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Biological sex is an important risk factor in cancer, but the underlying cell types and mechanisms remain obscure. Since tumor development is regulated by the immune system, we hypothesize that sex-biased immune interactions underpin sex differences in cancer. The male-biased glioblastoma multiforme (GBM) is an aggressive and treatment-refractory tumor in urgent need of more innovative approaches, such as considering sex differences, to improve outcomes. GBM arises in the specialized brain immune environment dominated by microglia, so we explored sex differences in this immune cell type. We isolated adult human TAM-MGs (tumor-associated macrophages enriched for microglia) and control microglia and found sex-biased inflammatory signatures in GBM and lower-grade tumors associated with pro-tumorigenic activity in males and anti-tumorigenic activity in females. We demonstrated that genes expressed or modulated by the inactive X chromosome facilitate this bias. Together, our results implicate TAM-MGs, specifically their sex chromosomes, as drivers of male bias in GBM.
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OBJECTIVE: Comprehensive data on treatment patterns of pediatric cerebral arteriovenous malformations (AVMs) are lacking. The authors' aim was to examine national trends, assess the effect of hospital volume on outcomes, and identify variables associated with treatment at high-volume centers. METHODS: Pediatric AVM admissions (for ruptured and unruptured lesions) occurring in the US in 2016 and 2019 were identified using the Kids' Inpatient Database. Demographics, treatment methods, costs, and outcomes were recorded. The effect of hospital AVM volume on outcomes and factors associated with treatment at higher-volume hospitals were analyzed. RESULTS: Among 2752 AVM admissions identified, 730 (26.5%) patients underwent craniotomy, endovascular treatment, or a combination. High-volume (vs low-volume) centers saw lower proportions of Black (8.7% vs 12.9%, p < 0.001) and lowest-income quartile (20.7% vs 27.9%, p < 0.001) patients, but were more likely to provide endovascular intervention (19.5%) than low-volume institutions (13.7%) (p = 0.001). Patients treated at high-volume hospitals had insignificantly lower numbers of complications (mean 2.66 vs 4.17, p = 0.105) but significantly lower odds of nonroutine discharge (OR 0.18 [95% CI 0.06-0.53], p = 0.009) and death (OR 0.13 [95% CI 0.02-0.75], p = 0.023). Admissions at high-volume hospitals cost more than at low-volume hospitals, regardless of whether intervention was performed ($64,811 vs $48,677, p = 0.001) or not ($64,137 vs $33,779, p < 0.001). Multivariable analysis demonstrated that Hispanic children, patients who received AVM treatment, and those in higher-income quartiles had higher odds of treatment at high-volume hospitals. CONCLUSIONS: In this largest study of US pediatric cerebral AVM admissions to date, higher hospital volume correlated with several better outcomes, particularly when patients underwent intervention. Multivariable analysis demonstrated that higher income and Hispanic race were associated with treatment at high-volume centers, where endovascular care is more common. The findings highlight the fact that ensuring access to appropriate treatment of patients of all races and socioeconomic classes must be a focus.
