence in 51.9%. The rate of functional independence decreased gradually with increasing number of recanalization attempts (p < 0.001). In both M2 occlusions and LVO, successful reperfusion within three attempts was associated with greater odds of functional independence, while success at ⩾fourth attempt was not. Patients with ⩾4 attempts exhibited higher rates of symptomatic intracranial hemorrhage in M2 occlusions (6.5% vs 2.7%, p = 0.02) and LVO (7.2% vs 3.5%, p < 0.001). CONCLUSION: This study suggests a clinical benefit of successful reperfusion within three recanalization attempts in endovascular therapy for M2 occlusions, which was similar in LVO. Our findings reduce concerns about the risk-benefit ratio of multiple attempts in M2 medium vessel occlusions. DATA ACCESS STATEMENT: The data that support the findings of this study are available on reasonable request after approval of the German Stroke Registry (GSR) steering committee. CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03356392.

Early neurological deterioration in patients with acute ischemic stroke is linked to unfavorable cerebral venous outflow.

INTRODUCTION: Early neurological deterioration (END) is associated with poor outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Causes of END after mechanical thrombectomy (MT) include unsuccessful recanalization and reperfusion hemorrhages. However, little is known about END excluding the aforementioned causes. We aimed to investigate factors associated with unexplained END (ENDunexplained) with regard to the cerebral collateral status. PATIENTS AND METHODS: Multicenter retrospective study of AIS-LVO patients with successful MT (mTICI 2b-3). On admission CT angiography (CTA), pial arterial collaterals and venous outflow (VO) were assessed using the modified Tan-Scale and the Cortical Vein Opacification Score (COVES), respectively. ENDunexplained was defined as an increase in NIHSS score of ⩾ 4 within the first 24 hours after MT without parenchymal hemorrhage on follow-up imaging. Multivariable regression analyses were performed to examine factors of ENDunexplained and unfavorable functional outcome (modified Rankin Scale score 3-6). RESULTS: A total of 620 patients met the inclusion criteria. ENDunexplained occurred in 10% of patients. While there was no significant difference in pial arterial collaterals, patients with ENDunexplained exhibited more often unfavorable VO (81% vs. 53%; P < 0.001). Unfavorable VO (aOR [95% CI]; 2.56 [1.02-6.40]; P = 0.045) was an independent predictor of ENDunexplained. ENDunexplained was independently associated with unfavorable functional outcomes at 90 days (aOR [95% CI]; 6.25 [2.06-18.94]; P = 0.001). DISCUSSION AND CONCLUSION: Unfavorable VO on admission CTA was associated with ENDunexplained. ENDunexplained was independently linked to unfavorable functional outcomes at 90 days. Identifying AIS-LVO patients at risk of ENDunexplained may help to select patients for intensified monitoring and guide to optimal treatment regimes.

Effect of short- versus long-term serum glucose levels on early ischemic water homeostasis and functional outcome in patients with large vessel occlusion stroke.

BACKGROUND AND PURPOSE: In ischemic stroke, the impact of short- versus long-term blood glucose level (BGL) on early lesion pathophysiology and functional outcome has not been assessed. The purpose of this study was to directly compare the effect of long-term blood glucose (glycated hemoglobin [HbA1c]) versus serum BGL on early edema formation and functional outcome. METHODS: Anterior circulation ischemic stroke patients who underwent mechanical thrombectomy after multimodal computed tomography (CT) on admission were analyzed. Endpoints were early ischemic cerebral edema, measured by quantitative net water uptake (NWU) on initial CT and functional independence at Day 90. RESULTS: A total of 345 patients were included. Patients with functional independence had significantly lower baseline NWU (3.1% vs. 8.3%; p < 0.001) and lower BGL (113 vs. 123 mg/dL; p < 0.001) than those without functional independence, while HbA1c levels did not differ significantly (5.7% vs. 5.8%; p = 0.15). A significant association was found for NWU and BGL (ß = 0.02, 95% confidence interval [CI] 0.006-0.03; p = 0.002), but not for HbA1c and NWU (ß = -0.16, 95% CI -0.53-0.21; p = 0.39). Mediation analysis showed that 67% of the effect of BGL on functional outcome was mediated by early edema formation. CONCLUSION: Aggravated early edema and worse functional outcome was associated with elevated short-term serum BGL, but not with HbA1c levels. Hence, the link between short-term BGL and early edema development might be used as a target for adjuvant therapy in patients with ischemic stroke.

