Diagnostic value of protein S100b as predictor of traumatic intracranial haemorrhage in elderly adults with low-energy falls: results from a retrospective observational study.

PURPOSE: The objectives of this study were to analyse the clinical value of protein S100b (S100b) in association with clinical findings and anticoagulation therapy in predicting traumatic intracranial haemorrhage (tICH) and unfavourable outcomes in elderly individuals with low-energy falls (LEF). METHODS: We conducted a retrospective study in the emergency department (ED) of the LMU University Hospital, Munich by consecutively including all patients aged ≥ 65 years presenting to the ED following a LEF between September 2014 and December 2016 and receiving an emergency cranial computed tomography (cCT) examination. Primary endpoint was the prevalence of tICH. Multivariate logistic regression models and receiver operating characteristics were used to measure the association between clinical findings, anticoagulation therapy and S100b and tICH. RESULTS: We included 2687 patients, median age was 81 years (60.4% women). Prevalence of tICH was 6.7% (180/2687) and in-hospital mortality was 6.1% (11/180). Skull fractures were highly associated with tICH (odds ratio OR 46.3; 95% confidence interval CI 19.3-123.8, p < 0.001). Neither anticoagulation therapy nor S100b values were significantly associated with tICH (OR 1.14; 95% CI 0.71-1.86; OR 1.08; 95% CI 0.90-1.25, respectively). Sensitivity of S100b (cut-off: 0.1 ng/ml) was 91.6% (CI 95% 85.1-95.9), specificity was 17.8% (CI 95% 16-19.6), and the area under the curve value was 0.59 (95% CI 0.54 - 0.64) for predicting tICH. CONCLUSION: In conclusion, under real ED conditions, neither clinical findings nor protein S100b concentrations or presence of anticoagulation therapy was sufficient to decide with certainty whether a cCT scan can be bypassed in elderly patients with LEF. Further prospective validation is required.

Cost-effectiveness of endovascular treatment versus best medical management in basilar artery occlusion stroke: A U.S. healthcare perspective.

INTRODUCTION: Two recent studies showed clinical benefit for endovascular treatment (EVT) in basilar artery occlusion (BAO) stroke up to 12 h (ATTENTION) and between 6 and 24 h from onset (BAOCHE). Our aim was to investigate the cost-effectiveness of EVT from a U.S. healthcare perspective. MATERIALS AND METHODS: Clinical input data were available for both trials, which were analyzed separately. A decision model was built consisting of a short-run model to analyze costs and functional outcomes within 90 days after the index stroke and a long-run Markov state transition model (cycle length of 12 months) to estimate expected lifetime costs and outcomes from a healthcare and a societal perspective. Incremental cost-effectiveness ratios (ICER) were calculated, deterministic (DSA) and probabilistic (PSA) sensitivity analyses were performed. RESULTS: EVT in addition to best medical management (BMM) resulted in additional lifetime costs of $32,063 in the ATTENTION trial and lifetime cost savings of $7690 in the BAOCHE trial (societal perspective). From a healthcare perspective, EVT led to incremental costs and effectiveness of $37,389 and 2.0 QALYs (ATTENTION) as well as $3516 and 1.9 QALYs (BAOCHE), compared to BMM alone. The ICER values were $-4052/QALY (BAOCHE) and $15,867/QALY (ATTENTION) from a societal perspective. In each trial, PSA showed EVT to be cost-effective in most calculations (99.9%) for a willingness-to-pay threshold of $100,000/QALY. Cost of EVT and age at stroke represented the greatest impact on the ICER. DISCUSSION: From an economic standpoint with a lifetime horizon, EVT in addition to BMM is estimated to be highly effective and cost-effective in BAO stroke.

Brain-derived Tau for Monitoring Brain Injury in Acute Ischemic Stroke.

