Publications by authors named "Uta Hanning"

89 Publications

Impact of intravenous alteplase on sub-angiographic emboli in high-resolution diffusion-weighted imaging following successful thrombectomy.

Eur Radiol 2021 May 8. Epub 2021 May 8.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.

Objective: Thrombus microfragmentation causing peripheral emboli (PE) during mechanical thrombectomy (MT) may modulate treatment effects, even in cases with successful reperfusion. This study aims to investigate whether intravenous alteplase is of potential benefit in reducing PE after successful MT.

Methods: Patients from a prospective study treated at a tertiary care stroke center between 08/2017 and 12/2019 were analyzed. The main inclusion criterion was successful reperfusion after MT (defined as expanded thrombolysis in cerebral infarction (eTICI) scale ≥ 2b50) of large vessel occlusion anterior circulation stroke. All patients received a high-resolution diffusion-weighted imaging (DWI) follow-up 24 h after MT for PE detection. Patients were grouped as "direct MT" (no alteplase) or as MT plus additional intravenous alteplase. The number and volume of ischemic core lesions and PE were then quantified and analyzed.

Results: Fifty-six patients were prospectively enrolled. Additional intravenous alteplase was administered in 46.3% (26/56). There were no statistically significant differences of PE compared by groups of direct MT and additional intravenous alteplase administration regarding mean numbers (12.1, 95% CI 8.6-15.5 vs. 11.1, 95% CI 7.0-15.1; p = 0.701), and median volume (0.70 mL, IQR 0.21-1.55 vs. 0.39 mL, IQR 0.10-1.62; p = 0.554). In uni- and multivariable linear regression analysis, higher eTICI scores were significantly associated with reduced PE, while the administration of alteplase was neither associated with numbers nor volume of peripheral emboli. Additional alteplase did not alter reperfusion success.

Conclusions: Intravenous alteplase neither affects the number nor volume of sub-angiographic DWI-PE after successful endovascular reperfusion. In the light of currently running randomized trials, further studies are warranted to validate these findings.

Key Points: • Thrombus microfragmentation during endovascular stroke treatment may cause peripheral emboli that are only detectable on diffusion-weighted imaging and may directly compromise treatment effects. • In this prospective study, the application of intravenous alteplase did not influence the occurrence of peripheral emboli detected on high-resolution diffusion-weighted imaging. • A higher degree of recanalization was associated with a reduced number and volume of peripheral emboli and better functional outcome, while contrariwise, peripheral emboli did not modify the effect of recanalization on modified Rankin Scale scores at day 90.
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http://dx.doi.org/10.1007/s00330-021-07980-0DOI Listing
May 2021

Expanding indications for endovascular thrombectomy-how to leave no patient behind.

Ther Adv Neurol Disord 2021 16;14:1756286421998905. Epub 2021 Mar 16.

Department of Neuroradiology, Clinic for Radiology & Nuclear Medicine, University Hospital Basel, Basel, Switzerland.

Endovascular thrombectomy (EVT) has become standard of care for large vessel occlusion strokes but current guidelines exclude a large proportion of patients from this highly effective treatment. This review therefore focuses on expanding indications for EVT in several borderline indications such as patients in the extended time window, patients with extensive signs of infarction on admission imaging, elderly patients and patients with pre-existing deficits. It also discusses the current knowledge on intravenous thrombolysis as an adjunct to EVT and EVT as primary therapy for distal vessel occlusions, for tandem occlusions, for basilar artery occlusions and in pediatric patients. We provide clear recommendations based on current guidelines and further literature.
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http://dx.doi.org/10.1177/1756286421998905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970189PMC
March 2021

Thrombectomy for Primary Distal Posterior Cerebral Artery Occlusion Stroke: The TOPMOST Study.

JAMA Neurol 2021 Apr;78(4):434-444

Department of Interventional Neuroradiology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.

Importance: Clinical evidence of the potential treatment benefit of mechanical thrombectomy for posterior circulation distal, medium vessel occlusion (DMVO) is sparse.

Objective: To investigate the frequency as well as the clinical and safety outcomes of mechanical thrombectomy for isolated posterior circulation DMVO stroke and to compare them with the outcomes of standard medical treatment with or without intravenous thrombolysis (IVT) in daily clinical practice.

Design, Setting, And Participants: This multicenter case-control study analyzed patients who were treated for primary distal occlusion of the posterior cerebral artery (PCA) of the P2 or P3 segment. These patients received mechanical thrombectomy or standard medical treatment (with or without IVT) at 1 of 23 comprehensive stroke centers in Europe, the United States, and Asia between January 1, 2010, and June 30, 2020. All patients who met the inclusion criteria were matched using 1:1 propensity score matching.

Interventions: Mechanical thrombectomy or standard medical treatment with or without IVT.

Main Outcomes And Measures: Clinical end point was the improvement of National Institutes of Health Stroke Scale (NIHSS) scores at discharge from baseline. Safety end point was the occurrence of symptomatic intracranial hemorrhage and hemorrhagic complications were classified based on the Second European-Australasian Acute Stroke Study (ECASSII). Functional outcome was evaluated with the modified Rankin Scale (mRS) score at 90-day follow-up.

Results: Of 243 patients from all participating centers who met the inclusion criteria, 184 patients were matched. Among these patients, the median (interquartile range [IQR]) age was 74 (62-81) years and 95 (51.6%) were female individuals. Posterior circulation DMVOs were located in the P2 segment of the PCA in 149 patients (81.0%) and in the P3 segment in 35 patients (19.0%). At discharge, the mean NIHSS score decrease was -2.4 points (95% CI, -3.2 to -1.6) in the standard medical treatment cohort and -3.9 points (95% CI, -5.4 to -2.5) in the mechanical thrombectomy cohort, with a mean difference of -1.5 points (95% CI, 3.2 to -0.8; P = .06). Significant treatment effects of mechanical thrombectomy were observed in the subgroup of patients who had higher NIHSS scores on admission of 10 points or higher (mean difference, -5.6; 95% CI, -10.9 to -0.2; P = .04) and in the subgroup of patients without IVT (mean difference, -3.0; 95% CI, -5.0 to -0.9; P = .005). Symptomatic intracranial hemorrhage occurred in 4 of 92 patients (4.3%) in each treatment cohort.

Conclusions And Relevance: This study suggested that, although rarely performed at comprehensive stroke centers, mechanical thrombectomy for posterior circulation DMVO is a safe, and technically feasible treatment option for occlusions of the P2 or P3 segment of the PCA compared with standard medical treatment with or without IVT.
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http://dx.doi.org/10.1001/jamaneurol.2021.0001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900924PMC
April 2021

Perfusion imaging-based tissue-level collaterals predict ischemic lesion net water uptake in patients with acute ischemic stroke and large vessel occlusion.

J Cereb Blood Flow Metab 2021 Feb 8:271678X21992200. Epub 2021 Feb 8.

Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.