Predictors of functional outcome after thrombectomy for M2 occlusions: a large scale experience from clinical practice.

Mechanical thrombectomy (MT) for acute ischemic stroke with medium vessel occlusions is still a matter of debate. We sought to identify factors associated with clinical outcome after MT for M2-occlusions based on data from the German Stroke Registry-Endovascular Treatment (GSR-ET). All patients prospectively enrolled in the GSR-ET from 05/2015 to 12/2021 were analyzed (NCT03356392). Inclusion criteria were primary M2-occlusions and availability of relevant clinical data. Factors associated with excellent/good outcome (modified Rankin scale mRS 0-1/0-2), poor outcome/death (mRS 5-6) and mRS-increase pre-stroke to day 90 were determined in multivariable logistic regression. 1348 patients were included. 1128(84%) had successful recanalization, 595(44%) achieved good outcome, 402 (30%) had poor outcome. Successful recanalization (odds ratio [OR] 4.27 [95% confidence interval 3.12-5.91], p < 0.001), higher Alberta stroke program early CT score (OR 1.25 [1.18-1.32], p < 0.001) and i.v. thrombolysis (OR 1.28 [1.07-1.54], p < 0.01) increased probability of good outcome, while age (OR 0.95 [0.94-0.95], p < 0.001), higher pre-stroke-mRS (OR 0.36 [0.31-0.40], p < 0.001), higher baseline NIHSS (OR 0.89 [0.88-0.91], p < 0.001), diabetes (OR 0.52 [0.42-0.64], p < 0.001), higher number of passes (OR 0.75 [0.70-0.80], p < 0.001) and intracranial hemorrhage (OR 0.26 [0.14-0.46], p < 0.001) decreased the probability of good outcome. Additional predictors of mRS-increase pre-stroke to 90d were dissections, perforations (OR 1.59 [1.11-2.29], p < 0.05) and clot migration, embolization (OR 1.67 [1.21-2.30], p < 0.01). Corresponding to large-vessel-occlusions, younger age, low pre-stroke-mRS, low severity of acute clinical disability, i.v. thrombolysis and successful recanalization were associated with good outcome while diabetes and higher number of passes decreased probability of good outcome after MT in M2 occlusions. Treatment related complications increased probability of mRS increase pre-stroke to 90d.

Brain edema growth after thrombectomy is associated with comprehensive collateral blood flow.

BACKGROUND: We determined whether a comprehensive assessment of cerebral collateral blood flow is associated with ischemic lesion edema growth in patients successfully treated by thrombectomy. METHODS: This was a multicenter retrospective study of ischemic stroke patients who underwent thrombectomy treatment of large vessel occlusions. Collateral status was determined using the cerebral collateral cascade (CCC) model, which comprises three components: arterial collaterals (Tan Scale) and venous outflow profiles (Cortical Vein Opacification Score) on CT angiography, and tissue-level collaterals (hypoperfusion intensity ratio) on CT perfusion. Quantitative ischemic lesion net water uptake (NWU) was used to determine edema growth between admission and follow-up non-contrast head CT (ΔNWU). Three groups were defined: CCC+ (good pial collaterals, tissue-level collaterals, and venous outflow), CCC- (poor pial collaterals, tissue-level collaterals, and venous outflow), and CCCmixed (remainder of patients). Primary outcome was ischemic lesion edema growth (ΔNWU). Multivariable regression models were used to assess the primary and secondary outcomes. RESULTS: 538 patients were included. 157 patients had CCC+, 274 patients CCCmixed, and 107 patients CCC- profiles. Multivariable regression analysis showed that compared with patients with CCC+ profiles, CCC- (ß 1.99, 95% CI 0.68 to 3.30, P=0.003) and CCC mixed (ß 1.65, 95% CI 0.75 to 2.56, P<0.001) profiles were associated with greater ischemic lesion edema growth (ΔNWU) after successful thrombectomy treatment. ΔNWU (OR 0.74, 95% CI 0.68 to 0.8, P<0.001) and CCC+ (OR 13.39, 95% CI 4.88 to 36.76, P<0.001) were independently associated with functional independence. CONCLUSION: A comprehensive assessment of cerebral collaterals using the CCC model is strongly associated with edema growth and functional independence in acute stroke patients successfully treated by endovascular thrombectomy.

