Thrombectomy in Childhood Stroke.

Background Several randomized trials have shown the efficacy of thrombectomy for large intracranial vessel occlusions in adults. However, the safety and efficacy of thrombectomy in children are unknown. We aimed to investigate the feasibility and outcome of thrombectomy in pediatric patients. Methods and Results We performed a retrospective analysis of all children (<18 years of age) who presented with large-vessel occlusion and were treated with mechanical thrombectomy at 3 German tertiary-care stroke centers. Interventional results and clinical outcomes were assessed using the Pediatric National Institutes of Health Stroke Scale at 24 hours and on day 7 after thrombectomy as well as after 3 months (modified Rankin Scale). After screening of local registries for all performed thrombectomies, 12 children were included. Median Pediatric National Institutes of Health Stroke Scale score on admission was 12.5 (interquartile range 8.0-21.5). Angiographic outcomes for thrombectomy were good in all patients (6×modified Treatment in Cerebral Infarction Score 3, 6×modified Treatment in Cerebral Infarction Score 2b). Moreover, most patients showed an improvement of neurological outcome after thrombectomy with a median Pediatric National Institutes of Health Stroke Scale of 3.5 (interquartile range 1-8) at day 7 and a modified Rankin Scale of 1.0 (interquartile range 0-2.0) at 3 months. No major periprocedural complications were observed. Conclusions In our retrospective study thrombectomy was safe in childhood stroke, and treated children had good neurological outcomes.

Imaging of Spontaneous and Traumatic Cervical Artery Dissection : Comparison of Typical CT Angiographic Features.

INTRODUCTION: Cervical artery dissection (CAD) is an important etiology of ischemic stroke and early recognition is vital to protect patients from the major complication of cerebral embolization by administration of anticoagulants. The etiology of arterial dissections differ and can be either spontaneous or traumatic. Even though the historical gold standard is still catheter angiography, recent studies suggest a good performance of computed tomography angiography (CTA) for detection of CAD. We conducted this research to evaluate the variety and frequency of possible imaging signs of spontaneous and traumatic CAD and to guide neuroradiologists' decision making. METHODS: Retrospective review of the database of our multiple injured patients admitted to the Department of Trauma, Hand, and Reconstructive Surgery of the University Hospital Münster in Germany (a level 1 trauma center) for patients with traumatic CAD (tCAD) and of our stroke database (2008-2015) for patients with spontaneous CAD (sCAD) and CT/CTA on initial clinical work-up. All images were evaluated concerning specific and sensitive radiological features for dissection by two experienced neuroradiologists. Imaging features were compared between the two etiologies. RESULTS: This study included 145 patients (99 male, 46 female; 45 ± 18.8 years of age), consisting of 126 dissected arteries with a traumatic and 43 with spontaneous etiology. Intimal flaps were more frequently observed after traumatic etiology (58.1% tCADs, 6.9% sCADs; p < 0.001); additionally, multivessel dissections were much more frequent in trauma patients (3 sCADs, 21 tCADs) and only less than half (42%) of the patients with traumatic dissections showed cervical spine fractures. CONCLUSION: Neuroradiologists should be aware that intimal flaps and multivessel dissections are more common after a traumatic etiology. In addition, it seems important to conduct a CTA in a trauma setting, even if no cervical spine fracture is detected.

Quantitative Rapid Assessment of Leukoaraiosis in CT : Comparison to Gold Standard MRI.

