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.

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 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.

Hypoperfusion Intensity Ratio Is Correlated With the Risk of Parenchymal Hematoma After Endovascular Stroke Treatment.

BACKGROUND: Parenchymal hematoma (PH) is a major complication after endovascular treatment (EVT) for ischemic stroke. The hypoperfusion intensity ratio (HIR) represents a perfusion parameter reflecting arterial collateralization and cerebral microperfusion in ischemic brain tissue. We hypothesized that HIR correlates with the risk of PH after EVT. METHODS: Retrospective multicenter cohort study of patients with large vessel occlusion who underwent EVT between 2013 and 2021 at one of the 2 comprehensive stroke centers (University Medical Center Hamburg-Eppendorf, Germany and Stanford University School of Medicine, CA). HIR was automatically calculated on computed tomography perfusion studies as the ratio of brain volume with time-to-max (Tmax) delay >10 s over volume with Tmax >6 s. Reperfusion hemorrhages were assessed according to the Heidelberg Bleeding Classification. Primary outcome was PH occurrence (PH+) or absence (PH-) on follow-up imaging. Secondary outcome was good clinical outcome defined as a 90-day modified Rankin Scale score of 0 to 2. RESULTS: A total of 624 patients met the inclusion criteria. We observed PH in 91 (14.6%) patients after EVT. PH+ patients had higher HIR on admission compared with PH- patients (median, 0.6 versus 0.4; P<0.001). In multivariable regression, higher admission blood glucose (adjusted odds ratio [aOR], 1.08 [95% CI, 1.04-1.13]; P<0.001), extensive baseline infarct defined as Alberta Stroke Program Early CT Score ≤5 (aOR, 2.48 [1.37-4.42]; P=0.002), and higher HIR (aOR, 1.22 [1.09-1.38]; P<0.001) were independent determinants of PH after EVT. Both higher HIR (aOR, 0.83 [0.75-0.92]; P<0.001) and PH on follow-up imaging (aOR, 0.39 [0.18-0.80]; P=0.013) were independently associated with lower odds of achieving good clinical outcome. CONCLUSIONS: Poorer (higher) HIR on admission perfusion imaging was strongly associated with PH occurrence after EVT. HIR as a surrogate for cerebral microperfusion might reflect tissue vulnerability for reperfusion hemorrhages. This automated and quickly available perfusion parameter might help to assess the need for intensive medical care after EVT.

Association Between Recanalization Attempts and Functional Outcome After Thrombectomy for Large Ischemic Stroke.

BACKGROUND: Recently, 3 randomized controlled trials provided high-level evidence that patients with large ischemic stroke achieved better functional outcomes after endovascular therapy than with medical care alone. We aimed to investigate whether the clinical benefit of endovascular therapy is associated with the number of recanalization attempts in extensive baseline infarction. METHODS: This retrospective multicenter study enrolled patients from the German Stroke Registry who underwent endovascular therapy for anterior circulation large vessel occlusion between 2015 and 2021. Large ischemic stroke was defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5. The study cohort was divided into patients with unsuccessful reperfusion (Thrombolysis in Cerebral Infarction score, 0-2a) and successful reperfusion (Thrombolysis in Cerebral Infarction score, 2b/3) at attempts 1, 2, 3, or ≥4. The primary outcome was favorable functional outcome defined as modified Rankin Scale score of 0 to 3 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage after 24 hours and death within 90 days. Multivariable logistic regression was used to identify independent determinants of primary and secondary outcomes. RESULTS: A total of 348 patients met the inclusion criteria. Successful reperfusion was observed in 83.3% and favorable functional outcomes in 36.2%. Successful reperfusion at attempts 1 (adjusted odds ratio, 5.97 [95% CI, 1.71-24.43]; P=0.008) and 2 (adjusted odds ratio, 6.32 [95% CI, 1.73-26.92]; P=0.008) increased the odds of favorable functional outcome, whereas success at attempts 3 or ≥4 did not. Patients with >2 attempts showed higher rates of symptomatic intracranial hemorrhage (12.8% versus 6.5%; P=0.046). Successful reperfusion at any attempt lowered the odds of death compared with unsuccessful reperfusion. CONCLUSIONS: In patients with large vessel occlusion and Alberta Stroke Program Early Computed Tomography Score of 3 to 5, the clinical benefit of endovascular therapy was linked to the number of recanalization attempts required for successful reperfusion. Our findings encourage to perform at least 2 recanalization attempts to seek for successful reperfusion in large ischemic strokes, while >2 attempts should follow a careful risk-benefit assessment in these highly affected patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03356392.