Haemorrhage after thrombectomy with adjuvant thrombolysis in unknown onset stroke depends on high early lesion water uptake.

BACKGROUND AND PURPOSE: In wake-up stroke, CT-based quantitative net water uptake (NWU) might serve as an alternative tool to MRI to guide intravenous thrombolysis with alteplase (IVT). An important complication after IVT is symptomatic intracerebral haemorrhage (sICH). As NWU directly implies ischaemic lesion progression, reflecting blood-brain barrier injury, we hypothesised that NWU predicts sICH in patients who had a ischaemic stroke undergoing thrombectomy with unknown onset. METHODS: Consecutive analysis of all patients who had unknown onset anterior circulation ischaemic stroke who underwent CT at baseline and endovascular treatment between December 2016 and October 2020. Quantitative NWU was assessed on baseline CT. The primary endpoint was sICH. The association of NWU and other baseline parameters to sICH was investigated using inverse-probability weighting (IPW) analysis. RESULTS: A total of 88 patients were included, of which 46 patients (52.3%) received IVT. The median NWU was 10.7% (IQR: 5.1-17.7). The proportion of patients with any haemorrhage and sICH were 35.2% and 13.6%. NWU at baseline was significantly higher in patients with sICH (19.1% vs 9.6%, p<0.0001) and the median Alberta Stroke Program Early CT Score (ASPECTS) was lower (5 vs 8, p<0.0001). Following IPW, there was no association between IVT and sICH in unadjusted analysis. However, after adjusting for ASPECTS and NWU, there was a significant association between IVT administration and sICH (14.6%, 95% CI: 3.3% to 25.6%, p<0.01). CONCLUSION: In patients with ischaemic stroke with unknown onset, the combination of high NWU with IVT is directly linked to higher rates of sICH. Besides ASPECTS for evaluating the extent of the early infarct lesion, quantitative NWU could be used as an imaging biomarker to assess the degree of blood-brain barrier damage in order to predict the risk of sICH in patients with wake up stroke.

Comparison of Thrombolysis In Cerebral Infarction (TICI) 2b and TICI 3 reperfusion in endovascular therapy for large ischemic anterior circulation strokes.

