Prediction of MYCN Gene Amplification in Pediatric Neuroblastomas: Development of a Deep Learning-Based Tool for Automatic Tumor Segmentation and Comparative Analysis of Computed Tomography-Based Radiomics Features Harmonization.

OBJECTIVE: MYCN oncogene amplification is closely linked to high-grade neuroblastoma with poor prognosis. Accurate quantification is essential for risk assessment, which guides clinical decision making and disease management. This study proposes an end-to-end deep-learning framework for automatic tumor segmentation of pediatric neuroblastomas and radiomics features-based classification of MYCN gene amplification. METHODS: Data from pretreatment contrast-enhanced computed tomography scans and MYCN status from 47 cases of pediatric neuroblastomas treated at a tertiary children's hospital from 2009 to 2020 were reviewed. Automated tumor segmentation and grading pipeline includes (1) a modified U-Net for tumor segmentation; (2) extraction of radiomic textural features; (3) feature-based ComBat harmonization for removal of variabilities across scanners; (4) feature selection using 2 approaches, namely, ( a ) an ensemble approach and ( b ) stepwise forward-and-backward selection method using logistic regression classifier; and (5) radiomics features-based classification of MYCN gene amplification using machine learning classifiers. RESULTS: Median train/test Dice score for modified U-Net was 0.728/0.680. The top 3 features from the ensemble approach were neighborhood gray-tone difference matrix (NGTDM) busyness, NGTDM strength, and gray-level run-length matrix (GLRLM) low gray-level run emphasis, whereas those from the stepwise approach were GLRLM low gray-level run emphasis, GLRLM high gray-level run emphasis, and NGTDM coarseness. The top-performing tumor classification algorithm achieved a weighted F1 score of 97%, an area under the receiver operating characteristic curve of 96.9%, an accuracy of 96.97%, and a negative predictive value of 100%. Harmonization-based tumor classification improved the accuracy by 2% to 3% for all classifiers. CONCLUSION: The proposed end-to-end framework achieved high accuracy for MYCN gene amplification status classification.

CT-based morphologic and radiomics features for the classification of MYCN gene amplification status in pediatric neuroblastoma.

PURPOSE: MYCN onco-gene amplification in neuroblastoma confers patients to the high-risk disease category for which prognosis is poor and more aggressive multimodal treatment is indicated. This retrospective study leverages machine learning techniques to develop a computed tomography (CT)-based model incorporating semantic and non-semantic features for non-invasive prediction of MYCN amplification status in pediatric neuroblastoma. METHODS: From 2009 to 2020, 54 pediatric patients treated for neuroblastoma at a specialized children's hospital with pre-treatment contrast-enhanced CT and MYCN status were identified (training cohort, n = 44; testing cohort, n = 10). Six morphologic features and 107 quantitative gray-level texture radiomics features extracted from manually drawn volume-of-interest were analyzed. Following feature selection and class balancing, the final predictive model was developed with eXtreme Gradient Boosting (XGBoost) algorithm. Accumulated local effects (ALE) plots were used to explore main effects of the predictive features. Tumor texture maps were also generated for visualization of radiomics features. RESULTS: One morphologic and 2 radiomics features were selected for model building. The XGBoost model from the training cohort yielded an area under the receiver operating characteristics curve (AUC-ROC) of 0.930 (95% CI, 0.85-1.00), optimized F1-score of 0.878, and Matthews correlation coefficient (MCC) of 0.773. Evaluation on the testing cohort returned AUC-ROC of 0.880 (95% CI, 0.64-1.00), optimized F1-score of 0.933, and MCC of 0.764. ALE plots and texture maps showed higher "GreyLevelNonUniformity" values, lower "Strength" values, and higher number of image-defined risk factors contribute to higher predicted probability of MYCN amplification. CONCLUSION: The machine learning model reliably classified MYCN amplification in pediatric neuroblastoma and shows potential as a surrogate imaging biomarker.

