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Background and Purpose Posterior cerebral artery occlusion (PCAo) can cause long-term disability, yet randomized controlled trials to guide optimal reperfusion strategy are lacking. We compared the outcomes of PCAo patients treated with endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) to patients treated with IVT alone. Methods From the multicenter retrospective Posterior cerebraL ArTery Occlusion (PLATO) registry, we included patients with isolated PCAo treated with reperfusion therapy within 24 hours of onset between January 2015 and August 2022. The primary outcome was the distribution of the modified Rankin Scale (mRS) at 3 months. Other outcomes comprised 3-month excellent (mRS 0–1) and independent outcome (mRS 0–2), early neurological improvement (ENI), mortality, and symptomatic intracranial hemorrhage (sICH). The treatments were compared using inverse probability weighted regression adjustment. Results Among 724 patients, 400 received EVT+/-IVT and 324 IVT alone (median age 74 years, 57.7% men). The median National Institutes of Health Stroke Scale score on admission was 7, and the occluded segment was P1 (43.9%), P2 (48.3%), P3–P4 (6.1%), bilateral (1.0%), or fetal posterior cerebral artery (0.7%). Compared to IVT alone, EVT+/-IVT was not associated with improved functional outcome (adjusted common odds ratio [OR] 1.07, 95% confidence interval [CI] 0.79–1.43). EVT increased the odds for ENI (adjusted OR [aOR] 1.49, 95% CI 1.05–2.12), sICH (aOR 2.87, 95% CI 1.23–6.72), and mortality (aOR 1.77, 95% CI 1.07–2.95). Conclusion Despite higher odds for early improvement, EVT+/-IVT did not affect functional outcome compared to IVT alone after PCAo. This may be driven by the increased risk of sICH and mortality after EVT.

Abstract Mechanical thrombectomy (MT) for acute ischemic stroke with medium vessel occlusions is still a matter of debate. We sought to identify factors associated with clinical outcome after MT for M2-occlusions based on data from the German Stroke Registry-Endovascular Treatment (GSR-ET). All patients prospectively enrolled in the GSR-ET from 05/2015 to 12/2021 were analyzed (NCT03356392). Inclusion criteria were primary M2-occlusions and availability of relevant clinical data. Factors associated with excellent/good outcome (modified Rankin scale mRS 0–1/0–2), poor outcome/death (mRS 5–6) and mRS-increase pre-stroke to day 90 were determined in multivariable logistic regression. 1348 patients were included. 1128(84%) had successful recanalization, 595(44%) achieved good outcome, 402 (30%) had poor outcome. Successful recanalization (odds ratio [OR] 4.27 [95% confidence interval 3.12–5.91], p

Background The optimal reperfusion technique in patients with isolated posterior cerebral artery (PCA) occlusion is uncertain. We compared clinical and technical outcomes with first‐line stent retriever (SR), contact aspiration (CA), or combined techniques in patients with isolated PCA occlusion. Methods This international case–control study was conducted at 30 sites in Europe and North America and included consecutive patients with isolated PCA occlusion presenting within 24 hours of time last seen well from January 2015 to August 2022. The primary outcome was the first‐pass effect (FPE), defined as expanded Treatment in Cerebral Infarction (TICI) 2c/3 on the first pass. Patients treated with SR, CA, or combined technique were compared with multivariable logistic regression. Results There were 326 patients who met inclusion criteria, 56.1% male, median age 75 (interquartile range 65–82) years, and median National Institutes of Health Stroke Scale score 8 (5–12). Occlusion segments were PCA‐P1 (53.1%), P2 (40.5%), and other (6.4%). Intravenous thrombolysis was administered in 39.6%. First‐line technique was SR, CA, and combined technique in 43 (13.2%), 106 (32.5%), and 177 (54.3%) patients, respectively; FPE was achieved in 62.8%, 42.5%, and 39.6%, respectively. FPE was lower in patients treated with first‐line CA or combined technique compared with SR (CA versus SR: adjusted odds ratio 0.45 [0.19–1.06]; P=0.07; combined versus SR: adjusted odds ratio 0.35 [0.016–0.80]; P=0.01). There were lower odds of functional independence (modified Rankin scale score 0–2) in the first‐line CA versus SR alone group (adjusted odds ratio 0.52 [0.28–0.95]; P=0.04). FPE was associated with higher rates of favorable outcomes (modified Rankin scale score 0–2: 58% versus 43.4%; P=0.01; modified Rankin scale score 0–1: 36.6% versus 25.8%; P=0.05). Overall, symptomatic intracranial hemorrhage was present in 5.6% (18/326) and mortality in 10.9% (35/326) without difference between first‐line technique. Conclusion In patients with isolated PCA occlusion, SR was associated with a higher rate of FPE compared with CA or combined techniques with no difference in final successful reperfusion. Functional independence at 90 days was more likely with first‐line SR compared with CA. FPE was associated with better 90‐day clinical outcomes.

