Arne Potreck

BACKGROUND AND PURPOSE: Patterns of the cerebral microcirculatory response with changes in the blood brain barrier and perfusion in patients with stroke and a large vessel occlusion are still unclear. We combined dynamic contrast enhancement (DCE) permeability and DSC perfusion MRI to detect such patterns beyond the borders of the diffusion-restricted infarct core after successful recanalization. MATERIALS AND METHODS: Combined DCE permeability and DSC perfusion MRI were performed prospectively in patients within 24h after successful mechanical recanalization of acute middle cerebral artery occlusion. Perfusion alterations were visually assessed on CBF and CBV maps, blood-brain-barrier disruptions (BBBD) on ktrans-maps and quantitatively evaluated with an ipsi-to contralateral ratio. Additionally, logistic regression analysis was performed for favorable early clinical outcome (NIHSS ≤2 at discharge). RESULTS: N=38 patients were included in the study. Subtle hyperperfusion beyond the DWI-lesion was present in 13/38 patients (34%) on CBF-maps and elevated CBV in 15/38 patients (39%). In these patients, the ratios between ipsi-and contralateral white matter CBF (p=0.01) and CBV (p<0.01) were elevated compared to patients with normal readings. Subtle, but visually and quantitatively elevated ktrans-values outside the DWI-lesion were observed in 7/38 patients (18%). None of these perfusion alterations were related to clinical outcome. CONCLUSIONS: Combined DCE-permeability and DSC-perfusion imaging is feasible in patients 24 hours after successful thrombectomy and reveals subtle hyperperfusion and BBBD occuring frequently beyond the diffusion restricted infarct core. ABBREVIATIONS: DCE = Dynamic Contrast Enhancement, BBBD = blood brain barrier disruption, MT = Mechanical thrombectomy.

BACKGROUND AND PURPOSE: Collaterals are important in large vessel occlusions (LVO), but the role of carotid artery disease (CAD) in this context remains unclear. This study aimed to investigate the impact of CAD on intracranial collateralization and infarct growth after thrombectomy in LVO. MATERIALS AND METHODS: All patients who underwent thrombectomy due to M1 segment occlusion from 01/2015 to 12/2021 were retrospectively included. Internal carotid artery stenosis according to NASCET was assessed on the affected and nonaffected sides. Collaterals were assessed according to the Tan score. Infarct growth was quantified by comparing ASPECTS on follow-up imaging with baseline ASPECTS. RESULTS: In total, 709 patients were included, 118 (16.6%) of whom presented with CAD (defined as severe stenosis ≥70% or occlusion ipsilaterally), with 42 cases (5.9%) being contralateral. Good collateralization (Tan 3) was present in 56.5% of the patients with ipsilateral CAD and 69.1% of the patients with contralateral CAD. The ipsilateral stenosis grade was an independent predictor of good collateral supply (adjusted OR: 1.01; NASCET point, 95% CI: 1.00–1.01; P = .009), whereas the contralateral stenosis grade was not (P = .34). Patients with ipsilateral stenosis of ≥70% showed less infarct growth (median ASPECTS decay: 1; IQR: 0–2) compared with patients with 0%–69% stenosis (median: 2; IQR: 1–3) (P = .005). However, baseline ASPECTS was significantly lower in patients with stenosis of 70%–100% (P < .001). The results of a multivariate analysis revealed that increasing ipsilateral stenosis grade (adjusted OR: 1.0; 95% CI: 0.99–1.00; P = .004) and good collateralization (adjusted OR: 0.5; 95% CI: 0.4–0.62; P < .001) were associated with less infarct growth. CONCLUSIONS: CAD of the ipsilateral ICA is an independent predictor of good collateral supply. Patients with CAD tend to have larger baseline infarct size but less infarct growth.

