Low-grade gliomas are the most common intracranial tumor in the pediatric population. Pediatric low-grade gliomas represent a heterogeneous group of tumors. Genetic alterations that result in upregulation of the MAPK/ERK pathway represent most of the genetic landscape of pediatric low-grade gliomas. BRAF-V600E mutant pediatric low-grade gliomas may represent a unique and aggressive subset of tumors that require targeted therapy especially if gross total resection is not feasible. Many patients with pediatric low-grade gliomas have demonstrated successful clinical and radiological responses to BRAF and/or MEK inhibitors. Given the high proportion of patients who fail to respond to the current standard chemotherapy and radiotherapy, these targeted therapies should be considered in future trials and further investigations. In this review of the literature, we summarize the molecular status of BRAF alterations among patients with pediatric low-grade gliomas and provide an update on previous and current BRAF and MEK inhibitors clinical trials.

Cranial sutures are fibrous joints between the bones of the cranial vault, acting as centers of osteogenesis of the embryonic mesenchyme. Skull growth is a strictly regulated process, controlled by several genetic pathways. A minor perturbation of these pathways may lead to premature fusion of the cranial sutures. Craniosynostosis occurs as a result of the premature fusion of the cranial sutures. The incidence of craniosynostosis is approximately 1 in 2,500 live births. Syndromic craniosynostoses such as Apert, Crouzon, and Pfeiffer comprise 15% of patients, while nonsyndromic craniosynostosis represents 85% of all patients. By the late 1800s, Lannelongue (Paris, 1890) and Lane (San Francisco, 1892) attempted the first surgical intervention (strip craniectomy) for the management of craniosynostosis. The inadequacy of simple suturectomies and strip craniectomies in the management of craniosynostosis led to the innovation of more complex procedures such as fronto-orbital advancement and posterior cranial vault distraction. However, these extensive surgical interventions are lengthy procedures and associated with more blood volume loss which requires blood transfusion. These limitations led to the modern era of minimally invasive endoscopic techniques. In this paper, we reviewed the body of the literature on the evolution of surgical management of craniosynostosis over the last century and the possible future directions.

Meningiomas are the most common intracranial tumors, predominantly affecting adults, with a higher incidence in female and elderly populations. Despite their prevalence, research on neurocognitive impairment in meningioma patients remains limited compared to intra-axial tumors such as gliomas. We conducted a comprehensive systematic review of the current literature on neurocognitive outcomes in meningioma patients pre- and post-surgery. Our review revealed significant disparities in reported neurocognitive outcomes, with prospective studies suggesting tumor-related factors as the primary contributors to postoperative deficits, while retrospective studies imply surgical intervention plays a significant role. Regardless of study design or specifics, most studies lack baseline preoperative neurocognitive assessments and standardized protocols for evaluating neurocognitive function. To address these gaps, we advocate for standardized neurocognitive assessment protocols, consensus on neurocognitive domains to be targeted in this population by tailored test batteries, and more prospective studies to elucidate correlations between tumor characteristics, patient attributes, surgical interventions, neurocognitive status, and planning for implementing tailored neurocognitive rehabilitation strategies early in the postoperative course which is crucial for achieving optimal long-term neurocognitive outcomes and enhancing patients' quality of life.

Abstract Craniopharyngioma is a rare epithelial brain tumor which arises from the embryological remnants of Rathke's pouch—a remnant of the primitive pharynx. The proximity of this tumor to the pituitary stalk, hypothalamus, third ventricle, optic chiasm, and optic nerves, as well as the major intracranial vessels bridging this area, makes safe surgical resection challenging. Given the recent advancement in endoscopic surgical techniques and the intraoperative assistance of neuronavigation and intraoperative magnetic resonance imaging, endoscopic endonasal transsphenoidal surgery (EETS) can be an alternative to the open transcranial approaches in the management of children with craniopharyngioma who fulfill the appropriate selection criteria. The comparison between the EETS and the open transcranial approach regarding the clinical and surgical outcomes could be subject to an inherent selection bias. In this article, we reviewed the body of the literature on the role of EETS in the management of pediatric craniopharyngioma and the proper selection criteria of children with craniopharyngioma, who might be suitable candidates for tumor resection via this minimally invasive endoscopic approach. We also looked at the preoperative assessment, surgical techniques, surgical and clinical outcomes, and the possible complications of endoscopic endonasal transsphenoidal surgery.

