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Circular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution of drug resistance and poor patient outcomes. Applying computational methods for the detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma tumors from 465 patients, we identify circular ecDNA in 82 patients (18%). Patients with ecDNA-positive medulloblastoma were more than twice as likely to relapse and three times as likely to die within 5 years of diagnosis. A subset of tumors harbored multiple ecDNA lineages, each containing distinct amplified oncogenes. Multimodal sequencing, imaging and CRISPR inhibition experiments in medulloblastoma models reveal intratumoral heterogeneity of ecDNA copy number per cell and frequent putative 'enhancer rewiring' events on ecDNA. This study reveals the frequency and diversity of ecDNA in medulloblastoma, stratified into molecular subgroups, and suggests copy number heterogeneity and enhancer rewiring as oncogenic features of ecDNA.

Objective  Mobilization of cranial nerve III (CNIII) at its dural entry site is commonly described to avoid damage from stretching during approaches to the parasellar, infrachiasmatic, posterior clinoid, and cavernous sinus regions. The histologic relationships of CNIII as it traverses the dura, and the associated surgical implications are nonetheless poorly described. We herein assess the histology of the CNIII-dura interface as it relates to surgical mobilization of the nerve. Methods  A fronto-orbitozygomatic temporopolar approach was performed on six adult cadaveric specimens. The CNIII-dural entry site was resected and histologically processed. The nerve-tissue planes were assessed by a neuropathologist. Results  Histologic analysis demonstrated that CNIII remained separate from the dura within the oculomotor cistern (porous oculomotorius up to the oculomotor foramen). Fusion of the epineurium of CNIII and the connective tissue of the dura was seen at the level of the foramen, with no clear histologic plane identified between these structures. Conclusion  CNIII may be directly mobilized within the oculomotor cistern, while dissections of CNIII distal to the oculomotor foramen should maintain a thin layer of connective tissue on the nerve.

PurposeTo highlight the clinical, neuroradiographic, neuropathologic, and molecular features of histologically identified neurocytoma in a pediatric cohort and highlight the evolving use methylation profiling in providing diagnostic clarity in difficult to diagnosis pediatric brain tumors.MethodsFive consecutive children (ages 9-13, 2 girls 3 boys) were histologically diagnosed with neurocytoma at Rady Children's Hospital San Diego from 2012 to 2018. Clinical and molecular features were analyzed with regards to treatment course and outcome.ResultsPresenting symptoms included seizures (n = 2), syncope (n = 1), headache (n = 2), visual disturbances (n = 2) and emesis (n = 2). Tumor location included intraventricular (n = 2), intraventricular with parenchymal spread (n = 1), and extraventricular (n = 2). Magnetic resonance imaging demonstrated reduced diffusivity (2/5), signal abnormality on susceptibility-weighted sequences (3/5), and varying degrees of contrast enhancement (4/5). All patients underwent surgical resection alone. Recurrence occurred in four children that were treated with surgery (4/4), adjuvant radiation (2/4), and chemoradiation (1/4). Neuropathologic features included positivity for GFAP (4/5), synaptophysin (4/5), NSE (2/2), NeuN (4/4), and variable Ki-67 (

Anatomic knowledge of the internal auditory canal (IAC) and surrounding structures is a prerequisite for performing skull base approaches to the IAC. We herein perform a morphometric analysis of the IAC and surgically relevant aspects of the posterior petrous bone during pediatric maturation, a region well-studied in adults but not children. Measurements of IAC length (IAC-L), porus (IAC-D) and midpoint (IAC-DM) diameter, and distance from the porus to the common crus (CC; P-CC) and posterior petrosal surface (PPS) to the posterior semicircular canal (PSC; PPS-PSC) were made on thin-cut axial CT scans from 60 patients (grouped by ages 0-3, 4-7, 8-11 12-15, 16-18, and > 18 years). IAC-L increased 27.5% from 8.7 ± 1.1 at age 0-3 to 11.1 ± 1.1 mm at adulthood (p = 0.001), with the majority of growth occurring by ages 8-11. IAC-D (p = 0.52) and IAC-DM (p = 0.167) did not significantly change from ages 0-3 to adult. P-CC increased 31.1% from 7.7 ± 1.5 at age 0-3 to 10.1 ± 1.5 mm at adulthood (p = 0.019). PPS-PSC increased 160% from 1.5 ± 0.7 at age 0-3 to 3.9 ± 1.2 mm at adulthood (p

