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Purpose: Various surgical nuances of the telovelar approach have been suggested. The necessity of removing the posterior arch of C1 to accomplish optimal tumor exposure is still debated. Therefore, we report on our experience and technical details of the fourth ventricular tumor resection in a modified prone position without systematic removal of the posterior arch of C1. Methods: A retrospective analysis of all pediatric patients, who underwent a fourth ventricular tumor resection in the modified prone position between 2012 and 2021, was performed. Results: We identified 40 patients with a median age of 6 years and a M:F ratio of 25:15. A telovelar approach was performed in all cases. In 39/40 patients, the posterior arch of C1 was not removed. In the remaining patient, the reason for removing C1 was tumor extension below the level of C2 with ventral extension. Gross or near total resection could be achieved in 34/39 patients, and subtotal resection in 5/39 patients. In none of the patients, a limited exposure, sight of view, or range of motion caused by the posterior arch of C1 was encountered, necessitating an unplanned removal of the posterior arch of C1. Importantly, in none of the cases, the surgeon had the impression of a limited sight of view to the most rostral parts of the fourth ventricle, which necessitated a vermian incision. Conclusion: A telovelar approach without the removal of the posterior arch of C1 allows for an optimal exposure of the fourth ventricle provided that critical nuances in patient positioning are considered. [ABSTRACT FROM AUTHOR]

Background: Intracranial teratoma represents a rare neoplasm, occurring predominantly during childhood. Characteristic symptoms depend on the location but are mainly hydrocephalus, visual disturbances, hypopituitarism, and diabetes insipidus. Initial diagnosis can be challenging due to similar radiological features in both teratomas and other lesions such as craniopharyngiomas. Gross total resection is recommended if feasible and associated with a good prognosis. Case description: A 10-year-old girl presented with newly diagnosed growth retardation, fatigue, cephalgia and bilateral hemianopia. Further laboratory analysis confirmed central hypothyroidism and hypercortisolism. Cranial magnetic resonance imaging showed a cystic space-occupying lesion in the sellar and suprasellar compartment with compression of the optic chiasm without hydrocephalus present, suspicious of craniopharyngioma. Subsequently, an endonasal endoscopic transsphenoidal near-total tumor resection with decompression of the optic chiasm was performed. During postoperative recovery the patient developed transient diabetes insipidus, the bilateral hemianopia remained unchanged. The patient could be discharged in a stable condition, while hormone replacement for multiple pituitary hormone deficiency was required. Surprisingly, histopathology revealed conspicuous areas of skin with formation of hairs and squamous epithelia, compatible with a mature teratoma. Conclusions: We present an extremely rare case of pediatric sellar teratoma originating from the pituitary gland and a review of literature focusing on the variation in presentation and treatment. Sellar teratomas are often mistaken for craniopharyngioma due to their similar radiographic appearances. However, the primary goal of treatment for both pathologies is to decompress eloquent surrounding structures such as the optic tract, and if applicable, resolution of hydrocephalus while avoiding damage to the pituitary stalk and especially the hypothalamic structures. If feasible, the aim of surgery should be gross total resection. [ABSTRACT FROM AUTHOR]

Objective: The challenge of pediatric brain tumor surgery is given due to a relative low prevalence but high heterogeneity in age, localization, and pathology. Improvements of long-term overall survival rates were achieved during the past decades stressing the importance of a multidisciplinary decision process guided by a national treatment protocol. We reviewed the entire spectrum of pediatric brain tumor surgeries from the perspective of an interdisciplinary pediatric neuro-oncology center in Germany. Methods: Every patient who underwent brain tumor surgery from January 2010 to June 2017 in our Pediatric Neurosurgery department was retrospectively included and evaluated regarding the course of treatment. Perioperative data such as tumor localization, timing of surgery, extent of resection, neuropathological diagnosis, transfusion rates, oncologic and radiation therapy, and neurological follow-up including morbidity and mortality were evaluated. Results: Two hundred ninety-three pediatric brain tumor patients were applicable (age: 8.28 ± 5.62 years, 1.22:1.0 m:f). A total of 531 tumor surgical interventions was performed within these patients (457 tumor resections, 74 tumor biopsies; mean interventions per patient 1.8 ± 1.2). Due to a critical neurologic status, 32 operations (6%) were performed on the day of admission. In 65.2% of all cases, tumor were approached supratentorially. Most frequent diagnoses of the cases were glial tumors (47.8%) and embryonal tumors (17.6%). Preoperative planned extent of resection was achieved in 92.7%. Pre- and postoperative neurologic deficits resolved completely in 30.7%, whereas symptom regressed in 28.6% of surgical interventions. New postoperative neurologic deficit was observed in 10.7%, which resolved or improved in 80% of these cases during 30 days. The mortality rate was 1%. Conclusion: We outlined the center perspective of a specialized pediatric neuro-oncological center describing the heterogeneous distribution of cases regarding age-related prevalence, tumor localization, and biology, which requires a high multidisciplinary expertise. The study contributes to define challenges in treating pediatric brain tumors and to develop quality indicators for pediatric neuro-oncological surgery. We assume that an adequate volume load of patients within a interdisciplinary infrastructure is warranted to aim for effective treatment and decent quality of life for the majority of long-term surviving pediatric tumor patients. [ABSTRACT FROM AUTHOR]

