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

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

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

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

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

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

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

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

Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial.

BACKGROUND: Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice. METHODS: In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and a large established infarct indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 were randomly assigned using a central, web-based system (using a 1:1 ratio) to receive either endovascular thrombectomy with medical treatment or medical treatment (ie, standard of care) alone up to 12 h from stroke onset. The study was conducted in 40 hospitals in Europe and one site in Canada. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days, assessed by investigators masked to treatment assignment. The primary analysis was done in the intention-to-treat population. Safety endpoints included mortality and rates of symptomatic intracranial haemorrhage and were analysed in the safety population, which included all patients based on the treatment they received. This trial is registered with ClinicalTrials.gov, NCT03094715. FINDINGS: From July 17, 2018, to Feb 21, 2023, 253 patients were randomly assigned, with 125 patients assigned to endovascular thrombectomy and 128 to medical treatment alone. The trial was stopped early for efficacy after the first pre-planned interim analysis. At 90 days, endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better outcome (adjusted common OR 2·58 [95% CI 1·60-4·15]; p=0·0001) and with lower mortality (hazard ratio 0·67 [95% CI 0·46-0·98]; p=0·038). Symptomatic intracranial haemorrhage occurred in seven (6%) patients with thrombectomy and in six (5%) with medical treatment alone. INTERPRETATION: Endovascular thrombectomy was associated with improved functional outcome and lower mortality in patients with acute ischaemic stroke from large vessel occlusion with established large infarct in a setting using non-contrast CT as the predominant imaging modality for patient selection. FUNDING: EU Horizon 2020.

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

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

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

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

Discordant and Converting Receptor Expressions in Brain Metastases from Breast Cancer: MRI-Based Non-Invasive Receptor Status Tracking.

Discordance and conversion of receptor expressions in metastatic lesions and primary tumors is often observed in patients with brain metastases from breast cancer. Therefore, personalized therapy requires continuous monitoring of receptor expressions and dynamic adaptation of applied targeted treatment options. Radiological in vivo techniques may allow receptor status tracking at high frequencies at low risk and cost. The present study aims to investigate the potential of receptor status prediction through machine-learning-based analysis of radiomic MR image features. The analysis is based on 412 brain metastases samples from 106 patients acquired between 09/2007 and 09/2021. Inclusion criteria were as follows: diagnosed cerebral metastases from breast cancer; histopathology reports on progesterone (PR), estrogen (ER), and human epidermal growth factor 2 (HER2) receptor status; and availability of MR imaging data. In total, 3367 quantitative features of T1 contrast-enhanced, T1 non-enhanced, and FLAIR images and corresponding patient age were evaluated utilizing random forest algorithms. Feature importance was assessed using Gini impurity measures. Predictive performance was tested using 10 permuted 5-fold cross-validation sets employing the 30 most important features of each training set. Receiver operating characteristic areas under the curves of the validation sets were 0.82 (95% confidence interval [0.78; 0.85]) for ER+, 0.73 [0.69; 0.77] for PR+, and 0.74 [0.70; 0.78] for HER2+. Observations indicate that MR image features employed in a machine learning classifier could provide high discriminatory accuracy in predicting the receptor status of brain metastases from breast cancer.

Predictors of aneurysm occlusion after treatment with flow diverters: a systematic literature review.