Ischemic lesion Net Water Uptake (NWU) quantifies cerebral edema formation and likely correlates with the microvascular perfusion status of patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). We hypothesized that favorable tissue-level collaterals (TLC) predict less NWU and good functional outcomes. We performed a retrospective multicenter analysis of AIS-LVO patients who underwent thrombectomy triage. TLC were measured on cerebral perfusion studies using the hypoperfusion intensity ratio (HIR; volume ratio of brain tissue with [Tmax > 10 sec/Tmax > 6 sec]); favorable TLC were regarded as HIR 0.4. NWU was determined using a quantitative densitometry approach on follow-up CT. Primary outcome was NWU. Secondary outcome was a good functional outcome (modified Rankin Scale [mRS] 0-2).580 patients met inclusion criteria. Favorable TLC ( 0.65; p < 0.001) predicted smaller NWU after treatment. Favorable TLC (OR: 2.35, [95% CI: 1.31-4.21]; p < 0.001), and decreased NWU (OR: 0.75, [95% CI: 0.70-0.79]; p < 0.001) predicted good functional outcome, while controlling for age, glucose, CTA collaterals, baseline NIHSS and good vessel reperfusion status.We conclude that favorable TLC predict less ischemic lesion NWU after treatment in AIS-LVO patients. Favorable TLC and decreased NWU were independent predictors of good functional outcome.
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http://dx.doi.org/10.1177/0271678X21992200DOI Listing
February 2021

In Reply: Early Prediction of Malignant Cerebellar Edema in Posterior Circulation Stroke Using Quantitative Lesion Water Uptake.

Neurosurgery 2021 Apr;88(5):E476-E477

Department of Diagnostic and Interventional Neuroradiology University Medical Center Hamburg-Eppendorf Hamburg, Germany.

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http://dx.doi.org/10.1093/neuros/nyab032DOI Listing
April 2021

Imaging-Based Outcome Prediction of Acute Intracerebral Hemorrhage.

Transl Stroke Res 2021 Feb 6. Epub 2021 Feb 6.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.

We hypothesized that imaging-only-based machine learning algorithms can analyze non-enhanced CT scans of patients with acute intracerebral hemorrhage (ICH). This retrospective multicenter cohort study analyzed 520 non-enhanced CT scans and clinical data of patients with acute spontaneous ICH. Clinical outcome at hospital discharge was dichotomized into good outcome and poor outcome using different modified Rankin Scale (mRS) cut-off values. Predictive performance of a random forest machine learning approach based on filter- and texture-derived high-end image features was evaluated for differentiation of functional outcome at mRS 2, 3, and 4. Prediction of survival (mRS ≤ 5) was compared to results of the ICH Score. All models were tuned, validated, and tested in a nested 5-fold cross-validation approach. Receiver-operating-characteristic area under the curve (ROC AUC) of the machine learning classifier using image features only was 0.80 (95% CI [0.77; 0.82]) for predicting mRS ≤ 2, 0.80 (95% CI [0.78; 0.81]) for mRS ≤ 3, and 0.79 (95% CI [0.77; 0.80]) for mRS ≤ 4. Trained on survival prediction (mRS ≤ 5), the classifier reached an AUC of 0.80 (95% CI [0.78; 0.82]) which was equivalent to results of the ICH Score. If combined, the integrated model showed a significantly higher AUC of 0.84 (95% CI [0.83; 0.86], P value <0.05). Accordingly, sensitivities were significantly higher at Youden Index maximum cut-offs (77% vs. 74% sensitivity at 76% specificity, P value <0.05). Machine learning-based evaluation of quantitative high-end image features provided the same discriminatory power in predicting functional outcome as multidimensional clinical scoring systems. The integration of conventional scores and image features had synergistic effects with a statistically significant increase in AUC.
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http://dx.doi.org/10.1007/s12975-021-00891-8DOI Listing
February 2021

ASPECTS Interobserver Agreement of 100 Investigators from the TENSION Study.

Clin Neuroradiol 2021 Jan 27. Epub 2021 Jan 27.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.

Purpose: Evaluating the extent of cerebral ischemic infarction is essential for treatment decisions and assessment of possible complications in patients with acute ischemic stroke. Patients are often triaged according to image-based early signs of infarction, defined by Alberta Stroke Program Early CT Score (ASPECTS). Our aim was to evaluate interrater reliability in a large group of readers.

Methods: We retrospectively analyzed 100 investigators who independently evaluated 20 non-contrast computed tomography (NCCT) scans as part of their qualification program for the TENSION study. Test cases were chosen by four neuroradiologists who had previously scored NCCT scans with ASPECTS between 0 and 8 and high interrater agreement. Percent and interrater agreements were calculated for total ASPECTS, as well as for each ASPECTS region.

Results: Percent agreements for ASPECTS ratings was 28%, with interrater agreement of 0.13 (95% confidence interval, CI 0.09-0.16), at zero tolerance allowance and 66%, with interrater agreement of 0.32 (95% CI: 0.21-0.44), at tolerance allowance set by TENSION inclusion criteria. ASPECTS region with highest level of agreement was the insular cortex (percent agreement = 96%, interrater agreement = 0.96 (95% CI: 0.94-0.97)) and with lowest level of agreement the M3 region (percent agreement = 68%, interrater agreement = 0.39 [95% CI: 0.17-0.61]).

Conclusion: Interrater agreement reliability for total ASPECTS and study enrollment was relatively low but seems sufficient for practical application. Individual region analysis suggests that some are particularly difficult to evaluate, with varying levels of reliability. Potential impairment of the supraganglionic region must be examined carefully, particularly with respect to the decision whether or not to perform mechanical thrombectomy.
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http://dx.doi.org/10.1007/s00062-020-00988-xDOI Listing
January 2021

Relationship between the degree of recanalization and functional outcome in acute ischemic stroke is mediated by penumbra salvage volume.

J Neurol 2021 Jan 24. Epub 2021 Jan 24.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.

Background: The presence of metabolically viable brain tissue that may be salvageable with rapid cerebral blood flow restoration is the fundament rationale for reperfusion therapy in patients with large vessel occlusion stroke. The effect of endovascular treatment (EVT) on functional outcome largely depends on the degree of recanalization. However, the relationship of recanalization degree and penumbra salvage has not yet been investigated. We hypothesized that penumbra salvage volume mediates the effect of thrombectomy on functional outcome.

Methods: 99 acute anterior circulation stroke patients who received multimodal CT and underwent thrombectomy with resulting partial to complete reperfusion (modified thrombolysis in cerebral infarction scale (mTICI) ≥ 2a) were retrospectively analyzed. Penumbra volume was quantified on CT perfusion and penumbra salvage volume (PSV) was calculated as difference of penumbra and net infarct growth from admission to follow-up imaging.

Results: In patients with complete reperfusion (mTICI ≥ 2c), the median PSV was significantly higher than the median PSV in patients with partial or incomplete (mTICI 2a-2b) reperfusion (median 224 mL, IQR: 168-303 versus 158 mL, IQR: 129-225; p < 0.01). A higher degree of recanalization was associated with increased PSV (+ 63 mL per grade, 95% CI: 17-110; p < 0.01). Higher PSV was also associated with improved functional outcome (OR/mRS shift: 0.89; 95% CI: 0.85-0.95, p < 0.0001).

Conclusions: PSV may be an important mediator between functional outcome and recanalization degree in EVT patients and could serve as a more accurate instrument to compare treatment effects than infarct volumes.
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http://dx.doi.org/10.1007/s00415-021-10410-2DOI Listing
January 2021

Imaging-based prediction of histological clot composition from admission CT imaging.

J Neurointerv Surg 2021 Jan 22. Epub 2021 Jan 22.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.