PURPOSE: The severity of white matter lesions (WML) is a risk factor of hemorrhage and predictor of clinical outcome after ischemic stroke; however, in contrast to magnetic resonance imaging (MRI) reliable quantification for this surrogate marker is limited for computed tomography (CT), the leading stroke imaging technique. We aimed to present and evaluate a CT-based automated rater-independent method for quantification of microangiopathic white matter changes. METHODS: Patients with suspected minor stroke (National Institutes of Health Stroke scale, NIHSS < 4) were screened for the analysis of non-contrast computerized tomography (NCCT) at admission and compared to follow-up MRI. The MRI-based WML volume and visual Fazekas scores were assessed as the gold standard reference. We employed a recently published probabilistic brain segmentation algorithm for CT images to determine the tissue-specific density of WM space. All voxel-wise densities were quantified in WM space and weighted according to partial probabilistic WM content. The resulting mean weighted density of WM space in NCCT, the surrogate of WML, was correlated with reference to MRI-based WML parameters. RESULTS: The process of CT-based tissue-specific segmentation was reliable in 79 cases with varying severity of microangiopathy. Voxel-wise weighted density within WM spaces showed a noticeable correlation (r = -0.65) with MRI-based WML volume. Particularly in patients with moderate or severe lesion load according to the visual Fazekas score the algorithm provided reliable prediction of MRI-based WML volume. CONCLUSION: Automated observer-independent quantification of voxel-wise WM density in CT significantly correlates with microangiopathic WM disease in gold standard MRI. This rapid surrogate of white matter lesion load in CT may support objective WML assessment and therapeutic decision-making during acute stroke triage.

Impact of Childhood Arterial Ischemic Stroke Standardized Classification and Diagnostic Evaluation Classification on Further Course of Arteriopathy and Recurrence of Childhood Stroke.

Background and Purpose- Arterial ischemic stroke (AIS) in childhood is a severe disease with potentially lifelong restrictions. Apart from cardiac or prothrombotic embolism, arteriopathy has been identified as a major cause and significant target of secondary stroke prevention. The Childhood Arterial Ischemic Stroke Standardized Classification and Diagnostic Evaluation (CASCADE) criteria facilitate a structured tool for categorizing and reporting childhood strokes according to the underlying cause. Our study aims to identify the prognostic value of CASCADE classification on admission for further course of arteriopathy and risk of stroke recurrence. Moreover, we give recommendations for follow-up imaging based on different CASCADE subgroups. Methods- Between 2004 and 2017, we identified 86 children with an acute arterial ischemic stroke classified in the 7-basic and 19-expanded subgroups of the acute CASCADE criteria. All included children were diagnosed and followed-up by magnetic resonance imaging. All arteriopathic strokes (basic subgroups 1-4 of acute CASCADE criteria) were further categorized into the chronic CASCADE criteria, including progressive, stable, reversible, and indeterminate course. Outcomes were defined as stroke recurrence and course of arteriopathy according to chronic CASCADE criteria. Associations between acute CASCADE criteria classification and stroke recurrence were assessed by Fisher exact test and between acute CASCADE criteria and chronic CASCADE criteria by Fisher exact test and Mann-Whitney U test. Results- A total of 86 children were included; of these, 57 presented with arteriopathic stroke (CASCADE 1-4) and 29 as nonarteriopathic. Unilateral cerebral arteriopathy (CASCADE 2; P=0.036) and bilateral cerebral arteriopathy (CASCADE 3; P=0.016) significantly correlated with stroke recurrence, and progressive arteriopathy significantly correlated with unilateral focal cerebral arteriopathy (P<0.001). Time points of progress of arteriopathy differed; whereas patients with unilateral focal cerebral arteriopathy presented with early median progress after 11 days, patients with bilateral cerebral arteriopathy had a significantly later median progress after 124 days (P=0.005). Conclusions- Initial CASCADE classification is associated with risk of recurrent strokes and progress of arteriopathy. Moreover, time points of arteriopathic progress vary according to the underlying cause.

Gadolinium-based contrast agents induce gadolinium deposits in cerebral vessel walls, while the neuropil is not affected: an autopsy study.