The Characteristics of Real-time Transvaginal Sono-elastography in Endometrial Cancer.

Background: Endometrial cancer is the most common gynecological cancer among women in developed countries. Sono-elastography is an extended ultrasonographic technique that has been shown to be useful in a wide range of conditions ranging from breast, prostate, and thyroid nodules to chronic liver disease and musculoskeletal conditions. The aim of this study is to compare the sonoelastographic features of endometrial malignancy and normal endometrium. Methods: This case-control observational study was conducted at a single institution. Participants with histologically proven endometrial cancer according to the results from microcurettage or hysteroscopic biopsy and scheduled for total hysterectomy were included as cases, while asymptomatic women scheduled for routine screening ultrasound examination were recruited as controls. Both cases and controls underwent conventional B-mode transvaginal ultrasonography and strain elastography. Demographic, ultrasonographic, and histopathologic findings were analyzed. Results: A total of 29 endometrial cancer patients (cases) and 28 normal females (controls) were included in the analysis. There was no significant difference in the mean age between the two groups, but the mean body weight was significantly higher in the case group (P < 0.001). The strain ratio and elastographic thickness ratio of the endometrium were statistically significantly different between the case and the control group (P ≤ 0.05) due to increased endometrial stiffness in cancer patients as compared to the normal group. Conclusion: Our results suggest that endometrial cancer can result in increased stiffness that is detectable by transvaginal sonoelastography. Sonoelastography may serve as an adjunct to conventional ultrasound in evaluating the endometrium of women with abnormal uterine bleeding.

Cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastoma.

BACKGROUND: Metastatic medulloblastoma (MB) portends a poor prognosis. Amongst the 4 molecular subtypes, Group 3 and Group 4 patients have a higher incidence of metastatic disease, especially involving the neuroaxis. At present, mechanisms underlying MB metastasis remain elusive. Separately, inflammation has been implicated as a key player in tumour development and metastasis. Cytokines and their inflammation-related partners have been demonstrated to act on autocrine and, or paracrine pathways within the tumour microenvironment for various cancers. In this study, the authors explore the involvement of cerebrospinal fluid (CSF) cytokines in Group 3 and 4 MB patients with disseminated disease. METHODS: This is an ethics approved, retrospective study of prospectively collected data based at a single institution. Patient clinicpathological data and corresponding bio-materials are collected after informed consent. All CSF samples are interrogated using a proteomic array. Resultant expression data of selected cytokines are correlated with each individual's clinical information. Statistical analysis is employed to determine the significance of the expression of CSF cytokines in Group 3 and 4 patients with metastatic MB versus non-metastatic MB. RESULTS: A total of 10 patients are recruited for this study. Median age of the cohort is 6.6 years old. Based on Nanostring gene expression analysis, 5 patients have Group 3 as their molecular subtype and the remaining 5 are Group 4. There are 2 non-metastatic versus 3 metastatic patients within each molecular subtype. Proteomic CSF analysis of all patients for both subtypes show higher expression of CCL2 in the metastatic group versus the non-metastatic group. Within the Group 3 subtype, the MYC-amplified Group 3 MB patients with existing and delayed metastases express higher levels of CXCL1, IL6 and IL8 in their CSF specimens at initial presentation. Furthermore, a longitudinal study of metastatic Group 3 MB observes that selected cytokines are differentially expressed in MYC-amplified metastatic Group 3 MB, in comparison to the non-MYC amplified metastatic Group 3 MB patient. CONCLUSION: This study demonstrates higher expression of selected CSF cytokines, in particular CCL2, in metastatic Group 3 and 4 MB patients. Although our results are preliminary, they establish a proof-of-concept basis for continued work in a larger cohort of patients affected by this devastating disease.

General anesthesia / sedation requirement influences the way MRI brain scans are ordered in a tertiary pediatric hospital.