Introduction The optimal reperfusion technique in patients with isolated posterior cerebral artery (PCA) occlusion is uncertain. Previous studies in LVO and MeVO have demonstrated a correlation between good clinical outcomes and the first pass effect (FPE, eTICI 2c/3 on the first pass) but no differences in FPE rates or clinical outcomes between first‐line endovascular therapy techniques.1‐6 We compared clinical and technical outcomes with first‐line stent‐retriever (SR), contact aspiration (CA), or combined techniques in patients with isolated PCA occlusion. Methods This international cohort study was conducted at 30 sites in Europe and North America and included consecutive patients with isolated PCA occlusion and pre‐stroke modified Rankin Scale (mRS) 0‐3, presenting within 24 hours of time last seen well from January 2015 to August 2022.7 The primary outcome was the first‐pass effect (FPE), defined as eTICI 2c/3 on the first pass. Secondary outcomes included final successful reperfusion (eTICI 2b‐3), 90‐day excellent outcome (mRS 0 to 1), 90‐day functional independence (mRS 0 to 2), sICH, and 90‐day mortality. Patients treated with SR, CA, or combined technique were compared with multivariable logistic regression. This study was registered under NCT05291637. Results There were 326 patients who met inclusion criteria, consisting of 56.1% male, median age 75 (IQR 65‐82) years and median NIHSS 8 (5‐12). Occlusion segments were PCA P1 (53.1%), P2 (40.5%), and other (6.4%). Intravenous thrombolysis was administered in 39.6%. First‐line technique was SR, CA, and combined technique in 43 (13.2%), 106 (32.5%), and 177 (54.3%) patients, respectively; FPE was achieved in 62.8%, 42.5%, and 39.6%, respectively. Compared to SR, FPE was lower in patients treated with first‐line combined technique and similar in patients treated with first‐line CA (combined vs. SR: aOR 0.35 [0.016‐0.80], p=0.01; CA vs. SR: aOR 0.45 [0.19‐1.06], p=0.07). Final successful reperfusion (eTICI 2b‐3) was present in 81% of cases with no differences between treatment groups. Excellent outcome (mRS 0‐1) occurred in 30.7% of patients and functional independence (mRS 0‐2) occurred in 50.0% of patients. There were lower odds of functional independence in the first‐line CA versus SR alone group (aOR 0.52 [0.28‐0.95], p=0.04). FPE was associated with higher rates of favorable outcomes (mRS 0‐2: 58% vs. 43.4%, p=0.01; mRS 0‐1: 36.6% vs. 25.8%, p=0.05). sICH was observed in 5.6% (18/326) and mortality in 10.9% (35/326) with no differences between first‐line technique. Conclusion In patients with isolated PCA occlusion undergoing EVT, first line SR was associated with a higher rate of FPE compared to CA or combined techniques with no difference in final successful reperfusion. Functional independence at 90‐days was more likely with first‐line SR compared to CA in adjusted analyses. FPE was associated with higher rates of 90‐day excellent outcomes and functional independence. No difference in sICH or mortality was noted across the three techniques. As the endovascular field evolves to treat patients with distal vessel occlusion and milder severity of stroke, optimizing the efficacy and safety of the procedure is essential.8

Background: Noncontrast Computed Tomography (NCCT) features are promising markers for acute hematoma expansion (HE) in patients with intracerebral hemorrhage (ICH). It remains unclear whether accurate identification of these markers is also reliable in raters with different levels of experience. Methods: Patients with acute spontaneous ICH admitted at four tertiary centers in Germany and Italy were retrospectively included from January 2017 to June 2020. In total, nine NCCT markers were rated by one radiology resident, one radiology fellow, and one neuroradiology fellow with different levels experience in ICH imaging. Interrater reliabilities of the resident and radiology fellow were evaluated by calculated Cohen’s kappa (κ) statistics in reference to the neuroradiology fellow who was referred as the gold standard. Gold-standard ratings were evaluated by calculated interrater κ statistics. Global interrater reliabilities were evaluated by calculated Fleiss kappa statistics across all three readers. A comparison of receiver operating characteristics (ROCs) was used to evaluate differences in the diagnostic accuracy for predicting acute hematoma expansion (HE) among the raters. Results: Substantial-to-almost-perfect interrater concordance was found for the resident with interrater Cohen’s kappa from 0.70 (95% CI 0.65–0.81) to 0.96 (95% CI 0.94–0.98). The interrater Cohen’s kappa for the radiology fellow was moderate to almost perfect and ranged from 0.58 (95% CI 0.52–0.65) to 94 (95% CI 92–0.97). The intrarater gold-standard Cohen’s kappa was almost perfect and ranged from 0.79 (95% CI 0.78–0.90) to 0.98 (95% CI 0.78–0.90). The global interrater Fleiss kappa ranged from 0.62 (95%CI 0.57–0.66) to 0.93 (95%CI 0.89–0.97). The diagnostic accuracy for the prediction of acute hematoma expansion (HE) was different for the island sign and fluid sign, with p-values < 0.05. Conclusion: The NCCT markers had a substantial-to-almost-perfect interrater agreement among raters with different levels of experience. Differences in the diagnostic accuracy for the prediction of acute HE were found in two out of nine NCCT markers. The study highlights the promising utility of NCCT markers for acute HE prediction.