Background: Thrombus composition has been shown to be a major determinant of recanalization success and occurrence of complications in mechanical thrombectomy. The most important parameters of thrombus behavior during interventional procedures are relative fractions of fibrin and red blood cells (RBCs). We hypothesized that quantitative information from admission non-contrast CT (NCCT) and CT angiography (CTA) can be used for machine learning based prediction of thrombus composition.

Methods: The analysis included 112 patients with occlusion of the carotid-T or middle cerebral artery who underwent thrombectomy. Thrombi samples were histologically analyzed and fractions of fibrin and RBCs were determined. Thrombi were semi-automatically delineated in CTA scans and NCCT scans were registered to the same space. Two regions of interest (ROIs) were defined for each thrombus: small-diameter ROIs capture vessel walls and thrombi, large-diameter ROIs reflect peri-vascular tissue responses. 4844 quantitative image markers were extracted and evaluated for their ability to predict thrombus composition using random forest algorithms in a nested fivefold cross validation.

Results: Test set receiver operating characteristic area under the curve was 0.83 (95% CI 0.80 to 0.87) for differentiating RBC-rich thrombi and 0.84 (95% CI 0.80 to 0.87) for differentiating fibrin-rich thrombi. At maximum Youden-Index, RBC-rich thrombi were identified at 77% sensitivity and 74% specificity; for fibrin-rich thrombi the classifier reached 81% sensitivity at 73% specificity.

Conclusions: Machine learning based analysis of admission imaging allows for prediction of clot composition. Perspectively, such an approach could allow selection of clot-specific devices and retrieval procedures for personalized thrombectomy strategies.
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http://dx.doi.org/10.1136/neurintsurg-2020-016774DOI Listing
January 2021

White matter integrity and structural brain network topology in cerebral small vessel disease: The Hamburg city health study.

Hum Brain Mapp 2021 Apr 8;42(5):1406-1415. Epub 2020 Dec 8.

Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Cerebral small vessel disease is a common finding in the elderly and associated with various clinical sequelae. Previous studies suggest disturbances in the integration capabilities of structural brain networks as a mediating link between imaging and clinical presentations. To what extent cerebral small vessel disease might interfere with other measures of global network topology is not well understood. Connectomes were reconstructed via diffusion weighted imaging in a sample of 930 participants from a population based epidemiologic study. Linear models were fitted testing for an association of graph-theoretical measures reflecting integration and segregation with both the Peak width of Skeletonized Mean Diffusivity (PSMD) and the load of white matter hyperintensities of presumed vascular origin (WMH). The latter were subdivided in periventricular and deep for an analysis of localisation-dependent correlations of cerebral small vessel disease. The median WMH volume was 0.6 mL (1.4) and the median PSMD 2.18 mm /s x 10 (0.5). The connectomes showed a median density of 0.880 (0.030), the median values for normalised global efficiency, normalised clustering coefficient, modularity Q and small-world propensity were 0.780 (0.045), 1.182 (0.034), 0.593 (0.026) and 0.876 (0.040) respectively. An increasing burden of cerebral small vessel disease was significantly associated with a decreased integration and increased segregation and thus decreased small-worldness of structural brain networks. Even in rather healthy subjects increased cerebral small vessel disease burden is accompanied by topological brain network disturbances. Segregation parameters and small-worldness might as well contribute to the understanding of the known clinical sequelae of cerebral small vessel disease.
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http://dx.doi.org/10.1002/hbm.25301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927298PMC
April 2021

Linking cortical atrophy to white matter hyperintensities of presumed vascular origin.

J Cereb Blood Flow Metab 2020 Dec 1:271678X20974170. Epub 2020 Dec 1.

Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

We examined the relationship between white matter hyperintensities (WMH) and cortical neurodegeneration in cerebral small vessel disease (CSVD) by investigating whether cortical thickness is a remote effect of WMH through structural fiber tract connectivity in a population at increased risk of CSVD. We measured cortical thickness on T1-weighted images and segmented WMH on FLAIR images in 930 participants of a population-based cohort study at baseline. DWI-derived whole-brain probabilistic tractography was used to define WMH connectivity to cortical regions. Linear mixed-effects models were applied to analyze the relationship between cortical thickness and connectivity to WMH. Factors associated with cortical thickness (age, sex, hemisphere, region, individual differences in cortical thickness) were added as covariates. Median age was 64 [IQR 46-76] years. Visual inspection of surface maps revealed distinct connectivity patterns of cortical regions to WMH. WMH connectivity to the cortex was associated with reduced cortical thickness ( = 0.009) after controlling for covariates. This association was found for periventricular WMH ( = 0.001) only. Our results indicate an association between WMH and cortical thickness via connecting fiber tracts. The results imply a mechanism of secondary neurodegeneration in cortical regions distant, yet connected to subcortical vascular lesions, which appears to be driven by periventricular WMH.
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http://dx.doi.org/10.1177/0271678X20974170DOI Listing
December 2020

Effect of thrombectomy on oedema progression and clinical outcome in patients with a poor collateral profile.

Stroke Vasc Neurol 2020 Nov 18. Epub 2020 Nov 18.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background And Purpose: The impact of the cerebral collateral circulation on lesion progression and clinical outcome in ischaemic stroke is well established. Moreover, collateral status modifies the effect of endovascular treatment and was therefore used to select patients for therapy in prior trials. The purpose of this study was to quantify the effect of vessel recanalisation on lesion pathophysiology and clinical outcome in patients with a poor collateral profile.

Materials And Methods: 129 patients who had an ischaemic stroke with large vessel occlusion in the anterior circulation and a collateral score (CS) of 0-2 were included. Collateral profile was defined using an established 5-point scoring system in CT angiography. Lesion progression was determined using quantitative lesion water uptake measurements on admission and follow-up CT (FCT), and clinical outcome was assessed using modified Rankin Scale (mRS) scores after 90 days.

Results: Oedema formation in FCT was significantly lower in patients with vessel recanalisation compared with patients with persistent vessel occlusion (mean 19.5%, 95% CI: 17% to 22% vs mean 27%, 95% CI: 25% to 29%; p<0.0001). In a multivariable linear regression analysis, vessel recanalisation was significantly associated with oedema formation in FCT (ß=-7.31, SD=0.015, p<0.0001), adjusted for CS, age and Alberta Stroke Program Early CT Score (ASPECTS). Functional outcome was significantly better in patients following successful recanalisation (mRS at day 90: 4.5, IQR: 2-6 vs 5, IQR: 5-6, p<0.001).

Conclusion: Although poor collaterals are known to be associated with poor outcome, endovascular recanalisation was still associated with significant oedema reduction and comparably better outcome in this patient group. Patients with poor collaterals should not generally be excluded from thrombectomy.
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http://dx.doi.org/10.1136/svn-2020-000570DOI Listing
November 2020

Computed tomography-based triage of extensive baseline infarction: ASPECTS and collaterals versus perfusion imaging for outcome prediction.

J Neurointerv Surg 2020 Nov 9. Epub 2020 Nov 9.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: Patients presenting with large baseline infarctions are often excluded from mechanical thrombectomy (MT) due to uncertainty surrounding its effect on outcome. We hypothesized that computed tomography perfusion (CTP)-based selection may be predictive of functional outcome in low Alberta Stroke Program Early CT Score (ASPECTS) patients.