BACKGROUND: MRI guidelines have been created to help clinicians order scans appropriately. Some scans in children are carried out under general anesthesia (GA) / sedation. PURPOSE: To evaluate if the requirement for GA/sedation influences the way MRI brain scans are ordered. STUDY TYPE: Retrospective. POPULATION: Children with MRI brain scans in 2015 to 2017. FIELD STRENGTH: 3T, 1.5T. ASSESSMENT: Institutional Review Board approval for waiver of consent was obtained. Clinical MRI brain reports for children were classified into whether they conformed to the American College of Radiology (ACR) 2013 guidelines by research assistants under supervision of a pediatric radiologist. Scans were sorted into those with normal brains or abnormality. STATISTICAL TEST: The statistical difference between groups was assessed using t-test for continuous variables and chi-square test for categorical variables with IBM SPSS 19. RESULTS: Of the total 1893 MRI scans, 431 were performed under GA and six under sedation. Of the 431 cases performed under GA/sedation, 383 (87.6%) were ordered according to guidelines. Of the 1456 cases that did not require GA/sedation, 710 (48.8%) conformed to guidelines. The percentage of scans ordered according to guidelines was 38.8% higher in those who had scans performed under GA/sedation (P < 0.001). MRI scans were normal in 635 (58.0%) out of the 1093 cases ordered according to guidelines and normal in 638 (79.8%) out of the 800 cases that did not follow guidelines. Scans not ordered according to guidelines had higher proportion of normal scans (21.8%) compared with those ordered according to guidelines (P < 0.001). DATA CONCLUSION: Higher adherence to imaging guidelines is seen in younger patients who were exposed to the risks of GA/sedation for the MRI. Scans not adhering to guidelines had a higher percentage of having no brain abnormality detected. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 6 J. Magn. Reson. Imaging 2019;49:e250-e255.

Clinical Relevance of the Nonvisualized Appendix on Ultrasonography of the Abdomen in Children.

OBJECTIVES: To evaluate the clinical relevance of the nonvisualized appendix on ultrasound imaging in children with right lower quadrant pain. STUDY DESIGN: We reviewed 1359 children admitted for abdominal pain between January and December 2013 who had abdominal ultrasound imaging for right lower quadrant pain. Patients who had scans for genitourinary symptoms or intussusception were excluded from the study. When the appendix was not visualized, secondary signs indicating right lower quadrant inflammatory pathology were noted. RESULTS: Of all admissions for abdominal pain, 810 had ultrasound scans. Thirty-eight did not evaluate the appendix and 131 were excluded for suspected intussusception, leaving 641 reports for children with a median age of 10.8 years (range, 1.3-21.3); 297 were boys (46.3%). There were 17 of 160 patients with a nonvisualized appendix (10.6%) who underwent appendectomy. Of these, 14 had secondary signs on ultrasound imaging and 3 (1.9%) had normal ultrasound reports. The 3 patients with normal ultrasound imaging had computed tomography imaging confirming appendicitis. There were 51 patients with a partially visualized appendix. The segment of appendix that could be seen was normal in 34 patients, none of whom had appendectomy. The remaining 17 had appendectomy, in whom the appendix seemed to be inflamed in 13 and equivocal in 4, all with histologically confirmed appendicitis. Overall, 232 children underwent appendectomy; 58 had no ultrasound imaging done, and 5 had a histologically normal appendix (overall negative appendectomy rate, 2.2%). Only 35 of 1359 patients (0.03%) had computed tomography scans. CONCLUSION: In patients with a nonvisualized appendix on ultrasound imaging and no evidence of secondary inflammatory changes, the likelihood of appendicitis is less than 2%. Generous use of ultrasonography as an adjunct to clinical examination can achieve low negative appendectomy rates without underdiagnosis of acute appendicitis.

A novel intronic variant in ROBO3 associated with horizontal gaze palsy with progressive scoliosis: case report and literature review.