Abstract Magnetic resonance imaging (MRI) is an important imaging modality in stroke. Computer based automated medical image processing is increasingly finding its way into clinical routine. The Ischemic Stroke Lesion Segmentation (ISLES) challenge is a continuous effort to develop and identify benchmark methods for acute and sub-acute ischemic stroke lesion segmentation. Here we introduce an expert-annotated, multicenter MRI dataset for segmentation of acute to subacute stroke lesions ( https://doi.org/10.5281/zenodo.7153326 ). This dataset comprises 400 multi-vendor MRI cases with high variability in stroke lesion size, quantity and location. It is split into a training dataset of n = 250 and a test dataset of n = 150. All training data is publicly available. The test dataset will be used for model validation only and will not be released to the public. This dataset serves as the foundation of the ISLES 2022 challenge ( https://www.isles-challenge.org/ ) with the goal of finding algorithmic methods to enable the development and benchmarking of automatic, robust and accurate segmentation methods for ischemic stroke.

Abstract Computed-tomography perfusion (CTP) is frequently used to screen acute ischemic stroke (AIS) patients for endovascular treatment (EVT), despite known problems with ischemic “core” overestimation. This potentially leads to the unfair exclusion of patients from EVT. We propose that net water uptake (NWU) can be used in addition to CTP to more accurately assess the extent and/or stage of tissue infarction. Patients treated for AIS between 06/2015 and 07/2020 were retrospectively analyzed. Baseline CTP-derived core volume (pCore) and NWU were determined. Logistic regression tested the relationship between baseline clinical and imaging variables and core-overestimation (primary outcome). The secondary outcomes comprised 90-day functional independence (modified Rankin score) and lesion growth. 284 patients were included. Median NWU was 7.2% (IQR 2.6–12.8). ASPECTS (RR 1.28, 95% CI 1.09–1.51), NWU (RR 0.94, 95% CI 0.89–0.98), onset to recanalization (RR 1.00, 95% CI 0.99–1.00) and imaging (RR 1.00, 95% CI 1.00–1.00) times, and pCore (RR 1.02, 95% CI 1.01–1.02) were significantly associated with core overestimation. Core-overestimation was more likely to occur in patients with large pCores and low NWU at baseline. NWU was significantly correlated with lesion growth. We conclude that NWU can be used as a supplemental tool to CTP during admission imaging to more accurately assess the extent of ischemia, particularly relevant for patients with large CTP-defined cores who would otherwise be excluded from treatment.

Abstract Background Follow-up imaging in intracerebral hemorrhage is not standardized and radiologists rely on different imaging modalities to determine hematoma growth. This study assesses the volumetric accuracy of different imaging modalities (MRI, CT angiography, postcontrast CT) to measure hematoma size. Methods 28 patients with acute spontaneous intracerebral hemorrhage referred to a tertiary stroke center were retrospectively included between 2018 and 2019. Inclusion criteria were (1) spontaneous intracerebral hemorrhage (supra- or infratentorial), (2) noncontrast CT imaging performed on admission, (3) follow-up imaging (CT angiography, postcontrast CT, MRI), and (4) absence of hematoma expansion confirmed by a third cranial image within 6 days. Two independent raters manually measured hematoma volume by drawing a region of interest on axial slices of admission noncontrast CT scans as well as on follow-up imaging (CT angiography, postcontrast CT, MRI) using a semi-automated segmentation tool (Visage image viewer; version 7.1.10). Results were compared using Bland–Altman plots. Results Mean admission hematoma volume was 18.79 ± 19.86 cc. All interrater and intrarater intraclass correlation coefficients were excellent (1; IQR 0.98–1.00). In comparison to hematoma volume on admission noncontrast CT volumetric measurements were most accurate in patients who received postcontrast CT (bias of − 2.47%, SD 4.67: n = 10), while CT angiography often underestimated hemorrhage volumes (bias of 31.91%, SD 45.54; n = 20). In MRI sequences intracerebral hemorrhage volumes were overestimated in T2* (bias of − 64.37%, SD 21.65; n = 10). FLAIR (bias of 6.05%, SD 35.45; n = 13) and DWI (bias of-14.6%, SD 31.93; n = 12) over- and underestimated hemorrhagic volumes. Conclusions Volumetric measurements were most accurate in postcontrast CT while CT angiography and MRI sequences often substantially over- or underestimated hemorrhage volumes.

Abstract Cerebral small vessel disease (CSVD) is a common cause of morbidity and cognitive decline in the elderly population. However, characterizing the disease pathophysiology and its association with potential clinical sequelae in early stages is less well explored. We applied fixel-based analysis (FBA), a novel framework of investigating microstructural white matter integrity by diffusion-weighted imaging, to data of 921 participants of the Hamburg City Health Study, comprising middle-aged individuals with increased cerebrovascular risk in early stages of CSVD. In individuals in the highest quartile of white matter hyperintensity loads (n = 232, median age 63 years; IQR 15.3 years), FBA detected significantly reduced axonal density and increased atrophy of transcallosal fiber tracts, the bilateral superior longitudinal fasciculus, and corticospinal tracts compared to participants in the lowest quartile of white matter hyperintensities (n = 228, mean age 55 years; IQR 10 years). Analysis of all participants (N = 921) demonstrated a significant association between reduced fiber density and worse executive functions operationalized by the Trail Making Test. Findings were confirmed by complementary analysis of diffusion tensor metrics.

