Characterization of aberrant splicing in pediatric central nervous system tumors reveals as a candidate oncogenic dependency.

Pediatric brain cancer is the leading cause of disease-related mortality in children, and many aggressive tumors still lack effective treatment strategies. We characterized aberrant alternative splicing across pediatric brain tumors, identifying pediatric high-grade gliomas (HGGs) among the most heterogeneous. Annotating these events with UniProt, we identified 11,940 splice events in 5,368 genes leading to potential protein function changes.

Intracranial complications secondary to acute bacterial sinusitis requiring neurosurgical intervention before and after the onset of the COVID-19 pandemic.

Objective: Intracranial complications of acute bacterial sinusitis are rare pathologies that occur in children, and are associated with significant neurological morbidity and mortality. There is a subjective concern among neurosurgeons that the incidence of this rare disease has increased since the onset of the novel COVID-19 pandemic. The primary objective of this study was to review the presentation and management of patients admitted at the authors' institution with intracranial extension of sinusitis, to better understand the local disease burden relative to the COVID-19 pandemic.

Primary intraosseous xanthoma of the frontal bone in a child: illustrative case.

Background: Skull lesions are a common finding in children, with dermoid cysts and eosinophilic granulomas observed most frequently. However, primary intraosseous xanthomas of the calvaria, which are lytic, expansile lesions that develop without underlying hyperlipidemic disease, are rare in children, with only one prior case reported.

Observations: The authors describe the case of a healthy 6-year-old male who presented with a 2-month history of an enlarging midline skull mass that developed after a recent minor trauma.

Use of a machine learning algorithm with a focus on spinopelvic parameters to predict development of symptomatic tethered cord after initial untethering surgery.

Objective: Among patients with a history of prior lipomyelomeningocele repair, an association between increased lumbosacral angle (LSA) and cord retethering has been described. The authors sought to build a predictive algorithm to determine which complex tethered cord patients will develop the symptoms of spinal cord retethering after initial surgical repair with a focus on spinopelvic parameters.

Methods: An electronic medical record database was reviewed to identify patients with complex tethered cord (e.

Burr Hole Hemispherotomy-Modification of Trans-Sylvian Peri-Insular Technique: 2-Dimensional Operative Video.

Trans-sylvian peri-insular hemispherotomy represents a functional hemispherectomy with minimal brain removal used for treatment of refractory hemispheric epilepsy.1 Exposure for this procedure is achieved by craniotomy. Refinement in the hemispherotomy technique, including trends toward minimizing cortical resection, has contributed to a substantial drop in complication rates.

Technical note: Traumatic atlanto-occipital dislocation and severe subaxial cervical distraction injury in an infant.

Introduction: Traumatic injuries of the spine requiring surgery are rare in infancy. Fusion procedures in the very young are not well-described at the atlanto-occipital junction or subaxial spine. Here we describe novel segmental posterior instrumentation in a severe spinal column disruption in an infant.

Systematic review and cumulative analysis of clinical properties of BRAF V600E mutations in PLNTY histological samples.

Purpose: Polymorphous low-grade neuroepithelial tumors of the young (PLNTY) represent a rare pediatric-type tumor that most commonly presents as medically refractory epilepsy. PLNTY has only recently been recognized as a distinct clinical entity, having been first described in 2016 and added to the World Health Organization classification of CNS tumors in 2021. Molecular studies have determined that PLNTY is uniformly driven by aberrant MAPK pathway activation, with most tumors carrying either a BRAF V600E mutation or activating FGFR2 or FGFR3 fusion protein.

Invasive Multimodality Neuromonitoring to Manage Cerebral Edema in Pediatric Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory disorder of the CNS with a variety of clinical manifestations, including cerebral edema.

Case Summary: A 7-year-old boy presented with headaches, nausea, and somnolence. He was found to have cerebral edema that progressed to brainstem herniation.

Middle meningeal artery embolization in the management of chronic subdural hematoma in medically complex pediatric neurosurgical patients: technical note.

Middle meningeal artery (MMA) embolization has gained acceptance as a treatment for chronic subdural hematoma (cSDH) in adult patients but has not been well described in pediatric patients. Standard cSDH treatment has historically consisted of burr hole drainage with or without subdural drain placement. However, due to the high rate of recurrence and frequency of comorbidities within this population, as both pediatric and adult patients with cSDH frequently have concurrent cardiac disease and a need for anticoagulant therapies, MMA embolization has increasingly demonstrated its value as both an adjunctive and primary treatment.

Dramatic Response to Anti-IL-6 Receptor Therapy in Children With Life-Threatening Myelin Oligodendrocyte Glycoprotein-Associated Disease.

Objectives: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an immune-mediated neuroinflammatory disorder leading to demyelination of the CNS. Interleukin (IL)-6 receptor blockade is under study in relapsing MOGAD as a preventative strategy, but little is known about the role of such treatment for acute MOGAD attacks.

Methods: We discuss the cases of a 7-year-old boy and a 15-year-old adolescent boy with severe acute CNS demyelination and malignant cerebral edema with early brain herniation associated with clearly positive serum titers of MOG-IgG, whose symptoms were incompletely responsive to standard acute therapies (high-dose steroids, IV immunoglobulins (IVIGs), and therapeutic plasma exchange).

OpenPBTA: The Open Pediatric Brain Tumor Atlas.

Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, the Children's Brain Tumor Network (CBTN) and Pacific Pediatric Neuro-Oncology Consortium (PNOC) created a systematic process for tumor biobanking, model generation, and sequencing with immediate access to harmonized data. We leverage these data to establish OpenPBTA, an open collaborative project with over 40 scalable analysis modules that genomically characterize 1,074 pediatric brain tumors.