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Hospitales de Alto Volumen , Hospitales de Bajo Volumen , Malformaciones Arteriovenosas Intracraneales , Humanos , Malformaciones Arteriovenosas Intracraneales/terapia , Malformaciones Arteriovenosas Intracraneales/epidemiología , Masculino , Femenino , Niño , Estudios Retrospectivos , Hospitales de Alto Volumen/estadística & datos numéricos , Adolescente , Hospitales de Bajo Volumen/estadística & datos numéricos , Resultado del Tratamiento , Preescolar , Procedimientos Endovasculares , Estados Unidos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Estudios de Cohortes , Lactante , Craneotomía/estadística & datos numéricosRESUMEN
INTRODUCTION: Pediatric intracranial aneurysms (IAs) are rare and have distinct clinical profiles compared to adult IAs. They differ in location, size, morphology, presentation, and treatment strategies. We present our experience with pediatric IAs over an 18-year period using surgical and endovascular treatments and review the literature to identify commonalities in epidemiology, treatment, and outcomes. METHODS: We identified all patients < 20 years old who underwent treatment for IAs at our institution between 2005 and 2020. Medical records and imaging were examined for demographic, clinical, and operative data. A systematic review was performed to identify studies reporting primary outcomes of surgical and endovascular treatment of pediatric IAs. Demographic information, aneurysm characteristics, treatment strategies, and outcomes were collected. RESULTS: Thirty-three patients underwent treatment for 37 aneurysms over 18 years. The mean age was 11.4 years, ranging from one month to 19 years. There were 21 males (63.6%) and 12 females (36.4%), yielding a male: female ratio of 1.75:1. Twenty-six (70.3%) aneurysms arose from the anterior circulation and 11 (29.7%) arose from the posterior circulation. Aneurysmal rupture occurred in 19 (57.5%) patients, of which 8 (24.2%) were categorized as Hunt-Hess grades IV or V. Aneurysm recurrence or rerupture occurred in five (15.2%) patients, and 5 patients (15.2%) died due to sequelae of their aneurysms. Twenty-one patients (63.6%) had a good outcome (modified Rankin Scale score 0-2) on last follow up. The systematic literature review yielded 48 studies which included 1,482 total aneurysms (611 with endovascular treatment; 656 treated surgically; 215 treated conservatively). Mean aneurysm recurrence rates in the literature were 12.7% and 3.9% for endovascular and surgical treatment, respectively. CONCLUSIONS: Our study provides data on the natural history and longitudinal outcomes for children treated for IAs at a single institution, in addition to our treatment strategies for various aneurysmal morphologies. Despite the high proportion of patients presenting with rupture, good functional outcomes can be achieved for most patients.
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Procedimientos Endovasculares , Aneurisma Intracraneal , Humanos , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/terapia , Aneurisma Intracraneal/diagnóstico por imagen , Niño , Adolescente , Masculino , Femenino , Procedimientos Endovasculares/métodos , Preescolar , Lactante , Adulto Joven , Procedimientos Neuroquirúrgicos/métodos , Resultado del TratamientoRESUMEN
Originally pioneered in adults, endoscopic endonasal approaches for skull base pathology are being increasingly applied as a minimally invasive alternative for young children. Intrinsic anatomic differences between these patient populations have sparked discussions on the feasibility, safety, and efficacy of these techniques in pediatric patients. This work aims to serve as a primer for clinicians engaged in the rapidly evolving field of pediatric endoscopic skull base surgery. A succinct overview of relevant embryology, sinonasal anatomy, and diagnostic workup is presented to emphasize key differences and unique technical considerations. Additional discussions regarding select skull base lesions, reconstructive paradigms, potential surgical complications, and postoperative care are also highlighted in the setting of multidisciplinary teams.
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There is an increased risk of cerebrovascular accidents (CVA) in individuals with PHACES, yet the precise causes are not well understood. In this analysis, we aimed to examine the role of arteriopathy in PHACES syndrome as a potential contributor to CVA. We analyzed clinical and radiological data from 282 patients with suspected PHACES syndrome. We analyzed clinical features, including the presence of infantile hemangioma and radiological features based on magnetic resonance angiography or computed tomography angiography, in individuals with PHACES syndrome according to the Garzon criteria. To analyze intravascular blood flow, we conducted a simulation based on the Fluid-Structure Interaction (FSI) method, utilizing radiological data. The collected data underwent statistical analysis. Twenty patients with PHACES syndrome were included. CVAs were noted in 6 cases. Hypoplasia (p = 0.03), severe tortuosity (p < 0.01), absence of at least one main cerebral artery (p < 0.01), and presence of persistent arteries (p = 0.01) were associated with CVAs, with severe tortuosity being the strongest predictor. The in-silico analysis showed that the combination of hypoplasia and severe tortuosity resulted in a strongly thrombogenic environment. Severe tortuosity, combined with hypoplasia, is sufficient to create a hemodynamic environment conducive to thrombus formation and should be considered high-risk for cerebrovascular accidents (CVAs) in PHACES patients.