Age-related cortical atrophy, approximated by cortical thickness measurements from magnetic resonance imaging, follows a characteristic pattern over the lifespan. Although its determinants remain unknown, mounting evidence demonstrates correspondence between the connectivity profiles of structural and functional brain networks and cortical atrophy in health and neurological disease. Here, we performed a cross-sectional multimodal neuroimaging analysis of 2633 individuals from a large population-based cohort to characterize the association between age-related differences in cortical thickness and functional as well as structural brain network topology. We identified a widespread pattern of age-related cortical thickness differences including “hotspots” of pronounced age effects in sensorimotor areas. Regional age-related differences were strongly correlated within the structurally defined node neighborhood. The overall pattern of thickness differences was found to be anchored in the functional network hierarchy as encoded by macroscale functional connectivity gradients. Lastly, the identified difference pattern covaried significantly with cognitive and motor performance. Our findings indicate that connectivity profiles of functional and structural brain networks act as organizing principles behind age-related cortical thinning as an imaging surrogate of cortical atrophy.

Aging is accompanied by structural brain changes that are thought to underlie cognitive decline and dementia. Yet little is known regarding the association between increasing age, structural brain damage, and alterations of functional brain connectivity. The aim of this study was to evaluate whether cortical thickness and white matter damage as markers of age-related structural brain changes are associated with alterations in functional connectivity in non-demented healthy middle-aged to older adults. Therefore, we reconstructed functional connectomes from resting-state functional magnetic resonance imaging (MRI) (rsfMRI) data of 976 subjects from the Hamburg City Health Study, a prospective population-based study including participants aged 45–74 years from the metropolitan region Hamburg, Germany. We performed multiple linear regressions to examine the association of age, cortical thickness, and white matter damage quantified by the peak width of skeletonized mean diffusivity (PSMD) from diffusion tensor imaging on whole-brain network connectivity and four predefined resting state networks (default mode, dorsal, salience, and control network). In a second step, we extracted subnetworks with age-related decreased functional connectivity from these networks and conducted a mediation analysis to test whether the effect of age on these networks is mediated by decreased cortical thickness or PSMD. We observed an independent association of higher age with decreased functional connectivity, while there was no significant association of functional connectivity with cortical thickness or PSMD. Mediation analysis identified cortical thickness as a partial mediator between age and default subnetwork connectivity and functional connectivity within the default subnetwork as a partial mediator between age and executive cognitive function. These results indicate that, on a global scale, functional connectivity is not determined by structural damage in healthy middle-aged to older adults. There is a weak association of higher age with decreased functional connectivity which, for specific subnetworks, appears to be mediated by cortical thickness.

Randomized trials supporting the benefit of endovascular treatment in acute ischemic stroke patients with a large early infarction are not yet available. Few retrospective studies exist that suggest a potential positive treatment effect on functional outcome, as well as procedural safety. However, potential benefit or harm of MT in patients with low initial ASPECTS is still a subject of current debate, and in particular, how to select these patients for treatment. The purpose of this pilot study was to evaluate how early tissue water uptake in acute ischemic brain might determine lesion fate and functional outcome in low ASPECTS patients undergoing MT. We observed that the degree of early water uptake measured by quantitative NWU was significantly associated with functional outcome in low ASPECTS patients, yielding a higher diagnostic power compared to other parameters such as ASPECTS, age, or NIHSS. No conclusive evidence of a beneficial effect of successful reperfusion was observed in patients with low ASPECTS and high NWU, which highlights the potential of NWU as a tool to specify patient selection.

Background and Purpose: Intracerebral hemorrhage (ICH) after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) remains a major complication and its early prediction is of high relevance. Baseline serum glucose (BGL) is a known predictor of ICH, but its interaction with early ischemic changes remains uncertain. We hypothesized that BGL interacts with the effect of tissue water uptake on the occurrence of ICH.Methods: Three hundred and thirty-six patients with acute ischemic stroke treated with MT were retrospectively analyzed. ICH was diagnosed within 24 h on non-enhanced CT (NECT) and classified according to the Heidelberg Bleeding Classification. Early tissue water homeostasis has been assessed using quantitative lesion net water uptake (NWU) on admission CT. Multivariate logistic regression was used to identify predictors of ICH.Results: One hundred and seven patients fulfilled the inclusion criteria of which 37 (34.6%) were diagnosed with ICH. Patients with ICH had a significant higher BGL on admission (median 177 mg/dl, IQR: 127–221.75, P < 0.001). In patients with low BGL (200 mg/dl). In multivariable logistic regression analysis, BGL (OR: 1.02, 95% CI: 1.00–1.04, P = 0.01) and NWU (OR: 2.32, 95% CI: 1.44–3.73, P < 0.001) were significantly and independently associated with ICH, showing a significant interaction (P = 0.04).Conclusion: A higher degree of early tissue water uptake and high admission BGL were both independent predictors of ICH. Higher BGL was significantly associated with accelerated effects of NWU on the likelihood of ICH. Although a clear causal relationship remains speculative, stricter BGL control and monitoring may be tested to reduce the risk of ICH in patients undergoing thrombectomy.