BACKGROUND: Optimal blood pressure (BP) management during endovascular stroke treatment is not well established. We studied whether an individualized approach for managing BP during endovascular stroke treatment gives a better clinical outcome than an approach with standardized systolic BP targets. METHODS: The INDIVIDUATE study (Individualized Blood Pressure Management During Endovascular Treatment of Acute Ischemic Stroke Under Procedural Sedation) is a randomized clinical trial with a prospective randomized open blinded end point (PROBE) design. Patients were recruited between October 1, 2020 and July 7, 2022 at a single center at a tertiary care university hospital. Patients were eligible, when they were suffering from acute ischemic stroke of the anterior circulation with occlusions of the internal carotid artery and middle cerebral artery and a National Institutes of Health Stroke Scale score of ≥8 receiving endovascular stroke treatment in procedural sedation. The intervention consists of an individualized BP management strategy, where preinterventional baseline systolic BP (SBP) values are used as intraprocedural BP targets. As a control, the standard treatment aims to maintain the intraprocedural SBP between 140 and 180 mm Hg. The main prespecified outcome is the proportion of favorable functional outcomes 90 days after stroke, defined as a modified Rankin Scale score of 0 to 2. RESULTS: Two hundred fifty patients were enrolled and included in the analysis, mean (SD) age was 77 (12) years, 142 (57%) patients were women, and mean (SD) National Institutes of Health Stroke Scale score on admission was 17 (5.2). In all, 123 (49%) patients were treated with individualized and 127 (51%) with standard BP management. Mean (SD) intraprocedural SBP was similar in the individualized versus standard BP management group (157 [19] versus 154 [18] mm Hg; P =0.16). The rate of favorable functional outcome after 3 months was not significantly different between the individualized versus the standard BP management group (25% versus 24%; adjusted odds ratio, 0.81 [95% CI, 0.41–1.61]; P =0.56). CONCLUSIONS: Among patients treated with endovascular stroke treatment due to an acute ischemic stroke of the anterior circulation, no significant difference was seen between the individualized BP management strategy, where intraprocedural SBP was targeted to baseline values, and the standardized regimen of targeting SBP between 140 and 180 mm Hg. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04578288.

Introduction: Endovascular stroke treatment (EST) is commonly performed for acute basilar artery occlusion (BAO). We aimed to identify the role of the exact location of BAO in patients receiving EST regarding the stroke etiology, recanalization success and prediction of favorable clinical outcome. Methods: Retrospective analysis of 191 consecutive patients treated for BAO with EST from 01/2013 until 06/2021 in a tertiary stroke center. Groups were defined according to exact location of BAO in I: proximal third, II: middle third, III: distal third and IV: tip of the basilar artery. Univariate and multivariate analyses were performed for BAO location comparing stroke etiology, recanalization result and favorable clinical outcome according to mRS 0–3 90 days after stroke onset. Results: Occlusion sides types I–IV were evenly distributed (37, 36, 60 and 58 patients). Types I and II were more often associated with large artery atherosclerosis (50 vs. 10 patients, p < 0.001). Distal/tip occlusion (types III/IV) occurred mostly in cardiac embolism or embolic stroke of unknown source (89 vs. 12 in types I/II, p < 0.001). Occlusion site correlated with the underlying stroke etiology (AUC [Area under the curve] 0.89, p < 0.0001, OR [odds ratio] for embolism in type IV: 245). Recanalization rates were higher in patients with distal occlusions (type III/IV OR 3.76, CI [95% confidence interval] 1.51–9.53, p = 0.0076). The BAO site is not predicting favorable clinical outcome. Conclusion: The exact basilar artery occlusion site in patients eligible for endovascular stroke treatment reflects the stroke etiology and is associated with differing recanalization success but does not predict favorable clinical outcome.

Background: Whether bridging therapy (intravenous thrombolysis [IVT] followed by mechanical thrombectomy) is superior to IVT alone in minor stroke with large vessel occlusion is unknown. Perfusion imaging may identify subsets of large vessel occlusion–related minor stroke patients with distinct response to bridging therapy. Methods: We conducted a multicenter international observational study of consecutive IVT-treated patients with minor stroke (National Institutes of Health Stroke Scale score ≤5) who had an anterior circulation large vessel occlusion and perfusion imaging performed before IVT, with a subset undergoing immediate thrombectomy. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month modified Rankin Scale score 0 to 1. We searched for an interaction between treatment group and mismatch volume (critical hypoperfusion–core volume). Results: Overall, 569 patients were included (172 and 397 in the bridging therapy and IVT groups, respectively). After propensity-score weighting, the distribution of baseline variables was similar across the 2 groups. In the entire population, bridging was associated with lower odds of achieving modified Rankin Scale score 0 to 1: odds ratio, 0.73 [95% CI, 0.55–0.96]; P =0.03. However, mismatch volume modified the effect of bridging on clinical outcome ( P _interaction =0.04 for continuous mismatch volume); bridging was associated with worse outcome in patients with, but not in those without, mismatch volume P _interaction =0.002). Conclusions: In our population of large vessel occlusion-related minor stroke patients, bridging therapy was associated with lower rates of good outcome as compared with IVT alone. However, mismatch volume was a strong modifier of the effect of bridging therapy over IVT alone, notably with worse outcome with bridging therapy in patients with mismatch volume ≤40 mL. Randomized trials should consider adding perfusion imaging for patient selection.