Prolactinomas are benign tumors that make up the majority of all pituitary adenoma cases and present most commonly in women. Prolactinomas presenting in adolescents and children, however, are extremely rare. We report a case of a 17-year-old male who presented with a six-month history of headaches and a previously unrecognized visual field deficit on examination. Neuroimaging revealed a large suprasellar tumor with imaging, more characteristic of a craniopharyngioma or suprasellar low-grade glioma impinging, on the left intracranial optic nerve causing right-sided hemianopsia. Due to the extensive mass effect and bitemporal hemianopsia on examination, the decision to proceed with initial surgical debulking was made following informed consent. A subtotal resection was performed where the pathology was consistent with a prolactinoma that correlated with markedly elevated prolactin (PRL) levels obtained pre and post-operatively that have not resulted until five days post procedure. The patient was subsequently treated with dopamine agonist (DA) cabergoline therapy and is now five-years disease-free with normal neurological examination and no residual tumor on neuroimaging. DA therapy has shown high clinical efficacy and should be considered prior to any surgical intervention; however, extensive mass effect may appropriate surgical debulking to increase therapy efficacy. Our case highlights an atypical appearance of a giant prolactinoma that may mimic other more common suprasellar tumors, a presentation associated with unrecognized visual field deficits, and the importance of rapid turnaround testing for serum PRL that may aid in the upfront diagnosis and management of prolactinomas.

BackgroundChordomas are rare malignant neoplasms that develop from the primitive notochord with < 5% of the tumors occurring in pediatric patients younger than the age of 20. Of these pediatric chordomas, those affecting the craniocervical junction (C1-C2) are even more rare; therefore, parameters for surgical management of these pediatric tumors are not well characterized.ObservationsIn this case, a 3-year-old male was found to have a clival chordoma on imaging with extension to the craniocervical junction resulting in spinal cord compression. Endoscopic-assisted transoral transclival approach for clival tumor resection was performed first. As a second stage, the patient underwent a left-sided far lateral craniotomy and cervical laminectomy for resection of the skull base chordoma and instrumented fusion of the occiput to C3. He made excellent improvements in strength and dexterity during rehab and was discharged after 3 weeks.LessonsIn pediatric patients with chordoma with extension to the craniocervical junction and spinal cord compression, decompression with additional occipito-cervical fusion appears to offer a good clinical outcome. Fusion performed as a separate surgery before or at the same time as the initial tumor resection surgery may lead to better outcomes.

Unicoronal craniosynostosis is notoriously difficult to treat, with long-term studies demonstrating high rates of relapse and the need for reoperation using open fronto-orbital advancement. Applying the principles of distraction osteogenesis to cranial vault remodeling has demonstrated promising short-term results that compare favorably with traditional methods, with simultaneous correction of both frontofacial and endocranial morphology, along with significant increases in intracranial volume. Here, the authors demonstrate their technique for rotation flap distraction osteogenesis in the treatment of unicoronal synostosis and provide case examples. The video can be found here: https://vimeo.com/519505008.