BACKGROUND: Flow diverters (FDs) have become an integral part of treatment for brain aneurysms. AIM: To summarize available evidence of factors associated with aneurysm occlusion (AO) after treatment with a FD. METHODS: References were identified using the Nested Knowledge AutoLit semi-automated review platform between January 1, 2008 and August 26, 2022. The review focuses on preprocedural and postprocedural factors associated with AO identified in logistic regression analysis. Studies were included if they met the inclusion criteria of study details (ie, study design, sample size, location, (pre)treatment aneurysm details). Evidence levels were classified by variability and significancy across studies (eg, low variability ≥5 studies and significance in ≥60% throughout reports). RESULTS: Overall, 2.03% (95% CI 1.22 to 2.82; 24/1184) of screened studies met the inclusion criteria for predictors of AO based on logistic regression analysis. Predictors of AO with low variability in multivariable logistic regression analysis included aneurysm characteristics (aneurysm diameter), particularly complexity (absence of branch involvement) and younger patient age. Predictors of moderate evidence for AO included aneurysm characteristics (neck width), patient characteristics (absence of hypertension), procedural (adjunctive coiling) and post-deployment variables (longer follow-up; direct postprocedural satisfactory occlusion). Variables with a high variability in predicting AO following FD treatment were gender, FD as re-treatment strategy, and aneurysm morphology (eg, fusiform or blister). CONCLUSION: Evidence of predictors for AO after FD treatment is sparse. Current literature suggests that absence of branch involvement, younger age, and aneurysm diameter have the highest impact on AO following FD treatment. Large studies investigating high-quality data with well-defined inclusion criteria are needed for greater insight into FD effectiveness.

How much of the outcome improvement after successful recanalization is explained by follow-up infarct volume reduction?

BACKGROUND: Follow-up infarct volume (FIV) is used as surrogate for treatment efficiency in mechanical thrombectomy (MT). However, previous works suggest that MT-related FIV reduction has only limited association with outcome comparing MT independently of recanalization success versus medical care. It remains unclear to what extent the relationship between successful recanalization versus persistent occlusion and functional outcome is explained by FIV reduction. OBJECTIVE: To determine whether FIV mediates the relationship between successful recanalization and functional outcome. METHODS: All patients from our institution enrolled in the German Stroke Registry (May 2015-December 2019) with anterior circulation stroke; availability of the relevant clinical data, and follow-up-CT were analyzed. The effect of FIV reduction on functional outcome (90-day modified Rankin Scale (mRS) score ≤2) after successful recanalization (Thrombolysis in Cerebral Infarction ≥2b) was quantified using mediation analysis. RESULTS: 429 patients were included, of whom, 309 (72 %) had successful recanalization and 127 (39%) had good functional outcome. Good outcome was associated with age (OR=0.89, P<0.001), pre-stroke mRS score (OR=0.38, P<0.001), FIV (OR=0.98, P<0.001), hypertension (OR=2.08, P<0.05), and successful recanalization (OR=3.57, P<0.01). Using linear regression in the mediator pathway, FIV was associated with Alberta Stroke program Early CT Score (coefficient (Co)=-26.13, P<0.001), admission National Institutes of Health Stroke Scale score (Co=3.69, P<0.001), age (Co=-1.18, P<0.05), and successful recanalization (Co=-85.22, P<0.001). Successful recanalization increased the probability of good outcome by 23 percentage points (pp) (95% CI 16pp to 29pp). 56% (95% CI 38% to 78%) of the improvement in good outcome was explained by FIV reduction. CONCLUSION: 56% (95% CI 38% to 78%) of outcome improvement after successful recanalization was explained by FIV reduction. Results corroborate pathophysiological assumptions and confirm the value of FIV as an imaging endpoint in clinical trials. 44% (95% CI 22% to 62%) of the improvement in outcome was not explained by FIV reduction and reflects the remaining mismatch between radiological and clinical outcome measures.

Effect of geometric distortion correction on thickness and volume measurements of cortical parcellations in 3D T1w gradient echo sequences.

OBJECTIVE: Automated brain volumetric analysis based on high-resolution T1-weighted MRI datasets is a frequently used tool in neuroimaging for early detection, diagnosis, and monitoring of various neurological diseases. However, image distortions can corrupt and bias the analysis. The aim of this study was to explore the variability of brain volumetric analysis due to gradient distortions and to investigate the effect of distortion correction methods implemented on commercial scanners. MATERIAL AND METHODS: 36 healthy volunteers underwent brain imaging using a 3T magnetic resonance imaging (MRI) scanner, including a high-resolution 3D T1-weighted sequence. For all participants, each T1-weighted image was reconstructed directly on the vendor workstation with (DC) and without (nDC) distortion correction. For each participant's set of DC and nDC images, FreeSurfer was used for the determination of regional cortical thickness and volume. RESULTS: Overall, significant differences were found in 12 cortical ROIs comparing the volumes of the DC and nDC data and in 19 cortical ROIs comparing the thickness of the DC and nDC data. The most pronounced differences for cortical thickness were found in the precentral gyrus, the lateral occipital and postcentral ROI (2.69, -2.91% and -2.79%, respectively) while cortical volumes differed most prominently in the paracentral, the pericalcarine and lateral occipital ROI (5.52%, -5.40% and -5.11%, respectively). CONCLUSION: Correcting for gradient non-linearities can have significant influence on volumetric analysis of cortical thickness and volume. Since the distortion correction is an automatic feature of the MR scanner, it should be stated by each study that applies volumetric analysis which images were used.