Methods: This was a double-center, retrospective analysis of patients presenting with ASPECTS≤5 who received multimodal admission CT imaging between May 2015 and June 2020. The predicted ischemic core (pCore) was defined as a reduction in cerebral blood flow (rCBF), while mismatch volume was defined using time to maximum (Tmax). The pCore perfusion mismatch ratio (CPMR) was also calculated. These parameters (pCore, mismatch volume, and CPMR), as well as a combined radiological score consisting of ASPECTS and collateral status (ASCO score), were tested in logistic regression and receiver operating characteristic (ROC) analyses. The primary outcome was favorable modified Rankin Scale (mRS) at discharge (≤3).

Results: A total of 113 patients met the inclusion criteria. The median ischemic core volume was 74.1 mL (IQR 43.8-121.8). The ASCO score was associated with favorable outcome at discharge (aOR 3.7, 95% CI 1.8 to 10.7, P=0.002), while no association was observed for the CTP parameters. A model including the ASCO score also had significantly higher area under the curve (AUC) values compared with the CTP-based model (0.88 vs 0.64, P=0.018).

Conclusions: The ASCO score was superior to the CTP-based model for the prediction of good functional outcome and could represent a quick, practical, and easily implemented method for the selection of low ASPECTS patients most likely benefit from MT.
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http://dx.doi.org/10.1136/neurintsurg-2020-016848DOI Listing
November 2020

Clinical Diffusion Mismatch to Select Pediatric Patients for Embolectomy 6 to 24 Hours After Stroke: An Analysis of the Save ChildS Study.

Neurology 2021 01 3;96(3):e343-e351. Epub 2020 Nov 3.

From the Department of Neuroradiology (P.B.S., M.-N.P., A.B.), Clinic for Radiology & Nuclear Medicine, University Hospital Basel, Switzerland; Department of Diagnostic and Interventional Neuroradiology (P.B.S., U.H., G.B., J.F.), University Medical Center Hamburg-Eppendorf, Hamburg; Departments of Pediatrics (R.S.), and Neurology (J.M.), University Hospital of Muenster; Department of Neuroradiology (R.C.), Alfried-Krupp Hospital, Essen; Department of Neuroradiology (H.H., E.H.), Klinikum Stuttgart, Germany; Department of Neuroradiology (A.G.), Medical University of Innsbruck, Austria; Department for Diagnostic and Interventional Neuroradiology (F.D.), University of Munich (LMU), Campus Grosshadern; Department of Neuroradiology (O.N., M.W.), RWTH Aachen University; Diagnostic and Interventional Neuroradiology (G.B.), Eberhard Karls University Tuebingen; Department of Radiology and Neuroradiology (A.W.), University Hospital Knappschaftskrankenhaus Bochum Langendreer; Department of Neuroradiology (D.K.), University Hospital Carl Gustav Carus, Dresden7; Department of Neuroradiology (U.Y.), Saarland University Hospital, Homburg, Germany; ASST Valcamonica (A.M.), Ospedale di Esine, UOSD Neurologia, Esine, Italy; Division of Neuroradiology and Musculoskeletal Radiology (W.M.), Department of Biomedical Imaging and Image-Guided Therapy, and Department of Biomedical Imaging and Image-Guided Therapy (R.N.), Division of Cardiovascular and Interventional Radiology, Medical University of Vienna, Austria; Department of Radiology and Neuroradiology (U.J.-K.), University Hospital of Schleswig-Holstein, Kiel; Section of Neuroradiology (M.B.), University of Ulm, Guenzburg; Department for Neuroradiology (S.S.), University Hospital Leipzig; Department of Neuroradiology (O.B.), University Hospital of Magdeburg; Department of Diagnostic and Interventional Neuroradiology (F.G.), Hannover Medical School, Germany; Institute of Neuroradiology (J.T.), Kepler University Hospital, Johannes Kepler University Linz, Austria; Institute of Neuroradiology (B.T.), University Hospital Duesseldorf; Department of Neuroradiology at Heidelberg University Hospital (M.M.); Department of Radiology (C.W.), University Hospital Regensburg; Department of Neuroradiology (P.S., A. Kemmling), University Hospital of Luebeck, Germany; Department of Neurology (P.L.M.), Massachusetts General Hospital, Harvard Medical School, Boston; Division of Child Neurology (S.L.), Department of Neurology, Stanford University, CA; Department of Neuroradiology (M.S.), University Hospital of Cologne; Department of Diagnostic and Interventional Radiology and Neuroradiology (A.R.), University Hospital Essen, University of Duisburg-Essen; Institute of Epidemiology and Social Medicine (A. Karch, N.R.), University of Muenster; and Department of Radiology, University of Munich (LMU) (M.W.), Campus Grosshadern, Germany.

Objective: To determine whether thrombectomy is safe in children up to 24 hours after onset of symptoms when selected by mismatch between clinical deficit and infarct.

Methods: A secondary analysis of the Save ChildS Study (January 2000-December 2018) was performed, including all pediatric patients (<18 years) diagnosed with arterial ischemic stroke who underwent endovascular recanalization at 27 European and United States stroke centers. Patients were included if they had a relevant mismatch between clinical deficit and infarct.

Results: Twenty children with a median age of 10.5 (interquartile range [IQR] 7-14.6) years were included. Of those, 7 were male (35%), and median time from onset to thrombectomy was 9.8 (IQR 7.8-16.2) hours. Neurologic outcome improved from a median Pediatric NIH Stroke Scale score of 12.0 (IQR 8.8-20.3) at admission to 2.0 (IQR 1.2-6.8) at day 7. Median modified Rankin Scale (mRS) score was 1.0 (IQR 0-1.6) at 3 months and 0.0 (IQR 0-1.0) at 24 months. One patient developed transient peri-interventional vasospasm; no other complications were observed. A comparison of the mRS score to the mRS score in the DAWN and DEFUSE 3 trials revealed a higher proportion of good outcomes in the pediatric compared to the adult study population.

Conclusions: Thrombectomy in pediatric ischemic stroke in an extended time window of up to 24 hours after onset of symptoms seems safe and neurologic outcomes are generally good if patients are selected by a mismatch between clinical deficit and infarct.

Classification Of Evidence: This study provides Class IV evidence that for children with acute ischemic stroke with a mismatch between clinical deficit and infarct size, thrombectomy is safe.
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http://dx.doi.org/10.1212/WNL.0000000000011107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884981PMC
January 2021

Republished: Interhospital teleproctoring of endovascular intracranial aneurysm treatment using a dedicated live-streaming technology: first experiences during the COVID-19 pandemic.

J Neurointerv Surg 2021 Feb 20;13(2):e1. Epub 2020 Oct 20.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

This is a report of the first three cases of endovascular aneurysm treatment that were proctored by a remote interventionalist using a novel high-resolution low-latency streaming technology. The proctor was located in a neurovascular centre and supported the treating interventional teams in two distant cities (up to 800 km/500 miles apart). All aneurysms were treated using the Woven EndoBridge (WEB) embolisation system, either electively or following subarachnoid haemorrhage. On-site proctoring was not possible due to travel restrictions during the COVID-19 pandemic. WEB placement was feasible in all cases. Good rapport between proctors and treating physicians was reported, enabled by the high-resolution image transmission and uninterrupted feedback/discussion via audiostream. No clinical complications were encountered. Short-term follow-up revealed adequate occlusion of all treated aneurysms. The employed streaming technology provided effective remote proctoring during complex aneurysm cases, including the management of technical complications.
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http://dx.doi.org/10.1136/neurintsurg-2020-016722.repDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848056PMC
February 2021

Early Prediction of Malignant Cerebellar Edema in Posterior Circulation Stroke Using Quantitative Lesion Water Uptake.