Purpose: A multimodality approach is generally considered for pediatric low-grade gliomas (LGG); however, the optimal management remains uncertain. The objective of the study was to evaluate treatment outcomes of pediatric LGG, focusing on long-term survival and factors related to outcomes. Methods: A retrospective review of 77 pediatric LGG cases treated at Ramathibodi Hospital, Thailand between 2000 and 2018 was performed. The inclusion criteria were all pediatric LGG cases aged ≤ 15 years. Diffuse intrinsic pontine gliomas and spinal cord tumors were excluded. Results: The median follow-up time was 8.2 years (range, 0.6–19.7). The median age at diagnosis was 6.2 years (interquartile range, 3.6–11.4). Treatments modality included tumor surgery (93%), chemotherapy (40%), and radiation therapy (14%). The 10-year overall survival (OS) and 10-year progression-free survival were 94% and 59%, respectively, for the entire cohort. The 10-year OS was 100% in three subgroups of patients: pilocytic subtype, WHO grade 1 tumors, and recipient of gross total resection. After multivariable analysis, no tumor surgery had a significantly unfavorable influence on overall survival. Conclusions: With a multimodality approach, pediatric LGGs had excellent outcome. Gross total resection is the standard primary treatment. Chemotherapy is the alternative standard treatment in incomplete resection cases, unresectable patients, or patients with progressive disease. Radiation therapy should be reserved as a salvage treatment option because of late complications that usually affect patients' quality of life. [ABSTRACT FROM AUTHOR]

Background: Pediatric gliomas are the most common central nervous system (CNS) tumors in children and adolescents and show different clinical and histopathological characteristics from the adult. The prognostic factors were poorly defined in pediatric intracranial gliomas. Methods: We collected pediatric intracranial glioma cases in our institution between February 2011 and June 2022. The patient clinical data, tumor growth characteristics, treatments, and follow-up data were analyzed by Cox regression analysis to identify impact factors on the prognosis of pediatric intracranial glioma patients. To corroborate our data, an independent cohort of pediatric intracranial glioma from the Surveillance, Epidemiology, and End Results Program (SEER) database was analyzed. Results: A total of 181 cases of pediatric low-grade glioma (PLGG) and 45 cases of pediatric high-grade glioma (PHGG) were included. In multivariate Cox regression analysis, tumor size > 59.5 mm (p = 0.006) and non-gross total resection (non-GTR; subtotal resection, STR, p = 0.042; biopsy, p = 0.012) were associated with decreased overall survival (OS) in PLGG patients. In PHGG patients, only chemotherapy (p = 0.023) was associated with OS while tumor size was marginally prognostic for OS (p = 0.051). Additional independent analysis of 2734 PLGG and 741 PHGG from the SEER database corroborated that larger tumor size was associated with decreased OS in LGG (p = 0.001) and HGG (p < 0.001) patients, separately. Conclusion: In this study, we found that tumor size was a significant prognostic factor for the OS of PLGG patients in our series. Besides the tumor size, the extent of resection also independently impacted the prognosis of PLGG patients. While in PHGG patients, only chemotherapy was associated with improved OS and tumor size was marginally prognostic. [ABSTRACT FROM AUTHOR]

Purpose : Atypical teratoid/rhabdoid tumors (AT/RTs) are malignant central nervous system (CNS) neoplasms of the young. Our study analyzed a large AT/RT cohort from the National Cancer Database (NCDB) to elucidate predictors of short-term mortality and overall survival (OS). Methods: Information was collected on patients with histologically confirmed AT/RT using the NCDB (2004–2016). Kaplan–Meier analysis indicated OS. Prognostic factors for 30-day mortality, 90-day mortality, and OS were determined via multivariate Cox proportional hazards (CPH) and logistic regression models. Results: Our cohort of 189 patients had a median age of 1 year (IQR [1, 4]) and tumor size of 4.7 ± 2.0 cm at diagnosis. Seventy-two percent were under 3 years old; 55.6% were male and 71.0% were Caucasian. Fifty (27.2%) patients received only surgery (S) (OS = 5.91 months), 51 (27.7%) received surgery and chemotherapy (S + CT) (OS = 11.2 months), and 9 (4.89%) received surgery and radiotherapy (S + RT) (OS = 10.3 months). Forty-five (24.5%) received S + CT + RT combination therapy (OS = 45.4 months), 13 (17.1%) received S + CT + BMT/SCT (bone marrow or stem cell transplant) (OS = 55.5 months), and 16 (8.70%) received S + CT + RT + BMT/SCT (OS = 68.4 months). Bivariate analysis of dichotomized age (HR = 0.550, 95% CI [0.357, 0.847], p = 0.0067) demonstrated significantly increased patient survival if diagnosed at or above 1 year old. On multivariate analysis, administration of S + CT + RT, S + CT + BMT/SCT, or S + CT + RT + BMT/SCT combination therapy predicted significantly (p < 0.05) increased OS compared to surgery alone. Conclusion: AT/RTs are CNS tumors where those diagnosed under 1 year old have a significantly worse prognosis. Our study demonstrates that while traditional CT, RT, and BMT/SCT combination regimens prolong life, overall survival in this population is still low. [ABSTRACT FROM AUTHOR]

Purpose: Children with a history of brain tumors do not appear to be at a significantly higher risk of sports-related injuries. Nevertheless, according to the systematic review and survey conducted by Perreault et al., 75% of healthcare professionals restrict their patients' participation in physical activities after brain tumor surgery. The aim of our study was to verify whether children after brain tumor surgery return to physical education (PE) classes. It was also an attempt to explore factors limiting return to physical activity. Methods: Patients after brain tumor surgery, ≤ 18 years old on admission with ≥ 1 year follow-up were included in the analysis. Data concerning the disease were collected and summarized in search of factors limiting return to physical activity. Meticulous information about return to sports and physical education at school was gathered during follow-up visits. Results: 71.43% of patients returned to school sports activities. Children who did not return to PE had markedly higher neoplasm WHO grade. Significant differences were also found between the groups in terms of hydrocephalus occurrence and need for additional oncological treatment. In univariate analysis, we identified neoplasm WHO grade, tumor location, presence of neurological deficit after the procedure, additional oncological treatment, and occurrence of hydrocephalus needing shunting as the risk factors for not returning to school physical education. Conclusions: The majority of pediatric brain tumor survivors return safely to physical education. Higher neoplasm WHO grade, presence of neurological deficit after the procedure, additional oncological treatment, and occurrence of hydrocephalus are risk factors for not returning to physical education. [ABSTRACT FROM AUTHOR]