Unfavorable cerebral venous outflow is associated with futile recanalization in acute ischemic stroke patients.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) has proven to be the standard of care for patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). However, high revascularization rates do not necessarily result in favorable functional outcomes. We aimed to investigate imaging biomarkers associated with futile recanalization, defined as unfavorable functional outcome despite successful recanalization in AIS-LVO patients. METHODS: A retrospective multicenter cohort study was made of AIS-LVO patients treated by MT. Successful recanalization was defined as modified Thrombolysis in Cerebral Infarction score of 2b-3. A modified Rankin Scale score of 3-6 at 90 days was defined as unfavorable functional outcome. Cortical Vein Opacification Score (COVES) was used to assess venous outflow (VO), and the Tan scale was utilized to determine pial arterial collaterals on admission computed tomography angiography (CTA). Unfavorable VO was defined as COVES ≤ 2. Multivariable regression analysis was performed to investigate vascular imaging factors associated with futile recanalization. RESULTS: Among 539 patients in whom successful recanalization was achieved, unfavorable functional outcome was observed in 59% of patients. Fifty-eight percent of patients had unfavorable VO, and 31% exhibited poor pial arterial collaterals. In multivariable regression, unfavorable VO was a strong predictor (adjusted odds ratio = 4.79, 95% confidence interval = 2.48-9.23) of unfavorable functional outcome despite successful recanalization. CONCLUSIONS: We observe that unfavorable VO on admission CTA is a strong predictor of unfavorable functional outcomes despite successful vessel recanalization in AIS-LVO patients. Assessment of VO profiles could help as a pretreatment imaging biomarker to determine patients at risk for futile recanalization.

Intravenous tPA (Tissue-Type Plasminogen Activator) Correlates With Favorable Venous Outflow Profiles in Acute Ischemic Stroke.

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<0.001) compared with tPA- patients. One hundred eighty-five patients (51%) in the tPA+ and 100 patients (28%) in the tPA- group exhibited favorable VO (P<0.001). Multivariable regression analysis showed that tPA administration was a strong independent predictor of favorable VO profiles (OR, 2.6 [95% CI, 1.7-4.0]; P<0.001) after control for favorable pial arterial CTA collaterals, favorable tissue-level collaterals on CT perfusion, age, presentation National Institutes of Health Stroke Scale, antiplatelet/anticoagulant treatment, history of atrial fibrillation and time from symptom onset to imaging. 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.

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.

Endovascular Thrombectomy for Large Ischemic Strokes with ASPECTS 0-2: a Meta-analysis of Randomized Controlled Trials.