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Hemangioma , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/diagnóstico por imagen , Arterias Cerebrales/patología , Angiografía por Resonancia Magnética , Hemangioma/patología , Tomografía Computarizada por Rayos XRESUMEN
Brain tumors in children are a devastating disease in a high proportion of patients. Owing to inconsistent results in clinical trials in unstratified patients, the role of immunotherapy remains unclear. We performed an in-depth survey of the single-cell transcriptomes and clonal relationship of intra-tumoral T cells from children with brain tumors. Our results demonstrate that a large fraction of T cells in the tumor tissue are clonally expanded with the potential to recognize tumor antigens. Such clonally expanded T cells display enrichment of transcripts linked to effector function, tissue residency, immune checkpoints and signatures of neoantigen-specific T cells and immunotherapy response. We identify neoantigens in pediatric brain tumors and show that neoantigen-specific T cell gene signatures are linked to better survival outcomes. Notably, among the patients in our cohort, we observe substantial heterogeneity in the degree of clonal expansion and magnitude of T cell response. Our findings suggest that characterization of intra-tumoral T cell responses may enable selection of patients for immunotherapy, an approach that requires prospective validation in clinical trials.
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Neoplasias Encefálicas , Linfocitos T , Humanos , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Niño , Linfocitos T/inmunología , Antígenos de Neoplasias/inmunología , Inmunoterapia/métodos , Preescolar , Masculino , Femenino , Adolescente , Linfocitos Infiltrantes de Tumor/inmunología , Análisis de la Célula Individual/métodos , Transcriptoma , Células ClonalesRESUMEN
OBJECTIVE: Rathke cleft cysts (RCCs) are benign, epithelial-lined sellar lesions that arise from remnants of the craniopharyngeal duct. Due to their rarity in the pediatric population, data are limited regarding the natural history and optimal management of growing or symptomatic RCCs. We present our institutional experience with the surgical management of RCCs. METHODS: We performed a retrospective study of consecutive RCC patients ≤ 18 years old treated surgically at our institution between 2006 and 2022. RESULTS: Overall, 567 patients with a diagnosis of pituitary mass or cyst were identified. Of these, 31 had a histopathological diagnosis of RCC, 58% female and 42% male. The mean age was 13.2 ± 4.2 years. Presenting symptoms included headache (58%), visual changes (32%), and endocrinopathies or growth delay (26%); 13% were identified incidentally and subsequently demonstrated growth on serial imaging. Six percent presented with symptomatic intralesional hemorrhage. Surgical approach was transsphenoidal for 90% of patients and orbitozygomatic for 10%. Preoperative headaches resolved in 61% of patients and preoperative visual deficits improvement in 55% after surgery. New pituitary axis deficits were seen in 9.7% of patients. Only two complications occurred from a first-time surgery: one cerebrospinal fluid leak requiring lumbar drain placement, and one case of epistaxis requiring cauterization. No patients experienced new visual or neurological deficits. Patients were followed postoperatively with serial imaging at a mean follow-up was 62.9 ± 58.4 months. Recurrence requiring reoperation occurred in 32% of patients. Five-year progression-free survival was 47.9%. Except for one patient with multiple neurological deficits from a concurrent tectal glioma, all patients had a modified Rankin Scale score of 0 or 1 (good outcome) at last follow-up. CONCLUSION: Due to their secretory epithelium, pediatric RCCs may demonstrate rapid growth and can cause symptoms due to local mass effect. Surgical management of symptomatic or growing pediatric RCCs via cyst fenestration or partial resection of the cyst wall can be performed safely, with good neurologic outcomes. There is a nontrivial risk of endocrinologic injury, and long-term follow up is needed due to high recurrence rates.
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Carcinoma de Células Renales , Quistes del Sistema Nervioso Central , Quistes , Neoplasias Renales , Humanos , Niño , Masculino , Femenino , Adolescente , Estudios Retrospectivos , Quistes del Sistema Nervioso Central/cirugíaRESUMEN
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.