BackgroundWhile several medical outreach models have been designed and executed to alleviate the unmet need for international neurosurgical care, disparate strategies have evolved. There is a need to determine the optimal pediatric neurosurgical outreach model through which resources are efficiently utilized while imparting the largest possible impact on global health. This study evaluates the efficacy of an international pediatric neurosurgery outreach model at transferring operative skill in a sustainable and scalable manner in Lima, Peru over a 15-year duration.MethodsThree 1-week neurosurgical missions were carried out (2004-2006) in Lima, Peru to teach neuroendoscopic techniques and to provide equipment to host neurosurgeons, equipping the hosts to provide care to indigent citizens beyond the duration of the missions. Follow-up data were obtained over a 15 year span, with collaboration maintained over email, two in-person visits, and video-conferencing services.ResultsSince the outreach missions in 2004-2006, the host neurosurgeons demonstrated sustainability of the neuroendoscopic instruction by independently performing neuroendoscopic operations on a growing caseload: at baseline, 0 cases were performed in 2003, but since 2012 and onwards, 40-45 cases have been performed annually. Scalability is illustrated by the fact that the institution established a rigorous neuroendoscopy training program to independently pass on the techniques to resident physicians.ConclusionThe described international pediatric neurosurgical outreach model, centered around teaching operative technique as opposed to solely providing care to citizens, allowed operative skill to be sustainably transferred to surgeons in Lima, Peru. Having served the neuroendoscopic needs of hundreds of citizens, the strategic design is replicable and should be mirrored by future medical endeavors seeking to substantially impact the deficit in global surgical care.

IntroductionNasal chondromesenchymal tumors (NCMT) are rare benign neoplasms that usually present in children

Medulloblastoma is among the most common malignant brain tumors in children. Recent studies have identified at least four subgroups of the disease that differ in terms of molecular characteristics and patient outcomes. Despite this heterogeneity, most patients with medulloblastoma receive similar therapies, including surgery, radiation, and intensive chemotherapy. Although these treatments prolong survival, many patients still die from the disease and survivors suffer severe long-term side effects from therapy. We hypothesize that each patient with medulloblastoma is sensitive to different therapies and that tailoring therapy based on the molecular and cellular characteristics of patients' tumors will improve outcomes. To test this, we assembled a panel of orthotopic patient-derived xenografts (PDX) and subjected them to DNA sequencing, gene expression profiling, and high-throughput drug screening. Analysis of DNA sequencing revealed that most medulloblastomas do not have actionable mutations that point to effective therapies. In contrast, gene expression and drug response data provided valuable information about potential therapies for every tumor. For example, drug screening demonstrated that actinomycin D, which is used for treatment of sarcoma but rarely for medulloblastoma, was active against PDXs representing Group 3 medulloblastoma, the most aggressive form of the disease. Functional analysis of tumor cells was successfully used in a clinical setting to identify more treatment options than sequencing alone. These studies suggest that it should be possible to move away from a one-size-fits-all approach and begin to treat each patient with therapies that are effective against their specific tumor. SIGNIFICANCE: These findings show that high-throughput drug screening identifies therapies for medulloblastoma that cannot be predicted by genomic or transcriptomic analysis.

PurposeTreatment of children with CNS tumors (CNSTs) demands a complex, interdisciplinary approach that is rarely available in low- and middle-income countries. We established the Cross-Border Neuro-Oncology Program (CBNP) between Rady Children's Hospital, San Diego (RCHSD), and Hospital General, Tijuana (HGT), Mexico, to provide access to neuro-oncology care, including neurosurgic services, for children with CNSTs diagnosed at HGT. Our purpose was to assess the feasibility of the CBNP across the United States-Mexico border and improve survival for children with CNSTs at HGT by implementing the CBNP.Patients and methodsWe prospectively assessed clinicopathologic profiles, the extent of resection, progression-free survival, and overall survival (OS) in children with CNSTs at HGT from 2010 to 2017.ResultsSixty patients with CNSTs participated in the CBNP during the study period. The most common diagnoses were low-grade glioma (24.5%) and medulloblastoma (22.4%). Of patients who were eligible for surgery, 49 underwent resection at RCHSD and returned to HGT for collaborative management. Gross total resection was achieved in 78% of cases at RCHSD compared with 0% at HGT (P < .001) and was a predictor of 5-year OS (hazard ratio, 0.250; 95% CI, 0.067 to 0.934; P = .024). Five-year OS improved from 0% before 2010 to 52% in 2017.ConclusionThe CBNP facilitated access to complex neuro-oncology care for underserved children in Mexico through binational exchanges of resources and expertise. Survival for patients in the CBNP dramatically improved. Gross total resection at RCHSD was associated with higher OS, highlighting the critical role of experienced neurosurgeons in the treatment of CNSTs. The CBNP model offers an attractive alternative for children with CNSTs in low- and middle-income countries who require complex neuro-oncology care, particularly those in close proximity to institutions in high-income countries with extensive neuro-oncology expertise.