PURPOSE: Randomized controlled trials (RCTs) demonstrated a treatment effect of endovascular thrombectomy in acute ischemic stroke with large infarct, commonly defined as an Alberta Stroke Program Early CT Score (ASPECTS) of 3-5. However, data on endovascular thrombectomy in patients with very low ASPECTS of 0-2 remain scarce. METHODS: We conducted a systematic review and meta-analysis of RCTs comparing endovascular thrombectomy versus medical treatment alone in acute ischemic anterior circulation stroke with very large infarct, defined as ASPECTS of 0-2. The primary outcome was the shift toward better functional outcomes on the 90-day modified Rankin Scale (mRS). Random effects meta-analysis was performed using the generic inverse variance method. RESULTS: Literature research identified four RCTs which evaluated the treatment effect of endovascular thrombectomy for large infarcts and provided a subgroup analysis of the mRS shift in patients with ASPECTS of 0-2. The pooled analysis showed a significant shift toward better 90-day mRS scores in favor of endovascular thrombectomy (pooled odds ratio, 1.62, 95% confidence interval, 1.29-2.04, P < 0.001). CONCLUSION: This meta-analysis suggests a treatment effect of endovascular thrombectomy in specific patients with very low ASPECTS of 0-2, challenging the use of ASPECTS for treatment selection in acute ischemic stroke due to large vessel occlusion. An individual patient meta-analysis of RCTs would strengthen evidence in the treatment of patients with ASPECTS of 0-2.

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.

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.

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.

Association between occlusion location, net water uptake and ischemic lesion growth in large vessel anterior circulation strokes.

Ischemic lesion net water uptake (NWU) represents a quantitative imaging biomarker for cerebral edema in acute ischemic stroke. Data on NWU for distinct occlusion locations remain scarce, but might help to improve the prognostic value of NWU. In this retrospective multicenter cohort study, we compared NWU between patients with proximal large vessel occlusion (pLVO; ICA or proximal M1) and distal large vessel occlusion (dLVO; distal M1 or M2). NWU was quantified by densitometric measurements of the early ischemic region. Arterial collateral status was assessed using the Maas scale. Regression analysis was used to investigate the relationship between occlusion location, NWU and ischemic lesion growth. A total of 685 patients met inclusion criteria. Early ischemic lesion NWU was higher in patients with pLVO compared with dLVO (7.7% vs 3.9%, P < .001). The relationship between occlusion location and NWU was partially mediated by arterial collateral status. NWU was associated with absolute ischemic lesion growth between admission and follow-up imaging (ß estimate, 5.50, 95% CI, 3.81-7.19, P < .001). This study establishes a framework for the relationship between occlusion location, arterial collateral status, early ischemic lesion NWU and ischemic lesion growth. Future prognostic thresholds for NWU might be optimized by adjusting for the occlusion location.

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.

CTA Supplemented by CTP Increases Interrater Reliability and Endovascular Treatment Use in Patients with Aneurysmal SAH.

BACKGROUND AND PURPOSE: Cerebral vasospasm is a common complication of aneurysmal SAH and remains a risk factor for delayed cerebral ischemia and poor outcome. The interrater reliability of CTA in combination with CTP has not been sufficiently studied. We aimed to investigate the reliability of CTA alone and in combination with CTP in the detection of cerebral vasospasm and the decision to initiate endovascular treatment. MATERIALS AND METHODS: This is a retrospective single-center study including patients treated for aneurysmal SAH. Inclusion criteria were a baseline CTA and follow-up imaging including CTP due to suspected vasospasm. Three neuroradiologists were asked to grade 15 intracranial arterial segments in 71 cases using a tripartite scale (no, mild <50%, or severe >50% vasospasm). Raters further evaluated whether endovascular treatment should be indicated. The ratings were performed in 2 stages with a minimum interval of 6 weeks. The first rating included only CTA images, whereas the second rating additionally encompassed CTP images. All raters were blinded to any clinical information of the patients. RESULTS: Interrater reliability for per-segment analysis of vessels was highly variable (κ = 0.16-0.61). We observed a tendency toward higher interrater reliability in proximal vessel segments, except for the ICA. CTP did not improve the reliability for the per-segment analysis. When focusing on senior raters, the addition of CTP images resulted in higher interrater reliability for severe vasospasm (κ = 0.28; 95% CI, 0.10-0.46 versus κ = 0.46; 95% CI, 0.26-0.66) and subsequently higher concordance (κ = 0.23; 95% CI, -0.01-0.46 versus κ = 0.73; 95% CI, 0.55-0.91) for the decision of whether endovascular treatment was indicated. CONCLUSIONS: CTA alone offers only low interrater reliability in the graduation of cerebral vasospasm. However, using CTA in combination with CTP might help, especially senior neuroradiologists, to increase the interrater reliability to identify severe vasospasm following aneurysmal SAH and to increase the reliability regarding endovascular treatment decisions.