Recent studies showed gadolinium depositions following serial administrations of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging examinations in various parts of the brain with the dentate nucleus (DN) being most affected. Even though no clinical correlates of the deposits are known yet, an intensive debate developed if this might be harmful. The aim of the current study was to specify the gadolinium distribution in brain tissue of patients who received serial injections of GBCAs in the low-µm range and to explore any potential pathological tissue changes caused by gadolinium deposits. Thirteen autopsy cases-eight receiving GBCA administrations, five serving as controls-were identified and analyzed. For all patients, total gadolinium quantification after acidic digestion by means of inductively coupled plasma-mass spectrometry (ICP-MS) was performed. Six cases were utilized for the spatially resolved quantification of gadolinium within the cerebellum and the basal ganglia by means of high-resolution laser ablation (LA)-ICP-MS. Histopathological and immunohistochemical examinations were performed to determine tissue reactions. LA-ICP-MS revealed gadolinium depositions in the walls of small blood vessels of the DN in all GBCA exposed patients, while no gadolinium was found in the control group. Additionally, the detection of phosphorus and metals like copper, zinc and iron provides evidence that transmetalation reactions might have occurred. No significant pathological changes of the brain tissue in the vicinity of the DN with respect to micro-/astrogliosis and neuronal loss were found in any of the patients. This notably holds true even for a patient who died from nephrogenic systemic fibrosis exhibiting extremely high gadolinium concentrations within the DN. The findings show that gadolinium depositions in the brain are restricted to blood vessel walls, while the neuropil is spared and apparent cellular reactions are absent.

Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis.

The histological and molecular features and even the mere existence of diffuse astrocytoma, IDH-wildtype, remain unclear. We therefore examined 212 diffuse astrocytomas (grade II WHO) in adults using IDH1(R132H) immunohistochemistry followed by IDH1/IDH2 sequencing and neuroimaging review. DNA methylation status and copy number profiles were assessed by Infinium HumanMethylation450k BeadChip. Only 25/212 patients harbored tumors without IDH1/IDH2 hotspot mutations and without contrast enhancement. By DNA methylation profiling, 10/25 tumors were classified as glioblastoma, IDH-wildtype, and an additional 7 cases could not be classified using methylome analysis, but showed genetic characteristics of glioblastoma. Histologically, all of these 17 tumors were low-grade diffuse astrocytomas. Nevertheless, 10/17 patients experienced early malignant progression. Other methylation classes included diffuse midline glioma, H3 K27M-mutant, diffuse astrocytoma, IDH-mutant, pilocytic astrocytoma, and normal or reactive brain tissue (total n = 8). In conclusion, no convincing diffuse astrocytoma, IDH-wildtype, was identified. Most IDH-wildtype tumors showing histopathological and radiological features of low-grade diffuse astrocytoma exhibit molecular and clinical features of high-grade glioma and may represent an early stage of primary glioblastoma. Our findings have implications for the biology, classification and neuropathological diagnosis of diffuse astrocytoma, IDH-wildtype in adults.

Spatially resolved quantification of gadolinium deposited in the brain of a patient treated with gadolinium-based contrast agents.

Due to its paramagnetic properties resulting from seven unpaired f-electrons, Gd is frequently applied in magnetic resonance imaging examinations. Due to the acute toxicity of free Gd3+, ligand ions based on polyaminocarboxylic acids are used to create thermodynamically stable linear or macrocyclic complexes. The highly water soluble Gd-based contrast agents (GBCAs) are known to be excreted fast and unmetabolized, mostly via the kidneys. Nevertheless, recent studies showed that Gd traces persists not only in animal but also in human brain. Aim of this study was the development and application of an analytical method for the spatially resolved quantification of gadolinium traces in human brain thin sections of a patient treated with GBCAs. For this retrospective study different human brain regions were selected to analyze the distribution of gadolinium. An additional patient served as control sample, as no GBCA was administered. Deep-frozen brain thin sections were analyzed by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) and matrix-matched gelatin standards were prepared to quantify the gadolinium deposits via an external calibration. LA-ICP-MS analyses with high spatial resolution showed gadolinium deposits in different brain regions with highest concentrations above 800ngg-1 more than two years after the last application of a GBCA. An excellent limit of quantification of 7ngg-1, which is far below the limits of detection of MRI methods, could be achieved. The found concentrations confirm recent reports on gadolinium depositions in human brain, which were obtained without high spatial resolution. LA-ICP-MS provides limits of quantification, which are well suited to detect ultratrace amounts of gadolinium in human brain. Therefore, it provides valuable information on the distribution of gadolinium traces in the human brain even after single administration of GBCAs.