Neurosurgery 2021 02;88(3):531-537

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: Malignant cerebellar edema (MCE) is a life-threatening complication of ischemic posterior circulation stroke that requires timely diagnosis and management. Yet, there is no established imaging biomarker that may serve as predictor of MCE. Early edematous water uptake can be determined using quantitative lesion water uptake, but this biomarker has only been applied in anterior circulation strokes.

Objective: To test the hypothesis that lesion water uptake in early posterior circulation stroke predicts MCE.

Methods: A total 179 patients with posterior circulation stroke and multimodal admission CT were included. A total of 35 (19.5%) patients developed MCE defined by using an established 10-point scale in follow-up CT, of which ≥4 points are considered malignant. Posterior circulation net water uptake (pcNWU) was quantified in admission CT based on CT densitometry and compared with posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) as predictor of MCE using receiver operating curve (ROC) analysis and logistic regression analysis.

Results: Acute pcNWU within the early ischemic lesion was 24.6% (±8.4) for malignant and 7.2% (±7.4) for nonmalignant infarctions, respectively (P < .0001). Based on ROC analysis, pcNWU above 14.9% identified MCE with high discriminative power (area under the curve: 0.94; 95% CI: 0.89-0.97). Early pcNWU (odds ratio [OR]: 1.28; 95% CI: 1.15-1.42, P < .0001) and pc-ASPECTS (OR: 0.71, 95% CI: 0.53-0.95, P = .02) were associated with MCE, adjusted for age and recanalization status.

Conclusion: Quantitative pcNWU in early posterior circulation stroke is an important marker for MCE. Besides pc-ASPECTS, lesion water uptake measurements may further support identifying patients at risk for MCE at an early stage indicating stricter monitoring and consideration for further therapeutic measures.
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http://dx.doi.org/10.1093/neuros/nyaa438DOI Listing
February 2021

Interhospital teleproctoring of endovascular intracranial aneurysm treatment using a dedicated live-streaming technology: first experiences during the COVID-19 pandemic.

BMJ Case Rep 2020 Oct 4;13(10). Epub 2020 Oct 4.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

This is a report of the first three cases of endovascular aneurysm treatment that were proctored by a remote interventionalist using a novel high-resolution low-latency streaming technology. The proctor was located in a neurovascular centre and supported the treating interventional teams in two distant cities (up to 800 km/500 miles apart). All aneurysms were treated using the Woven EndoBridge (WEB) embolisation system, either electively or following subarachnoid haemorrhage. On-site proctoring was not possible due to travel restrictions during the COVID-19 pandemic. WEB placement was feasible in all cases. Good rapport between proctors and treating physicians was reported, enabled by the high-resolution image transmission and uninterrupted feedback/discussion via audiostream. No clinical complications were encountered. Short-term follow-up revealed adequate occlusion of all treated aneurysms. The employed streaming technology provided effective remote proctoring during complex aneurysm cases, including the management of technical complications.
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http://dx.doi.org/10.1136/bcr-2020-016722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536784PMC
October 2020

Feasibility of a customizable training environment for neurointerventional skills assessment.

PLoS One 2020 17;15(9):e0238952. Epub 2020 Sep 17.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Objective: To meet increasing demands to train neuroendovascular techniques, we developed a dedicated simulator applying individualized three-dimensional intracranial aneurysm models ('HANNES'; Hamburg Anatomic Neurointerventional Endovascular Simulator). We hypothesized that HANNES provides a realistic and reproducible training environment to practice coil embolization and to exemplify disparities between neurointerventionalists, thus objectively benchmarking operators at different levels of experience.

Methods: Six physicians with different degrees of neurointerventional procedural experience were recruited into a standardized training protocol comprising catheterization of two internal carotid artery (ICA) aneurysms and one basilar tip aneurysm, followed by introduction of one framing coil into each aneurysm and finally complete coil embolization of one determined ICA aneurysm. The level of difficulty increased with every aneurysm. Fluoroscopy was recorded and assessed for procedural characteristics and adverse events.

Results: Physicians were divided into inexperienced and experienced operators, depending on their experience with microcatheter handling. Mean overall catheterization times increased with difficulty of the aneurysm model. Inexperienced operators showed longer catheterization times (median; IQR: 47; 30-84s) than experienced operators (21; 13-58s, p = 0.011) and became significantly faster during the course of the attempts (rho = -0.493, p = 0.009) than the experienced physicians (rho = -0.318, p = 0.106). Number of dangerous maneuvers throughout all attempts was significantly higher for inexperienced operators (median; IQR: 1.0; 0.0-1.5) as compared to experienced operators (0.0; 0.0-1.0, p = 0.014).

Conclusion: HANNES represents a modular neurointerventional training environment for practicing aneurysm coil embolization in vitro. Objective procedural metrics correlate with operator experience, suggesting that the system could be useful for assessing operator proficiency.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238952PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498089PMC
October 2020

Lesion Age Imaging in Acute Stroke: Water Uptake in CT Versus DWI-FLAIR Mismatch.

Ann Neurol 2020 12 2;88(6):1144-1152. Epub 2020 Oct 2.

Department of Neuroradiology, Westpfalz-Klinikum, Kaiserslautern, Germany.

Purpose: In acute ischemic stroke with unknown time of onset, magnetic resonance (MR)-based diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) estimates lesion age to guide intravenous thrombolysis. Computed tomography (CT)-based quantitative net water uptake (NWU) may be a potential alternative. The purpose of this study was to directly compare CT-based NWU to magnetic resonance imaging (MRI) at identifying patients with lesion age < 4.5 hours from symptom onset.

Methods: Fifty patients with acute anterior circulation stroke were analyzed with both imaging modalities at admission between 0.5 and 8.0 hours after known symptom onset. DWI-FLAIR lesion mismatch was rated and NWU was measured in admission CT. An established NWU threshold (11.5%) was used to classify patients within and beyond 4.5 hours. Multiparametric MRI signal was compared with NWU using logistic regression analyses. The empirical distribution of NWU was analyzed in a consecutive cohort of patients with wake-up stroke.

Results: The median time between CT and MRI was 35 minutes (interquartile range [IQR] = 24-50). The accuracy of DWI-FLAIR mismatch was 68.8% (95% confidence interval [CI] = 53.7-81.3%) with a sensitivity of 58% and specificity of 82%. The accuracy of NWU threshold was 86.0% (95% CI = 73.3-94.2%) with a sensitivity of 91% and specificity of 78%. The area under the curve (AUC) of multiparametric MRI signal to classify lesion age <4.5 hours was 0.86 (95% CI = 0.64-0.97), and the AUC of quantitative NWU was 0.91 (95% CI = 0.78-0.98). Among 87 patients with wake-up stroke, 46 patients (53%) showed low NWU (< 11.5%).