Background: Many efforts have been performed in the last decade to accomplish the genomic and proteomic characterization of pediatric adamantinomatous craniopharyngioma with the purpose to elucidate the molecular mechanisms underlying the onset and development of this pediatric brain tumor, its high recurrence rate, and, although classified as a histologically benign neoplasm, its aggressive behavior. Methods: The focus of this review is to perform the new comparison of the proteomic profiles of the solid component and the intracystic fluid of adamantinomatous craniopharyngioma based on our previous results, obtained by both the top-down and the bottom-up proteomic approaches, to disclose differences and similarities, and to discuss the results in the context of the most recent literature. Results and conclusions: Proteins and peptides identified in the cyst fluid and in the solid component of adamantinomatous craniopharyngioma (AC) include beyond markers of inflammation (i.e., alpha-defensins), proteins involved in cell migration and protein degradation (i.e., beta-thymosin and ubiquitin peptides), whose main role might be in tumor growth and infiltration of the surrounding neural structures. These last appeared different in the solid components compared with the cyst fluid, missing their terminal part in the solid tissue, a feature generally associated to malignancies, which might represent a distinct molecular site for an aggressive behavior of AC. [ABSTRACT FROM AUTHOR]

Purpose: To report on our institutional cohort of patients and review the literature of medulloblastoma patients who developed skull/subdural-based lesions following treatment. Methods: Following institutional review board (IRB) approval, we retrospectively reviewed the medical records of four children with a history of treated medulloblastoma who developed non-specific skull-based/subdural lesions incidentally found on surveillance imaging. Results: Biopsies of the lesions proved the pathology to be low grade and included inflammatory myofibroblastic tumor, cortical fibrous defect consistent with fibroma, fibrous tissue, and fibrous dysplasia. The finding of calvarial or subdural fibrous lesions in children following therapy for medulloblastoma was noted in four out of 201 (136 with available follow-up data) medulloblastoma patients seen or discussed in our institution over the past 10 years. Conclusions: These lesions can grow over time and pose a differential diagnostic challenge with metastatic disease when identified. The skull and subdural space should be scrutinized for secondary lesions on surveillance imaging of patients with medulloblastoma who have received craniospinal irradiation as knowledge of this benign occurrence will assist with management. [ABSTRACT FROM AUTHOR]

Purpose: About half of brain tumors are located in supratentorial regions and 20% of them in eloquent brain cortex areas. The use of fMRI and intraoperative neuromonitoring allows safe surgery of these areas. Carrying out awake brain surgery (ABS) operations provides additional opportunities for direct-function monitoring. In pediatric practice, this method has not been used widely yet. Methods: We present the retrospective analysis of the results of pre-operative examination and surgical treatment of 12 patients with glial tumors located in eloquent cortex areas. Two patients had ABS operations twice. Intraoperative neuromonitoring was used in all the cases. Results: Twelve patients in total underwent fourteen ABS operations. According to histology results, patients with low-grade tumors prevailed, 11 (91.7%) out of 12. Seven (58.3%) patients had the tumor located in the projection of speech cortex area, four (33.3%) patients in the motor cortex area, and one (8.4%) patient in the visual cortex area. The youngest male was 8 years old. Temporary neurological deficit was diagnosed in three (25%) cases. The tumor was removed completely in 66.7% (eight) cases. Three patients were operated upon twice, two of whom had ABS operations twice. The awake phase of the surgery lasted from 30 to 110 min, 61.2 min on average. Conclusions: Our experience has shown sufficient safety of pediatric ABS operations. The achieved functional result and radicality of tumor removal prove that further application and development of this method for children with eloquent brain area tumors (EBATs) is reasonable. [ABSTRACT FROM AUTHOR]

Background: Microcystic meningiomas are extra axial masses that are extremely rare in the pediatric population. Intraventricular meningiomas are also rarely seen. Case Presentation: This case reports an 18-year-old boy who had an intraventricular mass on magnetic resonance imaging at the age of 12 years and had shown growth at a 6-year follow-up after subtotal resection. The mass was removed by total resection and pathological examination indicated microcystic meningioma. Conclusion: The present case is the first pediatric intraventricular microcystic meningioma in the literature. We believe that this unique case presented with its radiological, pathological and clinical features will contribute to the literature. [ABSTRACT FROM AUTHOR]

Purpose: Molecular subgroups of pediatric brain tumors associated with divergent biological, clinical, and prognostic features have been identified. However, data regarding the impact of subgroup affiliation on the outcome of children with malignant brain tumors treated with radiation-sparing protocol is limited. We report long-term clinical outcomes and the molecular subgroups of malignant brain tumors in young children whose first-line treatment was high-dose chemotherapy without irradiation. Methods: Tumor subclassification was performed using the Illumina HumanMethylation450 BeadChip (450k) genome-wide methylation array profiling platform. Clinical information was obtained from chart review. Results: Methylation array profiling yielded information on molecular subgroups in 22 children. Median age at surgery was 26 months (range 1–119 months). Among medulloblastomas (MB), all 6 children in the infant sonic hedgehog (SHH) subgroup were long-term survivors, whereas all 4 children in subgroup 3 MB died. There was one long-term survivor in subgroup 4 MB. One out of five children with ependymoma was a long-term survivor (RELPOS). Both children with primitive neuroectodermal tumors died. One child with ATRT TYR and one child with choroid plexus carcinoma were long-term survivors. Conclusions: The efficacy of high-dose chemotherapy radiation-sparing treatment appears to be confined to favorable molecular subgroups of pediatric brain tumors, such as infant SHH MB. Identification of molecular subgroups that benefit from radiation-sparing therapy will aid in the design of prospective, "precision medicine"–driven clinical trials. [ABSTRACT FROM AUTHOR]