ObjectiveThis study aimed to assess the safety and efficacy of MR-guided stereotactic laser ablation (SLA) therapy in the treatment of pediatric brain tumors.MethodsData from 17 North American centers were retrospectively reviewed. Clinical, technical, and radiographic data for pediatric patients treated with SLA for a diagnosis of brain tumor from 2008 to 2016 were collected and analyzed.ResultsA total of 86 patients (mean age 12.2 ± 4.5 years) with 76 low-grade (I or II) and 10 high-grade (III or IV) tumors were included. Tumor location included lobar (38.4%), deep (45.3%), and cerebellar (16.3%) compartments. The mean follow-up time was 24 months (median 18 months, range 3-72 months). At the last follow-up, the volume of SLA-treated tumors had decreased in 80.6% of patients with follow-up data. Patients with high-grade tumors were more likely to have an unchanged or larger tumor size after SLA treatment than those with low-grade tumors (OR 7.49, p = 0.0364). Subsequent surgery and adjuvant treatment were not required after SLA treatment in 90.4% and 86.7% of patients, respectively. Patients with high-grade tumors were more likely to receive subsequent surgery (OR 2.25, p = 0.4957) and adjuvant treatment (OR 3.77, p = 0.1711) after SLA therapy, without reaching significance. A total of 29 acute complications in 23 patients were reported and included malpositioned catheters (n = 3), intracranial hemorrhages (n = 2), transient neurological deficits (n = 11), permanent neurological deficits (n = 5), symptomatic perilesional edema (n = 2), hydrocephalus (n = 4), and death (n = 2). On long-term follow-up, 3 patients were reported to have worsened neuropsychological test results. Pre-SLA tumor volume, tumor location, number of laser trajectories, and number of lesions created did not result in a significantly increased risk of complications; however, the odds of complications increased by 14% (OR 1.14, p = 0.0159) with every 1-cm3 increase in the volume of the lesion created.ConclusionsSLA is an effective, minimally invasive treatment option for pediatric brain tumors, although it is not without risks. Limiting the volume of the generated thermal lesion may help decrease the incidence of complications.

Noncoding genetic variation is a major driver of phenotypic diversity, but functional interpretation is challenging. To better understand common genetic variation associated with brain diseases, we defined noncoding regulatory regions for major cell types of the human brain. Whereas psychiatric disorders were primarily associated with variants in transcriptional enhancers and promoters in neurons, sporadic Alzheimer's disease (AD) variants were largely confined to microglia enhancers. Interactome maps connecting disease-risk variants in cell-type-specific enhancers to promoters revealed an extended microglia gene network in AD. Deletion of a microglia-specific enhancer harboring AD-risk variants ablated BIN1 expression in microglia, but not in neurons or astrocytes. These findings revise and expand the list of genes likely to be influenced by noncoding variants in AD and suggest the probable cell types in which they function.

Genome sequencing was performed on matched normal and tumor tissue from a 6.5-yr-old boy with a diagnosis of recurrent medulloblastoma. A pathogenic heterozygous c.432+1G>A canonical splice donor site variant in GNAS was detected on analysis of blood DNA. Analysis of tumor DNA showed the same splice variant along with copy-neutral loss of heterozygosity on Chromosome 20 encompassing GNAS, consistent with predicted biallelic loss of GNAS in the tumor specimen. This case strengthens the evidence implicating GNAS as a tumor-suppressor gene in medulloblastoma and highlights a scenario in which therapeutics targeting the cAMP pathway may be of great utility.