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Neoplasias Cerebelosas , Meduloblastoma , Neoplasias , Humanos , ADN Circular , Meduloblastoma/genética , Estudios Retrospectivos , Neoplasias/genética , Oncogenes , Neoplasias Cerebelosas/genéticaRESUMEN
OBJECTIVE: Septic cerebral venous sinus thrombosis (CVST) is a recognized complication of pediatric sinogenic and otogenic intracranial infections. The optimal treatment paradigm remains controversial. Proponents of anticoagulation highlight its role in preventing thrombus propagation and promoting recanalization, while others cite the risk of hemorrhagic complications, especially after a neurosurgical procedure for an epidural abscess or subdural empyema. Here, the authors investigated the diagnosis, management, and outcomes of pediatric patients with sinogenic or otogenic intracranial infections and a septic CVST. METHODS: All patients 21 years of age or younger, who presented with an intracranial infection in the setting of sinusitis or otitis media and who underwent neurosurgical treatment at Connecticut Children's, Rady Children's Hospital-San Diego, or Ann and Robert H. Lurie Children's Hospital of Chicago from March 2015 to March 2023, were retrospectively reviewed. Demographic, clinical, and radiological data were systematically collated. RESULTS: Ninety-six patients were treated for sinusitis-related and/or otitis media-related intracranial infections during the study period, 15 (15.6%) of whom were diagnosed with a CVST. Of the 60 patients who presented prior to the COVID-19 pandemic, 6 (10.0%) were diagnosed with a septic CVST, whereas of the 36 who presented during the COVID-19 pandemic, 9 (25.0%) had a septic CVST (p = 0.050). The superior sagittal sinus was involved in 12 (80.0%) patients and the transverse and/or sigmoid sinuses in 4 (26.7%). Only 1 (6.7%) patient had a fully occlusive thrombus. Of the 15 patients with a septic CVST, 11 (73.3%) were initiated on anticoagulation at a median interval of 4 (IQR 3-5) days from the most recent neurosurgical procedure. Five (45.5%) patients who underwent anticoagulation demonstrated complete recanalization on follow-up imaging, and 4 (36.4%) had partial recanalization. Three (75.0%) patients who did not undergo anticoagulation demonstrated complete recanalization, and 1 (25.0%) had partial recanalization. None of the patients treated with anticoagulation experienced hemorrhagic complications. CONCLUSIONS: Septic CVST is frequently identified among pediatric patients undergoing neurosurgical intervention for sinogenic and/or otogenic intracranial infections and may have become more prevalent during the COVID-19 pandemic. Anticoagulation can be used safely in the acute postoperative period if administered cautiously, in a monitored setting, and with interval cross-sectional imaging. However, some patients exhibit excellent outcomes without anticoagulation, and further studies are needed to identify those who may benefit the most from anticoagulation.
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COVID-19 , Otitis Media , Trombosis de los Senos Intracraneales , Humanos , Niño , Estudios Retrospectivos , Pandemias , COVID-19/complicaciones , Otitis Media/complicaciones , Otitis Media/tratamiento farmacológico , Otitis Media/cirugía , Anticoagulantes/uso terapéutico , Trombosis de los Senos Intracraneales/diagnóstico por imagen , Trombosis de los Senos Intracraneales/tratamiento farmacológico , Trombosis de los Senos Intracraneales/cirugíaRESUMEN
PURPOSE: Herein lies a brief historical review of the practice of artificial cranial deformation (ACD) in Tiwanaku, Bolivia, a pre-Columbian archeological ruin once regarded as one of the most powerful pre-Inca regions whose influence extended into present-day Peru and Chile from 600 to 1000 AD. We describe the history, purpose, and implications of ACD from both a neuroanatomical and cultural perspective. METHODS: A literature review was conducted through PubMed on the history of artificial cranial deformation in South America, concentrating on the Tiwanaku region. The authors searched all available data with no specific time reference, using the mentioned keywords: ACD, neuroanatomical implications of ACD, cultural and social functions of ACD, Tiwanaku society, and Andean civilization. RESULTS: Early Andean civilization was hierarchical and stratified. In Tiwanaku, the practice of ACD served to delineate one's social class, caste, lineage, and vocation. This was especially useful for warriors, who distinguished their fellow combatants from insurgents by differences in their cranial structure. ACD was usually conducted within the first few months of an infant's life before morphogenetic features became permanent. Two popular cranial styles-tabular and annular-were achieved by applying various mechanical apparatus and resulted in several cranial shapes (conical, box-like, flattened, etc.). Neuroanatomically, each deformation technique and the duration for which mechanical stress was applied influenced the solidification of cranial bones and shaped the frontal, occipital, parietal, and temporal bones differently. Cognitive deficits and plagiocephalic defects were recorded in limitation and may have been overlooked as the era's occupational demands were more labor-intensive than knowledge-driven. CONCLUSION: In Tiwanaku, the custom of ACD was used to demonstrate group identity, with alterations of the cranial shape corresponding to a particular headdress. ACD was used to distinguish an individual's social identity, separating different groups of society into castes, classes, and slaves (Brain, 1979). The custom has also been used to mark territory and emphasize ethnic differences among groups, with potential cognitive implications that were largely unrecorded.