Conclusion: The predictive power of CT-based lesion water imaging to identify patients within the time window of thrombolysis was comparable to multiparametric DWI-FLAIR MRI. A significant proportion of patients with wake-up stroke exhibit low NWU and may therefore be potentially suitable for thrombolysis. ANN NEUROL 2020;88:1144-1152.
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http://dx.doi.org/10.1002/ana.25903DOI Listing
December 2020

Early clinical surrogates for outcome prediction after stroke thrombectomy in daily clinical practice.

J Neurol Neurosurg Psychiatry 2020 10;91(10):1055-1059

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background And Purpose: To investigate early clinical surrogates for long-term independency of patients treated with thrombectomy for large vessel occlusion stroke in daily clinical routine.

Methods: All patients with anterior circulation stroke enrolled in the German Stroke Registry-Endovascular Treatment from 07/2015 to 04/2018 were analysed. National Institute of Health Stroke Scale (NIHSS) on admission, NIHSS percentage change, NIHSS delta and NIHSS at 24 hours as well as existing binary definitions of early neurological improvement (ENI; improvement of 8 (major ENI)/10 (dramatic ENI) NIHSS points or reaching 0/1 were compared for predicting functional outcome at 90 days using the modified Rankin Scale (mRS). Excellent and favourable outcome were defined as 0-1 and 0-2, respectively.

Results: Among 2262 endovasculary treated patients with acute ischaemic anterior circulation stroke, NIHSS at 24 hours had the highest discriminative ability to predict excellent (receiver operator characteristics (ROC) area under the curve (AUC) 0.86 (0.84-0.88)) and favourable long-term functional outcome (ROC AUC 0.86 (0.85-0.88)) in comparison to NIHSS percentage change (ROC AUC mRS ≤1: 0.81 (0.78-0.83) mRS ≤2: 0.81 (0.79-0.83)), NIHSS delta change (ROC AUC mRS ≤1: 0.74 (0.72-0.77), mRS ≤2: 0.77 (0.74-0.79)) and NIHSS admission (ROC AUC mRS ≤1: 0.70 (0.68-0.73), mRS ≤2: 0.67 (0.68-0.71)). Advanced age was the only independent predictor (adjusted OR 1.05, 95% CI 1.03 to 1.07, p<0.001) for turning the outcome prognosis from favourable (mRS ≤2) to poor (mRS ≥4) at 90 days.

Conclusion: The NIHSS at 24 hours postintervention with a threshold of ≤8 points serves best as a surrogate for long-term functional outcome after thrombectomy for anterior circulation stroke in daily clinical practice. Only advanced age significantly decreases its predictive value.
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http://dx.doi.org/10.1136/jnnp-2020-323742DOI Listing
October 2020

Clinical and Imaging Characteristics in Patients with SARS-CoV-2 Infection and Acute Intracranial Hemorrhage.

J Clin Med 2020 Aug 6;9(8). Epub 2020 Aug 6.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg Eppendorf, 20251 Hamburg, Germany.

Background And Purpose: Intracranial hemorrhage has been observed in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19), but the clinical, imaging, and pathophysiological features of intracranial bleeding during COVID-19 infection remain poorly characterized. This study describes clinical and imaging characteristics of patients with COVID-19 infection who presented with intracranial bleeding in a European multicenter cohort.

Methods: This is a multicenter retrospective, observational case series including 18 consecutive patients with COVID-19 infection and intracranial hemorrhage. Data were collected from February to May 2020 at five designated European special care centers for COVID-19. The diagnosis of COVID-19 was based on laboratory-confirmed diagnosis of SARS-CoV-2. Intracranial bleeding was diagnosed on computed tomography (CT) of the brain within one month of the date of COVID-19 diagnosis. The clinical, laboratory, radiologic, and pathologic findings, therapy and outcomes in COVID-19 patients presenting with intracranial bleeding were analyzed.

Results: Eighteen patients had evidence of acute intracranial bleeding within 11 days (IQR 9-29) of admission. Six patients had parenchymal hemorrhage (33.3%), 11 had subarachnoid hemorrhage (SAH) (61.1%), and one patient had subdural hemorrhage (5.6%). Three patients presented with intraventricular hemorrhage (IVH) (16.7%).

Conclusion: This study represents the largest case series of patients with intracranial hemorrhage diagnosed with COVID-19 based on key European countries with geospatial hotspots of SARS-CoV-2. Isolated SAH along the convexity may be a predominant bleeding manifestation and may occur in a late temporal course of severe COVID-19.
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http://dx.doi.org/10.3390/jcm9082543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464657PMC
August 2020

Physician factors influencing endovascular treatment decisions in the management of unruptured intracranial aneurysms.

Neuroradiology 2021 Jan 1;63(1):117-123. Epub 2020 Aug 1.

Department of Radiology and Clinical Neurosciences, Foothills Medical Centre, University of Calgary, 1403 29th St. NW, Calgary, AB, T2N2T9, Canada.

Purpose: Deciding about whether an unruptured intracranial aneurysm (UIA) should be treated or not is challenging because robust data on rupture risks, endovascular treatment complication rates, and treatment success rates are limited. We aimed to investigate how neurointerventionalists conceptually approach endovascular treatment decision-making in UIAs.

Methods: In a web-based international multidisciplinary case-based survey among neurointerventionalists, participants provided their demographics and UIA treatment-volumes, estimated 5-year rupture rates, endovascular treatment complication and success rates and gave their endovascular treatment decision for 15 pre-specified UIA case-scenarios. Differences in estimated 5-year rupture rates, endovascular treatment complication and success rates based on physician and hospital characteristics were evaluated with the Kruskal-Wallis test. Multivariable logistic regression analysis was used to derive adjusted effect size estimates for predictors of endovascular treatment decision.

Results: Two hundred-thirty-three neurointerventionalists from 38 countries participated in the survey (median age 47 years [IQR: 41-55], 25/233 [10.7%] females). The ranges of estimates for 5-year rupture risks, endovascular treatment complication rates, and particularly endovascular treatment success rates were wide, especially for UIAs in the posterior circulation. Estimated 5-year rupture risks, endovascular treatment complication and success rates differed significantly based on personal and institutional endovascular UIA treatment volume, and all three estimates were significantly associated with physicians' endovascular treatment decision.

Conclusion: Although several predictors of endovascular treatment decision were identified, there seems to be a high degree of uncertainty when estimating rupture risks, treatment complications, and treatment success for endovascular UIA treatment. More data on the clinical course of UIAs with and without endovascular treatment is needed.
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http://dx.doi.org/10.1007/s00234-020-02509-6DOI Listing
January 2021

Small thrombus size, thrombus composition, and poor collaterals predict pre-interventional thrombus migration.

J Neurointerv Surg 2021 May 20;13(5):409-414. Epub 2020 Jul 20.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: Different imaging characteristics such as clot burden score, collaterals, and pre-interventional thrombus migration are associated with functional outcome in patients with acute ischemic stroke. Moreover, histological thrombus composition is associated with pre-interventional thrombus migration. We hypothesized that smaller clots may more likely migrate and that collateral status in ischemic stroke patients may mediate this tendency of the clot to migrate.

Methods: In this prospective cohort of consecutive ischemic stroke patients, clot burden scores and collateral scores were rated and the retrieved thrombi were histologically analyzed. We then investigated the relationship between clot burden score, probability for thrombus migration, and collateral scores using mediation analysis.