Thrombectomy in M2 occlusion compared to M1 occlusion: treatment effects of Thrombolysis In Cerebral Infarction (TICI) 2b and TICI 3 recanalization on functional outcome.

BACKGROUND: Emerging data suggest that mechanical thrombectomy (MT) might also be safe and efficient for medium and distal occlusions. This study aims to compare average treatment effects on functional outcome of different degrees of recanalization after MT in patients with M2 occlusion and M1 occlusion. METHODS: All patients enrolled in the German Stroke Registry (GSR) between June 2015 and December 2021 were analyzed. Inclusion criteria were stroke with primary M1 occlusion or M2 occlusion, and availability of relevant clinical data. 4259 patients were included, thereof 1353 with M2 occlusion and 2906 with M1 occlusion. Treatment effects were analyzed using double-robust inverse-probability-weighted regression-adjustment (IPWRA) estimators to control for confounding covariates. Binarized endpoint metrics were defined as good outcome with modified Rankin Scale (mRS) ≤2 at 90 days, and linearized endpoint metrics were defined as mRS shift pre-stroke to 90 days. Effects were evaluated for near complete recanalization (Thrombolysis In Cerebral Infarction scale (TICI) 2b) and complete recanalization (TICI 3). RESULTS: Treatment effect estimation for TICI ≥2b versus TICI <2b in M2 occlusions showed an increase in the probability of a good outcome from 27% to 47% with a number-needed-to-treat (NNT) of 5. For M1 occlusions the probability of a good outcome increased from 16% to 38% with NNT 4.5. TICI 3 versus TICI 2b increased the probability of a good outcome by 7 percentage points in M1 occlusions; for M2 occlusions the beneficial effect was not significant. CONCLUSIONS: Results suggest that successful recanalization with TICI ≥2b versus TICI <2b after MT in M2 occlusions provides significant patient benefit with treatment effects comparable to M1 occlusions. The probability of functional independence increased by 20 percentage points (NNT 5) and stroke-related mRS increase was reduced by 0.9 mRS points. In contrast to M1 occlusions, complete recanalization TICI 3 versus TICI 2b had lower additional beneficial effect.

Early surrogates of outcome after thrombectomy in posterior circulation stroke.

BACKGROUND: Early surrogates for functional outcome in anterior circulation stroke have been described with the National Institute of Health Stroke Scale (NIHSS) at 24 h being reported as the most accurate metric. We compare discriminatory power of established definitions of early neurological improvement (ENI) and NIHSS scores at admission and 24 h to predict functional outcome at 90 days after thrombectomy in posterior circulation stroke (PCS). METHODS: All patients enrolled in the German Stroke Registry (June 2015-December 2019) with PCS and at least vertebral or basilar artery occlusions were included. NIHSS admission, 24 h and ENI definitions (improvement of 8/10 NIHSS points or 0/1 NIHSS points at 24 h) were compared for predicting functional outcome at 90 days. Favourable and good outcome were defined as modified Rankin Scale (mRS) 0-2 and 0-3. Multivariable logistic regression analysis was conducted to identify factors impairing predictive power. RESULTS: Three hundred and eighty-seven patients were included. NIHSS 24 h had the highest discriminative power with receiver operator characteristics area under the curve of 0.87 (95% confidence interval: 0.83; 0.90) for good and 0.89 (0.85; 0.92) for favourable outcome; optimal cut-off values were ≤9 and ≤5. Higher age (odds ratio = 1.10 [1.05; 1.16]), adverse events during treatment (9.46 [1.52; 72.5]) and until discharge (18.34 [2.33; 172]) and high NIHSS scores at 24 h (1.29 [1.10; 1.53]) were independent predictors for turning the outcome prognosis from good (mRS ≤3) to poor (mRS ≥4). CONCLUSIONS: NIHSS 24 h ≤9 points serves best as surrogate for good functional outcome after thrombectomy in PCS. Advanced age, severe neurological symptoms at admission and adverse events decrease its predictive value.