Background and Purpose: Ischemic brain edema can be measured in computed tomography (CT) using quantitative net water uptake (NWU), a recently established imaging biomarker. NWU determined in follow-up CT after mechanical thrombectomy (MT) has shown to be a strong predictor of functional outcome. However, disruption of the blood–brain barrier after MT may also lead to contrast staining, increasing the density on CT scans, and hence, directly impairing measurements of NWU. The purpose of this study was to determine whether dual-energy dual-layer CT (DDCT) after MT can improve the quantification of NWU by measuring NWU in conventional polychromatic CT images (CP-I) and virtual non-contrast images (VNC-I). We hypothesized that VNC-based NWU (vNWU) differs from NWU in conventional CT (cNWU).Methods: Ten patients with middle cerebral artery occlusion who received a DDCT follow-up scan after MT were included. NWU was quantified in conventional and VNC images as previously published and was compared using paired sample t-tests.Results: The mean cNWU was 3.3% (95%CI: 0–0.41%), and vNWU was 11% (95%CI: 1.3–23.4), which was not statistically different (p = 0.09). Two patients showed significant differences between cNWU and vNWU (Δ = 24% and Δ = 36%), while the agreement of cNWU/vNWU in 8/10 patients was high (difference 2.3%, p = 0.23).Conclusion: NWU may be quantified precisely on conventional CT images, as the underestimation of ischemic edema due to contrast staining was low. However, a proportion of patients after MT might show significant contrast leakage resulting in edema underestimation. Further research is needed to validate these findings and investigate clinical implications.

Background and Purpose: Identification of ischemic stroke patients at high risk of developing life-threatening malignant infarction at an early stage is critical to consider more rigorous monitoring and further therapeutic measures. We hypothesized that a score consisting of simple measurements of visually evident ischemic changes in non-enhanced CT (NEMMI score) predicts malignant middle cerebral artery (MCA) infarctions (MMI) with similar diagnostic power compared to other baseline clinical and imaging parameters.Methods: One hundred and nine patients with acute proximal MCA occlusion were included. Fifteen (13.8%) patients developed MMI. NEMMI score was defined using the sum of the maximum diameter (anterior-posterior plus medio-lateral) of the hypoattenuated lesion in baseline-CT multiplied by a hypoattenuation factor (3-point visual grading in non-enhanced CT, no/subtle/clear hypoattenuation = 1/2/3). Receiver operating characteristic (ROC) curve analysis and multivariable logistic regression analysis were used to calculate the predictive values of the NEMMI score, baseline clinical and other imaging parameters.Results: The median NEMMI score at baseline was 13.6 (IQR: 11.6–31.1) for MMI patients, and 7.7 (IQR: 3.9–11.2) for patients with non-malignant infarctions (p < 0.0001). Based on ROC curve analysis, a NEMMI score >10.5 identified MMI with good discriminative power (AUC: 0.84, sensitivity/specificity: 93.3/70.7%), which was higher compared to age (AUC: 0.76), NIHSS (AUC: 0.61), or ischemic core volume (AUC: 0.80). In multivariable logistic regression analysis, NEMMI score was significantly and independently associated with MMI (OR: 1.33, 95%CI: 1.13–1.56, p < 0.001), adjusted for recanalization status.Conclusion: The NEMMI score is a quick and simple rating tool of early ischemic changes on CT and could serve as an important surrogate marker for developing malignant edema. Its diagnostic accuracy was similar to CTP and clinical parameters.

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.

Background: 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.Methods: The analysis included NECT brain scans from 77 patients with acute ICH (n = 50 non-neoplastic, n = 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).Results: 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); P < 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); P = 0.01.Conclusion: 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.

Background: 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).Methods: 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.Results: 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.Conclusions: 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.

Background Stent‐retriever thrombectomy is the first‐line therapy in acute stroke with intracranial large vessel occlusion. In case of failure of stent‐retriever thrombectomy, rescue stent angioplasty might be the only treatment option to achieve permanent recanalization. This study aims at identifying predictors for poor outcome and complications in a large, multicenter cohort receiving rescue stent angioplasty. Methods and Results We performed a retrospective analysis of patients with large vessel occlusion who were treated with rescue stent angioplasty after stent‐retriever thrombectomy between 2012 and 2018 in 7 neurovascular centers. We defined 2 binary outcomes: (1) functional clinical outcome (good modified Rankin Scale, 0–2; and poor modified Rankin Scale, 4–6) and (2) early symptomatic intracerebral hemorrhage. Impacts of clinical, radiological, and interventional parameters on outcomewere assessed in uni‐ and multivariable logistic regression models. Two hundred ten patients were included with target vessels located within the anterior circulation (136 of 210; 64.8%) and posterior circulation (74 of 210; 35.2%). Symptomatic intracerebral hemorrhage occured in 22 patients, 86.4% (19 of 22) after anterior and 13.6% (3 of 22) after posterior circulation large vessel occlusion. Good functional outcome was observed in 44.8% (73 of 163). A higher National Institutes of Health Stroke Scale on admission (adjusted odds ratio, 1.10; P=0.002), a higher premorbid modified Rankin Scale (adjusted odds ratio, 2.02; P=0.049), and a modified Thrombolysis in Cerebral Infarction score of 0 to 2a after stenting (adjusted odds ratio, 23.24; P

