Search

Introduction: Outcomes for pineal region and superior cerebellar tumors in young children often hinge on extent of microsurgical resection, and thus choosing an approach that provides adequate visualization of pathology is essential. The occipital interhemispheric transtentorial (OITT) approach provides excellent exposure while minimizing cerebellar retraction. However, this approach has not been widely accepted as a viable option for very young children due to concerns for potential blood loss when incising the tentorium. The aim of this paper is to characterize our recent institutional experience with the occipital interhemispheric transtentorial approach (OITT) for tumor resection in infants and toddlers. Methods: A retrospective study was performed between 2016 and 2023 of pediatric patients less than 36 months of age who underwent OITT for tumor resection at a high-volume referral center. Patients with at least 3 months of postoperative follow-up and postoperative MRI were included. Primary outcomes included extent of resection, intraoperative and postoperative complications, and neurologic outcome. Secondary outcomes included length of stay and estimated blood loss. Results: Eight patients, five male, were included. The median age at the time of surgery was 10 months (range 5–36 months). Presenting symptoms included macrocephaly, nausea/vomiting, strabismus, gait instability, or milestone regression. Hydrocephalus was present preoperatively in all patients. Average tumor volume was 38.6 cm3, ranging from 1.3 to 71.9 cm3. All patients underwent an OITT approach for tumor resection with stereotactic guidance. No intraoperative complications occurred, and no permanent neurologic deficits developed postoperatively. Gross total resection was achieved in all cases per postoperative MRI report, and no instances of new cerebellar, brainstem, or occipital lobe ischemia were noted. Conclusions: OITT approach for tumor resection in very young children (≤ 36 months) is an effective strategy with an acceptable safety profile. In our series, no significant intraoperative or postoperative complications occurred. To our knowledge, this is the first report describing this technique specifically in patients less than 36 months of age. [ABSTRACT FROM AUTHOR]

Background: Texture analysis extracts many quantitative image features, offering a valuable, cost-effective, and non-invasive approach for individual medicine. Furthermore, multimodal machine learning could have a large impact for precision medicine, as texture biomarkers can underlie tissue microstructure. This study aims to investigate imaging-based biomarkers of radio-induced neurotoxicity in pediatric patients with metastatic medulloblastoma, using radiomic and dosiomic analysis. Methods: This single-center study retrospectively enrolled children diagnosed with metastatic medulloblastoma (MB) and treated with hyperfractionated craniospinal irradiation (CSI). Histological confirmation of medulloblastoma and baseline follow-up magnetic resonance imaging (MRI) were mandatory. Treatment involved helical tomotherapy (HT) delivering a dose of 39 Gray (Gy) to brain and spinal axis and a posterior fossa boost up to 60 Gy. Clinical outcomes, such as local and distant brain control and neurotoxicity, were recorded. Radiomic and dosiomic features were extracted from tumor regions on T1, T2, FLAIR (fluid-attenuated inversion recovery) MRI-maps, and radiotherapy dose distribution. Different machine learning feature selection and reduction approaches were performed for supervised and unsupervised clustering. Results: Forty-eight metastatic medulloblastoma patients (29 males and 19 females) with a mean age of 12 ± 6 years were enrolled. For each patient, 332 features were extracted. Greater level of abstraction of input data by combining selection of most performing features and dimensionality reduction returns the best performance. The resulting one-component radiomic signature yielded an accuracy of 0.73 with sensitivity, specificity, and precision of 0.83, 0.64, and 0.68, respectively. Conclusions: Machine learning radiomic-dosiomic approach effectively stratified pediatric medulloblastoma patients who experienced radio-induced neurotoxicity. Strategy needs further validation in external dataset for its potential clinical use in ab initio management paradigms of medulloblastoma. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to provide an exhaustive analysis of pediatric low-grade gliomas (pLGGs) in the cerebellar hemispheres, focusing on incidence, clinical characteristics, surgical outcomes, and prognosis. It seeks to enhance understanding and management of pLGGs in the pediatric population. Methods: We conducted an observational, descriptive, retrospective, and cross-sectional study at a pediatric hospital, reviewing medical records of 30 patients with cerebellar hemispheric pLGGs treated from December 2014 to January 2023. Data collection included demographics, clinical presentation, imaging findings, surgical approach, postoperative complications, histopathological diagnosis, hydrocephalus management, and follow-up. Molecular markers and adjuvant therapies were also analyzed. Results: The cohort predominantly presented with cerebellar symptoms, with 60% showing hydrocephalus at diagnosis. MRI with gadolinium was crucial for diagnosis. Surgical focus was on achieving gross total resection (GTR), accomplished in 70% of cases. Postsurgical hydrocephalus was less common, and cerebellar mutism was not reported. While a complete molecular analysis was not performed in all cases, available data suggest significant influence of molecular markers on prognosis and therapeutic options of pLGGs. Conclusions: This study highlights the unique clinical and molecular characteristics of cerebellar hemispheric pLGGs in children. The lower incidence of postoperative hydrocephalus and absence of cerebellar mutism are notable findings. Emphasizing a multidisciplinary approach, our findings contribute to a deeper understanding of pediatric pLGGs, underscoring the need for personalized treatment strategies and vigilant follow-up. [ABSTRACT FROM AUTHOR]