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.

Impact of Vaccination Status on Outcome of Patients With COVID-19 and Acute Ischemic Stroke Undergoing Mechanical Thrombectomy.

BACKGROUND: Data on impact of COVID-19 vaccination and outcomes of patients with COVID-19 and acute ischemic stroke undergoing mechanical thrombectomy are scarce. Addressing this subject, we report our multicenter experience. METHODS AND RESULTS: This was a retrospective analysis of patients with COVID-19 and known vaccination status treated with mechanical thrombectomy for acute ischemic stroke at 20 tertiary care centers between January 2020 and January 2023. Baseline demographics, angiographic outcome, and clinical outcome evaluated by the modified Rankin Scale score at discharge were noted. A multivariate analysis was conducted to test whether these variables were associated with an unfavorable outcome, defined as modified Rankin Scale score >3. A total of 137 patients with acute ischemic stroke (48 vaccinated and 89 unvaccinated) with acute or subsided COVID-19 infection who underwent mechanical thrombectomy attributable to vessel occlusion were included in the study. Angiographic outcomes between vaccinated and unvaccinated patients were similar (modified Thrombolysis in Cerebral Infarction ≥2b: 85.4% in vaccinated patients versus 86.5% in unvaccinated patients; P=0.859). The rate of functional independence (modified Rankin Scale score, ≤2) was 23.3% in the vaccinated group and 20.9% in the unvaccinated group (P=0.763). The mortality rate was 30% in both groups. In the multivariable analysis, vaccination status was not a significant predictor for an unfavorable outcome (P=0.957). However, acute COVID-19 infection remained significant (odds ratio, 1.197 [95% CI, 1.007-1.417]; P=0.041). CONCLUSIONS: Our study demonstrated no impact of COVID-19 vaccination on angiographic or clinical outcome of COVID-19-positive patients with acute ischemic stroke undergoing mechanical thrombectomy, whereas worsening attributable to COVID-19 was confirmed.

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.

Poor venous outflow profiles increase the risk of reperfusion hemorrhage after endovascular treatment.

To investigate whether unfavorable cerebral venous outflow (VO) predicts reperfusion hemorrhage after endovascular treatment (EVT), we conducted a retrospective multicenter cohort study of patients with acute ischemic stroke and large vessel occlusion (AIS-LVO). 629 AIS-LVO patients met inclusion criteria. VO profiles were assessed on admission CT angiography using the Cortical Vein Opacification Score (COVES). Unfavorable VO was defined as COVES ≤ 2. Reperfusion hemorrhages on follow-up imaging were subdivided into no hemorrhage (noRH), hemorrhagic infarction (HI) and parenchymal hematoma (PH). Patients with PH and HI less frequently achieved good clinical outcomes defined as 90-day modified Rankin Scale scores of ≤ 2 (PH: 13.6% vs. HI: 24.6% vs. noRH: 44.1%; p < 0.001). The occurrence of HI and PH on follow-up imaging was more likely in patients with unfavorable compared to patients with favorable VO (HI: 25.1% vs. 17.4%, p = 0.023; PH: 18.3% vs. 8.5%; p = <0.001). In multivariable regression analyses, unfavorable VO increased the likelihood of PH (aOR: 1.84; 95% CI: 1.03-3.37, p = 0.044) and HI (aOR: 2.05; 95% CI: 1.25-3.43, p = 0.005), independent of age, sex, admission National Institutes Health Stroke Scale scores and arterial collateral status. We conclude that unfavorable VO was associated with the occurrence of HI and PH, both related to worse clinical outcomes.