Background Patients aged ≥90 were excluded or under‐represented in past thrombectomy trials; thus, uncertainty remains whether treatment benefits can be expected regardless of age. This study investigates outcome and safety of thrombectomy in nonagenarians to improve decision making in a real‐world setting. Methods and Results All currently available data of patients aged ≥90 enrolled in the GSR‐ET (German Stroke Registry–Endovascular Treatment) were combined with a smaller cohort from 3 tertiary stroke centers. Baseline characteristics, procedural (Thrombolysis in Cerebral Infarction scale) and functional outcomes (modified Rankin Scale; mRS), as well as complications (symptomatic intracranial hemorrhage, serious adverse events; SAEs) were analyzed. Good functional outcome was defined as mRS ≤3 at 90‐days. 203 patients with anterior circulation stroke and prestroke mRS ≤3 were included. The rate of successful recanalization (Thrombolysis in Cerebral Infarction scale ≥2b) was 75.9% (154/203). Good functional outcome (mRS ≤3) was observed in 21.6% (41 of 193) at 90‐days. In‐hospital mortality was 27.1% (55 of 203) and increased significantly at 90 days to 48.9% (93 of 190; P

Background and Purpose: Recently, acute intracranial stenting (ICS) has gained more interest as a potential bailout strategy for large vessel occlusions (LVO) that are refractory to thrombectomy. However, there are currently no reports on ICS in patients with moderately severe stroke discussing the question if implementing a permanent stent is feasible and leads to improved recanalization after failed thrombectomy.Methods: We analyzed a large multicenter database of patients receiving ICS for anterior circulation LVO after failed thrombectomy. Inclusion criteria were defined as: Moderately severe stroke (National Institute Health Stroke Scale (NIHSS) ≤9 on admission), anterior circulation LVO, acute ICS after failed stent retriever MT. Primary endpoint was the rate of improved successful recanalization after ICS defined as a modified Thrombolysis In cerebral Infarction (mTICI) score≥2b. Favorable neurological outcome was defined as an early neurological improvement (ENI) of 4 points or reaching 0 with respect to baseline NIHSS.Results: Forty-one patients met the inclusion criteria. A median of 2 retrievals were performed (IQR 1–4) prior decision-making for ICS. ICS led in 90.2% (37/41) of cases to a final mTICI≥2b with significant improvement (p < 0.001) after the last retrieval attempt. The median NIHSS decreased (p = 0.178) from 7 (IQR 3.5–8) on admission to 2.5 (IQR 0–8.25) at discharge. ENI was observed in 47.4% (18/38). sICH occurred in 4.8% (2/41).Conclusion: ICS after failed thrombectomy appears to effectively improve recanalization rates in patients with moderately severe strokes. Thus, ICS should be considered also for patients with baseline NIHSS ≤9 if thrombectomy fails.

Quantitative MRI modalities, such as diffusion tensor imaging (DTI) or magnetization transfer imaging (MTI) are sensitive to the neuronal effects of aging of the cerebral white matter (WM), but lack the specificity for myelin content. Myelin water imaging (MWI) is highly specific for myelin and may be more sensitive for the detection of changes in myelin content inside the cerebral WM microstructure. In this multiparametric imaging study, we evaluated the performance of myelin water fraction (MWF) estimates as a marker for myelin alterations during normal-aging. Multiparametric MRI data derived from DTI, MTI and a novel, recently-proposed MWF-map processing and reconstruction algorithm were acquired from 54 healthy subjects (aged 18–79 years) and region-based multivariate regression analysis was performed. MWFs significantly decreased with age in most WM regions (except corticospinal tract) and changes of MWFs were associated with changes of radial diffusivity, indicating either substantial alterations or preservation of myelin content in these regions. Decreases of fractional anisotropy and magnetization transfer ratio were associated with lower MWFs in commissural fiber tracts only. Mean diffusivity had no regional effects on MWF. We conclude that MWF estimates are sensitive for the assessment of age-related myelin alterations in the cerebral WM of normal-aging brains.

ObjectiveTo 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.MethodsSix 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.ResultsPhysicians 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).ConclusionHANNES 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.