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Arqueología , Hueso Temporal , Lactante , Humanos , Bolivia , América del Sur , Perú , Arqueología/métodosRESUMEN
Microglia phenotypes are highly regulated by the brain environment, but the transcriptional networks that specify the maturation of human microglia are poorly understood. Here, we characterized stage-specific transcriptomes and epigenetic landscapes of fetal and postnatal human microglia and acquired corresponding data in induced pluripotent stem cell (iPSC)-derived microglia, in cerebral organoids, and following engraftment into humanized mice. Parallel development of computational approaches that considered transcription factor (TF) co-occurrence and enhancer activity allowed prediction of shared and state-specific gene regulatory networks associated with fetal and postnatal microglia. Additionally, many features of the human fetal-to-postnatal transition were recapitulated in a time-dependent manner following the engraftment of iPSC cells into humanized mice. These data and accompanying computational approaches will facilitate further efforts to elucidate mechanisms by which human microglia acquire stage- and disease-specific phenotypes.
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Células Madre Pluripotentes Inducidas , Microglía , Humanos , Ratones , Animales , Redes Reguladoras de Genes , Encéfalo , Regulación de la Expresión GénicaRESUMEN
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.
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The United Nations (UN) established an umbrella of organizations to manage distinct clusters of humanitarian aid. The World Health Organization (WHO) oversees the health cluster, giving it responsibility for global, national, and local medical responses to natural disasters. However, this centralized structure insufficiently engages local players, impeding robust local implementation. The Gorkha earthquake struck Nepal on April 25, 2015, becoming Nepal's most severe natural disaster since the 1934 Nepal-Bihar earthquake. In coordinated response, 2 organizations, Empower Nepali Girls and International Neurosurgical Children's Association, used a hybrid approach integrating continuous communication with local recipients. Each organization mobilized its principal resource strengths-material medical supplies or human capital-thereby efficiently deploying resources to maximize the impact of the medical response. In addition to efficient resource use, this approach facilitates dynamic medical responses from highly mobile organizations. Importantly, in addition to future earthquakes in Nepal, this medical response strategy is easily scalable to other natural disaster contexts and other medical relief organizations. Preemptively identifying partner organizations with complementary strengths, continuous engagement with recipient populations, and creating disaster- and region-specific response teams may represent viable variations of the WHO cluster model with greater efficacy in local implementation of treatment in acute disaster scenarios.