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, autosomal recessive inherited disorder caused by mutations in ROBO3 gene. The clinical features of HGPPS include horizontal gaze palsy, progressive scoliosis, other oculomotor abnormalities such as strabismus and nystagmus. Whole-exome sequencing (WES) is used to diagnose rare Mendelian disorders, when routine standard tests have failed to make a formal pathological diagnosis. However, WES may identify variants of uncertain significance (VUS) that may add further ambiguity to the diagnosis. We report the case of a 4-year-old boy with horizontal gaze palsy, progressive scoliosis, microcephaly, and mild developmental delay. WES identified an intronic VUS in ROBO3 gene. We performed minigene splicing functional analysis to confirm the pathogenicity of this VUS. This report illustrates that WES data analysis with supportive functional analysis provides an effective approach to improve the diagnostic yield for unsolved clinical cases. This case also highlights the phenotypic heterogeneity in patients with HGPPS.

Occult Antenatal Fetal Abdominal Emergencies Resulting in Unplanned Preterm Delivery.

Acute abdomen in the fetus can present as nonspecific fetal distress, and occasionally necessitate emergency cesarean section for the mother and subsequent emergency neonatal surgery. Often, preoperative diagnosis in utero is challenging. The authors herein report two cases, a case of primary segmental antenatal intestinal volvulus resulting in the mother presenting at 35 wk with symptoms and decreased fetal movements, and another case of a rapidly distending fetal abdominal mass at 31 wk manifesting as fetal hydrops. The postdelivery newborn management issues are presented. Early identification by the maternal and neonatal team allows for early neonatal surgery and can reduce morbidity and mortality. This can be facilitated by advanced maternal and child health services and efficient patient transport systems.

Should paediatric chest compression depth targets consider body habitus? - A chest computed tomography imaging study.

AIM: This study explored how body habitus in the paediatric population might potentially affect the use of one-third external anterior-posterior (APD) diameter when compared to age-appropriate absolute chest compression depth targets. It also explored how body habitus could potentially affect the relationship between one-third external and internal APD (compressible space) and if body habitus indices were independent predictors of internal APD at the lower half of the sternum. METHODS: This was a secondary analysis of a retrospective study of chest computed tomography (CT) scans of infants and children (>24-hours-of-life to less-than-18-years-old) from 2005 to 2017. Patients' scan images were reviewed for internal and external APDs at the mid-point of the lower half of the sternum. Body habitus and epidemiological data were extracted from the electronic medical records. RESULTS: Chest CT scans of 193 infants and 398 children were evaluated. There was poor concordance between one-third external APD measurements and age-specific absolute chest compression depth targets, especially in infants and overweight/obese adolescents. There was a co-dependent relationship between one-third external APD and internal APD measurements. Overweight/obese children's and adolescents' internal and external APDs were significant different from the normal/underweight groups. Body-mass-index (BMI) of children and adolescents (p = 0.009), but not weight-for-length (WFL) of infants (p = 0.511), was an independent predictor of internal APD at the compression landmark. CONCLUSION: This study demonstrated correlations between external and internal APDs which were affected by BMI but not WFL (infants). Clinical studies are needed to validate current chest compression guidelines especially for infants and overweight/obese adolescents.(250 words).

Corrigendum to "Should paediatric chest compression depth targets consider body habitus? - A chest computed tomography imaging study" [Resuscitation Plus 9 (2022) 100202].

[This corrects the article DOI: 10.1016/j.resplu.2022.100202.].

Improving children's cooperativeness during magnetic resonance imaging using interactive educational animated videos: a prospective, randomised, non-inferiority trial.