The evolution of infarcts varies widely among patients with acute ischemic stroke (IS) and influences treatment decisions. Neuroimaging is not applicable for frequent monitoring and there is no blood-based biomarker to track ongoing brain injury in acute IS. Here, we examined the utility of plasma brain-derived tau (BD-tau) as a biomarker for brain injury in acute IS. We conducted the prospective, observational Precision Medicine in Stroke [PROMISE] study with serial blood sampling upon hospital admission and at days 2, 3, and 7 in patients with acute ischemic stroke (IS) and for comparison, in patients with stroke mimics (SM). We determined the temporal course of plasma BD-tau, its relation to infarct size and admission imaging-based metrics of brain injury, and its value to predict functional outcome. Upon admission (median time-from-onset, 4.4h), BD-tau levels in IS patients correlated with ASPECTS (ρ=-0.21, P<.0001) and were predictive of final infarct volume (ρ=0.26, P<.0001). In contrast to SM patients, BD-tau levels in IS patients increased from admission (median, 2.9 pg/ml [IQR, 1.8-4.8]) to day 2 (median time-from-onset, 22.7h; median BD-tau, 5.0 pg/ml [IQR, 2.6-10.3]; P<.0001). The rate of change of BD-tau from admission to day 2 was significantly associated with collateral supply (R2=0.10, P<.0001) and infarct progression (ρ=0.58, P<.0001). At day 2, BD-tau was predictive of final infarct volume (ρ=0.59, P<.0001) and showed superior value for predicting the 90-day mRS score compared with final infarct volume. In conclusion, in 502 patients with acute IS, plasma BD-tau was associated with imaging-based metrics of brain injury upon admission, increased within the first 24 hours in correlation with infarct progression, and at 24 hours was superior to final infarct volume in predicting 90-day functional outcome. Further research is needed to determine whether BD-tau assessments can inform decision-making in stroke care.

Impact of postoperative baseline MRI on diagnostic confidence and performance in detecting local recurrence of soft-tissue sarcoma of the limb.

OBJECTIVE: To evaluate the impact of a postoperative baseline (PB) MRI on diagnostic confidence and performance in detecting local recurrence (LR) of soft-tissue sarcoma (STS) of the limb. MATERIALS AND METHODS: A total of 72 patients (8 with LR, 64 without LR) with primary STS of the limb were included. Routine follow-up MRI (1.5 T) at 6 and approximately 36 months (meanLR: 39.7 months; meanno LR: 34.9 months) after multimodal therapy or at time of LR were assessed by three independent readers using a 5-point Likert scale. Furthermore, the following imaging parameters were evaluated: presence of a mass, signal characteristics at T2- and T1-weighted imaging, contrast enhancement (CE), and in some of the cases signal intensity on the apparent diffusion coefficient (ADC). U-test, McNemar test, and ROC-analysis were applied. Interobserver reliability was calculated using Fleiss kappa statistics. A p value of 0.05 was considered statistically significant. RESULTS: The presence of a PB MRI significantly improved diagnostic confidence in detecting LR of STS (p < 0.001) and slightly increased specificity (mean specificity without PE 74.1% and with presence of PB MRI 81.2%); however, not to a significant level. The presence of a mass showed highest diagnostic performance and highest interreader agreement (AUC [%]; κ: 73.1-83.6; 0.34) followed by T2-hyperintensity (50.8-66.7; 0.08), CE (52.4-62.5; 0.13), and T1-hypointensity (54.7-77.3; 0.23). ADC showed an AUC of 65.6-96.6% and a κ of 0.55. CONCLUSION: The presence of a PB MRI increases diagnostic confidence in detecting LR of STS of the limb.

Circadian rhythm of ischaemic core progression in human stroke.

INTRODUCTION: Experimental stroke studies suggest an influence of the time of day of stroke onset on infarct progression. Whether this holds true after human stroke is unknown, but would have implications for the design of randomised controlled trials, especially those on neuroprotection. METHODS: We pooled data from 583 patients with anterior large-vessel occlusion stroke from three prospectively recruited cohorts. Ischaemic core and penumbra volumes were determined with CT perfusion using automated thresholds. Core growth was calculated as the ratio of core volume and onset-to-imaging time. To determine circadian rhythmicity, we applied multivariable linear and sinusoidal regression analysis adjusting for potential baseline confounders. RESULTS: Patients with symptom onset at night showed larger ischaemic core volumes on admission compared with patients with onset during the day (median, 40.2 mL vs 33.8 mL), also in adjusted analyses (p=0.008). Sinusoidal analysis indicated a peak of core volumes with onset at 11pm. Core growth was faster at night compared with day onset (adjusted p=0.01), especially for shorter onset-to-imaging times. In contrast, penumbra volumes did not change across the 24-hour cycle. DISCUSSION: These results suggest that human infarct progression varies across the 24-hour cycle with potential implications for the design and interpretation of neuroprotection trials.