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Planificación en Desastres , Desastres , Terremotos , Desastres Naturales , Niño , Femenino , Humanos , Nepal , Organización Mundial de la SaludRESUMEN
We present 4 children (diagnosed between 1 and 8 y, 3 females and 1 male) with molecularly distinct tectal gliomas (2 KRAS mutant, 1 EGFR mutant, 1 SRGAP3-RAF-1 fusion) that contributes to the growing literature of this uncommonly biopsied tumor. The patient with EGFR R222C mutation had a more severe course, earlier diagnosis, subsequent leptomeningeal metastatic disease, required more aggressive therapies, and died 9 years after diagnosis. Patients with KRAS mutations and SRGAP3-RAF-1 fusion had a more indolent course. Our series expands the molecular phenotype of tectal glioma with the potential for leptomeningeal dissemination. Future studies on establishing genotypic/phenotypic correlation from those who undergo biopsy are needed.
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Neoplasias Encefálicas , Neoplasias del Tronco Encefálico , Glioma , Femenino , Masculino , Humanos , Glioma/genética , Glioma/patología , Neoplasias del Tronco Encefálico/genética , Neoplasias del Tronco Encefálico/diagnóstico , Neoplasias del Tronco Encefálico/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Receptores ErbB/genética , Mutación , Neoplasias Encefálicas/genéticaRESUMEN
BACKGROUND: Dural closure is an important part of any pediatric spinal procedure with intradural pathology to prevent post-operative cerebrospinal fluid (CSF) egress and associated complications. Utilization of nonpenetrating titanium clips is one closure option that may have technical advantages such as ease of use and amenability to a narrow surgical corridor. No data exist on the efficacy of these clips for pediatric spinal dural closure. METHODS: A single surgeon case series of 152 pediatric patients underwent procedures involving lumbar durotomy with subsequent dural closure using the AnastoClip® nonpenetrating titanium clip closure system. Rates of infection and cerebrospinal fluid leak were measured during the follow-up period. RESULTS: A total of 152 pediatric patients (mean age: 6.25 ± 5.85 years, 50.7 % female) underwent intradural surgery with clip closure. The mean follow-up time was 57.0 ± 28.5 months. All patients were initially indicated for procedures involving spinal durotomy, with a majority being isolated tethered cord release (84.2 %). Others required tethered cord release and excision of a lipomyelomeningocele, spinal meningioma or arachnoid cyst (15.8 %). Post operative CSF leak occurred in two (1.32 %) patients at 11 and 18 days. Only one (0.66 %) patient was diagnosed with an infection, which was in a separate patient from those that had CSF leaks. CONCLUSION: The remarkably low incidence of post-operative CSF leak and infection with nonpenetrating titanium clips suggests a strong safety and efficacy profile for this form of dural closure in a pediatric cohort. Further research evaluating this technique is required to fully demonstrate its acceptability as a cost-effective alternative to traditional suture-based closure.
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Neoplasias Meníngeas , Titanio , Humanos , Femenino , Niño , Lactante , Preescolar , Masculino , Duramadre/cirugía , Instrumentos Quirúrgicos/efectos adversos , Pérdida de Líquido Cefalorraquídeo/complicaciones , Complicaciones Posoperatorias/etiología , Neoplasias Meníngeas/cirugíaRESUMEN
PURPOSE: To 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. METHODS: Five 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. RESULTS: Presenting 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 (< 1% to 15%). Next generation sequencing (3/5) and microarray (3/5) collectively were abnormal in four of five tumors. Methylation profiling was successfully performed on four of five samples which led to modification of diagnosis in two patients and the others were either unclassifiable or confirmatory with the histologic diagnosis. Mean time to follow up was 77 months (range 44-112 months). Mean progression free survival and overall survival were 24 months (range 6 to 52 months) and 100% respectively. CONCLUSION: Neurocytomas are a rare clinical entity that warrants further investigation into molecular and pathologic prognosticating features. Methylation profiling may aid in differentiation of neurocytoma from other difficult to diagnose tumors who share similar histologic features.