INTRODUCTION: A previous prospective, randomized controlled trial showed that animated videos shown to children before their magnetic resonance imaging (MRI) scan reduced the proportion of children needing repeated MRI sequences and improved confidence of staying still for at least 30 minutes. Children preferred the interactive video. We hypothesize that the interactive video is non-inferior to showing two videos (regular and interactive) in improving children's cooperativeness during MRI scans. METHODS: In this Institutional Review Board-approved prospective, randomized, non-inferiority trial, 558 children aged 3 to 20 scheduled for elective MRI scan from June 2017 to March 2019 were randomized into interactive video only and combined (regular and interactive) videos groups. Children were shown the videos before their scan. Repeated MRI sequences, general anesthesia (GA) requirement, and improvement in confidence of staying still for at least 30 minutes were assessed. RESULTS: In the interactive video group (n = 277), 86 (31.0%) children needed repeated MRI sequences, 2 (0.7%) needed GA, and the proportion of children who had confidence in staying still for greater than 30 minutes increased by 22.1% after the video. In the combined videos group (n = 281), 102 (36.3%) children needed repeated MRI sequences, 6 (2.1%) needed GA, and the proportion of children who had confidence in staying still for greater than 30 minutes increased by 23.2% after videos, not significantly different from the interactive video group. CONCLUSION: The interactive video group demonstrated non-inferiority to the combined videos group.

Association of anesthetic and surgical risk factors with outcomes of initial diagnostic biopsies in a current cohort of children with anterior mediastinal masses.

Background: Diagnostic biopsies of pediatric anterior mediastinal masses (AMMs) are high-risk procedures in which general anesthesia (GA) is traditionally avoided. However, awareness of historically recognized risk factors and corresponding perioperative management have improved over time and may now no longer strictly preclude the use of GA. Therefore, in this study, we examined the association of anesthetic and surgical risk factors and modalities with resulting procedural and survival outcomes in a current patient cohort. Methods: We retrospectively reviewed charts of 35 children with AMMs who underwent initial diagnostic biopsies between January 2001 and August 2019, and determined tracheal compression and deviation from archival CT scans and procedural and disease outcomes. Results: Twenty-three (65%) patients underwent GA while 12 (35%) received sedation. Among patients with available CT measurements, 13 of 25 (52%) had >50% anteroposterior tracheal diameter reduction. Patients with >50% anteroposterior tracheal compression received sedation more frequently (p=0.047) and were positioned upright (p=0.015) compared with patients with ≤50% compression, although 4 of 13 and 9 of 12, respectively, still received GA. Intraoperative adverse events (AEs) occurred in four (11.4%) patients: three received GA, and all were positioned supine or lateral. AEs were not associated with radiographic airway risk factors but were significantly associated with morphine and sevoflurane use (p<0.001) and with thoracoscopic biopsies (p=0.035). There were no on-table mortalities, but four delayed deaths occurred (three related to disease and one from late procedural complications). Conclusions: In a current cohort of pediatric AMM biopsies, patients with >50% anteroposterior tracheal compression were more frequently managed with a conservative perioperative management strategy, though not completely excluding GA. The corresponding reduction in frequency of procedural AEs in this traditionally high-risk group suggests that increased awareness of procedural risk factors and appropriate risk-guided perioperative management choices may obviate the procedural mortality historically associated with pediatric AMM biopsies.

What is the potential for over-compression using current paediatric chest compression guidelines? - A chest computed tomography study.

AIM: We explored the potential for over-compression from current paediatric chest compression depth guidelines using chest computed tomography(CT) images of a large, heterogenous, Asian population. METHODS: A retrospective review of consecutive children, less than 18-years old, with chest CT images performed between from 2005 to 2017 was done. Demographic data were extracted from the electronic medical records. Measurements for internal and external anterior-posterior diameters (APD) were taken at lower half of the sternum. Simulated chest compressions were performed to evaluate the proportion of the population with residual internal cavity dimensions less than 0 mm (RICD < 0 mm, representing definite over-compression; with chest compression depth exceeding internal APD), and RICD less than 10 mm (RICD < 10 mm, representing potential over-compression). RESULTS: 592 paediatric chest CT studies were included for the study. Simulated chest compressions of one-third external APD had the least potential for over-compression; no infants and 0.3% children had potential over-compression (RICD < 10 mm). 4 cm simulated chest compressions led to 18% (95% CI 13%-24%) of infants with potential over-compression, and this increased to 34% (95% CI 27%-41%) at 4.4 cm (upper limit of "approximately" 4 cm; 4 cm + 10%). 5 cm simulated compressions resulted in 8% (95% CI 4%-12%) of children 1 to 8-years-old with potential over-compression, and this increased to 22% (95% CI 16%-28%) at 5.5 cm (upper limit of "approximately" 5 cm, 5 cm + 10%). CONCLUSION: In settings whereby chest compression depths can be accurately measured, compressions at the current recommended chest compression of approximately 4 cm (in infants) and 5 cm (in young children) could result in potential for over-compression.