Ischemic Stroke: Histological Thrombus Composition and Pre-Interventional CT Attenuation Are Associated with Intervention Time and Rate of Secondary Embolism.

BACKGROUND AND PURPOSE: The introduction of stent retrievers has made the complete extraction and histological analysis of human thrombi possible. A number of large randomized trials have proven the efficacy of thrombectomy for ischemic stroke; however, thrombus composition could have an impact on the efficacy and risk of the intervention. We therefore investigated the impact of histologic thrombus features on interventional outcome and procedure-related embolisms. For a pre-interventional estimation of histologic features and outcome parameters, we assessed the pre-interventional CT attenuation of the thrombi. METHODS: We prospectively included all consecutive patients with occlusion of the middle cerebral artery who underwent thrombectomy between December 2013 and February 2016 at our university medical center. Samples were histologically analyzed (H&E, Elastica van Gieson, Prussian blue); additionally, immunohistochemistry for CD3, CD20, and CD68/KiM1P was performed. Main thrombus components (fibrin, erythrocytes, and white blood cells) were determined and compared to intervention time, frequency of secondary embolisms, as well as additional clinical and interventional parameters. Additionally, we assessed the pre-interventional CT attenuation of the thrombi in relation to the unaffected side (rHU) and their association with histologic features. RESULTS: One hundred eighty patients were included; of these, in 168 patients (93.4%), complete recanalization was achieved and 27 patients (15%) showed secondary embolism in the control angiogram. We observed a significant association of high amounts of fibrin (p < 0.001), low percentage of red blood cells (p < 0.001), and lower rHU (p < 0.001) with secondary embolism. Higher rHU values were significantly associated with higher amounts of fibrin (p ≤ 0.001) and low percentage of red blood cells (p ≤ 0.001). Additionally, high amounts of fibrin were associated with longer intervention times (p ≤ 0.001), whereas thrombi with high amounts of erythrocytes correlated with shorter intervention times (p ≤ 0.001). ROC analysis revealed reliable prediction of secondary embolisms for low rHU (AUC = 0.746; p ≤ 0.0001), low amounts of RBC (AUC = 0.764; p ≤ 0.0001), and high amounts of fibrin (AUC = 0.773; p ≤ 0.0001). CONCLUSIONS: Fibrin-rich thrombi with low erythrocyte percentage are significantly associated with longer intervention times. Embolisms in the thrombectomy process occur more often in thrombi with a small fraction of red blood cells and a low CT-density, suggesting a higher fragility of these thrombi.

Comparison of Spot Sign, Blend Sign and Black Hole Sign for Outcome Prediction in Patients with Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Blend sign (BS) and black hole sign (BHS) on non-contrast computed tomography (NCCT) and spot sign (SS) on CT-angiography (CTA) are indicators of early hematoma expansion in spontaneous intracerebral hemorrhage (ICH). However, their independent contributions to outcome have not been well explored. METHODS: In this retrospective study, inclusion criteria were: 1) spontaneous ICH and 2) NCCT and CTA performed on admission within 6 hours after onset of symptoms. Discharge outcome was dichotomized as good (modified Rankin Scale [mRS] 0-3) and poor (mRS 4-6) outcomes. The impacts of BHS, BS and SS on outcome were assessed in univariate and multivariable logistic regression models. RESULTS: Of 182 patients with spontaneous ICH, 26 (14.3%) presented with BHS, 37 (20.3%) with BS and 39 (21.4%) with SS. There was a substantial correlation between SS and BS (κ=0.701) and a moderate correlation between SS and BHS (κ=0.424). In univariable logistic regression, higher baseline hematoma volume (P<0.001), intraventricular hemorrhage (P=0.002) and the presence of BHS/BS/SS (all P<0.001) on admission CT scan were associated with poor outcome. Multivariable analysis identified intraventricular haemorrhage (odds ratio [OR] 2.22 per mL, P=0.022), baseline hematoma volume (OR 1.03 per mL, P<0.001) and SS on CTA (OR 11.43, P<0.001) as independent predictors of poor outcome, showing that SS compared to BS and BHS was more powerful to predict poor outcome. CONCLUSIONS: The NCCT BHS and BS are correlated with the CTA SS and are reliable predictors of poor outcome in patients with ICH. Of the CT variables indicating early hematoma expansion, SS on CTA was the most reliable outcome predictor. However, given their correlation with SS on CTA, BS and BHS on NCCT can be useful for predicting outcome if CTA is not obtainable.