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Neoplasias Encefálicas , Neurocitoma , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Niño , Femenino , Humanos , Antígeno Ki-67 , Imagen por Resonancia Magnética , Masculino , Metilación , Neurocitoma/patología , SinaptofisinaRESUMEN
BACKGROUND: Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare tumor, first described by the WHO Classification of Central Nervous System Tumors in 2016. The clinical course is variable. Most tumors have low-grade histological findings although some may have more aggressive features. The goal of this systematic review was to identify prognostic factors for poor overall survival (OS). MATERIAL AND METHODS: We performed a systematic review using three databases (PubMed, Google Scholar, and Embase) and the following search terms: diffuse leptomeningeal glioneuronal tumor, DLGNT, DLMGNT. Statistical analysis was performed using Statistica 13.3. RESULTS: We included 34 reports in our review comprising 63 patients, published from 2016 to 2022. The median OS was 19 months (range: 12-51 months). Using multivariable Cox survival analysis, we showed that Ki-67 ≥ 7%, age > 9 years, symptoms of elevated intracranial pressure (ICP) at admission, and the presence of contrast-enhancing intraparenchymal tumor are associated with poor OS. Receiver operating characteristic (ROC) analysis identified Ki-67 ≥ 7% as a significant predictor of poor OS. CONCLUSIONS: Signs or symptoms of increased ICP with imaging findings of diffuse leptomeningeal enhancement should raise suspicion for DLGNT. In our systematic review, Ki-67 ≥ 7% was the most important prognostic factor for OS in DLGNT. The presence of intraparenchymal tumor with contrast enhancement was thought to represent disease progression and, together with patient age, was associated with poor OS.
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Neoplasias del Sistema Nervioso Central , Neoplasias Meníngeas , Neoplasias Neuroepiteliales , Neoplasias del Sistema Nervioso Central/patología , Niño , Humanos , Antígeno Ki-67 , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/patología , Neoplasias Neuroepiteliales/patología , PronósticoRESUMEN
OBJECTIVE: Traditional and extended transnasal transsphenoidal approaches provide direct access to a variety of anterior skull base pathologies. Despite increased utilization of transnasal approaches in children, anatomic studies on pediatric skull base maturation are limited. We herein perform a surgically relevant morphometric analysis of the sella and parasellar regions during pediatric maturation. METHODS: Measurements of sellar length (SL), sellar depth (SDp), sellar diameter (SDm), interclinoid distance (ID), intercavernous distance (ICD), and the presence of sphenoid sinus pneumatization (SSP), and sphenoid sinus type (SST) were made on thin-cut CT scans from 60 patients (evenly grouped by ages 0-3, 4-7, 8-11 12-15, 16-18, and >18 years) for analysis. Data were analyzed by sex and age groups using t-tests and linear regression. RESULTS: Sella and parasellar parameters did not differ by sex. SL steadily increased from 8.5 ± 1.2 mm to 11.5 ± 1.6 mm throughout development. SDp and SDm increased from 6.0 ± 0.9 mm to 9.3 ± 1.4 mm and 9.0 ± 1.6 mm to 14.4 ± 1.8 mm during maturation, with significant interval growth from ages 16-18 to adult (p < 0.01). ID displayed significant growth from ages 0-3 to 4-7 (18.0 ± 2.4 mm to 20.7 ± 1.9 mm; p = 0.002) and ICD from ages 0-3 to 8-11 (12.0 ± 1.8 mm to 13.5 ± 2.1 mm; p < 0.001), without further significant interval growth. SSP was not seen in patients < 3, but was 100% by ages 8-11. SSTs progressed from conchal/presellar (60% at ages 4-7) to sellar/postsellar (80% at adulthood). CONCLUSION: The sella and parasellar regions have varied growth patterns with development. Knowledge of the expected maturation of key anterior skull base structures may augment surgical planning in younger patients.
Asunto(s)
Silla Turca , Seno Esfenoidal , Adolescente , Adulto , Niño , Preescolar , Humanos , Recién Nacido , Silla Turca/diagnóstico por imagen , Silla Turca/patología , Silla Turca/cirugía , Base del Cráneo/diagnóstico por imagen , Base del Cráneo/cirugía , Seno Esfenoidal/cirugía , Tomografía Computarizada por Rayos XRESUMEN
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 < 0.001). The majority of growth in P-CC and PPS-PSC occurred by ages 12-15. Knowledge of these patterns may facilitate safe exposure of the IAC in children.