Imaging of accidental paediatric head trauma.

Head trauma is the most common form of injury sustained in serious childhood trauma and remains one of the top three causes of death despite improved road planning and safety laws. CT remains the first-line investigation for paediatric head trauma, although MRI may be more sensitive at picking up the full extent of injuries and may be useful for prognosis. Follow-up imaging should be tailored to answer the specific clinical question and to look for possible complications.

Posterior retroperitoneoscopic adrenalectomy for pediatric adrenal tumors.

BACKGROUND/AIMS: Posterior retroperitoneoscoic adrenalectomy has been reported as an option for adrenal tumor resection but is not commonly performed in children owing to the extreme semikneeling position advocated to flatten the lumbar lordosis in order to achieve adequate retroperitoneal space. As children have smaller lordosis angles, flattening of the lordosis and creation of optimal retroperitoneal space may be achieved with less hip flexion. We used pediatric lumbar lordosis measurements to develop a modified prone jackknife position and report our experiences with this setup for posterior retroperitoneoscopic adrenalectomy for adrenal tumors. METHODS: Lordosis angles were measured on sagittal computed tomography (CT) and magnetic resonance imaging (MRI) studies of patients with adrenal tumors and compared to normal references. The data were used to develop our modified prone jackknife position. Selected patients with adrenal tumors underwent posterior retroperitoneoscopic adrenalectomy in this position. Patient demographics, diagnoses, operative times, complications, postop analgesia requirements, and length of hospitalization were analyzed. RESULTS: CT and MRI studies were analyzed for 20 patients with adrenal tumors diagnosed in our institution from 2012 to 2017; median lordosis angle was 27.84° (range: 15.50°-36.48°) - less than reference lordosis angles of respective age groups, and flexion angles of common operating tables. Five patients underwent retroperitoneoscopic adrenalectomy between June 2016 and June 2018. Histological diagnoses were neuroblastoma, adrenal hyperplasia, pheochromocytoma, and adrenal angiomatoid fibrous histiocytoma. Median age was 4 years [range: 1-11]. Median operating time was 137 min [range 111-181 min]. No conversions to open surgery were required. One patient had intraoperative bleeding from the adrenal vein. Only 1 patient required postoperative opioids for analgesia. Median length of hospitalization after surgery was 2 days (range: 2-3 days). CONCLUSIONS: Pediatric patients can achieve flattening of lumbar lordosis with less extreme positioning. Posterior retroperitoneoscopic adrenalectomy in a modified prone jackknife position is a feasible operation for pediatric patients with small adrenal masses. TYPE OF STUDY: Clinical research paper. LEVEL OF EVIDENCE: Level III.

Retroperitoneal tumors and congenital variations in vascular anatomy of retroperitoneal great vessels.