Ischemic Stroke: What Does the Histological Composition Tell Us About the Origin of the Thrombus?

BACKGROUND AND PURPOSE: The introduction of stent retrievers allows for a complete extraction and histological analysis of human thrombi. Ischemic stroke is a major health issue, and differentiation of underlying causes is highly relevant to prevent recurrent stroke. Therefore, histopathologic analysis of the embolic clots after removal may provide valuable information about underlying pathologies. This study analyzes histological clot composition and aims to identify specific patterns that might help to distinguish causes of ischemic stroke. METHODS: Patients with occlusion of the carotid-T or middle cerebral artery who underwent thrombectomy at our university medical center between December 2013 and February 2016 were included. Samples were histologically analyzed (hematoxylin and eosin, Elastica van Gieson, and Prussian blue), additionally immunohistochemistry for CD3, CD20, and CD68/KiM1P was performed. These data, along with additional clinical and interventional parameters, were compared for different stroke subtypes, as defined by the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. RESULTS: One hundred eighty-seven patients were included, of these, in 77 patients, cardioembolic; in 46 patients, noncardioembolic; and in 64 patients, cryptogenic pathogenesis was determined. Cardioembolic thrombi had higher proportions of fibrin/platelets (P=0.027), less erythrocytes (P=0.005), and more leucocytes (P=0.026) than noncardioembolic thrombi. We observed a strong overlap of cryptogenic strokes and cardioembolic strokes concerning thrombus histology. The immunohistochemical parameters CD3, CD20, and CD68/KiM1P showed no statistically noticeable differences between stroke subtypes. CONCLUSIONS: Histological thrombus features vary significantly according to the underlying cause and may help to differentiate between cardioembolic and noncardioembolic stroke. In addition, our study supports the hypothesis that most cryptogenic strokes have a cardioembolic cause.

CT versus MR Techniques in the Detection of Cervical Artery Dissection.

BACKGROUND: Spontaneous cervical artery dissection (sCAD) is an important etiology of juvenile stroke. The gold standard for the diagnosis of sCAD is convential angiography. However, magnetic resonance imaging (MRI)/MR angiography (MRA) and computed tomography (CT)/CT angiography (CTA) are frequently used alternatives. New developments such as multislice CT/CTA have enabled routine acquisition of thinner sections with rapid imaging times. The goal of this study was to compare the capability of recent developed 128-slice CT/CTA to MRI/MRA to detect radiologic features of sCAD. METHODS: Retrospective review of patients with suspected sCAD (n = 188) in a database of our Stroke center (2008-2014), who underwent CT/CTA and MRI/MRA on initial clinical work-up. A control group of 26 patients was added. All Images were evaluated concerning specific and sensitive radiological features for dissection by two experienced neuroradiologists. Imaging features were compared between the two modalities. RESULTS: Forty patients with 43 dissected arteries received both modalities (29 internal carotid arteries [ICAs] and 14 vertebral arteries [VAs]). All CADs were identified in CT/CTA and MRI/MRA. The features intimal flap, stenosis, and lumen irregularity appeared in both modalities. One high-grade stenosis was identified by CT/CTA that was expected occluded on MRI/MRA. Two MRI/MRA-confirmed pseudoaneurysms were missed by CT/CTA. None of the controls evidenced specific imaging signs for dissection. CONCLUSIONS: CT/CTA is a reliable and better available alternative to MRI/MRA for diagnosis of sCAD. CT/CTA should be used to complement MRI/MRA in cases where MRI/MRA suggests occlusion.

Acute Recanalization of Thrombo-Embolic Ischemic Stroke with pREset (ARTESp): the impact of occlusion time on clinical outcome of directly admitted and transferred patients.