Impact of Dynamic Contrast Enhanced and Diffusion-Weighted MR Imaging on Detection of Early Local Recurrence of Soft Tissue Sarcoma.

BACKGROUND: Diagnosis of residual or recurrent tumor in soft-tissue sarcomas (STS) is a differential diagnostic challenge since post-therapeutic changes impede diagnosis. PURPOSE: To evaluate the diagnostic accuracy of quantitative dynamic contrast enhanced (DCE)-MRI and diffusion-weighted imaging (DWI) to detect local recurrence of STS of the limb. STUDY TYPE: Prospective. POPULATION: A totalof 64 consecutive patients with primary STS of the limbs were prospectively included 3-6 months after surgery between January 2016 and July 2021. FIELD STRENGTH/SEQUENCE: A 1.5 T; axial DWI echo-planar imaging sequences and DCE-MRI using a 3D T1-weighted spoiled gradient-echo sequence. ASSESSMENT: The quantitative DCE-MRI parameters relative plasma flow (rPF) and relative mean transit time (rMTT) were calculated and ADC mapping was used to quantify diffusion restriction. Regions of interest of tumor growth and postoperative changes were drawn in consensus by two experts for diffusion and perfusion analysis. An additional morphological assessment was done by three independent and blinded radiologists. STATISTICAL TEST: Unpaired t-test, ROC-analysis, and a logistic regression model were applied. Interobserver reliability was calculated using Fleiss kappa statistics. A P value of 0.05 was considered statistically significant. RESULTS: A total of 11 patients turned out to have local recurrence. rPF was significantly higher in cases of local recurrence when compared to cases without local recurrence (61.1-4.5) while rMTT was slightly and significantly lower in local recurrence. ROC-analysis showed an area under the curve (AUC) of 0.95 (SEM ± 0.05) for rPF while a three-factor multivariate logistic regression model showed a high diagnostic accuracy of rPF (R2  = 0.71). Compared with morphological assessment, rPF had a distinct higher specificity and true positive value in detection of LR. DATA CONCLUSION: DCE-MRI is a promising additional method to differentiate local recurrence from benign postoperative changes in STS of the limb. Especially specificity in detection of LR is increased compared to morphological assessment. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Individual- and Connectivity-Based Real-Time fMRI Neurofeedback to Modulate Emotion-Related Brain Responses in Patients with Depression: A Pilot Study.

INTRODUCTION: Individual real-time functional magnetic resonance imaging neurofeedback (rtfMRI NF) might be a promising adjuvant in treating depressive symptoms. Further studies showed functional variations and connectivity-related changes in the dorsolateral prefrontal cortex (dlPFC) and the insular cortex. OBJECTIVES: The aim of this pilot study was to investigate whether individualized connectivity-based rtfMRI NF training can improve symptoms in depressed patients as an adjunct to a psychotherapeutic programme. The novel strategy chosen for this was to increase connectivity between individualized regions of interest, namely the insula and the dlPFC. METHODS: Sixteen patients diagnosed with major depressive disorder (MDD, ICD-10) and 19 matched healthy controls (HC) participated in a rtfMRI NF training consisting of two sessions with three runs each, within an interval of one week. RtfMRI NF was applied during a sequence of negative emotional pictures to modulate the connectivity between the dlPFC and the insula. The MDD REAL group was divided into a Responder and a Non-Responder group. Patients with an increased connectivity during the second NF session or during both the first and the second NF session were identified as "MDD REAL Responder" (N = 6). Patients that did not show any increase in connectivity and/or a decreased connectivity were identified as "MDD REAL Non-Responder" (N = 7). RESULTS: Before the rtfMRI sessions, patients with MDD showed higher neural activation levels in ventromedial PFC and the insula than HC; by contrast, HC revealed increased hemodynamic activity in visual processing areas (primary visual cortex and visual association cortex) compared to patients with MDD. The comparison of hemodynamic responses during the first compared to during the last NF session demonstrated significantly increased BOLD-activation in the medial orbitofrontal cortex (mOFC) in patients and HC, and additionally in the lateral OFC in patients with MDD. These findings were particularly due to the MDD Responder group, as the MDD Non-Responder group showed no increase in this region during the last NF run. There was a decrease of neural activation in emotional processing brain regions in both groups in the last NF run compared to the first: HC showed differences in the insula, parahippocampal gyrus, basal ganglia, and cingulate gyrus. Patients with MDD demonstrated deceased responses in the parahippocampal gyrus. There was no significant reduction of BDI scores after NF training in patients. CONCLUSIONS: Increased neural activation in the insula and vmPFC in MDD suggests an increased emotional reaction in patients with MDD. The activation of the mOFC could be associated with improved control-strategies and association-learning processes. The increased lOFC activation could indicate a stronger sensitivity to failed NF attempts in MDD. A stronger involvement of visual processing areas in HC may indicate better adaptation to negative emotional stimuli after repeated presentation. Overall, the rtfMRI NF had an impact on neurobiological mechanisms, but not on psychometric measures in patients with MDD.