BACKGROUND AND PURPOSE: Information of collateral flow may help to determine eligibility for thrombectomy. Our aim was to identify CT perfusion–based surrogate parameters of good collateral status in acute anterior circulation ischemic stroke. MATERIALS AND METHODS: In this retrospective study, we assessed the collateral status of 214 patients who presented with acute ischemic stroke due to occlusion of the MCA M1 segment or the carotid terminus. Collaterals were assessed on dynamic CTA images analogous to the multiphase CTA score by Menon et al. CT perfusion parameters (time-to-maximum, relative CBF, hypoperfusion intensity ratio, and CBV-index) were assessed with RAPID software. The Spearman rank correlation and receiver operating characteristic analyses were performed to identify the parameters that correlate with collateral scores and good collateral supply (defined as a collateral score of ≥4). RESULTS: The Spearman rank correlation was highest for a relative CBF < 38% volume (ρ = −0.66, P < .001), followed by the hypoperfusion intensity ratio (ρ = −0.49, P < .001), CBV-index (ρ = 0.51, P < .001), and time-to-maximum > 8 seconds (ρ = −0.54, P < .001). Good collateral status was better identified by a relative CBF < 38% at a lesion size 8 seconds (sensitivity of 68%, specificity of 76%). CONCLUSIONS: Automated CT perfusion analysis allows accurate identification of collateral status in acute ischemic stroke. A relative CBF < 38% may be a better perfusion-based indicator of good collateral supply compared with time-to-maximum, the hypoperfusion intensity ratio, and the CBV-index.

Background and Purpose: Outcome prediction after mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO) is commonly performed by focusing on favorable outcome (modified Rankin Scale, mRS 0–2) after 3 months but poor outcome representing severe disability and mortality (mRS 5 and 6) might be of equal importance for clinical decision-making. Methods: We retrospectively analyzed patients with AIS and LVO undergoing MT from 2009 to 2018. Prognostic variables were grouped in baseline clinical (A), MRI-derived variables including mismatch [apparent diffusion coefficient (ADC) and time-to-maximum (Tmax) lesion volume] (B), and variables reflecting speed and extent of reperfusion (C) [modified treatment in cerebral ischemia (mTICI) score and time from onset to mTICI]. Three different scenarios were analyzed: (1) baseline clinical parameters only, (2) baseline clinical and MRI-derived parameters, and (3) all baseline clinical, imaging-derived, and reperfusion-associated parameters. For each scenario, we assessed prediction for favorable and poor outcome with seven different machine learning algorithms. Results: In 210 patients, prediction of favorable outcome was improved after including speed and extent of recanalization [highest area under the curve (AUC) 0.73] compared to using baseline clinical variables only (highest AUC 0.67). Prediction of poor outcome remained stable by using baseline clinical variables only (highest AUC 0.71) and did not improve further by additional variables. Prediction of favorable and poor outcomes was not improved by adding MR-mismatch variables. Most important baseline clinical variables for both outcomes were age, National Institutes of Health Stroke Scale, and premorbid mRS. Conclusions: Our results suggest that a prediction of poor outcome after AIS and MT could be made based on clinical baseline variables only. Speed and extent of MT did improve prediction for a favorable outcome but is not relevant for poor outcome. An MR mismatch with small ischemic core and larger penumbral tissue showed no predictive importance.

Objectives Automated CT perfusion mismatch assessment is an established treatment decision tool in acute ischemic stroke. However, the reliability of this method in patients with head motion is unclear. We therefore sought to evaluate the influence of head movement on automated CT perfusion mismatch evaluation. Methods Using a realistic CT brain-perfusion-phantom, 7 perfusion mismatch scenarios were simulated within the left middle cerebral artery territory. Real CT noise and artificial head movement were added. Thereafter, ischemic core, penumbra volumes and mismatch ratios were evaluated using an automated mismatch analysis software (RAPID, iSchemaView) and compared with ground truth simulated values. Results While CT scanner noise alone had only a minor impact on mismatch evaluation, a tendency towards smaller infarct core estimates (mean difference of −5.3 (−14 to 3.5) mL for subtle head movement and −7.0 (−14.7 to 0.7) mL for strong head movement), larger penumbral estimates (+9.9 (−25 to 44) mL and +35 (−14 to 85) mL, respectively) and consequently larger mismatch ratios (+0.8 (−1.5 to 3.0) for subtle head movement and +1.9 (−1.3 to 5.1) for strong head movement) were noted in dependence of patient head movement. Conclusions Motion during CT perfusion acquisition influences automated mismatch evaluation. Potentially treatment-relevant changes in mismatch classifications in dependence of head movement were observed and occurred in favor of mechanical thrombectomy.