Cranial irradiation is associated with several adverse events such as endocrinopathy, growth retardation, neurocognitive impairment, secondary malignancies, cerebral vasculopathy, and potential stroke. The better side effects profile of proton beam therapy compared with that of photon radiation therapy is due to its physical properties, mainly the sharp dose fall-off after energy deposition in the Bragg peak. Despite the better toxicity profile of proton beam therapy, the risk of moyamoya syndrome still exists. We conducted a systematic review of the existing literature on moyamoya syndrome after receiving cranial radiation therapy for pediatric brain tumors to investigate the incidence of moyamoya syndrome after receiving photon versus proton radiation therapy. In this review, we report that the incidence of moyamoya syndrome after receiving proton beam therapy is almost double that of photon-induced moyamoya syndrome. Patients who received proton beam therapy for the management of pediatric brain tumors are more likely to develop moyamoya syndrome at the age of less than 5 years. Meanwhile, most patients with proton-induced moyamoya are more likely to be diagnosed within the first 2 years after the completion of their proton beam therapy.

Meningioma is the most common primary brain tumor in adults. Patients may become symptomatic due to the resultant mass effect and the peritumoral vasogenic edema. The majority of existing research on neurocognitive impairment in patients with brain tumors has focused on gliomas while less research has been conducted on the effects of tumor and/or surgical intervention on neurocognitive function in patients with meningioma. We conducted a prospective study on the utilization of the Cogmed Working Memory Training (CWMT) program in patients who underwent surgical resection of WHO grade I intracranial meningioma and experienced neurocognitive impairment after surgery. All patients had a significant improvement in their post-CWMT neurocognitive function evaluation compared to their baseline post-surgical neurocognitive evaluation, and the improvement was maintained at a three-month follow-up. This study is the first to evaluate the effectiveness of a neurocognitive rehabilitation program in augmenting the neurocognitive functioning of patients with Intracranial WHO Grade I Meningioma. The results of this study demonstrate the efficacy of the CWMT program in improving postoperative impaired neurocognitive function and potentially improving the quality of life of our patients.

Distraction osteogenesis is utilized to increase intracranial volume in the treatment of restrictive pathologies, most commonly syndromic synostosis. Children too young for open calvarial vault expansion or other systemic or local contraindications to a direct reconstructive approach benefit greatly from distraction osteogenesis, typically addressing posterior vault expansion. Wound infection, cerebrospinal fluid (CSF) leak, device failure, need for a second surgery for removal, and cost, are issues that can limit the use of this approach. These challenges are more pronounced in low- and middle-income countries (LMICs) due to lack of access to the device, the financial burden of the need for a second surgery, and the severity of the implications of infection and CSF leak. Over the last five decades, there has been an increased acceptance of bioresorbable instrumentation in craniofacial surgery. Poly L-lactic acid, polyglycolic acid, and polydioxanone are the most commonly used polymers. New resorbable fixation tools such as ultrasound-activated pins and heat-activated pins are superior to conventional bioresorbable screws in allowing attachment to thinner bone plates. In this paper, we present a review of the literature on cranial vault distraction and the use of bioresorbable materials and propose a novel design of a fully absorbable cranial distractor system using external magnetic distraction control, eliminating the need for external activation ports and a second surgery to remove the hardware. The application of this technology in LMIC settings could advance access to care and treatment options for patients with syndromic synostosis.

Cerebral palsy (CP) is the most common cause of physical disability for children worldwide. Many infants and toddlers are not diagnosed with CP until they fail to achieve obvious motor milestones. Currently, there are no effective pharmacologic interventions available for infants and toddlers to substantially improve their trajectory of neurodevelopment. Because children with CP from preterm birth also exhibit a sustained immune system hyper-reactivity, we hypothesized that neuro-immunomodulation with a regimen of repurposed endogenous neurorestorative medications, erythropoietin (EPO) and melatonin (MLT), could improve this trajectory. Thus, we administered EPO + MLT to rats with CP during human infant-toddler equivalency to determine whether we could influence gait patterns in mature animals. After a prenatal injury on embryonic day 18 (E18) that mimics chorioamnionitis at ∼25 weeks human gestation, rat pups were born and raised with their dam. Beginning on postnatal day 15 (P15), equivalent to human infant ∼1 year, rats were randomized to receive either a regimen of EPO + MLT or vehicle (sterile saline) through P20. Gait was assessed in young adult rats at P30 using computerized digital gait analyses including videography on a treadmill. Results indicate that gait metrics of young adult rats treated with an infantile cocktail of EPO + MLT were restored compared to vehicle-treated rats (p < 0.05) and similar to sham controls. These results provide reassuring evidence that pharmacological interventions may be beneficial to infants and toddlers who are diagnosed with CP well after the traditional neonatal window of intervention.

