Objective
Multiple variables beyond the extent of recanalization can impact the clinical outcome after acute ischemic stroke due to large vessel occlusions. Here, we assessed the influence of small ...vessel disease and cortical atrophy on clinical outcome using native cranial computed tomography (NCCT) in a large single-center cohort.
Methods
A total of 1103 consecutive patients who underwent endovascular treatment (EVT) due to occlusion of the middle cerebral artery territory were included. NCCT data were visually assessed for established markers of age-related white matter changes (ARWMC) and brain atrophy. All images were evaluated separately by two readers to assess the inter-observer variability. Regression and machine learning models were built to determine the predictive relevance of ARWMC and atrophy in the presence of important baseline clinical and imaging metrics.
Results
Patients with favorable outcome presented lower values for all measured metrics of pre-existing brain deterioration (
p
< 0.001). Both ARWMC (
p
< 0.05) and cortical atrophy (
p
< 0.001) were independent predictors of clinical outcome at 90 days when controlled for confounders in both regression analyses and led to a minor improvement of prediction accuracy in machine learning models (
p
< 0.001), with atrophy among the top-5 predictors.
Conclusion
NCCT-based cortical atrophy and ARWMC scores on NCCT were strong and independent predictors of clinical outcome after EVT.
Clinical relevance statement
Visual assessment of cortical atrophy and age-related white matter changes on CT could improve the prediction of clinical outcome after thrombectomy in machine learning models which may be integrated into existing clinical routines and facilitate patient selection.
Key Points
• Cortical atrophy and age-related white matter changes were quantified using CT-based visual scores.
• Atrophy and age-related white matter change scores independently predicted clinical outcome after mechanical thrombectomy and improved machine learning–based prediction models.
• Both scores could easily be integrated into existing clinical routines and prediction models.
Ipilimumab binds and blocks cytotoxic T-lymphocyte-associated antigen-4, causing enhanced T-cell reaction, antitumor response, and significant improvement of the overall survival of patients with ...metastatic melanoma. Patients treated with ipilimumab can develop immune-related adverse effects, primarily dermatitis, colitis, hepatitis, and hypophysitis. Although, in phase I-III studies, 64.2% of all patients suffered from immune-related adverse effects, ocular adverse effects occurred in 1.3% only. In the cases reported below, 2 patients with metastatic melanoma developed severe ocular myositis after treatment with ipilimumab. These are the first 2 reports of successful treatment of this condition by use of a combination of methylprednisolone and mycophenolate mofetil, and, in 1 of the cases, additional medication with intravenous immunoglobulin.
Background
Endovascular thrombectomy (EVT) duration is an important predictor for neurological outcome. Recently it was shown that an angle of ≤ 90° of the internal carotid artery (ICA) is predictive ...for longer EVT duration. As manual angle measurement is not trivial and time-consuming, deep learning (DL) could help identifying difficult EVT cases in advance.
Methods
We included 379 CT angiographies (CTA) of patients who underwent EVT between January 2016 and December 2020. Manual segmentation of 121 CTAs was performed for the aortic arch, common carotid artery (CCA) and ICA. These were used to train a nnUNet. The remaining 258 CTAs were segmented using the trained nnUNet with manual verification afterwards. Angles of left and right ICAs were measured resulting in two classes: acute angle ≤ 90° and > 90°. The segmentations together with angle measurements were used to train a convolutional neural network (CNN) determining the ICA angle. The performance was evaluated using Dice scores. The classification was evaluated using AUC and accuracy. Associations of ICA angle and procedural times was explored using median and Whitney‑U test.
Results
Median EVT duration for cases with ICA angle > 90° was 48 min and with ≤ 90° was 64 min (
p
= 0.001). Segmentation evaluation showed Dice scores of 0.94 for the aorta and 0.86 for CCA/ICA, respectively. Evaluation of ICA angle determination resulted in an AUC of 0.92 and accuracy of 0.85.
Conclusion
The association between ICA angle and EVT duration could be verified and a DL-based method for semi-automatic assessment with the potential for full automation was developed. More anatomical features of interest could be examined in a similar fashion.