CT after interhospital transfer in acute ischemic stroke: Imaging findings and impact of prior intravenous contrast administration.

Objectives: Large vessel occlusion (LVO) stroke patients routinely undergo interhospital transfer to endovascular thrombectomy capable centers. Imaging is often repeated with residual intravenous (IV) iodine contrast at post-transfer assessment. We determined imaging findings and the impact of residual contrast on secondary imaging. Anterior circulation LVO stroke patients were selected out of a consecutive cohort. Directly admitted patients were contrast naïve, and transferred patients had previously received IV iodine contrast for stroke assessment at the referring hospital. Two independent readers rated the visibility of residual contrast on non-contrast computed tomography (CT) after transfer and assessed the hyperdense vessel sign. Multivariate linear regression analysis was used to investigate the association of the Alberta Stroke Program Early CT score (ASPECTS) with prior contrast administration, time from symptom onset (TFSO), and CTP ischemic core volume in both directly admitted and transferred patients. Results: We included 161 patients, with 62 (39%) transferred and 99 (62%) directly admitted patients. Compared between these groups, transferred patients had a longer TFSO-to-imaging at our institution (median: 212 vs. 75 min, p < 0.001) and lower ASPECTS (median: 8 vs. 9, p < 0.001). Regression analysis presented an independent association of ASPECTS with prior contrast administration (ß = -0.25, p = 0.004) but not with TFSO (ß = -0.03, p = 0.65). Intergroup comparison between transferred and directly admitted patients pointed toward a stronger association between ASPECTS and CTP ischemic core volume in transferred patients (ß = -0.39 vs. ß = -0.58, p = 0.06). Detectability of the hyperdense vessel sign was substantially lower after transfer (66 vs. 10%, p < 0.001). Conclusion: Imaging alterations due to residual IV contrast are frequent in clinical practice and render the hyperdense vessel sign largely indetectable. Larger studies are needed to clarify the influence on the association between ASPECTS and ischemic core.

Reduction in Radiation Exposure of CT Perfusion by Optimized Imaging Timing Using Temporal Information of the Preceding CT Angiography of the Carotid Artery in the Stroke Protocol.

(1) Background: CT perfusion (CTP) is a fast, robust and widely available but dose-exposing imaging technique for infarct core and penumbra detection. Carotid CT angiography (CTA) can precede CTP in the stroke protocol. Temporal information of the bolus tracking series of CTA could allow for better timing and a decreased number of scans in CTP, resulting in less radiation exposure, if the shortening of CTP does not alter the calculated infarct core and penumbra or the resulting perfusion maps, which are essential for further treatment decisions. (2) Methods: 66 consecutive patients with ischemic stroke proven by follow-up imaging or endovascular intervention were included in this retrospective study approved by the local ethics committee. In each case, six simulated, stepwise shortened CTP examinations were compared with the original data regarding the perfusion maps, infarct core, penumbra and endovascular treatment decision. (3) Results: In simulated CTPs with 26, 28 and 30 scans, the infarct core, penumbra and PRR values were equivalent, and the resulting clinical decision was identical to the original CTP. (4) Conclusions: The temporal information of the bolus tracking series of the carotid CTA can allow for better timing and a lower radiation exposure by eliminating unnecessary scans in CTP.