Rhombencephalosynapsis is a rare congenital anomaly, characterized by partial or total agenesis of the cerebellar vermis with midline fusion of the cerebellar hemispheres, dentate nuclei, and the superior cerebellar peduncles, creating the distinctive keyhole appearance of the fourth ventricle. Rhombencephalosynapsis can be isolated or can occur in association with other congenital anomalies and syndromes such as Gómez-López-Hernández syndrome (GLHS) or VACTERL: vertebral anomalies (V), anal atresia (A), cardiovascular defects (C), esophageal atresia and/or tracheoesophageal fistula (TE), and renal (R) and limb/radial (L) anomalies. Recent advances in prenatal imaging have resulted in an increasing rate of prenatal diagnosis of abnormalities of the posterior fossa including rhombencephalosynapsis. Patients with rhombencephalosynapsis may present with motor developmental delay, ataxia, swallowing difficulties, muscular hypotonia, spastic quadriparesis, abnormal eye movements, and a characteristic "figure-of-eight" head shaking. Cognitive outcome varies from severe intellectual disability to normal intellectual function. Rhombencephalosynapsis with VACTERL is often associated with severe cognitive disabilities, whereas patients with GLHS may have better cognitive function. The most common associated findings with rhombencephalosynapsis include hydrocephalus, mesencephalosynapsis, holoprosencephaly, pontocerebellar hypoplasia, corpus callosum dysgenesis, and absence of septum pellucidum. Patients can be categorized into 4 groups: 1) rhombencephalosynapsis associated with GLHS; 2) rhombencephalosynapsis with VACTERL; 3) rhombencephalosynapsis with atypical holoprosencephaly, and 4) isolated rhomboencephalosynapsis. The etiology of rhombencephalosynapsis is unknown. Here, we discuss several hypotheses about its etiology.

The use of touchscreen technology to evaluate cognitive deficits in animal models has grown tremendously over the past 20 years. The touchscreen apparatus encompasses many advantages, namely a high level of standardization and translational capability. Improvements in technology in recent years have expanded the versatility of the touchscreen platform, as it is able to test distinct cognitive modalities including working memory, attention, discrimination, and association. Importantly, touchscreen technology has allowed researchers to explore deficits in multiple pillars of cognition in a wide variety of perinatal disorders with neurological sequelae across critical developmental windows. The touchscreen platform has been used to dissect deficits in antenatal CNS injury including fetal alcohol syndrome, prenatal opioid exposure, and chorioamnionitis, to peripartum insults such as term hypoxic-ischemic encephalopathy, to early postnatal insults including infantile traumatic brain injury. Most importantly, touchscreen technology offers the sensitivity necessary to detect subtle injury and treatment induced changes in cognition and executive function beyond those offered by more rudimentary tests of rodent cognition. Understanding the pathophysiology of these disorders in rodents is paramount to addressing these deficits in human infants and dissecting the neural circuitry essential to perinatal brain injury pathophysiology and responsiveness to novel therapeutics. Touchscreen testing provides an effective, facile, sophisticated technique to accelerate the goal of improving cognitive and behavioral outcomes of children who suffer perinatal brain injury.

Introduction Multiple studies have shown a decrease in the inflammatory response with minimized bypass circuits leading to less complications and mortality rate. On the other hand, some other studies showed that there is no difference in post-operative outcomes. So, the aim of this study is to investigate the clinical benefits of using the Minimized cardiopulmonary Bypass system in Coronary Artery Bypass Grafting and its effect on postoperative morbidity and mortality in diabetic patients as one of the high-risk groups that may benefit from these systems. Methods This is a retrospective study that included 114 diabetic patients who underwent Coronary artery bypass grafting (67 patients with conventional cardiopulmonary bypass system and 47 with Minimized cardiopulmonary bypass system). The patients' demographics, intra-operative characteristics and postoperative complications were compared between the two groups. Results Coronary artery bypass grafting was done on a beating heart less commonly in the conventional cardiopulmonary bypass group (44.78% vs. 63.83%, p = 0.045). There was no difference between the two groups in blood loss or transfusion requirements. Four patients in the conventional cardiopulmonary bypass group suffered perioperative myocardial infarction while no one had perioperative myocardial infarction in the Minimized cardiopulmonary bypass group. On the other hand, less patients in the conventional group had postoperative Atrial Fibrillation (4.55% vs. 27.5%, p = 0.001). The requirements for Adrenaline and Nor-Adrenaline infusions were more common the conventional group than the Minimized group. Conclusion The use of conventional cardiopulmonary bypass for Coronary Artery Bypass Grafting in diabetic patients was associated with higher use of postoperative vasogenic and inotropic support. However, that did not translate into higher complications rate or mortality.