Background: Ewing sarcoma typically arises in bone and is unrelated to intraparenchymal small blue cell embryonal central nervous system (CNS) tumors previously designated primitive neuroectodermal tumors (PNETs). When the CNS is impacted, it is usually secondary to local extension from either the epidural space, skull, or intracranial or spinal metastases. Primary examples within the cranial vault are rare, usually dural-based, and are largely case reports in the literature. We detail four pediatric patients with solitary, primary intracranial Ewing sarcoma, all manifesting the archetypal EWRS1 gene rearrangement that confirms diagnosis.Procedure: Neurosurgical Department records, spanning 21 years (1995–2016), were reviewed to identify patients. Demographics, clinical history, pathological/genetic features, and clinical course were retrieved from the medical record and personal files of the authors.Results: Four patients, one male and three females, age 5 to 16 years, were identified. One presented in extremis from a large lesion, two with soft tissue masses, and the fourth as an incidental finding after being involved in a motor vehicle collision. Three had clear bony involvement: a 10-year-old girl with a large left temporal lesion had clear origin in the skull, with spiculated calcified striations throughout the mass; a 9-year-old girl presented with a bony left petrous apex mass; and a 16-year-old girl presented with a left temporal mass with extension to the dura and underlying bone erosion. Only the 5-year-old boy had a large left frontoparietal mass traversing the falx with no bony contact. All four tumors manifested the diagnostic EWSR1 mutation and were treated with an Ewing sarcoma regimen. Outcomes were variable, with one patient showing progressive metastatic disease and death 3 years after presentation, one patient with disease-free survival 10.5 years after completion of therapy, and one alive and well at the completion of therapy 1 year after diagnosis. One patient completed therapy recently with post-therapy scans showing no evidence of disease.Conclusion: Testing for the EWSR1 mutation confirms the diagnosis of Ewing sarcoma and excludes other types of embryonal CNS tumors. Long-term disease-free survival is possible with adherence to the appropriate therapeutic regimen after gross surgical resection. [ABSTRACT FROM AUTHOR]

Background: Spontaneous regressions of brain stem gliomas are extremely rare. Only six cases have been reported in the literature. Case presentation: We describe the case of a patient who was diagnosed with a pontomedullary dorsal brain stem glioma at the age of 15 years. An open biopsy showed the presence of an anaplastic glioma. Because the patient and her parents refused conventional therapies, including radiation and chemotherapy, we followed up the patient by performing magnetic resonance imaging scans on her every 3 months. At 3 months after biopsy, we observed the radiological disappearance of her tumor. One year after biopsy, the tumor retained the spontaneous complete regression observed earlier. Conclusion: In this case report, we present the first report of the spontaneous complete regression of a brain stem glioma that was histologically proven to be a high-grade glioma and we believe that this regression was the natural progression of this case, as may be the scenario in a few other cases of brain stem gliomas. [ABSTRACT FROM AUTHOR]

Purpose: Cerebrospinal cavernous malformations (CCMs) are vascular lesions characterized by dilated and leaky capillary caverns. CCMs can cause seizures, focal neurological deficits or acute intracranial hemorrhage; however, most patients are asymptomatic. CCMs occur either sporadically or as a familial autosomal-dominant disorder. We present a clinical and molecular study of a patient with distinctive cerebral and spinal cavernous malformations following radiochemotherapy for a malignant brain tumor. Methods: The patient had multiple magnet resonance imaging (MRI) examinations of his brain and spine following radiochemotherapy for a primary intracranial germ cell tumor (GCT), as part of his oncologic follow-up. The MRI sequences included susceptibility-weighted imaging (SWI). The coding exons and their flanking intronic regions of KRIT1/CCM1 gene were analyzed for mutations by polymerase chain reaction (PCR) and direct sequencing. Results: MRI revealed numerous cerebral and spinal microhemorrhages and pronounced cavernous malformations that progressed with subsequent follow-up imaging. Genetic analysis demonstrated a novel heterozygous KRIT1/CCM1 two base pair deletion (c.1535_1536delTG) in exon 14. This deletion leads to a frameshift with a premature stop codon at nucleotide position 1553 and a highly likely loss of function of the KRIT1 protein. Conclusion: We describe a patient with a novel heterozygous germ line loss of function mutation in KRIT1, which is associated with rapid-onset and highly progressive CCMs after radiochemotherapy for a malignant brain tumor. [ABSTRACT FROM AUTHOR]

Purpose: Pediatric low-grade gliomas (LGGs) are the most frequent solid tumor in childhood. Based on an increasing number of literature reports, maximal safe resection is recommended as the first line of treatment whenever possible. However, distinguishing tumor tissue from the surrounding normal brain is often challenging with infiltrating neoplasms, even with the assistance of intraoperative, microscopic and conventional neuronavigation systems. Therefore, any technique that enhances the detection and visualization of LGGs intraoperatively is certainly desirable. Methods: In this paper, we reviewed the role of intraoperative conventional ultrasound and contrast-enhanced ultrasound (CEUS) as a tool for extending tumor resection in LGGs. Moreover, our experience with this technology is reported and discussed. Results: Both B-mode and CEUS are helpful in highlighting LGGs, detecting tumor margins and providing additional information such as vascularization, thus improving the safety of a more radical resection. Conclusions: Although the full potentialities of the method are yet to be explored, intraoperative ultrasound is a promising tool in oncologic surgery and LGG surgery. [ABSTRACT FROM AUTHOR]