Medulloblastoma, the most common malignant brain tumor in children, presents a complex treatment challenge due to its propensity for infiltrative growth within the posterior fossa and its potential attachment to critical anatomical structures. Central to the management of medulloblastoma is the surgical resection of the tumor, which is a key determinant of patient prognosis. However, the extent of surgical resection (EOR), ranging from gross total resection (GTR) to subtotal resection (STR) or even biopsy, has been the subject of extensive debate and investigation within the medical community. Today, the impact of neurosurgical EOR on the prognosis of medulloblastoma patients remains a complex and evolving area of investigation. The conflicting findings in the literature, the challenges posed by critical surrounding anatomical structures, the potential for surgical complications and neurologic morbidity, and the nuanced interactions with molecular subgroups all contribute to the complexity of this issue. As the field continues to advance, the imperative to strike a delicate balance between maximizing resection and preserving quality of life remains central to the management of medulloblastoma patients. [ABSTRACT FROM AUTHOR]

Background: Medulloblastoma is the most common malignant primary pediatric brain tumor. Over the years, an increase in published research has been observed on this topic. However, there is a lack of analysis on the characteristics and trends and the socioeconomic indicators associated with medulloblastoma research productivity and impact. Methods: The Scopus database was used to search all articles from inception to 2020. Bibliometric information was obtained from Scopus, and bibliometrics diagrams were created using VOSviewer software. Statistical analysis was performed using the GraphPad Prism software version 7. Results: A total of 4058 research articles on medulloblastoma research worldwide were included in this study. There has been an increase in published articles, with a steep increase observed in the last decade. The country with the most publications is the USA, with St. Jude Children's Research Hospital as the most productive institution in medulloblastoma research. The articles mainly focused on molecular biology, diagnosis, treatment, prognostic factors for medulloblastoma, and research on other pediatric tumors. The number of collaborations with other countries showed the strongest positive correlation with scientific productivity. Conclusion: This analysis showed the trend and characteristics of published articles. The results of this study emphasized the need to increase funding for research, support for researchers and physicians, and promote more collaborations with countries and institutions engaged in medulloblastoma research. [ABSTRACT FROM AUTHOR]

Purpose: During the last decade, there has been renewed interest in stereotactic approaches to diffuse intrinsic pontine gliomas (DIPGs) in children, due to the development of new concepts in molecular biology and management, and subsequent need for tissue sampling. Stereotactic frame-based and robot-assisted techniques are associated with reduced target error and have been incorporated into standard practice at our institution. Methods: Four children (age 2–7 years) underwent a robot-assisted frame-based transcerebellar approach using the Leksell G frame coupled with Renishaw's neuromate® stereotactic robot. The procedures included 3 biopsies (two brainstem tumors and one cerebellar hemispheric lesion) and 1 depth electrode implantation into a low-grade tumor remnant (ganglioglioma) of the middle cerebellar peduncle causing drug-resistant epilepsy in a young girl. Targeting was based on MRI, and in one case, 18F-FET-PET was coregistered to MRI to improve sampling accuracy. The frame was applied 180° rotated compared to standard orientation, and patients were positioned prone during surgery and stereotactic preoperative CT scan. Postoperative CT scan ruled out complications and was coregistered to preoperative MRI to check the target accuracy. Results: No complications occurred, and targeting was accurate in all cases. All tissue samplings provided proper histology; depth electrode EEG exploration was diagnostic and led subsequent resective surgery. Conclusions: According to our experience, the transcerebellar frame-based robotic stereotactic approach to the cerebellum and the brainstem is feasible, safe, and effective even in young children. [ABSTRACT FROM AUTHOR]

Objective: To describe disease outcomes including overall survival and relapse patterns by subgroup in young pediatric patients treated for medulloblastoma with a radiation-sparing approach. Methods: Retrospective analysis of clinical outcomes includes treatment, relapse, and salvage therapy and late effects in children treated for medulloblastoma with a radiation-sparing approach at British Columbia Children's Hospital (BCCH) between 2000 and 2020. Results: There were 30 patients (median age 2.8 years, 60% male) treated for medulloblastoma with a radiation-sparing approach at BCCH. Subgroups included Sonic Hedgehog (SHH) (n = 14), group 3 (n = 7), group 4 (n = 6), and indeterminate status (n = 3). Three- and 5-year event-free survival (EFS) were 49.0% (30.2–65.4%) and 42.0% (24.2–58.9%) and overall survival (OS) 66.0% (95% CI 46.0–80.1%) and 62.5% (95% CI 42.5 and 77.2%), respectively, with a median follow-up of 9.5 years. Relapse occurred in 12/25 patients following a complete response, of whom six (group 4: n = 4; group 3: n = 1; unknown: n = 1) were successfully salvaged with craniospinal axis (CSA) RT and remain alive at a median follow-up of 7 years. Disease/treatment-related morbidity included endocrinopathies (n = 8), hearing loss n = 16), and neurocognitive abnormalities (n = 9). Conclusions: This radiation sparing treatment approach for young patients with medulloblastoma resulted in a durable cure in most patients with SHH subgroup medulloblastoma. In those patients with groups 3 and 4 medulloblastoma, relapse rates were high; however, most group 4 patients were salvaged with RT. [ABSTRACT FROM AUTHOR]