OBJECTIVE The goal in this study was to outline unique differences between radiation-induced and nonradiation-induced pediatric meningiomas and to identify independent risk factors of tumor recurrence/progression. METHODS This is a retrospective cohort study of all pediatric meningiomas diagnosed and surgically treated at the authors' institution between 1993 and 2017. Multivariable Cox regression was applied to identify independent risk factors for tumor recurrence/progression. RESULTS Thirty-five patients were identified. The primary etiology was nonradiation-induced (n = 24: n = 3 with neurofibromatosis type 2) or radiation-induced (n = 11: acute lymphoblastic leukemia [n = 5], medulloblastoma [n = 4], germ cell tumor [n = 1], and primitive neuroectodermal tumor [n = 1]) meningioma. The mean age at time of diagnosis was 10.7 ± 5.7 years for nonradiation-induced and 17.3 ± 3.5 years for radiation-induced meningiomas. Overall, 8/24 patients with nonradiation-induced meningioma experienced either recurrence or progression of the tumor. Of the 8 patients with tumor recurrence or progression, the pathological diagnosis was clear cell meningioma (n = 3: 2 recurrent and 1 progressive); grade I (n = 2 progressive); grade I with atypical features (n = 2: 1 recurrent and 1 progressive); or atypical meningioma (n = 1 recurrent). None of the patients with radiation-induced meningioma experienced recurrence or progression. Predictors of tumor recurrence/progression by univariate analysis included age at time of diagnosis ≤ 10 years (p = 0.002), histological subtype clear cell meningioma (p = 0.003), and primary etiology nonradiation-induced meningioma (p = 0.04), and there was a notable trend with elevated MIB-1 staining index (SI) (p = 0.09). There was no significant difference between nonradiation-induced and radiation-induced meningiomas (p = 0.258), although there was a trend between recurrent and nonrecurrent meningiomas (p = 0.09). Multivariate Cox regression, adjusted for length of follow-up, identified younger age at diagnosis (p = 0.004) and a higher MIB-1 SI (p = 0.044) as independent risk factors for recurrence. Elevated MIB-1 SI statistically correlated with atypia (p < 0.001). However, there was no significant statistical correlation between tumor recurrence/progression and atypia (p = 0.2). CONCLUSIONS Younger patient age and higher MIB-1 SI are independent risk factors for recurrence. Atypia was not a predictor of recurrence.

BACKGROUND:The advancement of endoscopic techniques in the past decade has improved the surgical management of cerebellopontine angle (CPA) tumors. Endoscope-assisted microsurgery improves the ability to evaluate the extent of resection, achieve safe tumor resection and reduce the risk of surgery-related morbidity.METHODS:In this study, we used a cadaveric model to demonstrate a step by step endoscope-assisted microsurgery of the retrosigmoid approach to the lateral posterior fossa.RESULTS:Retrosigmoid craniotomies were performed on four latex-injected cadaver heads (eight CPAs). Microsurgical exposures were performed to identify neurovascular structures in each segment. 0° and 30° rigid endoscope lenses were subsequently introduced into each corridor and views were compared in this manner. The endoscopic images were compared with the standard microscopic views to determine the degree of visualization with each technique. In each case, better visualization was provided by both the 0° and 30° endoscope lenses. Endoscopic views frequently clarified neurovascular relationships in obscured anatomic regions.CONCLUSION:Endoscope-assisted microsurgery could allow better visualization of various regions of the posterior fossa. Surgical planning for posterior fossa lesions should include consideration of this combined approach.

OBJECTIVE The goal of this study was to identify the independent risk factors for recurrence or progression of pediatric craniopharyngioma and to establish predictors of the appropriate timing of intervention and best management strategy in the setting of recurrence/progression, with the aim of optimizing tumor control. METHODS This is a retrospective cohort study of all pediatric patients with craniopharyngioma who were diagnosed and treated at Boston Children's Hospital between 1990 and 2017. This study was approved by the institutional review board at Boston Children's Hospital. All statistical analyses were performed using Stata software. RESULTS Eighty patients (43 males and 37 females) fulfilled the inclusion criteria. The mean age at the time of diagnosis was 8.6 ± 4.4 years (range 1.2-19.7 years). The mean follow-up was 10.9 ± 6.5 years (range 1.3-24.6 years). Overall, 30/80 (37.5%) patients developed recurrence/progression. The median latency to recurrence/progression was 12.75 months (range 3-108 months). Subtotal resection with no adjuvant radiotherapy (p < 0.001) and fine calcifications (p = 0.008) are independent risk factors for recurrence/progression. An increase (%) in the maximum dimension of the tumor at the time of recurrence/progression was considered a statistically significant predictor of the appropriate timing of intervention. CONCLUSIONS Based on the identified independent risk factors for tumor recurrence/progression and the predictors of appropriate timing of intervention in the setting of recurrence/progression, the authors propose an algorithm for optimal management of recurrent pediatric craniopharyngioma to increase the likelihood of tumor control.