Results: 163 patients are included of which 36 (22.1%) had a clot migration. Probability of thrombus migration was significantly associated with lower collateral scores (P<0.01), higher clot burden scores (P<0.01), shorter thrombi (P<0.01), and higher RBC count (P<0.01). In the mediator pathway, higher collateral scores were significantly associated with higher clot burden scores (P<0.01) and younger age (P=0.029). The total effect of an increase in clot burden score by one grade on thrombus migration is composed of the direct effect (+18%, P<0.01) and the collateral score-mediated indirect effect (-5%, P<0.01).

Conclusions: Smaller, erythrocyte-rich thrombi tend to migrate more often. Good collaterals seem to have a considerable effect on limiting migration. This supports the hypothesis that larger clots have stronger adherence with the vessel wall and that good collaterals increase the counter pressure distal of the clot.
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http://dx.doi.org/10.1136/neurintsurg-2020-016228DOI Listing
May 2021

Feasibility and safety of thrombectomy for isolated occlusions of the posterior cerebral artery: a multicenter experience and systematic literature review.

J Neurointerv Surg 2021 Mar 11;13(3):217-220. Epub 2020 Jun 11.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: Substantial clinical evidence supporting the benefit of mechanical thrombectomy (MT) for distal occlusions within the posterior circulation is still missing. This study aims to investigate the procedural feasibility and safety of MT for isolated occlusions of the posterior cerebral artery.

Methods: We retrospectively reviewed patients from three stroke centers with acute ischemic stroke attributed to isolated posterior cerebral artery occlusion (IPCAOs) who underwent MT between January 2014 and December 2019. Procedural and safety assessment included successful recanalization rates (defined as Thrombolysis in Cerebral Infarction Scale (TICI) ≥2b), number of MT attempts and first-pass effect (TICI 3), intracranial hemorrhage (ICH), mortality, and intervention-related serious adverse events. Treatment effects were evaluated by the rate of early neurological improvement (ENI) and early functional outcome was assessed with the modified Rankin Scale (mRS) at discharge. A systematic literature review was conducted to identify and summarize previous reports on MT for IPCAOs.

Results: Forty-three patients with IPCAOs located in the P1 (55.8%, 24/43), P2 (37.2%, 16/43), and P3 segment (7%, 3/43) were analyzed. The overall rate of successful recanalization (TICI ≥2b) was 86% (37/43), including a first pass-effect of 48.8% (21/43) leading to TICI 3. sICH occurred in 7% (3/43) and there were two cases with iatrogenic vessel dissection and one perforation. ENI was observed in 59% (23/39) and excellent functional outcome (mRS ≤1) in 46.2% (18/39) of patients who were discharged. The in-hospital mortality rate was 9.3% (4/43).

Conclusion: Our study suggests the technical feasibility and safety of thrombectomy for IPCAOs. Further studies are needed to investigate safety and long-term functional outcomes with posterior circulation stroke-adjusted outcome assessment.
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http://dx.doi.org/10.1136/neurintsurg-2020-016059DOI Listing
March 2021

Network Localisation of White Matter Damage in Cerebral Small Vessel Disease.

Sci Rep 2020 06 8;10(1):9210. Epub 2020 Jun 8.

Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Cerebral small vessel disease (CSVD) is a widespread condition associated to stroke, dementia and depression. To shed light on its opaque pathophysiology, we conducted a neuroimaging study aiming to assess the location of CSVD-induced damage in the human brain network. Structural connectomes of 930 subjects of the Hamburg City Health Study were reconstructed from diffusion weighted imaging. The connectome edges were partitioned into groups according to specific schemes: (1) connection to grey matter regions, (2) course and length of underlying streamlines. Peak-width of skeletonised mean diffusivity (PSMD) - a surrogate marker for CSVD - was related to each edge group's connectivity in a linear regression analysis allowing localisation of CSVD-induced effects. PSMD was associated with statistically significant decreases in connectivity of most investigated edge groups except those involved in connecting limbic, insular, temporal or cerebellar regions. Connectivity of interhemispheric and long intrahemispheric edges as well as edges connecting subcortical and frontal brain regions decreased most severely with increasing PSMD. In conclusion, MRI findings of CSVD are associated with widespread impairment of structural brain network connectivity, which supports the understanding of CSVD as a global brain disease. The pattern of regional preference might provide a link to clinical phenotypes of CSVD.
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http://dx.doi.org/10.1038/s41598-020-66013-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280237PMC
June 2020

Neoplastic and Non-neoplastic Acute Intracerebral Hemorrhage in CT Brain Scans: Machine Learning-Based Prediction Using Radiomic Image Features.

Front Neurol 2020 5;11:285. Epub 2020 May 5.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Early differentiation of neoplastic and non-neoplastic intracerebral hemorrhage (ICH) can be difficult in initial radiological evaluation, especially for extensive ICHs. The aim of this study was to evaluate the potential of a machine learning-based prediction of etiology for acute ICHs based on quantitative radiomic image features extracted from initial non-contrast-enhanced computed tomography (NECT) brain scans. The analysis included NECT brain scans from 77 patients with acute ICH ( = 50 non-neoplastic, = 27 neoplastic). Radiomic features including shape, histogram, and texture markers were extracted from non-, wavelet-, and log-sigma-filtered images using regions of interest of ICH and perihematomal edema (PHE). Six thousand and ninety quantitative predictors were evaluated utilizing random forest algorithms with five-fold model-external cross-validation. Model stability was assessed through comparative analysis of 10 randomly drawn cross-validation sets. Classifier performance was compared with predictions of two radiologists employing the Matthews correlation coefficient (MCC). The receiver operating characteristic (ROC) area under the curve (AUC) of the test sets for predicting neoplastic vs. non-neoplastic ICHs was 0.89 [95% CI (0.70; 0.99); < 0.001], and specificities and sensitivities reached >80%. Compared to the radiologists' predictions, the machine learning algorithm yielded equal or superior results for all evaluated metrics. The MCC of the proposed algorithm at its optimal operating point (0.69) was significantly higher than the MCC of the radiologist readers (0.54); = 0.01. Evaluating quantitative features of acute NECT images in a machine learning algorithm provided high discriminatory power in predicting non-neoplastic vs. neoplastic ICHs. Utilized in the clinical routine, the proposed approach could improve patient care at low risk and costs.
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http://dx.doi.org/10.3389/fneur.2020.00285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232581PMC
May 2020

Effect of Balloon Guide Catheter Utilization on the Incidence of Sub-angiographic Peripheral Emboli on High-Resolution DWI After Thrombectomy: A Prospective Observational Study.