Purpose: Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Current treatment allows decent survival rates but often with life-long morbidity. Molecular classification provides a base for novel therapeutic approaches. However, these groups are heterogeneous. MicroRNA-125a has a tumor suppressor function. It is downregulated in several tumors. The expression of microRNA-125a in MB patients remains unclear. Therefore, this study was designed to evaluate the expression of microRNA-125a in molecular groups of pediatric MB patients in Egyptian population and its clinical significance. Methods: Formalin-fixed, paraffin-embedded tissue blocks from 50 pediatric MB patients were retrospectively collected. Immunohistochemistry for β-catenin, GAB1, YAP1, and p53 was done for molecular classification. MicroRNA-125a expression analysis was done using qRT-PCR. Follow-up data were obtained from patients' records. Results: MicroRNA-125a expression was significantly lower in MB patients showing large cell/anaplastic (LC/A) histology and in the non-WNT/non-SHH group. Lower levels of microRNA-125a showed a tendency toward poor survival rates; however, difference was not significant. Infants and larger preoperative tumor size were significantly associated with lower survival rates. On a multivariate analysis, preoperative tumor size was an independent prognostic factor. Conclusion: MicroRNA-125a expression was significantly lower in categories of pediatric MB patients with worse prognosis namely LC/A histology and the non-WNT/non-SHH group suggesting a pathogenetic role. MicroRNA-125a expression could represent a promising prognostic factor and a potential therapeutic target in the non-WNT/non-SHH group which represents the most common and the most heterogeneous group of pediatric MBs coupled with the highest rates of disseminated disease. Preoperative tumor size represents an independent prognostic factor. [ABSTRACT FROM AUTHOR]

The odds ratio of having mutism was 156 for patients with bilateral DTC absence, 14.8 for patients with unilateral right DTC absence, and 7.4 for patients with unilateral left absence compared to that for patients with bilateral intact DTC. B Friday 9 September 2022 b B Abstracts listed in presenting order, unless stated otherwise b B Radiology Session b B Cerebellar-PAG "survival circuits" and the core symptoms of cerebellar mutism syndrome (CMS) b B U McAfee S u b SP B U 1 u b sp , Zhang S SP 1 sp , Zou P SP 1 sp , Conklin H SP 1 sp , Raches D SP 1 sp , Robinson G SP 1 sp , Gajjar A SP 1 sp , Khan R SP 1 sp , Patay Z SP 1 sp , Scoggins M SP 1 sp SP I 1 i sp I St Jude Children's Research Hospital, Memphis, United States i CMS patients exhibit a varying aggregate of transient and lasting symptoms, and our understanding of which neuronal systems underpin which symptoms is poor. B Paediatric Neuropsychological Outcomes of Cerebellar Mutism Following Posterior Fossa Tumour Resection b B U Davis A u b SP B U 1 u b sp , B U Mucci G u b SP B U 2 u b sp SP I 1 i sp I Ball State University, Muncie, USA, i SP I 2 i sp I CHOC Children's Hospital, Orange, USA i Cerebellar mutism syndrome (CMS), also referred to as posterior fossa syndrome, is a possible complication of posterior fossa tumour resection. Neuropsychological and academic long-term outcomes of patients with CCAS were compared to two control groups of PFT patients (treated with either surgery or surgery followed by radio-/chemotherapy) without the syndrome. [Extracted from the article]

Introduction: Medulloblastoma (MB) is the most common malignant pediatric brain tumor. The mainstay of treatment is maximum surgical resection and craniospinal radiation, which may be followed by chemotherapy. The debilitating effect of the tumor and the intensive treatment approaches in MB lead to long-term neuropsychological, physical, and chronic medical problems. We conducted a systematic review to assess the quality of life (QoL) in the long-term survivors of MB and the factors leading to compromised QoL. Methods: We utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for our review. A comprehensive literature search was performed using PubMed, Cochrane Library, Digital Commons Network, and Wiley Online Library databases to search for articles having quality of life, medulloblastoma, and pediatric survivors in title or abstract. We removed duplicates and screened through titles, and full texts. Twelve articles were included in our study. Articles using and reporting all domains of PaedsQL were included in the meta-analysis. The PaedsQL scores of survivors and their caregivers were compared. Subgroup analysis was conducted for craniospinal and proton radiotherapy groups. Results: As compared to other posterior fossa tumors, MB survivors have the lowest QoL scores. There is a difference in the perception of QoL of survivors between caregivers and survivors themselves with survivors rating themselves higher in several domains. The overall PaedsQL scores were significantly different for both groups (p < 0.001). Subgroup analysis showed that the difference between those who were treated with craniospinal or proton radiation was not significant (p = 0.76). For the subscales, physical (p = 0.005), psychosocial (p = 0.0003), and school (p = 0.03) perceptions were significantly different for the survivors and their caregivers; however, psychosocial (p = 0.80) and emotional (p = 0.93) scales were not different for the survivors or caregivers. Patient characteristics related to a worse QoL included disease severity, metastatic disease, lesser family income, smaller current ventricle size, need for permanent hydrocephalus treatment, and lesser age at diagnosis. Conclusion: An analysis of various studies, using different measures of QoL, concludes that QoL is compromised in all pediatric survivors of MB; however, the perception of QoL of the survivors is better than objective or caretaker-rated QoL. [ABSTRACT FROM AUTHOR]