Object: Glioneuronal tumors are common neoplasms among the cerebral hemisphere during childhood. They consist of several histological types, of which gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNTs) are most common and often present with seizures. A great majority of glioneuronal tumors are benign. However, there are conflict reports regarding postoperative tumor recurrence rates and seizure control. The authors analyzed and compared these tumors for their locations and histology and the tumor and seizure control following resection. Methods: The authors conducted a retrospective analysis of patients with pediatric glioneuronal tumors in the cerebral hemisphere. All histology reports and neuroimaging are reviewed. Seizure group and non-seizure group were compared with their tumor types and locations. The extent of tumor resections were divided into gross total resection (GTR) and subtotal resection (STR). Postoperative tumor recurrence-free survival (RFS) and seizure-free survival for patients who had the initial surgery done at our institution were calculated using Kaplan-Meier method. Results: There were 90 glioneuronal tumors including 58 GGs, 22 DNTs, 3 papillary glioneuronal tumor, 3 desmoplastic infantile gangliogliomas, 3 anaplastic GGs, and 1 central neurocytoma. Seventy-one patients (seizure group) presented with seizures. The temporal lobe is the most common location, 50 % in this series. GTR was attained in 79 patients and STR in 11. All of the patients with GTR had lesionectomy, and only six of them had extended corticectomy or partial lobectomy. Postoperative seizure outcome showed that 64 (90 %) of seizure group had Engel's class I, but five patients subsequently developed recurrent seizures. Patients with DNTs had a higher seizure recurrence rate. Tumor RFS was 87 % at 5 years and 75.5 % at 10 years. There are no significant difference in tumor recurrences between GGs and DNTs ( p = 0.876). Comparison between GRT (67) and STR (9) showed that in spite of the better 5-year tumor RFSs among GRT group (94 %) than STR group (66 %), the 10-year RFSs showed no significant difference between GRT and STR groups ( p = 0.719). Recurrent seizures are often related to recurrent tumor. Conclusion: Lesionectomy alone often provides a high-rate seizure freedom. GGs and DNTs are benign tumor, but recurrences of GGs and DNTs are not uncommon. They may show late recurrences in spite of GTR. These patients need longer follow-up for 10 years. Recurrent seizures are often related to a tumor recurrence. [ABSTRACT FROM AUTHOR]

Background: Cediranib (AZD2171), an oral pan-vascular endothelial growth factor (VEGF) inhibitor, was evaluated in this phase I study to determine its toxicity profile, dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics in children and adolescents with recurrent or refractory primary central nervous system (CNS) tumors. Methods: Children and adolescents <22 years were enrolled into one of two strata: stratum I-those not receiving enzyme-inducing anticonvulsant drugs (EIACD) and stratum II-those receiving EIACDs. Dose-level selection was based on the continual reassessment method (CRM). Results: Thirty-six eligible patients with median age of 12.7 years (range, 5.4-21.7 years) in stratum I (24 males) and 12 patients (7 males) in stratum II with median age of 13.4 years (range, 8.9-19.5 years) were initially assessed over a 4-week DLT evaluation period, modified to 6 weeks during the study. An MTD of 32 mg/m/day was declared; however, excessive toxicities (transaminitis, proteinuria, diarrhea, hemorrhage, palmer-planter syndrome, reversible posterior leukoencephalopathy) in the expansion cohort treated at this dose suggested that it might not be tolerated over a longer time period. An expansion cohort at 20 mg/m/day also demonstrated poor longer-term tolerability. Diffusion and perfusion MRI and PET imaging variables as well as biomarker analysis were performed and correlated with outcome. At 20 mg/m/day, the median plasma area under the concentration-time curve at steady state was lower than that observed in adults at similar dosages. Conclusions: While the MTD of once daily oral cediranib in children with recurrent or progressive CNS tumors was initially defined as 32 mg/m/day, this dose and 20 mg/m/day were not considered tolerable over a protracted time period. [ABSTRACT FROM AUTHOR]

Purpose: There is little information on pediatric oligodendroglial tumor located in the brainstem because of its rarity. Methods: Here, we present two pediatric cases of pontine oligodendroglial tumors with radiological findings atypical for diffuse intrinsic pontine glioma. Results: The first patient was an 8-year-old boy. Brain magnetic resonance imaging (MRI) demonstrated diffuse high-intensity changes in the pons, left middle cerebellar peduncle, and part of the left cerebellar hemisphere on T2-weighted and fluid-attenuated inversion recovery images, with an enhanced spot lesion in the left cerebellar hemisphere. The pathological diagnosis was anaplastic oligodendroglioma, and we identified a mutation in histone H3.3 in the tumor specimen. He succumbed to massive disseminated relapse 7 months from diagnosis despite local radiation therapy. The second patient, a 2-year-old girl, was diagnosed with oligoastrocytoma. Brain MRI revealed a large mass in her rostral pons extended to the fourth ventricle with obstructive hydrocephalus. The tumor recurred with intracranial dissemination 56 months post-surgery. Conclusions: Pediatric brainstem oligodendroglial tumors can include histone H3.3-mutated tumors and have a tendency to disseminate throughout the neuroaxis at the time of relapse. [ABSTRACT FROM AUTHOR]