Renal dysfunction (RD) is overall associated with unfavorable functional outcome and higher risk of mortality after acute ischemic stroke. Associations between RD and outcome in patients with acute ...vertebrobasilar stroke treated with thrombectomy have not been evaluated so far.
Consecutive patients with vertebrobasilar stroke treated with mechanical thrombectomy between October 2010 and July 2017 at our center were analyzed. RD was defined as glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 at admission. Endpoints were (I) poor clinical outcome (modified Rankin Scale > 2) at 3 months, (II) 3-month mortality, and (III) intracerebral hemorrhage (ICH) after treatment.
Overall, 106 patients were included. Median age was 73.0 years (interquartile range 62.0-80.0), and RD was present in 20.8%. Multivariate analysis revealed that RD was associated with a higher risk for any ICH (OR 3.54; 95% CI 1.09-11.49; p = 0.035). Stroke severity at onset predicted poor clinical outcome (OR 1.08; 95% CI 1.03-1.14; p = 0.003). Neither low GFR nor any ICH, but stroke severity (OR 1.08; 95% CI 1.03-1.14; p = 0.002) and poor recanalization results (OR 11.38; 95% CI 2.01-64.41; p = 0.006) were associated with a higher risk for mortality.
Patients with RD and acute vertebrobasilar stroke should be thoroughly monitored to prevent ICH after thrombectomy. Our results support performing mechanical thrombectomy in acute stroke patients with large vessel occlusions of the posterior circulation, irrespective of their renal function.
This study aims to evaluate the impact of tumor location on key molecular alterations on a single voxel level in patients with newly diagnosed glioma.
A consecutive series of n = 237 patients with ...newly diagnosed glioblastoma and n = 131 patients with lower-grade glioma was analyzed. Volumetric tumor segmentation was performed on preoperative MRI with a semi-automated approach and images were registered to the standard Montreal Neurological Institute 152 space. Using a voxel-based lesion symptom mapping (VLSM) analysis, we identified specific brain regions that were associated with tumor-specific molecular alterations. We assessed a predefined set of n = 17 molecular characteristics in the glioblastoma cohort and n = 2 molecular characteristics in the lower-grade glioma cohort. Permutation adjustment (n = 1000 iterations) was used to correct for multiple testing, and voxel t-values that were greater than the t-value in >95% of the permutations were retained in the VLSM results (α = 0.05, power > 0.8).
Tumor location predilection for isocitrate dehydrogenase (IDH) mutant tumors was found in both glioblastoma and lower-grade glioma cohorts, each showing a concordant predominance in the frontal lobe adjacent to the rostral extension of the lateral ventricles (permutation-adjusted P = 0.021 for the glioblastoma and 0.013 for the lower-grade glioma cohort). Apart from that, the VLSM analysis did not reveal a significant association of the tumor location with any other key molecular alteration in both cohorts (permutation-adjusted P > 0.05 each).
Our study highlights the unique properties of IDH mutations and underpins the hypothesis that the rostral extension of the lateral ventricles is a potential location for the cell of origin in IDH-mutant gliomas.
Abstract Background The purpose of this study was to elucidate the relationship between distinct brain regions and molecular subtypes in glioblastoma (GB), focusing on integrating modern statistical ...tools and molecular profiling to better understand the heterogeneity of Isocitrate Dehydrogenase wild-type (IDH-wt) gliomas. Methods This retrospective study comprised 441 patients diagnosed with new IDH-wt glioma between 2009 and 2020 at Heidelberg University Hospital. The diagnostic process included preoperative magnetic resonance imaging (MRI) and molecular characterization, encompassing IDH-status determination and subclassification, through DNA-methylation profiling. To discern and map distinct brain regions associated with specific methylation subtypes, a support-vector regression-based lesion-symptom mapping (SVR-LSM) was employed. Lesion maps were adjusted to 2 mm³ resolution, accounting for lesion volume. Significance was assessed with beta maps, using a threshold of p < 0.005, with 10,000 permutations and a cluster size minimum of 100 voxels. Results Of 441 initially screened glioma patients, 423 (95.9%) met the inclusion criteria. Following DNA-methylation profiling, patients were classified into RTK II (40.7%), MES (33.8%), RTK I (18%), and other methylation subclasses (7.6%). Between molecular subtypes, there was no difference in tumor volume. Using SVR-LSM, distinct brain regions correlated with each subclass were identified: MES subtypes were associated with left-hemispheric regions involving the superior temporal gyrus and insula cortex, RTK I with right frontal regions, and RTK II with three clusters in the left hemisphere. Conclusions This study linked molecular diversity and spatial features in glioblastomas using SVR-LSM. Future studies should validate these findings in larger, independent cohorts to confirm the observed patterns.