Moyamoya syndrome was associated with NF1 in 10 patients, with Down Syndrome in 3 patients, with radiotherapy for OPG in 5 patients, and with a rare disease in 3 patients (PHACE syndrome, Encefalocraniolipomatosis, and Lenz Majewski) Clinical and radiologic follow-up for all patients ranges from 3 months to 13 years. In 104 patients, we have performed surgical strategies and reached the shunt independence, assessed by a long-term follow up. B Results b : During the follow-up of patients with VPS, we have paid unceasing attention both to patients with shunt failure that gave an opportunity for shunt weaning and also to those long-time shunted patients in a good health condition to whom we then have performed shunt removal surgeries whenever possible. One year after surgery, 28 patients (68.3%) had an outcome of ILAE class I. Residual tumor tissue was suspected in 15 cases and a second operation was performed in 11 patients, which led to 35 patients (85.4%) being seizure free at the last follow-up. We have compared shunt-dependent patients both to shunt-free patients and to patients which shunt freedom surgery failed; we have retrospectively analyzed patients' clinical data and focused on diagnosis, time of shunting, number and type of surgical procedure in order to have an accurate overall view. Etiology was: HH-9 patients, TS-1 patient, DNET- patient, Focal Cortical Dysplasia-3 patients, Rasmussen Encephalitis (1 patient, who underwent hemispheric deconnection). [Extracted from the article]

Introduction: Medulloblastoma is the commonest malignant brain tumour in children. Pre-operative hydrocephalus is present in up to 90% of these patients at presentation. Following posterior fossa surgery, despite resolution of fourth ventricular obstruction, a proportion of these children will still require cerebrospinal fluid (CSF) diversion for management of persistent or new hydrocephalus. Various scoring systems have been developed to predict the risk for CSF diversion following posterior fossa surgery. However, no accurate tool exists regarding which pathological subset or group of medulloblastoma patients will require a shunt post-operatively. In this study we investigated the impact of molecular subgroup of medulloblastoma on shunt dependency post-operatively in paediatric patients. Methods: We undertook a retrospective multi-centre study of children with medulloblastoma who underwent tumour resection. Those with available molecular subgroup were identified. Demographic data and clinical parameters including age, sex, presence of pre-operative hydrocephalus, extent of surgical resection, evidence of metastasis/leptomeningeal disease and need for CSF diversion post-operatively were further analysed. Results: Sixty-nine children with medulloblastoma with available molecular data were identified during the study period with male to female ratio of 1.5:1 (42M:27F). Twelve patients (17.4%) belonged to SHH, 10 (14.5%) Wnt, 19 (27.5%) Group 3 and 15 (21.7%) Group 4; 13 (18.8%) were non-specified Group 3 or 4. A total of 18 (26%) patients had evidence of leptomeningeal disease at presentation (20% of Wnt, 42% of Group 3, 33% of group 4, 23% of group 3/4, and 0% of SHH). Fifteen patients (22%) underwent post-operative ventriculoperitoneal (VP) shunt insertion. No patient in the Wnt group required ventriculoperitoneal (VP) shunt post-operatively in this cohort. Need for shunt was associated with pre-operative hydrocephalus, leptomeningeal disease, with molecular group 3 or 4 demonstrating higher rate of leptomeningeal disease, and pre-operative hydrocephalus. Age, extent of resection and pre-operative EVD were not associated with need for shunt in this cohort. Regression analysis identified only pre-operative hydrocephalus and leptomeningeal disease as independent predictors of need for shunt post-resection in this cohort. Conclusion: All patients requiring permanent post-operative VP shunt belonged to non-Wnt groups, particularly group 3 and 4. Although medulloblastoma subgroup does not independently predict need for post-operative shunt, presence of leptomeningeal disease and pre-operative hydrocephalus, and their higher prevalence in group 3 and 4, likely account for observed higher rate of shunting in these groups. [ABSTRACT FROM AUTHOR]

Purpose: Given the rarity of disseminated disease at the time of initial evaluation for pediatric brain tumor patients, we sought to identify clinical and radiographic predictors of spinal metastasis (SM) at the time of presentation. Methods: We performed a single-institution retrospective chart review of pediatric brain tumor patients who first presented between 2004 and 2018. We extracted information regarding patient demographics, radiographic attributes, and presenting symptoms. Univariate and multivariate logistic regression was used to estimate the association between measured variables and SMs. Results: We identified 281 patients who met our inclusion criteria, of whom 19 had SM at initial presentation (6.8%). The most common symptoms at presentation were headache (n = 12; 63.2%), nausea/vomiting (n = 16; 84.2%), and gait abnormalities (n = 8; 41.2%). Multivariate models demonstrated that intraventricular and posterior fossa tumors were more frequently associated with SM (OR: 5.28, 95% CI: 1.79–15.59, p = 0.003), with 4th ventricular (OR: 7.42, 95% CI: 1.77–31.11, p = 0.006) and cerebellar parenchymal tumor location (OR: 4.79, 95% CI: 1.17–19.63, p = 0.030) carrying the highest risk for disseminated disease. In addition, evidence of intracranial leptomeningeal enhancement on magnetic resonance imaging (OR: 46.85, 95% CI: 12.31–178.28, p < 0.001) and hydrocephalus (OR: 3.19; 95% CI: 1.06–9.58; p = 0.038) were associated with SM. Conclusions: Intraventricular tumors and the presence of intracranial leptomeningeal disease were most frequently associated with disseminated disease at presentation. These findings are consistent with current clinical expectations and offer empirical evidence that heightened suspicion for SM may be prospectively applied to certain subsets of pediatric brain tumor patients at the time of presentation. [ABSTRACT FROM AUTHOR]