Purpose: MRI alone has its limitations for target selection in biopsy or resection in newly diagnosed and pretreated pediatric brain tumor patients. F-FET-PET imaging is considered to identify metabolically active tumor tissue and to differentiate it from therapy-associated changes. We retrospectively analyzed our experience with F-FET-PET in targeted surgical interventions for pediatric brain tumors. Methods: In 26 cases with lesions suspicious of a growing brain tumor on MRI, either newly diagnosed or after antitumoral treatment led to F-FET-PET imaging for target selection prior to stereotactic biopsy, navigated open biopsy or navigated microsurgical tumor resection. Indications for F-FET-PET imaging were visualization of metabolic active tumor tissue within diffuse tumors or pretreated lesions as well as depicting their extent. Results: F-FET-PET integration in surgery was feasible in all patients using stereotaxy or neuronavigation. Sensitivity for tumor detection was 20/24. F-FET-PET was false positive in two pretreated patients. Conclusion: F-FET-PET imaging is helpful for target selection and can be integrated in surgical guidance. F-FET-PET image-guided surgical targeting yielded histological diagnosis with decent specificity and high sensitivity in our cohort of pediatric brain tumor patients. Our results warrant further evaluation of F-FET-PET imaging for surgical guidance. [ABSTRACT FROM AUTHOR]

Rosette-forming glioneuronal tumor (RGNT) was first published in 2002 and was described as a benign and indolent tumor. It was also included in the 2007 World Health Organization (WHO) classification of tumors as a grade 1 tumor for its benign clinical behavior and the possibility of surgical cure. Pathologically, RGNT is a mixed neuronal-glial tumor which consists of two distinct histological components-one with uniform neurocytes forming rosettes and/or perivascular pseudorosettes and the other being astrocytic in nature resembling pilocytic astrocytoma (biphasic pattern). We present the clinical course and pathological findings of two distinctively different cases. The first one was a 4-year-old girl with head trauma and a tumor which was incidentally found by CT. Pathology revealed that the tumor contained neurocytoma components and areas of relatively high proliferative ability with the first report of the presence of midsized bright elliptic cells. The other case was a 19-year-old girl whose imaging studies showed hydrocephalus and a brain stem tumor. She underwent endoscopic third ventriculostomy and biopsy, followed by observation. An MRI taken 6 months later showed progression of the tumor and she subsequently had the tumor excised. We are considering the possibility for our RGNT cases to correspond to a higher WHO grade as they have shown rapid progression, contrary to the already established, and their character, origin, differential diagnosis, and treatment plans have been discussed. [ABSTRACT FROM AUTHOR]

Background: Pilomyxoid astrocytoma (PMA) was recently classified as a variant of pilocytic astrocytoma (PA) with significantly more aggressive clinical features than those of PA. Like PAs, PMAs frequently arise in the chiasmatic/hypothalamic regions. The cerebellum is also a common site of occurrence for PAs but not for PMAs. Case description: We present the case of a 31-month-old boy with cerebellar PMA that showed rapid regrowth during the 3 months following the first subtotal resection. Gross total resection was achieved in the second surgery, followed by radiation to the tumor bed. Results: During follow-up over the next 12 years, there has been no evidence of recurrence on magnetic resonance imaging. Conclusions: Although the prognosis of cerebellar PMAs remains unknown because of the paucity of cases, the relevant literature reports a more favorable outcome for cerebellar PMAs than for PMAs occurring at other locations. The results of this case study and a review of the relevant literature advocate radical resection, sometimes involving multiple surgeries, for cerebellar PMAs because gross total or near total resection is more feasible in the cerebellum than in other locations. [ABSTRACT FROM AUTHOR]

Introduction: Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a rare subtype of primitive neuroectodermal tumors first reported in 2000. It is rare among the group of embryonal central nervous system tumors with approximately 50 reported cases. ETANTR has been suggested to be a separate entity among this group of tumors. Case report: Herein, we present only the second autopsy case of ETANTR, which occurred in a 17-month-old boy, and was located in the brainstem. The tumor was inoperable, and despite chemotherapy, the child died 3 months after initial hospitalization. A brain only autopsy was performed. Discussion: Neuropathological and neuroimaging examinations suggest ETANTR grew by expansion rather than invasion distorting anatomical structures of the posterior fossa. We suggest that the characteristic histopathological picture of the tumor is the result of multifocal and dispersed germinative activity surrounded by mature neuropil-like areas. Conclusion: ETANTR is a pediatric tumor occurring in children under 4 with a significantly poor prognosis with more cases and research required to characterize this rare embryonal tumor. [ABSTRACT FROM AUTHOR]

Objective: Fronto-cerebellar association fibers (FCF) are involved in neurocognitive regulatory circuitry. This may also be relevant for cerebellar mutism syndrome (CMS) as a complication following posterior fossa tumor removal in children. In the present study, we investigated FCF by diffusion tensor imaging in affected children and controls. Methods: Diffusion-weighted MR imaging at 3 T (GE) allowed tractography of FCF using a fiber tracking algorithm software (Brainlab 2.6) in 29 patients after posterior fossa tumor removal and in 10 healthy peers. Fiber tract volumes were assessed and fiber signals were evaluated in a semiquantitative manner along the anatomical course. Results: Volumes of FCF revealed significant diminished values in pediatric patients with symptoms of CMS (19.3 ± 11.7 cm) when compared with patients without symptoms of CMS (26.9 ± 11.9 cm) and with healthy peers (36.5 ± 13.82 cm). In medulloblastoma patients, the volume of FCF was also significantly reduced in patients with symptoms of CMS despite having the same antitumor therapy. In semiquantitative analysis of the fiber tract signals, differences were observed in the superior cerebellar peduncles and midline cerebellar structures in patients with symptoms of CMS. Conclusion: Using DTI, which allows the visualization of fronto-cerebellar fiber tracts, lower FCF tract volumes and diminished fiber signal intensities at the level of the superior cerebellar peduncles and in midline cerebellar structures were identified in patients with postoperative symptoms of CMS. Our study refers to the role of a neural circuitry between frontal lobes and the cerebellum being involved in neurocognitive impairment after posterior fossa tumor treatment in children. [ABSTRACT FROM AUTHOR]