How Much of the Thrombectomy Related Improvement in Functional Outcome Is Already Apparent at 24 Hours and at Hospital Discharge?

BACKGROUND: Early neurological status has been described as predictor of functional outcome in patients with anterior circulation stroke after mechanical thrombectomy. It remains unclear to what proportion the improvement of functional outcome at day 90 is already apparent at 24 hours and at hospital discharge and how later factors impact outcome. METHODS: All patients enrolled in the German Stroke Registry (June 2015-December 2019) with anterior circulation stroke and availability of baseline data and neurological status were included. A mediation analysis was conducted to investigate the effect of successful recanalization (Thrombolysis in Cerebral Infarction scale score ≥2b) on good functional outcome (modified Rankin Scale score ≤2 at day 90) with mediation through neurological status (National Institutes of Health Stroke Scale [NIHSS] at 24 hours and at hospital discharge). RESULTS: Three thousand fifty-seven patients fulfilled the inclusion criteria, thereof 2589 (85%) with successful recanalization and 1180 (39%) with good functional outcome. In a multivariate logistic regression analysis, probability of good outcome was significantly associated with age (odds ratio [95% CI], 0.95 [0.94-0.96]), prestroke modified Rankin Scale (0.48 [0.42-0.55]), admission-NIHSS (0.96 [0.94-0.98]), 24-hour NIHSS (0.83 [0.81-0.84]), diabetes (0.56 [0.43-0.72]), proximal middle cerebral artery occlusions (0.78 [0.62-0.97]), passes (0.88 [0.82-0.95]), Alberta Stroke Program Early CT Score (1.07 [1.00-1.14]), successful recanalization (2.39 [1.68-3.43]), intracerebral hemorrhage (0.51 [0.35-0.73]), and recurrent strokes (0.54 [0.32-0.92]). Mediation analysis showed a 20 percentage points (95% CI' 17-24 percentage points) increase of probability of good functional outcome after successful recanalization. Fifty-four percent (95% CI' 44%-66%) of the improvement in functional outcome was explained by 24-hour NIHSS and 75% (95% CI' 62%-90%) by NIHSS at hospital discharge. CONCLUSIONS: Fifty-four percent of the improvement in functional outcome after successful recanalization is apparent in NIHSS at 24 hours, 75% in NIHSS at hospital discharge. Other unknown factors not apparent in NIHSS at the 2 time points investigated account for the remaining effect on long term outcome, suggesting, among others, clinical relevance of delayed neurological improvement and deterioration. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03356392.

Midline Shift in Chronic Subdural Hematoma : Interrater Reliability of Different Measuring Methods and Implications for Standardized Rating in Embolization Trials.

OBJECTIVE: Evaluation of chronic subdural hematoma (cSDH) treatment success relies on radiologic measures, in particular hematoma volume, width and midline shift (MLS). Nevertheless, there are no validated standards for MLS measurement in cSDH. Aim of this study was to identify the most reliable measurement location and technique for MLS. METHODS: Admission CT scans of 57 patients with unilateral cSDH were retrospectively analyzed. Axial slices were evaluated by 4 raters with MLS measurement in 4 locations, foramen of Monro (FM), thalamus (Th), mid-septum pellucidum (SP), maximum overall MLS (max) with 2 different techniques: displacement perpendicular to anatomical (ideal) midline (MLS-M), and displacement relative to the tabula interna in relation to the width of the intracranial space (MLS-T). Intraclass correlation coefficients (ICC) were calculated to assess interrater reliability and agreement of MLS­M and MLS­T measurement techniques. Measurements of cSDH volume and width were conducted for further data alignment. RESULTS: The ICCs between readers were excellent (> 0.9) for all MLS­M locations and for MLS-T_Th and ML-T_FM. The ICC was higher for MLS­M than for MLS­T in all locations. MLS-M_max showed the highest correlation coefficient of 0.78 with cSDH volume. Variance of MLS-M_max was explained in 64% of cases (adj. R squared) by cSDH volume based on a simple linear regression model. An increase of 10 ml cSDH volume resulted in an average increase of 0.8 mm MLS-M_max. CONCLUSION: The MLS measurement in cSDH patients should be standardized, and due to its high interrater reliability, the MLS­M technique should be preferred.