Background and Purpose- Stroke is a leading cause of long-term disability. Limited treatment options exist for patients with chronic stroke and substantial functional deficits. The current study examined safety and preliminary efficacy estimates of intravenous allogeneic mesenchymal stem cells in this population. Methods- Entry criteria included ischemic stroke >6 months prior and substantial impairment (National Institutes of Health Stroke Scale score ≥6) and disability. Enrollees received a single intravenous dose of allogeneic ischemia-tolerant mesenchymal stem cells. Phase 1 used a dose-escalation design (3 tiers, n=5 each). Phase 2 was an expanded safety cohort. The primary end point was safety over 1-year. Secondary end points examined behavioral change. Results- In phase 1 (n=15), each dose (0.5, 1.0, and 1.5 million cells/kg body weight) was found safe, so phase 2 subjects (n=21) received 1.5 million cells/kg. At baseline, subjects (n=36) averaged 4.2±4.6 years poststroke, age 61.1±10.8 years, National Institutes of Health Stroke Scale score 8 (6.5-10), and Barthel Index 65±29. Two were lost to follow-up, one was withdrawn and 2 died (unrelated to study treatment). Of 15 serious adverse events, none was possibly or probably related to study treatment. Two mild adverse events were possibly related to study treatment, a urinary tract infection and intravenous site irritation. Treatment was safe based on serial exams, electrocardiograms, laboratory tests, and computed tomography scans of chest/abdomen/pelvis. All behavioral end points showed significant gains over the 12-months of follow-up. For example, Barthel Index scores increased by 6.8±11.4 points (mean±SD) at 6-months (P=0.002) and by 10.8±15.5 points at 12-months (P

BACKGROUND:Pediatric intracavernous sinus tumors are exceedingly rare and thus poorly characterized. Their neurosurgical management is challenging and diagnostic, and management guidelines are limited. OBJECTIVE:To report our institutional experience with the surgical resection of pediatric intracavernous sinus tumors. We also compare and contrast our results with the 14 cases of pediatric intracavernous sinus lesions in the current literature. METHODS:A retrospective descriptive analysis of consecutive pediatric patients (ages 0-18 yr) presenting to our institution with a diagnosis of an intracavernous sinus lesion was performed. From January 2012 to January 2017, 5 cases were identified. Eleven patients with secondary invasion of the cavernous sinus (2 meningiomas, 7 pituitary adenomas) or dermoid tumors involving the cavernous sinus (2) were not included in our review. RESULTS:Surgical resection via a frontotemporal orbitozygomatic approach was performed in all cases by a single senior neurosurgeon (M.L.). There were no perioperative or postoperative complications attributable to the surgery or approach. Four of 5 patients remained neurologically stable throughout the perioperative and postoperative period. The fifth patient had a complete resolution of their cranial neuropathies postoperatively. A pathological diagnosis that guided long-term management was obtained in all cases. CONCLUSION:Neurosurgical management of pediatric cavernous sinus lesions can be safely performed and critically guide future therapies. Surgeon familiarity with cavernous sinus and skull-base anatomy is critical to the successful management of these patients. The benefits of surgery should be balanced against the potential complications and need for a tissue diagnosis in children. The senior author had a significant experience with cavernous sinus approaches in adults prior to initiating use of the approach in the pediatric population.

Paediatric high-grade gliomas, including glioblastoma and anaplastic astrocytoma, make up 8%-12% of paediatric central nervous system tumours 1 and have poor prognosis, with 2-year survival less than 30% 2 and overall survival less than 10%. The only known prognostic factors in this population include extent of resection and tumour histological grade. We present the case of a 9-year-old boy with disseminated anaplastic astrocytoma treated with subtotal resection, craniospinal radiation and temozolomide, with 8-year survival despite metastatic disease at presentation and subtotal resection. Next generation cancer gene panel sequencing revealed an usual pattern of 12 amplifications and four mutations not previously described.