Background: Microcystic meningioma (MM) is a World Health Organization grade I tumor that is rare in the pediatric population. Meningiomas account for approximately 2-4 % of all childhood central nervous system (CNS) tumors compared to approximately 20 % of all adult CNS tumors. The authors present one of the few confirmed cases of microcystic meningioma in a child and discuss the characteristic radiographic appearance and histological findings. History: We report the case of an 11-year-old boy who presented with first-time seizure and imaging consistent with brain tumor. There was significant vasogenic edema within the entire right hemisphere, disproportionate to the size of the falcine-based tumor. Histopathological analysis revealed the microcystic subtype of meningioma. Discussion: We review the radiographic characteristics, histopathological findings, and reported pediatric cases of MM in conjunction with our case. Conclusion: MM has distinct radiographic characteristics (variable enhancement, lack of a dural tail, and disproportionate vasogenic edema) that can be misinterpreted in the pediatric population, suggesting a more aggressive tumor. [ABSTRACT FROM AUTHOR]

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare aggressive infantile neoplasm of uncertain origin. This study was performed to assess the clinicopathologic and immunohistochemical features of four AT/RT cases. Two cases were male and two were female, and their ages ranged from 8 to 103 months. Tumors were located in the cerebellum (two cases), frontoparietal lobe (one case), and third ventricle (one case). Histopathologically, the tumors were composed of rhabdoid cells and undifferentiated small cells mixed with epithelial or mesenchymal components. However, one of the tumors was composed predominantly of a mesenchymal component mimicking a sarcoma. Immunohistochemically, vimentin (4/4), epithelial membrane antigen (4/4), cytokeratin (3/4), smooth muscle actin (4/4), glial fibrillary acidic protein (4/4), S-100 (4/4), and synaptophysin (1/4) were positive in varying proportions, while desmin and INI-1 were negative in all the cases. All of the patients died within a mean of 14 months due to tumor progression despite the chemotherapy. Only one of our patients lived for 40 months after the diagnosis. In conclusion, AT/RTs are aggressive tumors. They can occur in a variety of locations, such as the third ventricle. Morphologically, a large spectrum can be seen, like predominantly sarcoma in appearance, but immunohistochemistry is helpful in the correct diagnosis. [ABSTRACT FROM AUTHOR]

Case report: An 8-year-old boy presented to the emergency department after a generalized tonic-clonic seizure that lasted for 5 min. Magnetic resonance imaging showed a 2×2 cm, intraaxial, contrast-enhanced cortical lesion in the posterior right frontal lobe. On several images the lesion appeared to be dural-based and was presumed to be a meningioma. The patient was placed on dilantin and returned 1 month later for elective surgical resection. Outcome: At surgery, a rim of intact pia was identified between the dura and the tumor. Although initial frozen-section analysis was consistent with meningioma, subsequent immunohistochemical staining and review at an outside institution established the diagnosis of intracerebral schwannoma. The patient's postoperative course was uncomplicated and he remains seizure-free with no sign of recurrence at 18 months. Conclusion: Intracerebral schwannomas are uncommon cortical lesions in children. Imaging characteristics alone can be misleading; neuropathological support is essential for accurate diagnosis. [ABSTRACT FROM AUTHOR]

Objects: A pilomyxoid astrocytoma (PmA) is considered to be either a more aggressive variant of a pediatric pilocytic astrocytoma (PA) or a tumor of a separate entity. Methods: We present two cases of pediatric optic-chiasmatic PmA. Proton magnetic resonance spectroscopic imaging (MRSI) of the PmA revealed decreased concentrations of total choline (Cho), creatine (Cr), and N-acetyl aspartate (NAA). In contrast, proton MR spectra of PAs showed elevated Cho and decreased Cr and NAA signals. Conclusion: Low metabolite concentrations in PmAs detected by MRSI may therefore help to distinguish PmAs from PAs preoperatively. [ABSTRACT FROM AUTHOR]

Pediatric cerebellar astrocytomas are frequently curable by complete surgical resection. However, even incompletely resected tumors may lie dormant indefinitely or spontaneously involute, and tumors thought to be completely excised have reappeared in the same location several years later. Because of the unpredictable nature of some cerebellar astrocytomas, this study was designed to analyze several variables for their potential value in predicting disease progression. The charts of 78 children treated at a children's hospital between 1966 and 1993 were reviewed; 62 tumors were pilocytic, 13 were fibrillary, and 3 were mixed oligoastrocytomas. Four children had the additional diagnosis of neurofibromatosis type 1, and those children were considered separately. Of the remaining 74 children, 48 underwent postoperative contrast-enhanced computerized tomography or magnetic resonance imaging. Of those 48 children, 17 had residual disease, and in 15 cases the tumor volume could be measured. Frequently the surgeon's report conflicted with the postoperative scan regarding the presence of residual disease. However, the surgeon's report of brainstem infiltration correlated highly with residual disease on postoperative imaging. On univariate Cox analysis, sex, age, tumor location, and tumor morphology did not show prognostic significance. In spite of their differences, the surgeon's report of residual tumor and the presence of residual disease on postoperative imaging were similar in their correlation with disease progression. However, on multivariate analysis, the volume of residual tumor was most closely linked with disease progression. Only the presence of fibrillary histology significantly complemented the volume of residual tumor as a negative prognostic indicator. [ABSTRACT FROM AUTHOR]