End-to-End Deep Learning Approach for Perfusion Data: A Proof-of-Concept Study to Classify Core Volume in Stroke CT.

(1) Background: CT perfusion (CTP) is used to quantify cerebral hypoperfusion in acute ischemic stroke. Conventional attenuation curve analysis is not standardized and might require input from expert users, hampering clinical application. This study aims to bypass conventional tracer-kinetic analysis with an end-to-end deep learning model to directly categorize patients by stroke core volume from raw, slice-reduced CTP data. (2) Methods: In this retrospective analysis, we included patients with acute ischemic stroke due to proximal occlusion of the anterior circulation who underwent CTP imaging. A novel convolutional neural network was implemented to extract spatial and temporal features from time-resolved imaging data. In a classification task, the network categorized patients into small or large core. In ten-fold cross-validation, the network was repeatedly trained, evaluated, and tested, using the area under the receiver operating characteristic curve (ROC-AUC). A final model was created in an ensemble approach and independently validated on an external dataset. (3) Results: 217 patients were included in the training cohort and 23 patients in the independent test cohort. Median core volume was 32.4 mL and was used as threshold value for the binary classification task. Model performance yielded a mean (SD) ROC-AUC of 0.72 (0.10) for the test folds. External independent validation resulted in an ensembled mean ROC-AUC of 0.61. (4) Conclusions: In this proof-of-concept study, the proposed end-to-end deep learning approach bypasses conventional perfusion analysis and allows to predict dichotomized infarction core volume solely from slice-reduced CTP images without underlying tracer kinetic assumptions. Further studies can easily extend to additional clinically relevant endpoints.

Cost-Effectiveness of Endovascular Thrombectomy in Childhood Stroke: An Analysis of the Save ChildS Study.

BACKGROUND AND PURPOSE: The Save ChildS Study demonstrated that endovascular thrombectomy (EVT) is a safe treatment option for pediatric stroke patients with large vessel occlusions (LVOs) with high recanalization rates. Our aim was to determine the long-term cost, health consequences and cost-effectiveness of EVT in this patient population. METHODS: In this retrospective study, a decision-analytic Markov model estimated lifetime costs and quality-adjusted life years (QALYs). Early outcome parameters were based on the entire Save ChildS Study to model the EVT group. As no randomized data exist, the Save ChildS patient subgroup with unsuccessful recanalization was used to model the standard of care group. For modeling of lifetime estimates, pediatric and adult input parameters were obtained from the current literature. The analysis was conducted in a United States setting applying healthcare and societal perspectives. Probabilistic sensitivity analyses were performed. The willingness-to-pay threshold was set to $100,000 per QALY. RESULTS: The model. RESULTS: yielded EVT as the dominant (cost-effective as well as cost-saving) strategy for pediatric stroke patients. The incremental effectiveness for the average age of 11.3 years at first stroke in the Save ChildS Study was determined as an additional 4.02 lifetime QALYs, with lifetime cost-savings that amounted to $169,982 from a healthcare perspective and $254,110 when applying a societal perspective. Acceptability rates for EVT were 96.60% and 96.66% for the healthcare and societal perspectives. CONCLUSIONS: EVT for pediatric stroke patients with LVOs resulted in added QALY and reduced lifetime costs. Based on the available data in the Save ChildS Study, EVT is very likely to be a cost-effective treatment strategy for childhood stroke.

Functional and clinical outcomes of FMRI-based neurofeedback training in patients with alcohol dependence: a pilot study.

Identifying treatment options for patients with alcohol dependence is challenging. This study investigates the application of real-time functional MRI (rtfMRI) neurofeedback (NF) to foster resistance towards craving-related neural activation in alcohol dependence. We report a double-blind, placebo-controlled rtfMRI study with three NF sessions using alcohol-associated cues as an add-on therapy to the standard treatment. Fifty-two patients (45 male; 7 female) diagnosed with alcohol dependence were recruited in Munich, Germany. RtfMRI data were acquired in three sessions and clinical abstinence was evaluated 3 months after the last NF session. Before the NF training, BOLD responses and clinical data did not differ between groups, apart from anger and impulsiveness. During NF training, BOLD responses of the active group were decreased in medial frontal areas/caudate nucleus, and increased, e.g. in the cuneus/precuneus and occipital cortex. Within the active group, the down-regulation of neuronal responses was more pronounced in patients who remained abstinent for at least 3 months after the intervention compared to patients with a relapse. As BOLD responses were comparable between groups before the NF training, functional variations during NF cannot be attributed to preexisting distinctions. We could not demonstrate that rtfMRI as an add-on treatment in patients with alcohol dependence leads to clinically superior abstinence for the active NF group after 3 months. However, the study provides evidence for a targeted modulation of addiction-associated brain responses in alcohol dependence using rtfMRI.

