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.

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.

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.

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 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.

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.

Magnetic resonance 4D flow analysis of cerebrospinal fluid dynamics in Chiari I malformation with and without syringomyelia.

OBJECTIVE: To analyse cerebrospinal fluid (CSF) hydrodynamics in patients with Chiari type I malformation (CM) with and without syringomyelia using 4D magnetic resonance (MR) phase contrast (PC) flow imaging. METHODS: 4D-PC CSF flow data were acquired in 20 patients with CM (12 patients with presyrinx/syrinx). Characteristic 4D-CSF flow patterns were identified. Quantitative CSF flow parameters were assessed at the craniocervical junction and the cervical spinal canal and compared with healthy volunteers and between patients with and without syringomyelia. RESULTS: Compared with healthy volunteers, 17 CM patients showed flow abnormalities at the craniocervical junction in the form of heterogeneous flow (n = 3), anterolateral flow jets (n = 14) and flow vortex formation (n = 5), most prevalent in patients with syringomyelia. Peak flow velocities at the craniocervical junction were significantly increased in patients (-15.5 ± 11.3 vs. -4.7 ± 0.7 cm/s in healthy volunteers, P < 0.001). At the level of C1, maximum systolic flow was found to be significantly later in the cardiac cycle in patients (30.8 ± 10.3 vs. 22.7 ± 4.1%, P < 0.05). CONCLUSIONS: 4D-PC flow imaging allowed comprehensive analysis of CSF flow in patients with Chiari I malformation. Alterations of CSF hydrodynamics were most pronounced in patients with syringomyelia.

Prediction of malignant middle cerebral artery infarction using computed tomography-based intracranial volume reserve measurements.

BACKGROUND AND PURPOSE: Early decompressive surgery in patients with malignant middle cerebral artery (MCA) infarction improves outcome. Elevation of intracranial pressure depends on both the space occupying brain edema and the intracranial volume reserve (cerebrospinal fluid [CSF]). However, CSF volume was not investigated as a predictor of malignant infarction so far. We hypothesize that assessment of CSF volume in addition to admission infarct size improves early prediction of malignant MCA infarction. METHODS: Stroke patients with carotid-T or MCA main stem occlusion and ischemic lesion (reduced cerebral blood volume [CBV]) on perfusion CT were considered for the analysis. The end point malignant MCA infarction was defined by clinical signs of herniation. Volumes of CSF and CBV lesion were determined on admission. Receiver-operator characteristics analysis was used to calculate predictive values for radiological and clinical measurements. RESULTS: Of 52 patients included, 26 (50%) developed malignant MCA infarction. Age, a decreased level of consciousness on admission, CBV lesion volume, CSF volume, and the ratio of CBV lesion volume to CSF volume were significantly different between malignant and nonmalignant groups. The best predictor of a malignant course was the ratio of CBV lesion volume to CSF volume with a cut-off value of 0.92 (96.2% sensitivity, 96.2% specificity, 96.2% positive predictive value, and 96.2% negative predictive value). CONCLUSIONS: Based on admission native CT and perfusion CT measurements, the ratio of ischemic lesion volume to CSF volume predicts the development of malignant MCA infarction with higher accuracy than other known predictors, including ischemic lesion volume or clinical characteristics.

Magnetic resonance 4D flow characteristics of cerebrospinal fluid at the craniocervical junction and the cervical spinal canal.

OBJECTIVES: To evaluate the applicability of 4D phase contrast (4D PC) MR imaging in the assessment of cerebrospinal fluid dynamics in healthy volunteers and patients with lesions at the craniocervical junction or the cervical spinal canal. METHODS: Ten healthy volunteers and four patients with lesions including Chiari I malformation and cervical canal stenoses were examined by a cardiac-gated 4D PC imaging sequence on 1.5T MRI. Phase contrast images were postprocessed allowing for flow quantification and flow pathline visualisation. Velocity data were compared with conventional axial 2D phase contrast images. RESULTS: The 4D PC sequence allowed for flow quantification and visualisation in all individuals. Bland-Altman analysis showed good agreement of 2D and 4D PC velocity data. In healthy volunteers, CSF flow was homogeneously distributed in the anterior and anterolateral subarachnoid space with the flow directed caudally during systole and cranially during diastole. Flow velocities were closely related to the width of the subarachnoid space. Patients showed grossly altered CSF flow patterns with formation of flow jets with increased flow velocities. CONCLUSIONS: 4D PC MR imaging allows for a detailed assessment of CSF flow dynamics helping to distinguish physiological from complex pathological flow patterns at the craniocervical junction and the cervical spine.

Brachioradial pruritus as a result of cervical spine pathology: the results of a magnetic resonance tomography study.