Background and aims: Current standard treatment for metastatic medulloblastoma consists of 36 Gray (Gy) of craniospinal irradiation (CSI) supplemented with local irradiation and adjuvant chemotherapy after surgery. Although contemporary protocols have been designed to limit a radiation dose using risk-adapted CSI dosing to reduce neurocognitive morbidity, high-dose CSI remains the standard of care. Recently, the molecular classification of medulloblastoma has been emerging but its clinical significance has not been established particularly in patients with metastatic medulloblastoma treated with lower dose of CSI. Methods: We molecularly analyzed three cases of metastatic medulloblastoma treated with 24.0 Gy of CSI by DNA methylation analysis using the Illumina EPIC array. Results: All three patients had spinal metastases at the time of diagnosis. Postoperative treatment included multiple courses of chemotherapy, 24 Gy of CSI with focal boost to primary and metastatic sites, and high-dose chemotherapy. There was no disease progression observed during the 9.0, 7.7, and 5.7 years post-diagnosis follow-up. The molecular diagnosis was Group 3/4 in all three cases. Cases 1 and 2 belonged to Subtypes 7 and 4, both of which were reported to be good prognostic subtypes among the group. Case 3 belonged to Subtype 5 with MYC amplification. Conclusions: The present cases suggest that the novel subtype classification in Group 3/4 medulloblastoma may be useful for risk stratification of patients with metastatic medulloblastoma who received lower dose of CSI than standard treatment. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor of the journal "Child's Nervous System" discussing the significance of the dentate nucleus (DN) in relation to cerebellar mutism in pediatric posterior fossa tumor resection. The DN is a deep cerebellar nucleus that plays a role in functions such as cognition, planning, and controlling movements. The letter expands on the anatomy and function of the DN, including its efferent tracts and their motor and cognitive functions. It also highlights the importance of understanding the DN in surgical planning to avoid complications. The letter emphasizes that children are more susceptible to cerebellar mutism due to their higher incidence of posterior fossa tumors and less mature nervous system. [Extracted from the article]

Medulloblastoma (MB) is a rapidly growing malignant solid tumor that arises from stem cells located in the subependymal germinal matrix or outer granular layer of the cerebellum. It represents 15 to 30% of pediatric brain tumors and less than 1% of primary brain tumors. The reason for the high incidence of MB in children compared to adults is the embryonic origin of the tumor. In typical cases, MB manifests as a solitary lesion in the fourth ventricle or in the cerebellar parenchyma; cases of synchronous multifocal and disseminated MB are quite rare in patients without familial tumor syndromes. To date, only 7 cases in adults and a single pediatric case with Gorlin syndrome have been described previously. Here, the authors report a new case of synchronous multifocal classic cerebrospinal histologically confirmed MB in a 10-year-old male patient revealed by bilateral decreased visual acuity without any other localizing neurological signs. The authors will proceed with a review of the current literature regarding this rare entity. [ABSTRACT FROM AUTHOR]

Introduction: Cerebellar mutism syndrome is a well-known complication following posterior fossa tumor resection. Its incidence is markedly increased among patients with medulloblastoma. Patients typically present with an inability to communicate verbally due to disruption of the dentato-thalamocortical pathway. Case Description: We present a unique case of cerebellar mutism in a three-year-old girl who underwent gross total resection of medulloblastoma occupying the cerebellar vermis. In addition to mutism, the patient developed hyperphagia. Discussion: This case report aims to contribute to current understanding of the role of cerebello-hypothalamic connections in cerebellar mutism and their clinical significance. [ABSTRACT FROM AUTHOR]

Introduction: Medulloblastoma is the commonest embryonal brain tumor in children. Their association with other neuroepithelial brain tumors is less known. Here we discuss a pediatric patient who developed esthesioneuroblastoma 2 years after treatment of medulloblastoma. Materials and methods: A 12-year-old male presented with features of raised intracranial hypertension, and radiology showed posterior fossa midline lesion. The tumor was excised, and biopsy revealed medulloblastoma (non-WNT non-SHH type). He received chemoradiation. Two years later he presented with loss of vision, and radiology revealed a sinonasal mass with subfrontal extension. Subtotal resection was done, and biopsy showed blue round cell tumor in favor of esthesioneuroblastoma. Result: Parents refused further treatment and the patient died 8months after the second surgery. Conclusion: Mixed embryonal and neuroepithelial brain tumors are rare. These may have a common genetic abnormality. They have an aggressive course and bear a poor prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Diaschisis of cerebrocerebellar loops contributes to cognitive and motor deficits in pediatric cerebellar brain tumor survivors. We used a cerebellar white matter atlas and hypothesized that lesion symptom mapping may reveal the critical lesions of cerebellar tracts. Methods: We examined 31 long-term survivors of pediatric posterior fossa tumors (13 pilocytic astrocytoma, 18 medulloblastoma). Patients underwent neuronal imaging, examination for ataxia, fine motor and cognitive function, planning abilities, and executive function. Individual consolidated cerebellar lesions were drawn manually onto patients' individual MRI and normalized into Montreal Neurologic Institute (MNI) space for further analysis with voxel-based lesion symptom mapping. Results: Lesion symptom mapping linked deficits of motor function to the superior cerebellar peduncle (SCP), deep cerebellar nuclei (interposed nucleus (IN), fastigial nucleus (FN), ventromedial dentate nucleus (DN)), and inferior vermis (VIIIa, VIIIb, IX, X). Statistical maps of deficits of intelligence and executive function mapped with minor variations to the same cerebellar structures. Conclusion: We identified lesions to the SCP next to deep cerebellar nuclei as critical for limiting both motor and cognitive function in pediatric cerebellar tumor survivors. Future strategies safeguarding motor and cognitive function will have to identify patients preoperatively at risk for damage to these critical structures and adapt multimodal therapeutic options accordingly. [ABSTRACT FROM AUTHOR]