BACKGROUND: Landmark thrombectomy trials have provided evidence that selected patients with large ischemic stroke benefit from successful endovascular therapy, commonly defined as incomplete (modified Thrombolysis In Cerebral Infarction (mTICI) 2b) or complete reperfusion (mTICI 3). We aimed to investigate whether mTICI 3 improves functional outcomes compared with mTICI 2b in large ischemic strokes. METHODS: This retrospective multicenter cohort study was conducted to compare mTICI 2b versus mTICI 3 in large ischemic strokes in the anterior circulation. Patients enrolled in the German Stroke Registry between 2015-2021 were analyzed. Large ischemic stroke was defined as an Alberta Stroke Program Early CT Score (ASPECTS) of 3-5. Patients were matched by final mTICI grade using propensity score matching. Primary outcome was the 90-day modified Rankin Scale (mRS) score. RESULTS: After matching, 226 patients were included. Baseline and imaging characteristics were balanced between mTICI 2b and mTICI 3 patients. There was no shift on the mRS favoring mTICI 3 compared with mTICI 2b in large ischemic strokes (adjusted common odds ratio (acOR) 1.12, 95% confidence interval (95% CI) 0.64 to 1.94, P=0.70). The rate of symptomatic intracranial hemorrhage was higher in mTICI 2b than in mTICI 3 patients (12.6% vs 4.5%, P=0.03). Mortality at 90 days did not differ between mTICI 3 and mTICI 2b (33.6% vs 37.2%; adjusted OR 0.69, 95% CI 0.33 to 1.45, P=0.33). CONCLUSIONS: In endovascular therapy for large ischemic strokes, mTICI 3 was not associated with better 90-day functional outcomes compared with mTICI 2b. This study suggests that mTICI 2b might be warranted as the final angiographic result, questioning the benefit/risk ratio of additional maneuvers to seek for mTICI 3 in large ischemic strokes. TRIAL REGISTRATION NUMBER: NCT03356392.

Edema Reduction versus Penumbra Salvage: Investigating Treatment Effects of Mechanical Thrombectomy in Ischemic Stroke.

OBJECTIVE: Mechanical thrombectomy (MT) is of benefit to patients with ischemic stroke; however, the effect of recanalization on lesion pathophysiology is not yet well understood. The aim of this study was to quantitatively assess how the effect of vessel recanalization on clinical outcome is mediated by edema reduction versus penumbra salvage. METHODS: Consecutive analysis was made of anterior circulation ischemic stroke patients triaged by multimodal computed tomography (CT) undergoing MT. Edema reduction was defined using the difference of quantitative net water uptake (NWU) determined on baseline and follow-up CT (∆NWU). Penumbra salvage volume (PSV) was defined as the difference between admission penumbra and net infarct growth volumes to follow-up. Mediation analyses were performed with vessel recanalization as independent variable (modified Thrombolysis in Cerebral Infarction ≥ 2b) and ∆NWU/PSV as mediator variables. Modified Rankin Scale scores at 90 days served as endpoint. RESULTS: Of 422 included patients, 321 (76%) achieved successful recanalization. The median ∆NWU was 6.8% (interquartile range [IQR] = 3.9-10.4), and the median PSV was 66ml (IQR = 8-124). ∆NWU, PSV, and recanalization were significantly associated with functional outcome in logistic regression analysis. ∆NWU and PSV partially mediated the relationship between recanalization and outcome. Sixty-six percent of the relationship between recanalization and functional outcome could be explained by treatment-induced edema reduction, whereas 22% was mediated by PSV (p < 0.0001). INTERPRETATION: Compared to penumbra salvage, edema reduction was a stronger mediator of the effect of recanalization on functional outcome. Given the current trials on adjuvant neuroprotectants also targeting ischemic edema formation, combining reperfusion with antiedematous neuroprotectants may have synergistic effects resulting in better outcomes in patients with ischemic stroke. ANN NEUROL 2023.

Investigating Neurologic Improvement After IV Thrombolysis: The Effect of Time From Stroke Onset vs Imaging-Based Tissue Clock.