Access to deep-seated brain lesions (e.g., tumors, aneurysms, hematomas, and other malformations) is challenging due to the potential for retraction-induced injury. Traditionally, neurosurgeons use dissection and blade retractors to push apart tissue to visualize and operate on target lesions. These blades apply focal pressure onto the brain, resulting in ischemia, edema, and parenchymal trauma, leading to complications in up to 29% of cases. Tubular retractors were introduced to distribute forces radially and have led to improved safety and clinical outcomes. However, reports indicate that tubular retractors still led to complications in up to 9.1% of cases. Other concerns include significant pressure in the direction of insertion and the displacement of anatomic landmarks leading to inaccurate stereotaxis. We present a novel, minimally-invasive brain retractor that utilizes an expandable soft balloon to further reduce retraction-induced injury and increase stereotactic accuracy with a minimal port of entry. The device consists of a balloon catheter system, a clear sheath, and integration with neuronavigation stylets. This approach can reduce the rate of iatrogenic injury and improve clinical outcomes for brain lesion operations. Furthermore, we illustrate the efficacy of this device in use compared to those of conventional tubular and blade retractors in a pig cadaver.

Abstract INTRODUCTION Although primarily a respiratory disorder, the coronavirus pandemic has paralyzed almost all aspects of healthcare delivery. Neurosurgeons provide critical care and their role in this pandemic is necessary and yet evolving. METHODS Through professional registries and internet resources, we surveyed neurosurgeons from around the world. We looked at the national burden of illness, perception of preparedness, cancellation of clinics, surgeries and cessation of research and educational activities. Chi-square, Fisher's exact tests, and multivariate logistic regression model were used to analyze variables. RESULTS Our survey was completed on April 3, 2020, and was well-received (661 completed, 60.7% response rate, 96 nations). Neurosurgeons in affluent nations still lacked adequate resources to combat this pandemic primarily due to lack of preparedness and insufficient medical equipment. The challenges to lower-income nations were similar but also included knowledge dissemination and inadequate resources. Hospital preparedness was central to effective healthcare delivery but also influenced the cancellation of surgeries and clinics. The impact on education, conferences and research was also significant. CONCLUSION Neurosurgical disorders are significant casualties of the COVID-19 pandemic. Reduction of services, lack of preparedness, inadequate education, insufficient supplies and resources are important contributors. Improved preparedness requires careful planning, real-time surveillance and allocation of resources. This is more critical in poorer nations.

Fouda, Mohammed A MD; Karsten, Madeline; Staffa, Steven; Scott, R. Michael MD; Marcus, Karen; Baird, Lissa C MD Author Information

Purpose To demonstrate the paradigm shift in management strategies of pediatric craniopharyngioma at our institution over the past six decades. Methods Retrospective analysis of all pediatric patients with craniopharyngioma treated at Boston Children's Hospital between 1960 and 2017. Results One hundred seventy-eight patients with craniopharyngioma were treated between 1960 and 2017; 135 (70 males and 65 females) fulfilled the inclusion criteria. Forty-five patients were treated in the old era (1960-1984) and 90 patients were treated in the new era (1985-2017). Gross total resection (GTR) was achieved in 4% and 43% of patients in old and new eras respectively. Sub-total resection (STR) and radiotherapy (XRT) were performed in 27% and 28% of patients in old and new eras respectively. STR without XRT was performed in 20% and 29% of patients in old and new era respectively. Cyst drainage and adjuvant radiotherapy were performed in 49% of patients in the old era while no patients in the new era underwent such conservative management. Aggressive surgical resection was associated with a higher risk of worsening visual outcomes (20% vs 16%), panhypopituitarism and diabetes insipidus (86% vs 53%), psycho-social impairment (42% vs 26%), and new-onset obesity (33% vs 22%). The mortality rate was higher in the old era in comparison with that of the new one (9% vs 2%). Conclusion There was a paradigm shift in management strategies of pediatric craniopharyngioma over the past six decades which in turn affected the long-term outcomes and quality of life of patients.