Abstract
OBJECTIVE
To assess the validity and pathophysiology of the T2/FLAIR mismatch sign for non-invasive identification of IDH-mutant 1p/19q non-codeleted glioma.
METHODS
MRI scans from 408 ...consecutive patients with newly diagnosed glioma (113 lower-grade glioma and 295 glioblastoma) were evaluated for the presence of a T2/FLAIR-mismatch sign (defined as complete/near-complete hyperintense signal on T2w, simultaneous hypointense signal on FLAIR except for a hyperintense peripheral rim) by two independent reviewers. Sensitivity, specificity, accuracy, positive and negative predictive value (PPV, NPV) were calculated to assess the performance of the T2/FLAIR-mismatch sign for identifying IDH-mutant 1p/19q non-codeleted tumors. An exploratory analysis of spatial differences in ADC and rCBV values comparing the FLAIR-hypointense core vs. hyperintense rim in cases with presence of a T2/FLAIR-mismatch sign was performed.
RESULTS
There was substantial interrater agreement to identify the T2/FLAIR-mismatch sign (Cohen’s Kappa = 0.75 95% CI 0.57–0.93). The T2/FLAIR-mismatch sign was present in 12 cases with lower-grade glioma (10.6%), all of them were IDH-mutant, 1p/19q non-codeleted tumors (sensitivity=10.9%, specificity=100%, PPV=100%, NPV=3.0%, accuracy=13.3%). The T2/FLAIR-mismatch sign was not identified in any other molecular subgroup, especially not in any of the IDH-mutant glioblastoma cases (n=5). In tumors with T2/FLAIR-mismatch sign the ADC values were significantly lower in the rim as compared to the core (p=0.0005) whereas there was no difference in rCBV values (p=0.4258).
CONCLUSION
This study confirms the high specificity of the T2/FLAIR-mismatch sign for non-invasive identification of IDH-mutant 1p/19q non-codeleted gliomas, although sensitivity is low and applicability is limited to lower-grade gliomas. The identified spatial differences in ADC values between the core and rim of tumors with a T2/FLAIR-mismatch sign potentially reflects differences in tumor cellularity and microenvironment.
Transvenous embolization (TVE) is an emerging technique for the endovascular treatment of cerebral arteriovenous malformations (AVMs). The aim of this study was to investigate two in vivo AVM models ...and to assess TVE techniques using these models.
Blood flow in the porcine rete mirabile (RM) was modified by either creating a carotid-jugular fistula or by placing a balloon guide catheter in the carotid artery. The RM was embolized with precipitating hydrophobic injectable liquid (PHIL) 25% via transarterial embolization (TAE; control group) and compared with TVE applying the transvenous retrograde pressure cooker technique and TVE using a Woven EndoBridge (WEB) device for flow control (n=6, respectively). The embolization extent (penetration of the RM), the number of events of reflux or embolization distal to the RM and the procedure times were assessed.
The modified RM could be successfully used for embolization in all cases. There were no significant differences regarding the outcome parameters between the two AVM models (fistula or balloon). TVE using the pressure cooker technique led to a higher extent of embolization (median 98.8% vs 63.5%; p=0.008), a lower number of reflux or distal embolization events (p<0.001) and a shorter procedure time (p<0.001) compared with conventional TAE. TVE using a WEB device for flow control was technically feasible and achieved a moderate extent of embolization (median 83.8%).
After surgical or endovascular modification, the porcine RM is a feasible in vivo AVM model for the investigation of TVE techniques. TVE using the pressure cooker technique is superior to conventional TAE in this experimental model.
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