To investigate the reliability and accuracy of Alberta Stroke Program Early Computed Tomography Scores (ASPECTS) derived from flatpanel detector computed tomography pooled blood volume maps compared to non-contrast computed tomography and multidetector computed tomography perfusion cerebral blood volume maps. ASPECTS from pooled blood volume maps were evaluated retrospectively by two experienced readers for 37 consecutive patients with acute middle cerebral artery (MCA) M1 occlusion who underwent flatpanel detector computed tomography perfusion imaging before mechanical thrombectomy between November 2016 and February 2019. For comparison with ASPECTS from non-contrast computed tomography and cerebral blood volume maps, a matched-pair analysis according to pre-stroke modified Rankin scale, age, stroke severity, site of occlusion, time from stroke onset to imaging and final modified thrombolysis in cerebral infarction (mTICI) was performed in a separate group of patients who underwent multimodal computed tomography prior to mechanical thrombectomy between June 2015 and February 2019. Follow-up ASPECTS were derived from either non-contrast computed tomography or from magnetic resonance imaging (in seven patients) one day after mechanical thrombectomy. Interrater agreement was best for non-contrast computed tomography ASPECTS (w-kappa = 0.74, vs. w-kappa = 0.63 for cerebral blood volume ASPECTS and w-kappa = 0.53 for pooled blood volume ASPECTS). Also, accuracy, defined as correlation between acute and follow-up ASPECTS, was best for non-contrast computed tomography ASPECTS (Spearman ρ = 0.86 (0.65–0.97), P < 0.001), while it was lower and comparable for pooled blood volume ASPECTS (ρ = 0.58 (0.32–0.79), P < 0.001) and cerebral blood volume ASPECTS (ρ = 0.52 (0.17–0.80), P = 0.001). It was noteworthy that cases of relevant infarct overestimation by two or more ASPECTS regions (compared to follow-up imaging) were observed for both acute pooled blood volume and cerebral blood volume ASPECTS but occurred more often for acute pooled blood volume ASPECTS (25% vs. 5%, P = 0.02). Non-contrast computed tomography ASPECTS outperformed both pooled blood volume ASPECTS and cerebral blood volume ASPECTS in accuracy and reliability. Importantly, relevant infarct overestimation was observed more often in pooled blood volume ASPECTS than cerebral blood volume ASPECTS, limiting its present clinical applicability for acute stroke imaging.

Background and Purpose: To determine reasons for failed recanalization in mechanical thrombectomy (MT) of the posterior circulation. Methods: Retrospective single center analysis of reasons for MT failure in the posterior circulation. Failed MTs were categorized according to the reason for procedure failure in failed vascular access, failed passage of the target vessel occlusion and MT failure after passing the occluded target vessel. Patient characteristics were compared between failed and successful MT. Results: Patients with failed MT (30/218 patients, 13.8%) were categorized into futile vascular access (13/30, 43.3%), abortive passage of the target vessel occlusion (6/30, 20.0%) and MT failure after passing the vessel occlusion (11/30, 36.7%). In 188/218 (86.2%) successful MTs alternative vascular access, local intra-arterial (i.a.) thrombolysis and emergency stent-assisted PTA prevented 65 MT failures. Patients with failed MT showed a higher NIHSS at discharge, a higher pc-ASPECTS in follow-up imaging, a higher mRS 90 days after stroke onset and a high mortality rate of 77.0% (mRS at 90 days, median (IQR): 6 (6–6) vs. 4 (2–6) for successful MT, p-value < 0.001). Co-morbidities and stroke etiology were not different compared to sufficient recanalization with atherosclerotic disease as the leading stroke etiology in both groups. Conclusion: Failure of MT in posterior circulation ischemic stroke patients is associated with a high mortality rate. Reasons for MT failure are diverse with futile vascular access and MT failure after passing the vessel occlusion as the leading causes. Alternative vascular access, local i.a. thrombolysis and stent-assisted PTA can prevent MT failure.