SUMMARY: Diffuse leptomeningeal glioneuronal tumor is a newly defined entity under the neuronal and mixed neuronal-glial tumors category in the 2016 World Health Organization classification of brain tumors. In this series, we report clinical, radiologic, and histologic findings in 7 cases of diffuse leptomeningeal glioneuronal tumor. Our cases and literature review indicate that the most characteristic imaging finding is diffuse intracranial and intraspinal nodular leptomeningeal thickening and enhancement. This is often associated with small cyst-like, nonenhancing lesions. It should be noted that tumors sometimes bear nontypical features, for example, presenting as a solitary spinal cord mass without leptomeningeal involvement or with a dominant intracranial mass. In children with characteristic imaging findings and without clinical features of infection, the radiologist has an opportunity to promptly raise the possibility of diffuse leptomeningeal glioneuronal tumor, and thereby, affect streamlined diagnostic evaluation.

Glioblastoma (GBM) is the most common primary intracranial malignant tumor and consists of three molecular subtypes: proneural (PN), mesenchymal (MES) and classical (CL). Transition between PN to MES subtypes (PMT) is the glioma analog of the epithelial‐mesenchymal transition (EMT) in carcinomas and is associated with resistance to therapy. CXCR4 signaling increases the expression of MES genes in glioma cell lines and promotes EMT in other cancers. RNA sequencing (RNAseq) data of PN GBMs in The Cancer Genome Atlas (TCGA) and secondary high‐grade gliomas (HGGs) from an internal cohort were examined for correlation between CXCR4 expression and survival as well as expression of MES markers. Publicly available single‐cell RNA sequencing (scRNAseq) data was analyzed for cell type specific CXCR4 expression. These results were validated in a genetic mouse model of PN GBM. Higher CXCR4 expression was associated with significantly reduced survival and increased expression of MES markers in TCGA and internal cohorts. CXCR4 was expressed in immune and tumor cells based on scRNAseq analysis. Higher CXCR4 expression within tumor cells on scRNAseq was associated with increased MES phenotype, suggesting a cell‐autonomous effect. In a genetically engineered mouse model, tumors induced with CXCR4 exhibited a mesenchymal phenotype and shortened survival. These results suggest that CXCR4 signaling promotes PMT and shortens survival in GBM and highlights its inhibition as a potential therapeutic strategy.

Introduction: Computed tomography angiography (CTA) is used to screen patients for cerebrovascular injury after blunt trauma, but risk factors are not clearly defined in children. This modality has inherent radiation exposure. We set out to better delineate the risk factors associated with blunt cervical vascular injury (BCVI) in children with attention to the predictive value of seatbelt sign of the neck. Methods: We collected demographic, clinical and radiographic data from the electronic medical record and a trauma registry for patients less than age 18 years who underwent CTA of the neck in their evaluation at a Level I trauma center from November 2002 to December 2014 (12 years). The primary outcome was BCVI. Results: We identified 11,446 pediatric blunt trauma patients of whom 375 (2.7%) underwent CTA imaging. Fifty-three patients (0.4%) were diagnosed with cerebrovascular injuries. The average age of patients was 12.6 years and included 66% males. Nearly half of the population was white (52%). Of those patients who received CTA, 53 (14%) were diagnosed with arterial injury of various grades (I-V). We created models to evaluate factors independently associated with BCVI. The independent predictors associated with BCVI were Injury Severity Score >/= 16 (odds ratio [OR] [2.35]; 95% confidence interval [CI] [1.11-4.99%]), infarct on head imaging (OR [3.85]; 95% CI [1.49-9.93%]), hanging mechanism (OR [8.71]; 95% CI [1.52-49.89%]), cervical spine fracture (OR [3.84]; 95% CI [1.94-7.61%]) and basilar skull fracture (OR [2.21]; 95% CI [1.13-4.36%]). The same independent predictors remained associated with BCVI when excluding hanging mechanism from the multivariate regression analysis. Seatbelt sign of the neck was not associated with BCVI (p=0.68). Conclusion: We have found independent predictors of BCVI in pediatric patients. These may help in identifying children that may benefit from screening with CTA of the neck.

Background: Orthostatic headaches can be noted in spontaneous intracranial hypotension and orthostatic intolerance. We present a case series of young patients diagnosed with spontaneous intracranial hypotension and were treated for the same but subsequently developed orthostatic intolerance. Methods: We retrospectively reviewed charts for seven young patients with orthostatic headaches related to spontaneous intracranial hypotension and orthostatic intolerance. Results: Patients were diagnosed with spontaneous intracranial hypotension. Diagnosis was confirmed by identifying epidural contrast leakage and three of seven patients were noted to have early renal contrast excretion on computerized tomography myelography. Patients were treated with epidural blood patches. All patients showed persistent symptoms of autonomic dysfunction after treatment of spontaneous intracranial hypotension and orthostatic intolerance was confirmed with head-up tilt table test. Conclusions: Patients with spontaneous intracranial hypotension failing to improve following epidural blood patching should be evaluated for orthostatic intolerance.