Cost-effectiveness of short-protocol emergency brain MRI after negative non-contrast CT for minor stroke detection.

OBJECTIVES: To investigate the cost-effectiveness of supplemental short-protocol brain MRI after negative non-contrast CT for the detection of minor strokes in emergency patients with mild and unspecific neurological symptoms. METHODS: The economic evaluation was centered around a prospective single-center diagnostic accuracy study validating the use of short-protocol brain MRI in the emergency setting. A decision-analytic Markov model distinguished the strategies "no additional imaging" and "additional short-protocol MRI" for evaluation. Minor stroke was assumed to be missed in the initial evaluation in 40% of patients without short-protocol MRI. Specialized post-stroke care with immediate secondary prophylaxis was assumed for patients with detected minor stroke. Utilities and quality-of-life measures were estimated as quality-adjusted life years (QALYs). Input parameters were obtained from the literature. The Markov model simulated a follow-up period of up to 30 years. Willingness to pay was set to $100,000 per QALY. Cost-effectiveness was calculated and deterministic and probabilistic sensitivity analysis was performed. RESULTS: Additional short-protocol MRI was the dominant strategy with overall costs of $26,304 (CT only: $27,109). Cumulative calculated effectiveness in the CT-only group was 14.25 QALYs (short-protocol MRI group: 14.31 QALYs). In the deterministic sensitivity analysis, additional short-protocol MRI remained the dominant strategy in all investigated ranges. Probabilistic sensitivity analysis results from the base case analysis were confirmed, and additional short-protocol MRI resulted in lower costs and higher effectiveness. CONCLUSION: Additional short-protocol MRI in emergency patients with mild and unspecific neurological symptoms enables timely secondary prophylaxis through detection of minor strokes, resulting in lower costs and higher cumulative QALYs. KEY POINTS: • Short-protocol brain MRI after negative head CT in selected emergency patients with mild and unspecific neurological symptoms allows for timely detection of minor strokes. • This strategy supports clinical decision-making with regard to immediate initiation of secondary prophylactic treatment, potentially preventing subsequent major strokes with associated high costs and reduced QALY. • According to the Markov model, additional short-protocol MRI remained the dominant strategy over wide variations of input parameters, even when assuming disproportionally high costs of the supplemental MRI scan.

Correlations Between the DMN and the Smoking Cessation Outcome of a Real-Time fMRI Neurofeedback Supported Exploratory Therapy Approach: Descriptive Statistics on Tobacco-Dependent Patients.

The aim of this study was to explore the potential of default mode network (DMN) functional connectivity for predicting the success of smoking cessation in patients with tobacco dependence in the context of a real-time function al MRI (RT-fMRI) neurofeedback (NF) supported therapy.Fifty-four tobacco-dependent patients underwent three RT-fMRI-NF sessions including resting-state functional connectivity (RSFC) runs over a period of 4 weeks during professionally assisted smoking cessation. Patients were randomized into two groups that performed either active NF of an addiction-related brain region or sham NF. After preprocessing, the RSFC baseline data were statistically evaluated using seed-based ROI (SBA) approaches taking into account the smoking status of patients after 3 months (abstinence/relapse).The results of the real study group showed a widespread functional connectivity in the relapse subgroup (n = 10) exceeding the DMN template and mainly low correlations and anticorrelations in the within-seed analysis. In contrast, the connectivity pattern of the abstinence subgroup (n = 8) primarily contained the core DMN in the seed-to-whole-brain analysis and a left lateralized correlation pattern in the within-seed analysis. Calculated Multi-Subject Dictionary Learning (MSDL) matrices showed anticorrelations between DMN regions and salience regions in the abstinence group. Concerning the sham group, results of the relapse subgroup (n = 4) and the abstinence subgroup (n = 6) showed similar trends only in the within-seed analysis.In the setting of a RT-fMRI-NF-assisted therapy, a widespread intrinsic DMN connectivity and a low negative coupling between the DMN and the salience network (SN) in patients with tobacco dependency during early withdrawal may be useful as an early indicator of later therapy nonresponse.