Imaging-based outcome prediction in posterior circulation stroke.

BACKGROUND AND PURPOSE: We developed a machine learning model to allow early functional outcome prediction for patients presenting with posterior circulation (pc)-stroke based on CT-imaging and clinical data at admission. The proposed algorithm utilizes quantitative information from automated multidimensional assessments of posterior circulation Acute Stroke Prognosis Early CT-Score (pc-ASPECTS) regions. Discriminatory power was compared to predictions based on conventional pc-ASPECTS ratings. METHODS: We retrospectively analyzed non-contrast CTs and clinical data of 172 pc-stroke patients. 90 days outcome was dichotomized into good and poor using modified Rankin Scale (mRS) cut-offs. Predictive performance was assessed for outcome differentiation at mRS 2, 3, 4 and survival prediction (mRS ≤ 5) using random forest algorithms. Results were compared to conventional pc-ASPECTS and clinical parameters. Models were evaluated in a nested fivefold cross-validation approach. RESULTS: Receiver operating characteristic areas under the curves (ROC-AUCs) of the test sets using conventionally rated pc-ASPECTS reached 0.63 for mRS ≤ 4 to 0.68 for mRS ≤ 5 and 0.73 for mRS ≤ 5 to 0.85 for mRS ≤ 2 if clinical data were considered. Pure imaging-based machine learning classifier ROC-AUCs were lowest for mRS ≤ 4 (0.81) and highest for mRS ≤ 5 (0.87). The combined clinical data and machine learning-based model had the highest predictive performance with ROC-AUCs reaching 0.90 for mRS ≤ 2. CONCLUSION: Machine learning-based evaluation of pc-ASPECTS regions predicts functional outcome of pc-stroke patients with higher accuracy than conventional assessments. This could optimize triage for additional diagnostics and allocation of best possible medical care and might allow required arrangements of the social environment at an early point of time.

Common data elements reported on middle meningeal artery embolization in chronic subdural hematoma: an interactive systematic review of recent trials.

Cross study heterogeneity has limited the evidence based evaluation of middle meningeal artery embolization (MMAE) as a treatment for chronic subdural hematoma (CSDH). Ongoing trials and prospective studies suggest that heterogeneity in upcoming publications may detract from subsequent meta-analyses and systemic reviews. This study aims to describe this data heterogeneity to promote harmonization with common data elements (CDEs) in publications. ClinicalTrials.gov and PubMed were searched for published or ongoing prospective trials of MMAE. The Nested Knowledge AutoLit living review platform was utilized to classify endpoints from randomized control trials (RCTs) and prospective cohort studies comparing MMAE with other treatments. The qualitative synthesis feature was used to determine cross study overlap of outcome related data elements. Eighteen studies were included: 12 RCTs, two non-randomized controlled studies, two prospective single arm trials, one combined prospective and retrospective controlled study, and one prospective cohort study. The most commonly reported data element was recurrence (15/18), but seven heterogenous (non-comparable) definitions were used for 'recurrence'. Mortality was reported in 10/18 studies, but no common timepoint was reported in more than four studies. Re-intervention and CSDH volume were reported in eight studies, CSDH width in seven, and no other outcome was common across more than five studies. There was significant heterogeneity in data element collection even among prospective registered trials of MMAE. Even among CDEs, variation in definition and timepoints prevented harmonization. A standardized approach based on CDEs may be necessary to facilitate future meta-analyses and evidence driven evaluation of MMAE treatment of CSDH.