BACKGROUND/OBJECTIVES: Variations in vascular anatomy (VIVAs) of the retroperitoneal great vessels are uncommon but can potentially complicate surgical procedures and negatively affect treatment outcomes, yet their incidence and clinical impact are poorly studied. We sought to assess the incidence and clinical impact of VIVAs of retroperitoneal great vessels in patients with retroperitoneal tumors. METHODS: We retrospectively analyzed imaging, surgical, treatment and survival data of all pediatric patients with retroperitoneal tumors who underwent resection between January 2007 and October 2016, comparing preoperative scans with corresponding intraoperative observations, and subsequent surgical outcomes. RESULTS: Among 66 children with renal, adrenal and paravertebral tumors, 6 (9%) had retroperitoneal VIVAs. Retroperitoneal VIVAs were present only with right-sided tumors and significantly associated with more frequent intraoperative complications (P = 0.013). While the presence of retroperitoneal VIVAs was not directly associated with survival outcomes, relapse was more frequent in patients with VIVAs (33%) than those without (18.3%, P = 0.378), and relapse was also associated with lower overall and event-free survival (P < 0.001). CONCLUSIONS: VIVAs of retroperitoneal great vessels occurred in 9% of our patients with retroperitoneal tumors. Retroperitoneal VIVAs were associated with higher rates of intraoperative complications and disease relapse but was not directly related to survival outcomes. TYPE OF STUDY: Retrospective review study. LEVEL OF EVIDENCE: Level III Retrospective comparative study.

Superior sagittal sinus thrombosis: subtle signs on neuroimaging.

INTRODUCTION: The aim of this study was to review the clinical, computed tomography (CT) and magnetic resonance imaging (MRI) diagnosis and the frequency of positive neuroimaging findings in patients with cerebral venous thrombosis (CVT) involving the superior sagittal sinus. MATERIALS AND METHODS: A clinical and radiological database of patients with final diagnosis of CVT was compiled from the inpatient hospital information service of a tertiary neurological hospital over 5 years. CT and MRI studies in 22 patients were retrospectively examined for direct signs of venous sinus thrombosis and for complications of CVT. The diagnosis of CVT before and after CT and MRI was reviewed. RESULTS: Clinical diagnosis of possible CVT was suspected in only 1 patient. When the diagnosis was not suspected, CT diagnosis was difficult and there was a high false negative rate of 52.6%. MRI fared better, but the false negative rate was still 11%. Directs signs of venous sinus thrombosis such as the triangle sign, empty delta sign on CT and loss of the normal flow voids on MRI, could be retrospectively detected in 57.9%, 100% and 100% of patients respectively. Although 4 patients presented with subarachnoid haemorrhage, these direct signs were present in 3 patients. CONCLUSION: Clinical diagnosis of CVT is rarely suspected before CT and MRI, and although subtle positive signs are often present, these may not be appreciated unless there is a high index of suspicion or image review at multidisciplinary team meetings.

Altered Sensory Insular Connectivity in Chronic Postsurgical Pain Patients.

Chronic postsurgical pain (CPSP) occurs in up to 50% of individuals after surgeries and 32% after hysterectomy, leading to major adverse effects on quality of life and socioeconomic burden. Little is known about whether and how large-scale neural networks being affected in CPSP, particularly with regard to the functional connectivity (FC) of insula which is known to be the hub of the intrinsic neural network playing a critical role in pain processing. Here, we sought to examine the dynamics of insular FC in the context of noxious stimuli in CPSP patients. To this aim, resting state fMRI data were acquired, before and after acute heat pain stimulation, from 11 individuals with chronic post-hysterectomy pain (CPHP) and 22 age-matched healthy controls (HCs) who had a hysterectomy but without chronic post-surgical pain. We examined whole-brain FC were mapped by seeding at the sensorimotor and chemosensory subfields of the insula and found significant group × stimulation interaction effects. Specifically, the HC group had increased FC between the left sensorimotor insula and right angular and middle occipital gyrus (MOG) and increased FC between the left chemosensory insula and bilateral angular and MOG following pain stimulation. In contrast, such pain stimulation related FC changes were absent in the CPHP group. Furthermore, higher insular FC at baseline and smaller increased insular FC after pain stimulation correlated with clinical pain scores in CPHP patients. Our findings suggest that CPSP is associated with altered dynamics of large-scale functional networks anchored in the insula.