Course of Early Neurologic Symptom Severity after Endovascular Treatment of Anterior Circulation Large Vessel Occlusion Stroke: Association with Baseline Multiparametric CT Imaging and Clinical Parameters.

BACKGROUND: Neurologic symptom severity and deterioration at 24 hours (h) predict long-term outcomes in patients with acute large vessel occlusion (LVO) stroke of the anterior circulation. We aimed to examine the association of baseline multiparametric CT imaging and clinical factors with the course of neurologic symptom severity in the first 24 h after endovascular treatment (EVT). METHODS: Patients with LVO stroke of the anterior circulation were selected from a prospectively acquired consecutive cohort of patients who underwent multiparametric CT, including non-contrast CT, CT angiography and CT perfusion before EVT. The symptom severity was assessed on admission and after 24 h using the 42-point National Institutes of Health Stroke Scale (NIHSS). Clinical and imaging data were compared between patients with and without early neurological deterioration (END). END was defined as an increase in ≥4 points, and a significant clinical improvement as a decrease in ≥4 points, compared to NIHSS on admission. Multivariate regression analyses were used to determine independent associations of imaging and clinical parameters with NIHSS score increase or decrease in the first 24 h. RESULTS: A total of 211 patients were included, of whom 38 (18.0%) had an END. END was significantly associated with occlusion of the internal carotid artery (odds ratio (OR), 4.25; 95% CI, 1.90-9.47) and the carotid T (OR, 6.34; 95% CI, 2.56-15.71), clot burden score (OR, 0.79; 95% CI, 0.68-0.92) and total ischemic volume (OR, 1.01; 95% CI, 1.00-1.01). In a comprehensive multivariate analysis model including periprocedural parameters and complications after EVT, carotid T occlusion remained independently associated with END, next to reperfusion status and intracranial hemorrhage. Favorable reperfusion status and small ischemic core volume were associated with clinical improvement after 24 h. CONCLUSIONS: The use of imaging parameters as a surrogate for early NIHSS progression in an acute LVO stroke after EVT reached limited performance with only carotid T occlusion as an independent predictor of END. Reperfusion status and early complications in terms of intracranial hemorrhage are critical factors that influence patient outcome in the acute stroke phase after EVT.

Late Thrombectomy in Clinical Practice : Retrospective Application of DAWN/DEFUSE3 Criteria within the German Stroke Registry.

BACKGROUND AND PURPOSE: To provide real-world data on outcome and procedural factors of late thrombectomy patients. METHODS: We retrospectively analyzed patients from the multicenter German Stroke Registry. The primary endpoint was clinical outcome on the modified Rankin scale (mRS) at 3 months. Trial-eligible patients and the subgroups were compared to the ineligible group. Secondary analyses included multivariate logistic regression to identify predictors of good outcome (mRS ≤ 2). RESULTS: Of 1917 patients who underwent thrombectomy, 208 (11%) were treated within a time window ≥ 6-24 h and met the baseline trial criteria. Of these, 27 patients (13%) were eligible for DAWN and 39 (19%) for DEFUSE3 and 156 patients were not eligible for DAWN or DEFUSE3 (75%), mainly because there was no perfusion imaging (62%; n = 129). Good outcome was not significantly higher in trial-ineligible (27%) than in trial-eligible (20%) patients (p = 0.343). Patients with large trial-ineligible CT perfusion imaging (CTP) lesions had significantly more hemorrhagic complications (33%) as well as unfavorable outcomes. CONCLUSION: In clinical practice, the high number of patients with a good clinical outcome after endovascular therapy ≥ 6-24 h as in DAWN/DEFUSE3 could not be achieved. Similar outcomes are seen in patients selected for EVT ≥ 6 h based on factors other than CTP. Patients triaged without CTP showed trends for shorter arrival to reperfusion times and higher rates of independence.