Front Neurol 2020 7;11:386. Epub 2020 May 7.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Thrombus fragmentation causing distal emboli is a feared complication during mechanical thrombectomy (MT). We aimed to investigate the impact of procedural parameters and thrombus properties on the incidence of peripheral emboli after MT for large vessel occlusions (LVO). We performed a prospective analysis of patients with LVO stroke successfully treated with MT, defined as a score of 2b, 2c, or 3 on the thrombolysis in cerebral infarction (TICI) scale. A follow-up MRI including high-resolution diffusion-weighted imaging (DWI) was performed within 24 h following MT. The primary endpoint was the number and volume of peripheral emboli, classified as punctuate DWI lesions distant to the diffusion-restricted core lesion. Further analysis included the influence of baseline characteristics, procedural and outcome parameters, and thrombus properties on peripheral emboli. Thirty-seven patients with successful MT met the inclusion criteria. Use of a balloon guide catheter (BGC) and TICI were the only independent predictors for a reduced number of peripheral emboli. The use of a BGC led to a significant reduction in the number and volume of peripheral emboli, with a median number/volume of peripheral emboli of 4.5/287 μl (IQR 1.25-8.25/76-569 μl) vs. 12/938 μl (IQR 4-19/242-1,836 μl). In cases where BGC was not employed, the number of peripheral emboli increased with decreasing TICI scores. BGC-aided MT reduces the number of peripheral emboli in successful but incomplete reperfusion (TICI 2b and 2c). The effectiveness of this strategy therefore goes above and beyond that which can be demonstrated by the TICI score alone.
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http://dx.doi.org/10.3389/fneur.2020.00386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221024PMC
May 2020

Predictors of poor clinical outcome despite complete reperfusion in acute ischemic stroke patients.

J Neurointerv Surg 2021 Jan 15;13(1):14-18. Epub 2020 May 15.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg, Hamburg, Hamburg, Germany.

Background: In patients suffering from acute ischemic stroke from large vessel occlusion (LVO), mechanical thrombectomy (MT) often leads to successful reperfusion. Only approximately half of these patients have a favorable clinical outcome. Our aim was to determine the prognostic factors associated with poor clinical outcome following complete reperfusion.

Methods: Patients treated with MT for LVO from a prospective single-center stroke registry between July 2015 and April 2019 were screened. Complete reperfusion was defined as Thrombolysis in Cerebral Infarction (TICI) grade 3. A modified Rankin scale at 90 days (mRS90) of 3-6 was defined as 'poor outcome'. A logistic regression analysis was performed with poor outcome as a dependent variable, and baseline clinical data, comorbidities, stroke severity, collateral status, and treatment information as independent variables.

Results: 123 patients with complete reperfusion (TICI 3) were included in this study. Poor clinical outcome was observed in 67 (54.5%) of these patients. Multivariable logistic regression analysis identified greater age (adjusted OR 1.10, 95% CI 1.04 to 1.17; p=0.001), higher admission National Institutes of Health Stroke Scale (NIHSS) (OR 1.14, 95% CI 1.02 to 1.28; p=0.024), and lower Alberta Stroke Program Early CT Score (ASPECTS) (OR 0.6, 95% CI 0.4 to 0.84; p=0.007) as independent predictors of poor outcome. Poor outcome was independent of collateral score.

Conclusion: Poor clinical outcome is observed in a large proportion of acute ischemic stroke patients treated with MT, despite complete reperfusion. In this study, futile recanalization was shown to occur independently of collateral status, but was associated with increasing age and stroke severity.
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http://dx.doi.org/10.1136/neurintsurg-2020-015889DOI Listing
January 2021

Posterior circulation stroke: machine learning-based detection of early ischemic changes in acute non-contrast CT scans.

J Neurol 2020 Sep 11;267(9):2632-2641. Epub 2020 May 11.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

Objectives: Triage of patients with basilar artery occlusion for additional imaging diagnostics, therapy planning, and initial outcome prediction requires assessment of early ischemic changes in early hyperacute non-contrast computed tomography (NCCT) scans. However, accuracy of visual evaluation is impaired by inter- and intra-reader variability, artifacts in the posterior fossa and limited sensitivity for subtle density shifts. We propose a machine learning approach for detecting early ischemic changes in pc-ASPECTS regions (Posterior circulation Alberta Stroke Program Early CT Score) based on admission NCCTs.

Methods: The retrospective study includes 552 pc-ASPECTS regions (144 with infarctions in follow-up NCCTs) extracted from pre-therapeutic early hyperacute scans of 69 patients with basilar artery occlusion that later underwent successful recanalization. We evaluated 1218 quantitative image features utilizing random forest algorithms with fivefold cross-validation for the ability to detect early ischemic changes in hyperacute images that lead to definitive infarctions in follow-up imaging. Classifier performance was compared to conventional readings of two neuroradiologists.

Results: Receiver operating characteristic area under the curves for detection of early ischemic changes were 0.70 (95% CI [0.64; 0.75]) for cerebellum to 0.82 (95% CI [0.77; 0.86]) for thalamus. Predictive performance of the classifier was significantly higher compared to visual reading for thalamus, midbrain, and pons (P value < 0.05).

Conclusions: Quantitative features of early hyperacute NCCTs can be used to detect early ischemic changes in pc-ASPECTS regions. The classifier performance was higher or equal to results of human raters. The proposed approach could facilitate reproducible analysis in research and may allow standardized assessments for outcome prediction and therapy planning in clinical routine.
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http://dx.doi.org/10.1007/s00415-020-09859-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419359PMC
September 2020

Prognostic Value of Non-Contrast CT Markers and Spot Sign for Outcome Prediction in Patients with Intracerebral Hemorrhage under Oral Anticoagulation.

J Clin Med 2020 Apr 10;9(4). Epub 2020 Apr 10.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Introduction: In patients with spontaneous intracerebral hemorrhage (ICH), several non-contrast computed tomography (NCCT) markers and the spot sign (SS) in computed tomography (CT) angiography (CTA) have been established for the prediction of hematoma growth and neurological outcome. However, the prognostic value of these markers in patients under oral anticoagulation (ORAC) is unclear. We hypothesized that outcome prediction by these imaging markers may be significantly different between patients with and without ORAC. Therefore, we aimed to investigate the predictive value of NCCT markers and SS in patients with ICH under ORAC.

Methods: This is a retrospective study of the database for patients with ICH at a German tertiary stroke center. Inclusion criteria were (1) patients with ICH, (2) oral anticoagulation within the therapeutic range, and (3) NCCT and CTA performed on admission within 6 h after onset of symptoms. We defined a binary outcome: modified Rankin Scale (mRS) ≤ 3 = good outcome versus mRS > 3 = poor outcome at discharge. The predictive value of each sign was assessed in uni- and multivariable logistic regression models.

Results: Of 129 patients with ICH under ORAC, 76 (58.9%) presented with hypodensities within the hematoma in admission NCCT, 64 (52.7%) presented with an irregular shape of the hematoma, 60 (46.5%) presented with a swirl sign, 49 (38.0%) presented with a black hole sign, and 46 (35.7%) presented with a heterogeneous density of the hematoma. Moreover, 44 (34.1%) patients had a satellite sign, in 20 (15.5%) patients, an island sign was detected, 18 (14.0%) patients were blend-sign positive, and 14 (10.9%) patients presented with a CTA spot sign. Inter-rater agreement was very high for all included characteristics between the two readers. Multivariable logistic regression analysis identified the presence of black hole sign (odds ratio 10.59; < 0.001), swirl sign (odds ratio 14.06; < 0.001), and satellite sign (odds ratio 6.38; = 0.011) as independent predictors of poor outcome.

Conclusions: The distribution and prognostic value of several NCCT markers and CTA spot sign in ICH patients under ORAC is comparable to those with spontaneous ICH, even though these parameters are partly based on coagulant status. These findings suggest that a similar approach can be used for further research regarding outcome prediction in ICH patients under ORAC and those with spontaneous ICH.
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http://dx.doi.org/10.3390/jcm9041077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230516PMC
April 2020