Introduction: A major challenge in the surgical resection of brainstem tumors is distinguishing tumor from normal tissue. One approach for addressing this problem is the use of fluorescent tracers such as sodium fluorescein (NaFl). NaFl disseminates through a disruption in the blood-brain barrier (BBB) and accumulates in the extracellular space of brain tumors. Intraoperative fluorescence microscopy can be performed to identify tumor tissue and avoid damage to adjacent, normal tissue. Here, we present the case of a 16-year-old male who underwent a left retrosigmoid craniotomy with splitting of the tentorium to remove a large exophytic brainstem tumor involving the cerebellar peduncle and with superior extension into the midbrain and thalamus. Objectives: The primary objective of this study was to investigate the effectiveness of sodium fluorescein as an intraoperative technique and evaluate its potential benefit for resection of tumors in eloquent regions in the pediatric population. To do so, we focused on a case study approach; however, we also performed a literature review and evaluated different intraoperative fluorescent techniques and their benefits for tumor resection. Methods: We performed a literature search using PubMed and Google Scholar by the key words "sodium fluorescein," "brain stem tumor," and "central nervous system neoplasms." Twenty-nine articles including both pediatric and adult populations were selected for analysis and qualitative review. Results: In this case study, sodium fluorescein helped the surgeons to identify and obtain a gross total resection of a large brainstem tumor. The marker was especially helpful for discerning the inferior pole of the tumor buried inconspicuously in cerebellar tissue. We evaluate different fluorescent tracers, 5-ALA and ICG, and discuss their application and benefits in tumor resection surgery. We present different cases that found sodium fluorescein to be helpful in achieving a gross total resection. Conclusion: The application of sodium fluorescein proved to be a safe and effective technique for the resection of brain stem tumors as shown in this case study. It helped to expose concealed areas and illuminate the tumor capsule. Further studies should test the clinical use of sodium fluorescein on brain stem tumor resection. [ABSTRACT FROM AUTHOR]

Medulloblastomas are one of the most common malignant pediatric brain tumors. Therapy has evolved into multimodality treatments consisting of surgery, radiation, and adjuvant chemotherapy. While craniospinal radiation remains standard for patients older than 3 years of age, it is not free of side effects and long-term complications. The development of malignant gliomas following therapy is a well-documented phenomenon. However, the majority of these radiation-induced glioblastomas (RIG) are intracranial, and intraspinal lesions are rare. The patient is a 22-year-old female with a history of a posterior fossa medulloblastoma diagnosed 8 years prior for which she underwent surgical resection followed by adjuvant chemotherapy and craniospinal radiation. Surveillance imaging showed no evidence of recurrence or new lesions for the following 5 years. She presented with nausea and vomiting and imaging revealing a new intramedullary cervical spinal cord lesion. She then developed acute quadriplegia several days after presentation. She underwent a cervical laminectomy and resection of this lesion, which was initially diagnosed as recurrent medulloblastoma before genomic analysis ultimately revealed it to be a RIG. Spinal RIGs that occur secondary to treatment for an intracranial neoplasm are exceedingly rare. The majority of spinal cord RIGs have been reported secondary to treatment for tumors outside of the neuroaxis, while the majority of RIGs secondary to treatment for intracranial tumors remain intracranial. Nevertheless, RIGs are associated with a short clinical history, aggressive progression, and poor outcome. [ABSTRACT FROM AUTHOR]

Quantitative mass spectrometry (MS)–based approaches have allowed further characterization of medulloblastoma (MB) classification and clinical/biological behavior. By investigating protein expression, as well as the role of post-translational modifications in shaping cellular activity, novel avenues of research will clarify the current subgrouping, providing elements for tumor treatment—new molecular targets and signaling cascades—and introducing serum, urinary, and CSF markers of tumor growth and recurrence. We systematically searched and reviewed original research articles treating MB proteomics on PubMed. Reviews, opinion papers, and abstracts were excluded from the final work. A total of 30 novel articles treating the proteomic characterization of MB were included in our review. Research conducted on tissue samples, cell lines, CSF, and urine, as well as exosome and medullospheres, was considered, to picture a broad view of the different directions MS-based proteomic analysis is moving toward. In this review, we collect, summarize, and interpret the current literature on this topic. Significant progress has been achieved in the last decade in MB characterization, paving the way for further exploration of large biobanks of MB and other tissues that will allow a more systematic understanding of MB functioning and clinical progression. [ABSTRACT FROM AUTHOR]