Computed Tomography Perfusion Deficit Volumes Predict Functional Outcome in Patients With Basilar Artery Occlusion.

Background and Purpose: Basilar artery occlusion is associated with high morbidity and mortality. Optimal imaging and treatment strategy are still controversial and prognosis estimation challenging. We, therefore, aimed to determine the predictive value of computed tomography perfusion (CTP) parameters for functional outcome in patients with basilar artery occlusion in the context of endovascular treatment. Methods: Patients with basilar artery occlusion who underwent endovascular treatment were selected from a prospectively acquired cohort. Ischemic changes were assessed with the posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score on noncontrast computed tomography, computed tomography angiography (CTA) source images, and CTP maps. Basilar artery on CTA score, posterior-circulation CTA score, and posterior-circulation collateral score were evaluated on CTA. Perfusion deficit volumes were quantified on CTP maps. Good functional outcome was defined as modified Rankin Scale score ≤3 at 90 days. Statistical analysis included binary logistic regressions and receiver operating characteristics analyses. Results: Among 49 patients who matched the inclusion criteria, 24 (49.0%) achieved a good outcome. In univariate analysis, age, National Institutes of Health Stroke Scale score on admission, posterior cerebral artery involvement, absence of or hypoplastic posterior communicating arteries, basilar artery on CTA score, posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score, and perfusion deficit volumes on all CTP parameter maps presented significant association with functional outcome (P<0.05). In multivariate analyses, Basilar artery on CTA score, posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score (odds ratio range, 1.31­2.10 [95% CI, 1.00­7.24]), and perfusion deficit volumes on all CTP maps (odds ratio range, 0.77­0.98 [95% CI, 0.63­1.00]) remained as independent outcome predictors. Cerebral blood flow deficit volume yielded the best performance for the classification of good clinical outcome with an area under the curve of 0.92 (95% CI, 0.84­0.99). Age and admission National Institutes of Health Stroke Scale had lower discriminatory power (area under the curve, <0.7). Conclusions: CTP imaging parameters contain prognostic information for functional outcome in patients with stroke due to basilar artery occlusion and may identify patients with higher risk of disability at an early stage of hospitalization.

Decomposing Acute Symptom Severity in Large Vessel Occlusion Stroke: Association With Multiparametric CT Imaging and Clinical Parameters.

Background and Purpose: Acute ischemic stroke of the anterior circulation due to large vessel occlusion (LVO) is a multifactorial process, which causes neurologic symptoms of different degree. Our aim was to examine the impact of neuromorphologic and vascular correlates as well as clinical factors on acute symptom severity in LVO stroke. Methods: We selected LVO stroke patients with known onset time from a consecutive cohort which underwent multiparametric CT including non-contrast CT, CT angiography and CT perfusion (CTP) before thrombectomy. Software-based quantification was used to calculate CTP total ischemic and ischemic core volume. Symptom severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) upon admission. Multivariable regression analysis was performed to determine independent associations of admission NIHSS with imaging and clinical parameters. Receiver operating characteristics (ROC) analyses were used to examine performance of imaging parameters to classify symptom severity. Results: We included 142 patients. Linear and ordinal regression analyses for NIHSS and NIHSS severity groups identified significant associations for total ischemic volume [ß = 0.31, p = 0.01; Odds ratio (OR) = 1.11, 95%-confidence-interval (CI): 1.02-1.19], clot burden score (ß = -0.28, p = 0.01; OR = 0.76, 95%-CI: 0.64-0.90) and age (ß = 0.17, p = 0.04). No association was found for ischemic core volume, stroke side, collaterals and time from onset. Stroke topography according to the Alberta Stroke Program CT Score template did not display significant influence after correction for multiple comparisons. AUC for classification of the NIHSS threshold ≥6 by total ischemic volume was 0.81 (p < 0.001). Conclusions: We determined total ischemic volume, clot burden and age as relevant drivers for baseline NIHSS in acute LVO stroke. This suggests that not only mere volume but also degree of occlusion influences symptom severity. Use of imaging parameters as surrogate for baseline NIHSS reached limited performance underlining the need for combined clinical and imaging assessment in acute stroke management.