BACKGROUND: Brachioradial pruritus (BRP) describes a rare form of itching occurring at the dorsolateral part of the forearms. Recent case reports suggest that BRP may be attributed to cervical lesions or spine neoplasms. OBJECTIVE: We sought to determine the incidence of cervical spine changes in BRP and to correlate the localization of spinal lesions with the dermatomal presence of pruritus. METHODS: Magnetic resonance tomography (MRT) of the cervical spinal cord, a chest x-ray, and a skin biopsy were performed in 41 patients (28 female, 13 male; 59.0 ± 10.6 years) with BRP. Patients completed an itch questionnaire (NeuroDerm Questionnaire) that included a dermatome chart and the Northwick Park Neck Pain Questionnaire. RESULTS: The patients marked the locations C5 (90.2%) and C6 (100%) on the dermatome chart. All patients had detectable MRT changes. In 80.5% of the patients, stenosis of the intervertebral foramen or protrusions of the cervical disk led to nerve compression. The location of the nerve compression lesions correlated significantly with the dermatomal localization of the pruritus (Spearman correlation coefficient 0.893; P < .01). No spinal neoplasm was observed, and 19.5% of the patients had degenerative changes without significant correlation to the dermatomal localization of pruritus. LIMITATION: No healthy control group without pruritus was investigated. CONCLUSION: BRP may result from cervical nerve compression, and rarely, it may also stem from degenerative changes. Our findings suggest that even slight cervical changes detected on MRT may alter itch afferents and lead to BRP. Spinal cord tumors are rare and should be ruled out by a cervical spine MRT.

Case report of MR perfusion imaging in sinking skin flap syndrome: growing evidence for hemodynamic impairment.

BACKGROUND: The syndrome of the sinking skin flap (SSSF) with delayed sensorimotor deficits after craniectomy is not well known and often neglected. Among various postulated causes, there is evidence that disturbed brain perfusion may be related to the observed symptoms, and that cranioplasty reliably alleviates these symptoms. We report a case of sinking skin flap syndrome (SSFS) with recovery from neurological sensorimotor deficits after cranioplasty correlated with pre- and postsurgical MR brain perfusion studies. CASE PRESENTATION: A 42-year-old woman presented with slowly progressive sensorimotor paresis of her left arm after decompressive extensive craniectomy due to subarachnoid hemorrhage four months ago. Her right cranium showed a "sinking skin flap". After cranioplastic repair of her skull defect, the patient fully recovered from her symptoms. Before cranioplasty, reduced brain perfusion in the right central cortical region was observed in MR-perfusion images. After cranioplasty, a marked increase in brain perfusion was observed which correlated with objective clinical recovery. CONCLUSION: There is increasing evidence that impaired blood flow is responsible for delayed motor deficits in patients with sinking skin flap syndrome in the area of compressed brain regions. Symptoms should be evaluated by brain perfusion imaging complementing surgical decision-making.

Anticoagulation in childhood-onset arterial ischemic stroke with non-moyamoya arteriopathy: findings from the Colorado and German (COAG) collaboration.

BACKGROUND AND PURPOSE: Childhood arterial ischemic stroke treatment guidelines recommend extended anticoagulation in cardioembolism and dissection. We sought to investigate the safety of extended anticoagulation in childhood arterial ischemic stroke with nonmoyamoya arteriopathy, for which the risk of recurrent stroke is high. METHODS: Thirty-seven patients with childhood-onset arterial ischemic stroke with acute arteriopathy (excluding moyamoya) were diagnosed between 1999 and 2007 and treated with anticoagulation for at least 4 weeks. Patients were followed in hospital-based cohort studies at 2 centers and systematically assessed for bleeding episodes and recurrent events. RESULTS: Over a cumulative anticoagulation duration of 1329 patient-months, there were no major bleeding episodes and 2 clinically relevant bleeding episodes. Cumulative probability of recurrent arterial ischemic stroke at 1 year was 14%. CONCLUSIONS: Anticoagulation can be used safely for secondary arterial ischemic stroke prevention in children with acute nonmoyamoya arteriopathy. Anticoagulation is worthy of evaluation in future randomized, controlled treatment trials in this disease.

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.

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.

Brain tumors in children: initial symptoms and their influence on the time span between symptom onset and diagnosis.

Brain tumors are the most common solid tumor entity in childhood. Symptoms are often unspecific, depending not only on the localization of the tumor, but also on the age of the child. The aim of this study was to detect factors influencing the time span between the occurrence of symptoms and the diagnosis to alert health professionals to the early symptoms of pediatric brain tumors. The records of 245 consecutive patients treated for brain tumors between 1980 and 2004 at the neuropediatric department of the University of Muenster were analyzed regarding their primary symptoms, tumor location, entity, and, in 151 cases, the primary electroencephalogram findings. The median time span between symptom onset and diagnosis in our study was 24 days. Multivariate analysis showed a significant influence of 6 parameters on the interval between symptom onset and diagnosis. An additional symptom had a significant influence on the time span between symptom onset and diagnosis in the univariate analysis. The findings that several symptoms influence the interval between symptom onset and diagnosis emphasize the necessity to systematically inquire about the key symptoms of brain tumors. The challenge for every consultant is to decide in which cases cerebral imaging is appropriate. As the most frequent symptoms are unspecific and often underestimated, a detailed anamnesis is crucial to detect possible brain tumor patients. In doubtful cases, a systematic interrogation regarding the catalogue of symptoms can be helpful.

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.