Purpose: Tumorigenesis of medulloblastoma is believed to be associated with granule cell progenitor neurogenesis of the cerebellum. Nevertheless, congenital medulloblastomas are rarely found. Here, we report a case of congenital medulloblastoma that showed spontaneous albeit transient regression. Methods: A one-month-old baby presented with abnormal antenatal and postnatal imaging findings. Upon ultrasonography at 26 weeks of gestational age, Dandy-Walker malformation with vermian hypoplasia and cystic change was suspected. Brain MRI at 1 week after birth revealed gadolinium-enhancing lesions in the cerebellum with apparent infiltrative features along the cerebellar folia accompanied by three independent cysts in the upper and inferolateral sides of the lesion. Serial MRIs taken up to 5 months of age showed a decrease in the size and extent of enhancing solid portions. The baby did not show any abnormal signs or developmental delay. MRI at the age of 7 months showed enlargement of the lesion, and surgery was performed. Results: The lesion was diagnosed as medulloblastoma with histologically extensive nodularity (MBEN), genetically SHH-activated and TP53-wildtype. Conclusion: This case provides an unusual chance of observing an early phase of medulloblastoma development and raises a suspicion that medulloblastoma may initiate itself very early in cerebellar organogenesis and progress later at a certain time of postnatal development. [ABSTRACT FROM AUTHOR]

Medulloblastoma is the second-most common malignant tumor in children. Medulloblastoma has been categorized into four distinct molecular subgroups: WNT, sonic hedgehog (SHH), group 3, and group 4. We report on a male child with medulloblastoma, in whom an enlarged ventricle was diagnosed in utero. Magnetic resonance imaging showed cyst formation in the cerebellar hemisphere initially, with tumor growth being indicated later. Tumor resection was performed when the boy was 12 months old. The histological findings showed extensive nodularity. Further genetic analysis revealed the tumor to be SHH type. This is the first description of a medulloblastoma observed from the fetal stage. Our findings in this case indicate that cyst formation may be the pre-neoplastic lesion of SHH-subtype medulloblastomas. [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]

Background: Long-term outcome for children who underwent surgery for brain tumors in the first 3 years of life is not well-known. Methods: We performed a retrospective study on surgical morbidity, mortality rate, academic achievement, and work participation in children below 3 years of age who underwent primary tumor resection for a brain tumor in the period from 1973 to 1998. Gross motor function and activities of daily life were scored according to the Barthel Index. Long-term survivors were defined as with a survival from primary diagnosis of 20 years or more. Findings: Ninety-seven consecutive children were included. No patient was lost to follow-up. Gross total resection was achieved in 67 children during the primary procedure, 25 had subtotal resections, and 5 had only partial resection. The 20-year survival figures for the 46 children with high-grade tumors was 33%, and the corresponding figures for 51 patients treated for low-grade tumors was 82%. Five of the 57 20-year-survivors died 21, 29, 30, 30, and 41 years, respectively, following primary surgery. Fifty of the 52 long-term survivors had a Barthel Index (BI) of 100, while the remaining two had a BI of 40. Twelve patients were long-term survivors after treatment for HG tumors (26%), while 40 of the 51 patients treated for LG tumors (78%) were alive. Thirty-two of the 52 long-term survivors were in full-time work and 29 of them after treatment for LG tumors. Another 10 were in part-time work, while the last 10 individuals had no working capacity. Conclusion: Survival is better for patients with low-grade tumors compared with those with high-grade tumors. The functional level of long-term survivors is affected by adjuvant therapy and radiotherapy in particular. Neurosurgical intervention in itself is safe and plausible for pediatric brain tumor patients below 3 years of age. However, there should be a focus on potential late affects, and survivors should be followed by knowledgeable clinical staff for the neoplastic disease as well as for potential side effects. In this consecutive series, a 33% 20-year survival for children treated for HG tumors and 82% for patients with LG tumors was observed. The patients with LG tumors who had been treated with surgical resection without any adjuvant therapy showed a good clinical outcome as adults, and two-thirds of them were in full-time work. [ABSTRACT FROM AUTHOR]

Resection or biopsy of intraventricular brain tumors using an endoscope has become common, but the limitations of these procedures are not clear. Manipulation to access a tumor that arises from the blind angle of the rigid endoscope, such as the anterior part of the aqueduct, is limited. We report here that we successfully resected a recurrent medulloblastoma in the anterior part of the aqueduct using only a flexible endoscope. This method appears to be suitable for poorly vascularized and suctionable tumors that arise in the blind angle of a rigid endoscope. [ABSTRACT FROM AUTHOR]