Diffuse leptomeningeal glioneuronal tumor in a child masquerading as an intramedullary spinal pilocytic astrocytoma.

Diffuse leptomeningeal glioneuronal tumor (DLGNT) occurs predominantly in children and is typically characterized by diffuse leptomeningeal lesions throughout the neuroaxis with focal segments of parenchymal involvement. Recent reports have identified cases without diffuse leptomeningeal involvement that retain classic glioneuronal features on histology. In this report, we present a case of a 4-year-old boy with a large cystic-solid intramedullary spinal cord lesion that on surgical biopsy revealed a biphasic astrocytic tumor with sparsely distributed eosinophilic granular bodies and Rosenthal fibers.

Intracranial Cannula Implantation for Serial Locoregional Chimeric Antigen Receptor (CAR) T Cell Infusions in Mice.

Pediatric CNS tumors are responsible for the majority of cancer-related deaths in children and have poor prognoses, despite advancements in chemotherapy and radiotherapy. As many tumors lack efficacious treatments, there is a crucial need to develop more promising therapeutic options, such as immunotherapies; the use of chimeric antigen receptor (CAR) T cell therapy directed against CNS tumors is of particular interest. Cell surface targets such as B7-H3, IL13RA2, and the disialoganglioside GD2 are highly expressed on the surface of several pediatric and adult CNS tumors, raising the opportunity to use CAR T cell therapy against these and other surface targets.

Preprocedural Electrophysiological Monitoring in Craniofacial Surgery for a Patient with Chiari Malformation.

Head and neck positioning is a key element of craniofacial reconstructive surgery and can become challenging when intervention necessitates broad exposure of the calvarium. We present a case of craniosynostosis secondary to Apert's syndrome requiring anterior and posterior cranial vault access during surgical correction. A modified sphinx position was used that required significant neck extension.

Stereoelectroencephalography before 2 years of age.

Objective: Stereoelectroencephalography (SEEG) is a widely used technique for localizing seizure onset zones prior to resection. However, its use has traditionally been avoided in children under 2 years of age because of concerns regarding pin fixation in the immature skull, intraoperative and postoperative electrode bolt security, and stereotactic registration accuracy. In this retrospective study, the authors describe their experience using SEEG in patients younger than 2 years of age, with a focus on the procedure's safety, feasibility, and accuracy as well as surgical outcomes.

Development of GPC2-directed chimeric antigen receptors using mRNA for pediatric brain tumors.

Background: Pediatric brain tumors are the leading cause of cancer death in children with an urgent need for innovative therapies. Glypican 2 (GPC2) is a cell surface oncoprotein expressed in neuroblastoma for which targeted immunotherapies have been developed. This work aimed to characterize GPC2 expression in pediatric brain tumors and develop an mRNA CAR T cell approach against this target.

Thoracic spinal arachnoid cyst in a pediatric patient presenting with isolated bladder and bowel incontinence.

Spinal arachnoid cysts (SAC) are uncommon benign spinal cord lesions, particularly in children, that can result in a variety of neurologic symptoms, including neurogenic bladder. Here we present the case of a 7-year-old female with new onset, isolated urinary and stool incontinence who was found to have a T4-T7 SAC. Though this was initially believed to be an incidental imaging finding, after thorough work-up and persistence of her symptoms despite conservative measures she underwent neurosurgical intervention with complete resolution of incontinence.

Surgical management and outcomes of intracranial metastatic Wilms' tumor in the pediatric population: a case series.

Purpose: Approximately 1 to 2% of patients with Wilms' tumor (WT), or nephroblastoma, will have metastasis to the brain. Due to the rarity of intracranial metastasis, the clinical characteristics, prognosis, and a standardized treatment approach to this occurrence remain poorly understood. Here we review the surgical management and treatment outcome of WT patients with intracranial metastasis at our institution.

Pediatric Pituitary Surgery.

Lesions of the pituitary and sellar region in children comprise a wide variety of pathologic conditions, but advances in surgical technology and techniques have enabled both biopsy and resection of such lesions despite age-dependent anatomic constraints. In this article, the authors discuss the common pathologic conditions encountered, perioperative management of these patients, surgical techniques required to address these lesions and repair the pediatric skull base, points of controversy, and future areas of work.

Parietal bone thickness for predicting operative transfusion and blood loss in patients undergoing spring-mediated cranioplasty for nonsyndromic sagittal craniosynostosis.

Objective: Variables that can predict outcomes in patients with craniosynostosis, including bone thickness, are important for surgical decision-making, yet are incompletely understood. Recent studies have demonstrated relative risks and benefits of surgical techniques for correcting head shape in patients with nonsyndromic sagittal craniosynostosis. The purpose of this study was to characterize the relationships between parietal bone thickness and perioperative outcomes in patients who underwent spring-mediated cranioplasty (SMC) for nonsyndromic sagittal craniosynostosis.

Urgent Neurosurgical Interventions in the COVID-19-Positive Pediatric Population.

Background: Urgent neurosurgical interventions for pediatric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are rare. These cases pose additional stress on a potentially vulnerable dysregulated inflammatory response that can place the child at risk of further clinical deterioration. Our aim was to describe the perioperative course of SARS-CoV-2-positive pediatric patients who had required an urgent neurosurgical intervention.

Development of an Intraoperative Pipeline for Holographic Mixed Reality Visualization During Spinal Fusion Surgery.

. Holographic mixed reality (HMR) allows for the superimposition of computer-generated virtual objects onto the operator's view of the world. Innovative solutions can be developed to enable the use of this technology during surgery.