OBJECTIVES: Acute Recanalization of Thrombo-Embolic Ischemic Stroke with pREset (ARTESp) is a prospective multicenter study assessing the efficacy and safety of the pREset stent retriever for the treatment of intracranial vessel occlusion. Determination of the effect of transfer status on clinical outcome was a secondary objective. METHODS: Efficacy was measured by recanalization success (Thrombolysis in Cerebral Infarction score ≥2b) and favorable clinical outcome at 90 days (modified Rankin Scale 0-2). Intracranial hemorrhage (ICH) and death at 90 days were safety measures. The outcome of directly admitted (DAP) and transferred (TP) patients was investigated using multivariable regression models. RESULTS: Four study centers included 100 patients (mean age 68.3 years, median National Institutes of Health Stroke Scale score 15). Recanalization success was achieved in 84.4% after a mean of 1.7 passes. ICH was detected in 14.0%, with 2.0% being symptomatic. At 90 days, 62.5% of the patients had a favorable outcome and 7.3% died. TP had longer occlusion times (289 vs 180 minutes, p<0.001) and a lower rate of favorable outcome (58.0% vs 78.4%, p=0.046) than DAP. Multivariable regression revealed occlusion time as the critical determinant (OR=0.963, 95% CI 0.931 to 0.997, p=0.032), whereas transfer status itself showed no significant association (OR=0.565, CI 0.133 to 2.393, p=0.438). CONCLUSIONS: pREset proved to be safe and effective for the treatment of acute intracranial vessel occlusion. Increased occlusion time impaired clinical outcome in TP. TRIAL REGISTRATION NUMBER: NCT02437409; Results.

Computed Tomographic Blend Sign Is Associated With Computed Tomographic Angiography Spot Sign and Predicts Secondary Neurological Deterioration After Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Significant early hematoma growth in patients with intracerebral hemorrhage is an independent predictor of poor functional outcome. Recently, the novel blend sign (BS) has been introduced as a new imaging sign for predicting hematoma growth in noncontrast computed tomography. Another parameter predicting increasing hematoma size is the well-established spot sign (SS) visible in computed tomographic angiography. We, therefore, aimed to clarify the association between established SS and novel BS and their values predicting a secondary neurological deterioration. METHODS: Retrospective study inclusion criteria were (1) spontaneous intracerebral hemorrhage confirmed on noncontrast computed tomography and (2) noncontrast computed tomography and computed tomographic angiography performed on admission within 6 hours after onset of symptoms. We defined a binary outcome (secondary neurological deterioration versus no secondary deterioration). As secondary neurological deterioration, we defined (1) early hemicraniectomy under standardized criteria or (2) secondary decrease of Glasgow Coma Scale of >3 points, both within the first 48 hours after symptom onset. RESULTS: Of 182 patients with spontaneous intracerebral hemorrhage, 37 (20.3%) presented with BS and 39 (21.4%) with SS. Of the 81 patients with secondary deterioration, 31 (38.3%) had BS and SS on admission. Multivariable logistic regression analysis identified hematoma volume (odds ratio, 1.07 per mL; P≤0.001), intraventricular hemorrhage (odds ratio, 3.08; P=0.008), and the presence of BS (odds ratio, 11.47; P≤0.001) as independent predictors of neurological deterioration. CONCLUSIONS: The BS, which is obtainable in noncontrast computed tomography, shows a high correlation with the computed tomographic angiography SS and is a reliable predictor of secondary neurological deterioration after spontaneous intracerebral hemorrhage.

Automated assessment of early hypoxic brain edema in non-enhanced CT predicts outcome in patients after cardiac arrest.