Background and Purpose Blend sign (BS) and black hole sign (BHS) on non-contrast computed tomography (NCCT) and spot sign (SS) on CT-angiography (CTA) are indicators of early hematoma expansion in spontaneous intracerebral hemorrhage (ICH). However, their independent contributions to outcome have not been well explored. Methods In this retrospective study, inclusion criteria were: 1) spontaneous ICH and 2) NCCT and CTA performed on admission within 6 hours after onset of symptoms. Discharge outcome was dichotomized as good (modified Rankin Scale [mRS] 0-3) and poor (mRS 4-6) outcomes. The impacts of BHS, BS and SS on outcome were assessed in univariate and multivariable logistic regression models. Results Of 182 patients with spontaneous ICH, 26 (14.3%) presented with BHS, 37 (20.3%) with BS and 39 (21.4%) with SS. There was a substantial correlation between SS and BS (κ=0.701) and a moderate correlation between SS and BHS (κ=0.424). In univariable logistic regression, higher baseline hematoma volume (P

Introduction: Acute stroke care delivered by interdisciplinary teams is time-sensitive. Simulation-based team training is a promising tool to improve team performance in medical operations. It has the potential to improve process times, team communication, patient safety, and staff satisfaction. We aim to assess whether a multi-level approach consisting of a stringent workflow revision based on peer-to-peer review and 2–3 one-day in situ simulation trainings can improve acute stroke care processing times in high volume neurocenters within a 6 months period.Methods and Analysis: The trial is being carried out in a pre-test-post-test design at 7 tertiary care university hospital neurocenters in Germany. The intervention is directed at the interdisciplinary multiprofessional stroke teams. Before and after the intervention, process times of all direct-to-center stroke patients receiving IV thrombolysis (IVT) and/or endovascular therapy (EVT) will be recorded. The primary outcome measure will be the “door-to-needle” time of all consecutive stroke patients directly admitted to the neurocenters who receive IVT. Secondary outcome measures will be intervention-related process times of the fraction of patients undergoing EVT and effects on team communication, perceived patient safety, and staff satisfaction via a staff questionnaire.Interventions: We are applying a multi-level intervention in cooperation with three “STREAM multipliers” from each center. First step is a central meeting of the multipliers at the sponsor's institution with the purposes of algorithm review in a peer-to-peer process that is recorded in a protocol and an introduction to the principles of simulation training and debriefing as well as crew resource management and team communication. Thereafter, the multipliers cooperate with the stroke team trainers from the sponsor's institution to plan and execute 2–3 one-day simulation courses in situ in the emergency department and CT room of the trial centers whereupon they receive teaching materials to perpetuate the trainings.Clinical Trial Registration: STREAM is a registered trial at https://clinicaltrials.gov/ct2/show/NCT03228251.

Background and Purpose: Intracranial hemorrhage (ICH) remains a major complication of endovascular treatment (ET) in acute stroke. The aim of this study was to identify clinical and imaging predictors for ICH in patients with acute ischemic stroke undergoing successful ET.Methods: We performed a retrospective analysis of patients with large vessel occlusion in the anterior circulation who underwent successful ET at our university medical center between 2015 and 2018. ICH was diagnosed on non-enhanced CT and a binary outcome was defined: ICH occurrence in the immediate post-interventional phase within 12–36 h (yes/no). The impacts of clinical, radiological, and interventional parameters on outcome were assessed in logistic regression models.Results: One hundred and seven patients fulfilled the inclusion criteria. 37 (34.6%) showed an ICH of which 7 (6.5%) patients were diagnosed as symptomatic and 30 (28.04%) as asymptomatic. Multivariable regression analyses identified a lower ASPECTS (adjusted odds ratio (OR) 1.95, 95%CI: 1.4–3.63, P = 0.037), low collateral score (adjusted OR 0.12, 95%CI: 0.03–0.49, P = 0.003) and high Net Water Uptake (NWU) (adjusted OR 1.56, 95%CI: 2.34–1.03, P = 0.007) as independent predictors of ICH after successful ET.Conclusions: CT-based quantitative NWU, ASPECTS, and collateral score mediate tissue vulnerability and are reliable independent predictors of a bleeding event after successful ET. This imaging-based prediction model might be useful for early stratification of patients at high risk of a bleeding event after ET, especially with low ASPECTS.

Background Several randomized trials have shown the efficacy of thrombectomy for large intracranial vessel occlusions in adults. However, the safety and efficacy of thrombectomy in children are unknown. We aimed to investigate the feasibility and outcome of thrombectomy in pediatric patients. Methods and Results We performed a retrospective analysis of all children (