Internal drainage of cerebrospinal fluid (CSF) to the abdominal cavity via a ventriculo-peritoneal shunt (VPS) is a procedure that is commonly used for the treatment of obstructive hydrocephalus. As this condition is often caused by brain tumors blocking the natural CSF pathways, a VPS, as an artificial anastomosis, can provide the means for tumor cells to be spread with the CSF. A review of the literature reveals 35 VPS-related abdominal metastases from pediatric brain tumors; 17 in patients aged 0–9 (group A) and 18 in patients aged 10–18 years (group B); the mean age of male patients was 10.5, and that of female patients, 7 years. The male-to-female ratio was 1.9 (group A 1.1, group B 3.5), and the mean interval between shunt operation and diagnosis of metastases, 16.7 months (group A 11.6, group B 22.6 months; boys 21.6, girls 7.5 months). During the observation period, 22/30=73.3% of the patients died (group A 13/15=86.7%, group B 9/15=60%; boys 13/21=61.9%, girls 9/9=100%); their mean survival time after shunting was 18.7 months (group A 15.7, group B 23.1 months; boys 25.5, girls 9 months). The four most common sources of metastases were germinomas (9 cases=25.7%; group A none, group B 9), medulloblastomas (8 cases=22.9%, group A 7, group B 1), endodermal sinus tumors (5 cases=14.3%, group A 1, group B 4), and astrocytomas (4 cases=11.4%, group A 4, group B none). Metastases via VPS are rare, but should be considered as a possible complication and mode of systemic spread in children with primary intracranial malignancy. They have a more favorable prognosis in boys and in the second decade of life. [ABSTRACT FROM AUTHOR]

We report a retrospective study of 35 cases of medulloblastoma in pediatric patients treated at our institution during an 18-year period. Ten of the patients were infants (age <2 years) and 25 were children (age >2 years). The main factors affecting prognosis were total removal of the tumor ( P<0.01) and tumor stage ( P<0.01). There were no differences between the survival rate of infants and children, infants had a worse prognosis in regard to quality of life than children. [ABSTRACT FROM AUTHOR]

Using the monoclonal antibody Ki-67, proliferating cells were demonstrated immunohistochemically in 16 tumors of the nervous system in children, and these findings compared with those in 44 adult tumors. The antibody, which reacts with a nuclear protein expressed during the G1, S, G2, and M phases of the cell cycle, was demonstrated in frozen (13 cases) or smear (3 cases) sections using the peroxidase-antiperoxidase method. The percentage of stained tumor cells in children was in general agreement with the histological grade, ranging from 0.2% in a schwannoma to 12.4% in a juvenile type of glioblastoma. In a medulloblastoma, the fraction of labeled nuclei was 10.2%. In malignant gliomas of children, the percentage of stained cells did not differ from that in adult tumors. However, some cases demonstrated an unusually higher number of positive cells associated with higher cellularity than did adult tumors; this is in agreement with the content of small immature tumor cells in many pediatric tumors. The use of Ki-67 staining could become an important additional criterion for predicting the biologic behavior of nervous system neoplasms in children. [ABSTRACT FROM AUTHOR]

Posterior fossa craniotomy is generally done starting with two lateral burr holes. Single midline burr hole is often avoided for the fear of injury to the venous sinuses. In this paper, we retrospectively evaluated the risk of dural tear or venous sinus injury with the latter approach. Patients who had a posterior fossa craniotomy at the Children’s Hospital of Michigan between 2003 and 2009 were analyzed. Seventy-one patients had been operated for a posterior fossa lesion, and 154 had a Chiari I decompression. Suboccipital craniotomy was performed utilizing a starting midline suboccipital burr hole. The craniotomy was completed using Midas Rex with B1 foot plate starting laterally from the burr hole and then over to the foramen magnum including the foramen magnum lip. In patients who had a tumor resection, the bone flap was replaced and secured with plates on both sides. One patient had a dural tear along the inferior aspect of the craniotomy not extending into the foramen magnum. There was no instance of venous sinus injury or undue bleeding from the burr hole. None of the patients had an infection requiring removal of the bone flap. This paper confirms the safety of utilizing midline burr hole for starting a posterior fossa craniotomy. [ABSTRACT FROM AUTHOR]

Symptomatic subependymomas in the pediatric age group are rare. A 14-year-old girl with a IV ventricle subependymoma is described. She had a 2-month history of progressive headache, neck stiffness and nausea. Computed tomography revealed hydrocephalus for which a ventriculoperitoneal shunt was inserted. A nuclear magnetic resonance (NMR) scan later displayed a mass lesion in the roof of the IV ventricle. A suboccipital craniectomy was performed with total excision of a subependymoma. [ABSTRACT FROM AUTHOR]

Intraparenchymal hemorrhage in the left frontal lobe suddenly occurred in a 7-year-old girl who had undergone partial removal of an undifferentiated brain stem glioma and received craniospinal (30 Gy) and posterior fossa booster (20 Gy) irradiation at the age of 20 months. The brain hemorrhage was thought to be delayed irradiation effect. Follow-up neuro-imaging at age 9 years showed two more small occult chronic and subacute hemorrhages in the brain. The possibility of repeated hemorrhage as a delayed reaction to brain irradiation is emphasized. [ABSTRACT FROM AUTHOR]

A case of congenital desmoplastic fibroma of the right parietal area between the two skull tables is presented. [ABSTRACT FROM AUTHOR]