Radiological Evaluation Criteria for Chronic Subdural Hematomas : Review of the Literature.

BACKGROUND: The methodology of measuring chronic subdural hematoma (cSDH) extent and its effect on intracranial structures is relevant for patient classification and outcome measurements and affects the external validity of cSDH studies. With embolization of the middle meningeal artery (MMA) as a possible treatment of cSDHs, the topic has gained substantial interest. We sought to summarize the heterogeneity of radiologic measurements, specifically in the evaluation of cSDHs based on literature review. METHODS: In this review, we identified and described the most common radiological methodologies for measurements of cSDH thickness, cSDH volume and of midline shift. CONCLUSION: There are numerous published methods on how to evaluate cSDH thickness, cSDH volume and midline shift but no common standard. The definition of measurement methods and reporting standards for MMA embolization in cSDH patients and their validation needs to be addressed.

T1 Relaxation Times in the Cortex and Thalamus Are Associated With Working Memory and Information Processing Speed in Patients With Multiple Sclerosis.

Background: Cortical and thalamic pathologies have been associated with cognitive impairment in patients with multiple sclerosis (MS). Objective: We aimed to quantify cortical and thalamic damage in patients with MS using a high-resolution T1 mapping technique and to evaluate the association of these changes with clinical and cognitive impairment. Methods: The study group consisted of 49 patients with mainly relapsing-remitting MS and 17 age-matched healthy controls who received 3T MRIs including a T1 mapping sequence (MP2RAGE). Mean T1 relaxation times (T1-RT) in the cortex and thalami were compared between patients with MS and healthy controls. Additionally, correlation analysis was performed to assess the relationship between MRI parameters and clinical and cognitive disability. Results: Patients with MS had significantly decreased normalized brain, gray matter, and white matter volumes, as well as increased T1-RT in the normal-appearing white matter, compared to healthy controls (p < 0.001). Partial correlation analysis with age, sex, and disease duration as covariates revealed correlations for T1-RT in the cortex (r = -0.33, p < 0.05), and thalami (right thalamus: r = -0.37, left thalamus: r = -0.50, both p < 0.05) with working memory and information processing speed, as measured by the Symbol-Digit Modalities Test. Conclusion: T1-RT in the cortex and thalamus correlate with information processing speed in patients with MS.

Value of Perfusion CT in the Prediction of Intracerebral Hemorrhage after Endovascular Treatment.

BACKGROUND: Intracerebral hemorrhage (ICH) is a serious complication of endovascular treatment (EVT) in stroke patients with large vessel occlusion (LVO) and associated with increased morbidity and mortality. AIMS: Identification of radiological predictors is highly relevant. We investigated the predictive power of computed tomography perfusion (CTP) parameters concerning ICH in patients receiving EVT. METHODS: 392 patients with anterior circulation LVO with multimodal CT imaging who underwent EVT were analyzed. CTP parameters were visually evaluated for modified ASPECTS regions and compared between patients without ICH, those with hemorrhagic infarction (HI), and those with parenchymal hematoma (PH) according to the ECASS criteria at follow-up imaging and broken down by ASPECTS regions. RESULTS: 168 received intravenous thrombolysis (IV-rtPA), and 115 developed subsequent ICH (29.3%), of which 74 were classified as HI and 41 as PH. Patients with HI and PH had lower ASPECTS than patients without ICH and worse functional outcome after 90 days (p < 0.05). In 102 of the 115 patients with ICH, the deep middle cerebral artery (MCA) territory was affected with differences between patients without ICH, those with HI, and those with PH regarding cerebral blood volume (CBV) and blood-brain barrier permeability measured as flow extraction product (FED) relative to the contralateral hemisphere (p < 0.05). Patients with PH showed larger perfusion CT infarct core than patients without ICH (p < 0.01). CONCLUSION: None of the examined CTP parameters was found to be a strong predictor of subsequent ICH. ASPECTS and initial CTP core volume were more reliable and may be useful and even so more practicable to assess the risk of subsequent ICH after EVT.