INTRODUCTION: Early prediction of potential neurological recovery in patients after cardiac arrest is challenging. Recent studies suggest that the densitrometic gray-white matter ratio (GWR) determined from cranial computed tomography (CT) scans may be a reliable predictor of poor outcome. We evaluated an automated, rater independent method to determine GWR in CT as an early objective imaging predictor of clinical outcome. METHODS: We analyzed imaging data of 84 patients after cardiac arrest that underwent noncontrast CT within 24h after arrest. To determine GWR in CT we applied two methods using a recently published automated probabilistic gray-white matter segmentation algorithm (GWR_aut) and conventional manual measurements within gray-white regions of interest (GWR_man). Neurological outcome was graded by the cerebral performance category (CPC). As part of standard routine CPC was assessed by the treating physician in the intensive care unit at admission and at discharge to normal ward. The performance of GWR measures (automated and manual) to predict the binary clinical endpoints of poor (CPC3-5) and good outcome (CPC1-2) was assessed by ROC analysis with increasing discrimination thresholds. Results of GWR_aut were compared to GWR_man of two raters. RESULTS: Of 84 patients, 55 (65%) showed a poor outcome. ROC curve analysis revealed reliable outcome prediction of GWR_aut (AUC 0.860) and GWR_man (AUC 0.707 and 0.699, respectively). Predictive power of GWR_aut was higher than GWR_man by each rater (p=0.019 and p=0.021, respectively) at an optimal cut-off of 1.084 to predict poor outcome (optimal criterion with 92.7% sensitivity, 72.4% specificity). Interrater reliability of GWR_man by intra-class correlation coefficient (ICC) was moderate (0.551). CONCLUSION: Automated quantification of GWR in CT may be used as an objective observer-independent imaging marker for outcome in patients after cardiac arrest.

Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors.

Dysembryoplastic neuroepithelial tumor (DNET) is a benign brain tumor associated with intractable drug-resistant epilepsy. In order to identify underlying genetic alterations and molecular mechanisms, we examined three family members affected by multinodular DNETs as well as 100 sporadic tumors from 96 patients, which had been referred to us as DNETs. We performed whole-exome sequencing on 46 tumors and targeted sequencing for hotspot FGFR1 mutations and BRAF p.V600E was used on the remaining samples. FISH, copy number variation assays and Sanger sequencing were used to validate the findings. By whole-exome sequencing of the familial cases, we identified a novel germline FGFR1 mutation, p.R661P. Somatic activating FGFR1 mutations (p.N546K or p.K656E) were observed in the tumor samples and further evidence for functional relevance was obtained by in silico modeling. The FGFR1 p.K656E mutation was confirmed to be in cis with the germline p.R661P variant. In 43 sporadic cases, in which the diagnosis of DNET could be confirmed on central blinded neuropathology review, FGFR1 alterations were also frequent and mainly comprised intragenic tyrosine kinase FGFR1 duplication and multiple mutants in cis (25/43; 58.1 %) while BRAF p.V600E alterations were absent (0/43). In contrast, in 53 cases, in which the diagnosis of DNET was not confirmed, FGFR1 alterations were less common (10/53; 19 %; p < 0.0001) and hotspot BRAF p.V600E (12/53; 22.6 %) (p < 0.001) prevailed. We observed overexpression of phospho-ERK in FGFR1 p.R661P and p.N546K mutant expressing HEK293 cells as well as FGFR1 mutated tumor samples, supporting enhanced MAP kinase pathway activation under these conditions. In conclusion, constitutional and somatic FGFR1 alterations and MAP kinase pathway activation are key events in the pathogenesis of DNET. These findings point the way towards existing targeted therapies.

Computed Tomography Perfusion Improves Diagnostic Accuracy in Acute Posterior Circulation Stroke.

BACKGROUND AND PURPOSE: Computed tomography perfusion (CTP) has a high diagnostic value in the detection of acute ischemic stroke in the anterior circulation. However, the diagnostic value in suspected posterior circulation (PC) stroke is uncertain, and whole brain volume perfusion is not yet in widespread use. We therefore studied the additional value of whole brain volume perfusion to non-contrast CT (NCCT) and CT angiography source images (CTA-SI) for infarct detection in patients with suspected acute ischemic PC stroke. METHODS: This is a retrospective review of patients with suspected stroke in the PC in a database of our stroke center (n = 3,011) who underwent NCCT, CTA and CTP within 9 h after stroke onset and CT or MRI on follow-up. Images were evaluated for signs and pc-ASPECTS locations of ischemia. Three imaging models - A (NCCT), B (NCCT + CTA-SI) and C (NCCT + CTA-SI + CTP) - were compared with regard to the misclassification rate relative to gold standard (infarction in follow-up imaging) using the McNemar's test. RESULTS: Of 3,011 stroke patients, 267 patients had a suspected stroke in the PC and 188 patients (70.4%) evidenced a PC infarct on follow-up imaging. The sensitivity of Model C (76.6%) was higher compared with that of Model A (21.3%) and Model B (43.6%). CTP detected significantly more ischemic lesions, especially in the cerebellum, posterior cerebral artery territory and thalami. CONCLUSIONS: Our findings in a large cohort of consecutive patients show that CTP detects significantly more ischemic strokes in the PC than CTA and NCCT alone.