We present the case of a 13-year-old boy with a very unusual periventricular atypical central neurocytoma with unique molecular features treated with subtotal surgical resection and photon intensity-modulated radiotherapy. Histological features were most consistent with atypical central neurocytoma. However, next-generation sequencing analysis revealed a novel EWSR1-ATF1 gene fusion (EWSR1-ATF1) as well as a MUTYH mutation. The EWSR1-ATF1 raised the possibility of Ewing sarcoma or angiomatoid fibrous histiocytoma, however, FLI-1 immunohistochemistry was negative. MUTYH mutations have been reported in diffuse midline paediatric glioma. The role of EWSR1-ATF1 and MUTYH mutations in central nervous system tumours is not well established. We present the first case of EWSR1-ATF1 and MUTYH mutation in a rare paediatric atypical central neurocytoma. Further studies are indicated to elucidate the consequences of these gene alterations in the context of paediatric central nervous system tumours as well as to investigate the potential role for targeted therapies.

Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment. Transfer to a tissue culture environment resulted in rapid and extensive down-regulation of microglia-specific genes that were induced in primitive mouse macrophages after migration into the fetal brain. Substantial subsets of these genes exhibited altered expression in neurodegenerative and behavioral diseases and were associated with noncoding risk variants. These findings reveal an environment-dependent transcriptional network specifying microglia-specific programs of gene expression and facilitate efforts to understand the roles of microglia in human brain diseases.

Medulloblastoma (MB) is a highly malignant pediatric brain tumor. Despite aggressive therapy, many patients succumb to the disease, and survivors experience severe side effects from treatment. MYC-driven MB has a particularly poor prognosis and would greatly benefit from more effective therapies. We used an animal model of MYC-driven MB to screen for drugs that decrease viability of tumor cells. Among the most effective compounds were histone deacetylase inhibitors (HDACIs). HDACIs potently inhibit survival of MYC-driven MB cells in vitro, in part by inducing expression of the FOXO1 tumor suppressor gene. HDACIs also synergize with phosphatidylinositol 3-kinase inhibitors to inhibit tumor growth in vivo. These studies identify an effective combination therapy for the most aggressive form of MB.

Sonic hedgehog (SHH) medulloblastoma (MB) subtype is driven by a proliferative CD15+ tumor propagating cell (TPC), also considered in the literature as a putative cancer stem cell (CSC). Despite considerable research, much of the biology of this TPC remains unknown. We report evidence that phosphatase and tensin homolog (PTEN) and phosphoinositide 3-kinase (PI-3K) play a crucial role in the propagation, survival and potential response to therapy in this CD15+ CSC/TPC-driven malignant disease. Using the ND2-SmoA1 transgenic mouse model for MB, mouse genetics and patient-derived xenografts (PDXs), we demonstrate that the CD15+TPCs are 1) obligately required for SmoA1Tg-driven tumorigenicity 2) regulated by PTEN and PI-3K signaling 3) selectively sensitive to the cytotoxic effects of pan PI-3K inhibitors in vitro and in vivo but resistant to chemotherapy 4) in the SmoA1Tg mouse model are genomically similar to the SHH human MB subgroup. The results provide the first evidence that PTEN plays a role in MB TPC signaling and biology and that PI-3K inhibitors target and suppress the survival and proliferation of cells within the mouse and human CD15+ cancer stem cell compartment. In contrast, CD15+ TPCs are resistant to cisplatinum, temozolomide and the SHH inhibitor, NVP-LDE-225, agents currently used in treatment of medulloblastoma. These studies validate the therapeutic efficacy of pan PI-3K inhibitors in the treatment of CD15+ TPC dependent medulloblastoma and suggest a sequential combination of PI-3K inhibitors and chemotherapy will have augmented efficacy in the treatment of this disease.