Background and Objective: In multiple sclerosis (MS) patients, Double Inversion Recovery (DIR) magnetic resonance imaging (MRI) can be used to detect cortical lesions (CL). While the quantity and distribution of CLs seems to be associated with patients' disease course, literature lacks frequent assessments of CL volumes (CL-V) in this context. We investigated the reliability of DIR for the longitudinal assessment of CL-V development with frequent follow-up MRIs and examined the course of CL-V progressions in relation to white-matter lesions (WML), contrast enhancing lesions (CEL) and clinical parameters in patients with Relapsing-Remitting Multiple Sclerosis (RRMS).Methods: In this post-hoc analysis, image- and clinical data of a subset of 24 subjects that were part of a phase IIa clinical trial on the “Safety, Tolerability and Mechanisms of Action of Boswellic Acids in Multiple Sclerosis (SABA)” (ClinicalTrials.gov, NCT01450124) were included. The study was divided in three phases (screening, treatment, study-end). All patients received 12 MRI follow-up-examinations (including DIR) during a 16-months period. CL-Vs were assessed for each patient on each follow-up MRI separately by two experienced neuroradiologists. Results of neurological screening tests, as well as other MRI parameters (WML number and volume and CELs) were included from the SABA investigation data.Results: Inter-rater agreement regarding CL-V assessment over time was good-to-excellent (κ = 0.89). Mean intraobserver variability was 1.1%. In all patients, a total number of 218 CLs was found. Total CL-Vs of all patients increased during the 4 months of baseline screening followed by a continuous and significant decrease from month 5 until study-end (p < 0.001, Kendall'W = 0.413). A positive association between WML volumes and CL-Vs was observed during baseline screening. Decreased CL-V were associated with lower EDSS and also with improvements of SDMT- and SCRIPPS scores.Conclusion: DIR MRI seems to be a reliable tool for the frequent assessment of CL-Vs. Overall CL-Vs decreased during the follow-up period and were associated with improvements of cognitive and disability status scores. Our results suggest the presence of short-term CL-V dynamics in RRMS patients and we presume that the laborious evaluation of lesion volumes may be worthwhile for future investigations.Clinical Trial Numbers:www.ClinicalTrials.gov, “The SABA trial”; number: NCT01450124

Leukocyte sequestration is an established therapeutic concept in multiple sclerosis (MS) as represented by the trafficking drugs natalizumab (NAT) and fingolimod (FTY). However, the precise consequences of targeting immune cell trafficking for immunoregulatory network functions are only incompletely understood. In the present study, we performed an in-depth longitudinal characterization of functional and phenotypic immune signatures in peripheral blood (PB) and cerebrospinal fluid (CSF) of 15 MS patients during switching from long-term NAT to FTY treatment after a defined 8-week washout period within a clinical trial (ToFingo successor study; ClinicalTrials.gov: NCT02325440). Unbiased visualization and analysis of high-dimensional single cell flow-cytometry data revealed that switching resulted in a profound alteration of more than 80% of investigated innate and adaptive immune cell subpopulations in the PB, revealing an unexpectedly broad effect of trafficking drugs on peripheral immune signatures. Longitudinal CSF analysis demonstrated that NAT and FTY both reduced T cell subset counts and proportions in the CSF of MS patients with equal potency; NAT however was superior with regard to sequestering non-T cell populations out of the CSF, including B cells, natural killer cells and inflammatory monocytes, suggesting that disease exacerbation in the context of switching might be driven by non-T cell populations. Finally, correlation of our immunological data with signs of disease exacerbation in this small cohort suggested that both (i) CD49d expression levels under NAT at the time of treatment cessation and (ii) swiftness of FTY-mediated effects on immune cell subsets in the PB together may predict stability during switching later on.

Background and aim The clinical importance and management of vasospasm as a complication during endovascular stroke treatment (EVT) has not been well studied. We sought to investigate current expert opinions in neurointervention and therapeutic strategies of iatrogenic vasospasm during EVT.Methods We conducted an anonymous international online survey (4 April 2023 to 15 May 2023) addressing treatment standards of neurointerventionalists (NIs) practising EVT. Several illustrative cases of patients with vasospasm during EVT were shown. Two study groups were compared according to the NI’s opinion regarding the potential influence of vasospasm on patient outcome after EVT using descriptive analysis.Results In total, 534 NI from 56 countries responded, of whom 51.5% had performed >200 EVT. Vasospasm was considered a complication potentially influencing the patient’s outcome by 52.6% (group 1) whereas 47.4% did not (group 2). Physicians in group 1 more often added vasodilators to their catheter flushes during EVT routinely (43.7% vs 33.9%, p=0.033) and more often treated severe large-vessel vasospasm with vasodilators (75.3% vs 55.9%; p

Background and purpose In wake-up stroke, CT-based quantitative net water uptake (NWU) might serve as an alternative tool to MRI to guide intravenous thrombolysis with alteplase (IVT). An important complication after IVT is symptomatic intracerebral haemorrhage (sICH). As NWU directly implies ischaemic lesion progression, reflecting blood-brain barrier injury, we hypothesised that NWU predicts sICH in patients who had a ischaemic stroke undergoing thrombectomy with unknown onset.Methods Consecutive analysis of all patients who had unknown onset anterior circulation ischaemic stroke who underwent CT at baseline and endovascular treatment between December 2016 and October 2020. Quantitative NWU was assessed on baseline CT. The primary endpoint was sICH. The association of NWU and other baseline parameters to sICH was investigated using inverse-probability weighting (IPW) analysis.Results A total of 88 patients were included, of which 46 patients (52.3%) received IVT. The median NWU was 10.7% (IQR: 5.1–17.7). The proportion of patients with any haemorrhage and sICH were 35.2% and 13.6%. NWU at baseline was significantly higher in patients with sICH (19.1% vs 9.6%, p

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