Comparison of a Balloon Guide Catheter and a Non-Balloon Guide Catheter for Mechanical Thrombectomy.

Purpose To evaluate the effectiveness of mechanical thrombectomy with the use of a stent retriever in acute ischemic stroke, performed by using a balloon guide catheter or non-balloon guide catheter. Materials and Methods In accordance with the institutional review board approval obtained at the two participating institutions, retrospective analysis was performed in 183 consecutive patients treated between 2013 and 2014 for occlusions in the middle cerebral artery or carotid terminus by using a stent retriever with a balloon guide catheter (n = 102) at one center and a non-balloon guide catheter (n = 81) at the other center. Data on procedure duration, number of passes, angiographic findings, type of stent retriever used, and expertise of the operators were collected. Successful recanalization was defined as grade 3 or 2b modified Treatment in Cerebral Ischemia recanalization accomplished in up to three passes. Univariate and multivariate subgroup analyses were conducted to control for the confounding variables of prior thrombolysis, location of occlusion, and operator expertise. Results Successful recanalization with the balloon guide catheter was achieved in 89.2% of thrombectomies (91 of 102) versus 67.9% (55 of 81) achieved with the non-balloon guide catheter (P = .0004). The one-pass thrombectomy rate with the balloon guide catheter was significantly higher than for that with the non-balloon guide catheter (63.7% [65 of 102] vs 35.8% [29 of 81], respectively; P = .001). The procedure duration was significantly shorter by using the balloon guide catheter than the non-balloon guide catheter (median, 20.5 minutes vs 41.0 minutes, respectively; P < .0001). Conclusion The effectiveness of mechanical thrombectomy with stent retrievers in acute ischemic stroke in the anterior circulation in terms of angiographic results and procedure duration was improved when performed in combination with the balloon guide catheter. (©) RSNA, 2016.

The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors.

BACKGROUND: Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. OBJECTIVE: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. METHODS: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. RESULTS: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. CONCLUSION: Age, tumor volume, and F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined.

Acute tonsillar cerebellar herniation in a patient with traumatic dural tear and VAC therapy after complex trauma.

BACKGROUND CONTEXT: Cases of cerebral hypotension and tonsillar herniation after accidental lumbar cerebrospinal fluid (CSF) drainage or chest tube drainage with intrathoracic CSF leaks have been reported. To the authors' knowledge, this case presents the first report of severe intracranial hypotension because of suction of CSF by a Vacuum-Assisted Closure (VAC) device. PURPOSE: The purpose of this study was to report a life-threatening intracranial hypotension in a polytraumatized patient after VAC therapy. STUDY DESIGN: This study is a case report. METHODS: A 23-year-old woman suffered of a Grade 3 open pelvic fracture after a motor vehicle accident. After a VAC therapy, the patient became nonresponsive. A cranial computer tomography (CCT) showed signs of intracranial hypotension with narrowing of the basal cisterns and sagging of the cerebellar tonsils. The VAC was removed. Further neuroradiological diagnostic showed a tear in the dural sac at the L5-S1 level. The patient consequently underwent neurosurgery. After a dural patch, she was oriented postoperatively and the CCT improved to a normal state. RESULTS: Fifteen days after admission, the patient was discharged without neurologic sequelae. CONCLUSIONS: Severely injured patients undergoing VAC therapy with secondary neurologic deterioration not because of head injury should be appropriately diagnosed to rule out dural laceration and cranial hypotension.