Medulloblastoma is the most common malignant brain tumor in children. Although aggressive surgery, radiation, and chemotherapy have improved outcomes, survivors suffer severe long-term side effects, and many patients still succumb to their disease. For patients whose tumors are driven by mutations in the sonic hedgehog (SHH) pathway, SHH antagonists offer some hope. However, many SHH-associated medulloblastomas do not respond to these drugs, and those that do may develop resistance. Therefore, more effective treatment strategies are needed for both SHH and non-SHH-associated medulloblastoma. One such strategy involves targeting the cells that are critical for maintaining tumor growth, known as tumor-propagating cells (TPC). We previously identified a population of TPCs in tumors from patched mutant mice, a model for SHH-dependent medulloblastoma. These cells express the surface antigen CD15/SSEA-1 and have elevated levels of genes associated with the G2-M phases of the cell cycle. Here, we show that CD15(+) cells progress more rapidly through the cell cycle than CD15(-) cells and contain an increased proportion of cells in G2-M, suggesting that they might be vulnerable to inhibitors of this phase. Indeed, exposure of tumor cells to inhibitors of Aurora kinase (Aurk) and Polo-like kinases (Plk), key regulators of G2-M, induces cell-cycle arrest, apoptosis, and enhanced sensitivity to conventional chemotherapy. Moreover, treatment of tumor-bearing mice with these agents significantly inhibits tumor progression. Importantly, cells from human patient-derived medulloblastoma xenografts are also sensitive to Aurk and Plk inhibitors. Our findings suggest that targeting G2-M regulators may represent a novel approach for treatment of human medulloblastoma.

A myriad of geopolitical and financial obstacles have kept modern neurosurgery from effectively reaching the citizens of the developing world. Targeted neurosurgical outreach by academic neurosurgeons to equip neurosurgical operating theaters and train local neurosurgeons is one method to efficiently and cost effectively improve sustainable care provided by international charity hospitals. The International Neurosurgical Children’s Association (INCA) effectively improved the available neurosurgical care in the Maria Auxiliadora Hospital of Lima, Peru through the advancement of local specialist education and training.Neurosurgical equipment and training were provided for the local neurosurgeons by a mission team from the University of California at San Diego.At the end of 3 years, with one intensive week trip per year, the host neurosurgeons were proficiently and independently applying microsurgical techniques to previously performed operations, and performing newly learned operations such as neuroendoscopy and minimally invasive neurosurgery.Our experiences may serve as a successful template for the execution of other small scale, sustainable neurosurgery missions worldwide.

The objective of this study is to report our initial experience treating pediatric patients with central nervous system tumors using a frameless, optically guided linear accelerator.Pediatric patients were selected for treatment after evaluation by a multidisciplinary neuro-oncology team including neurosurgery, neurology, pathology, oncology, and radiation oncology. Prior to treatment, all patients underwent treatment planning using magnetic resonance imaging (MRI) and treatment simulation on a standard computed tomography scanner (CT). For CT simulation, patients were fitted with a customized plastic face mask with a bite block attached to an optical array with four reflective markers. After ensuring adequate reproducibility, these markers were tracked during treatment by an infra-red camera. All treatments were delivered on a Varian Trilogy linear accelerator. The follow-up period ranges from 1–18 months, with a median follow-up of 6 months.Nine patients, ages ranging from 12 to 19 years old (median age 15 years old), with a variety of tumors have been treated. Patients were treated for juvenile pilocytic astrocytoma (JPA; n = 2), pontine low-grade astrocytoma (n = 1), pituitary adenoma (n = 3), metastatic medulloblastoma (n = 1), acoustic neuroma (n = 1), and pineocytoma (n = 1). We followed patients for a median of 12 months (range 3–18 months) with no in-field failures and were able to obtain encouraging toxicity profiles.Frameless stereotactic optically guided radiosurgery and radiotherapy provides a feasible and accurate tool to treat a number of benign and malignant tumors in children with minimal treatment-related morbidity.

The biology of both normal and tumor development clearly possesses overlapping and parallel features. Oncogenes and tumor suppressors are relevant not only in tumor biology, but also in physiological developmental regulators of growth and differentiation. Conversely, genes identified as regulators of developmental biology are relevant to tumor biology. This is particularly relevant in the context of brain tumors, where recent evidence is mounting that the origin of brain tumors, specifically gliomas, may represent dysfunctional developmental neurobiology. Neural stem cells are increasingly being investigated as the cell type that originally undergoes malignant transformation - the cell of origin - and the evidence for this is discussed.