BACKGROUND AND OBJECTIVES: Time from stroke onset is associated with clinical response to intravenous thrombolysis (IVT) with alteplase and is therefore used to select patients for treatment. Alternatively, neuroimaging may be used for treatment in the uncertain or extended time window. We hypothesized that the patient-specific imaging indicator of ischemic lesion progression ("tissue clock") using CT perfusion (CTP) or quantitative net water uptake (NWU) is a predictor of early neurologic improvement (ENI) independent of time. METHODS: Observational study of anterior circulation ischemic stroke patients with proximal vessel occlusion and known time from symptom onset triaged by multimodal CT undergoing endovascular treatment. Quantitative NWU using an established threshold (11.5%) or CTP lesion core mismatch (EXTEND criteria) was used to estimate ischemic lesion progression. The treatment effect of IVT depending on lesion progression defined by tissue clock vs time clock was assessed by inverse probability weighting (IPW). End points were binarized ENI and functional independence at day 90. RESULTS: Four hundred nine patients were included, of which 223 (54.5%) received IVT. The proportion of patients within an early time window (<4.5 hours), low NWU, and CTP mismatch were 45.0%, 86.5%, and 80.3%. In IPW, IVT was associated with higher rates of ENI (%-difference: 7.3%, p = 0.02). For patients with CTP mismatch or low NWU, IVT was associated with a 9.6% or 7.2% higher rate of ENI, which was different than the effect of IVT in patients without CTP mismatch or high NWU (-9.3%/-7.3%; p = 0.004/p = 0.03), whereas early treatment window did not modify the effect of IVT. DISCUSSION: CT-based measures of the "tissue clock" might identify patients who benefit from IVT more accurately than conventional time windows. Considering the high number of patients with early "tissue clock" (low NWU/CTP mismatch) within an extended time window, considerable benefit from IVT using imaging indicators of the "tissue clock" may be achieved.

Thrombectomy for M2 Occlusions: Predictors of Successful and Futile Recanalization.

BACKGROUND: Patient-specific factors associated with successful recanalization in mechanical thrombectomy (MT) have been evaluated for acute ischemic stroke with large vessel occlusion. However, MT for M2 occlusions is still a matter of debate, and predictors of successful and futile recanalization have not been assessed in detail. We sought to identify predictors of recanalization success in patients with M2 occlusions undergoing MT based on large-scale clinical data. METHODS: All patients prospectively enrolled in the German Stroke Registry (May, 2015 to December, 2021) were screened (N=13 082). Inclusion criteria for the complete case analysis were isolated M2 occlusions. Standard descriptive statistics and multivariable logistic regression analysis were used to identify factors associated with successful recanalization (Thrombolysis in Cerebral Infarction [TICI]≥2b), complete recanalization (TICI=3) and futile recanalization (TICI≥2b with 90-day modified Rankin Scale [mRS] score >2). RESULTS: One thousand two hundred ninety-four patients were included, thereof 439 (33.9%) with TICI=2b and 643 (49.7%) with TICI=3. Five hundred sixty-nine (44%) patients had good functional outcome (90-day mRS score ≤2). In multivariable logistic regression, general anesthesia (adjusted odds ratio [aOR], 1.47 [95% CI, 1.05-2.09]; P<0.05) was associated with higher probability of TICI≥2b while intraprocedural change from local to general anesthesia (aOR, 0.49 [0.26-0.95]; P<0.05) and higher pre-mRS (aOR, 0.75 [0.67-0.85]; P<0.001) lowered probability of successful recanalization. Futile recanalization was associated with higher age (aOR, 1.05 [1.04-1.07]; P<0.001), higher prestroke mRS (aOR, 3.12 [2.49-3.91]; P<0.001), higher NIHSS at admission (aOR, 1.11 [1.08-1.14]; P<0.001), diabetes (aOR, 1.96 [1.38-2.8]; P<0.001), higher number of passes (aOR, 1.29 [1.14-1.46]; P<0.001), and adverse events (aOR, 1.82 [1.2-2.74]; P<0.01). Higher Alberta Stroke Program Early CT Score (aOR, 0.85 [0.76-0.94]; P<0.01) and IV thrombolysis (aOR, 0.71 [0.52-0.97]; P<0.05) reduced risk of futile recanalization. CONCLUSIONS: In patients with M2 occlusions, successful recanalization was significantly associated with general anesthesia and low prestroke mRS, while intraprocedural change from conscious sedation to general anesthesia increased risk of unsuccessful recanalization, presumably caused by difficult anatomy and movement of patients in these cases. Futile recanalization was associated with severe prestroke mRS, comorbidity diabetes, number of passes and adverse events during treatment. IV thrombolysis reduced the risk of futile recanalization.