Purpose: In neurogenesis, ASPM (abnormal spindle-like microcephaly-associated) gene is expressed mainly in the ventricular zone of posterior fossa and is the major determinant in the cerebral cortex. Besides its role in embryonic development, ASPM overexpression promotes tumor growth, including central nervous system (CNS) tumors. This study aims to investigate ASPM expression levels in most frequent posterior fossa brain tumors of childhood and adolescence: medulloblastoma (MB), ependymoma (EPN), and astrocytoma (AS), correlating them with clinicopathological characteristics and tumor solid portion size. Methods: Quantitative reverse transcription (qRT-PCR) is used to quantify ASPM mRNA levels in 80 pre-treatment tumor samples: 28 MB, 22 EPN, and 30 AS. The tumor solid portion size was determined by IOP-GRAACC Diagnostic Imaging Center. We correlated these findings with clinicopathological characteristics and tumor solid portion size. Results: Our results demonstrated that ASPM gene was overexpressed in MB (p = 0.007) and EPN (p = 0.0260) samples. ASPM high expression was significantly associated to MB samples from patients with worse overall survival (p = 0.0123) and death due to disease progression (p = 0.0039). Interestingly, two patients with AS progressed toward higher grade showed ASPM overexpression (p = 0.0046). No correlation was found between the tumor solid portion size and ASPM expression levels in MB (p = 0.1154 and r = − 0.4825) and EPN (p = 0.1108 and r = − 0.3495) samples. Conclusion: Taking in account that ASPM gene has several functions to support cell proliferation, as mitotic defects and premature differentiation, we suggest that its overexpression, presumably, plays a critical role in disease progression of posterior fossa brain tumors of childhood and adolescence. [ABSTRACT FROM AUTHOR]

Introduction: Pilocytic astrocytoma (PA) is the most common brain tumor that affects the pediatric population. Even though PA is benign and treatment only involves surgery, recurrent or unresectable tumors require chemo- and radiotherapy. Besides BRAF, CDKN2A, or IDH mutations, the hyperactivation of the nuclear factor NF-κB contributes to tumor growth and survival. Methods: In the present study, we used publicly available data for the in silico analysis of NF-κB subunits (RELA, RELB, REL, NF-κB1, and NF-κB2) expression in PA samples. Besides, in vitro assays were performed to evaluate proliferation, migration, cell death, on the PA cell line Res286 comparing to human primary astrocytes. Sensitization to radiation therapy and temozolomide (TMZ) was also assayed. Results: Our results showed that all the members of the NF-kB family are upregulated in PA datasets compared to normal brain tissues. Moreover, DHMEQ treatment significantly reduced cell growth and motility, while sensitized cells to ionizing radiation and TMZ, as previously seen in high-grade gliomas. Conclusions: This drug presents a potential application in clinical practice for the treatment of recurrent or inoperable PA. Moreover, its use might assist adjuvant chemotherapy and reduce irradiation doses to avoid toxicity to the surrounding tissues. [ABSTRACT FROM AUTHOR]

Introduction: Tumors of the cerebellum are the most common brain tumors in children. Modern treatment and aggressive surgery have improved the overall survival. Consequently, growing numbers of survivors are at high risk for developing adverse and long-term neurological deficits including deficits of cognition, behavior, speech, and language. Post-operative cerebellar mutism syndrome (pCMS) is a well-known and frequently occurring complication of cerebellar tumor surgery in children. In the acute stage, children with pCMS may show deterioration of cerebellar motor function as well as pyramidal and cranial neuropathies. Most debilitating is the mutism or the severe reduction of speech and a range of neurobehavioral symptoms that may occur. In the long term, children that recover from pCMS continue to have more motor, behavioral, and cognitive problems than children who did not develop pCMS after cerebellar tumor surgery. The severity of these long-term sequelae seems to be related to the length of the mute phase. Aim of this narrative review: The impact of pCMS on patients and families cannot be overstated. This contribution aims to discuss the present knowledge on the natural course, recovery, and rehabilitation of children with pCMS. We suggest future priorities in developing rehabilitation programs in order to improve the long-term quality of life and participation of children after cerebellar tumor surgery and after pCMS in particular. [ABSTRACT FROM AUTHOR]

Purpose: A preliminary survey of pediatric neurosurgeons working at different centers around the world suggested differences in clinical practice resulting in variation in the risk of pediatric cerebellar mutism (CM) and cerebellar mutism syndrome (CMS) after posterior fossa (PF) tumor resection. The purposes of this study were (1) to determine the incidence and severity of CM and CMS after midline PF tumor resection in children treated at these centers and (2) to identify potentially modifiable factors related to surgical management (rather than tumor biology) that correlate with the incidence of CM/CMS. Methods: Attending pediatric neurosurgeons at British Columbia's Children's Hospital (BCCH) and neurosurgeons who completed a pediatric neurosurgery fellowship at BCCH were invited to provide data from the center where they currently practiced. Children aged from birth to less than 18 years who underwent initial midline PF tumor resection within a contemporary, center-selected 2-year period were included. Data was obtained by retrospective chart and imaging review. Modifiable surgical factors that were assessed included pre-resection surgical hydrocephalus treatment, surgical positioning, ultrasonic aspirator use, intraoperative external ventricular drain (EVD) use, surgical access route to the tumor, and extent of resection. CM was defined as decreased or absent speech output postoperatively and CMS as CM plus new or worsened irritability. Results: There were 263 patients from 11 centers in 6 countries (Canada, Germany, the Netherlands, India, Indonesia, and the USA). Median age at surgery was 6 years (range < 1 to 17 years). The overall incidence of postoperative CM was 23.5% (range 14.7–47.6% for centers with data on ≥ 20 patients). The overall incidence of CMS was 6.5% (range 0–10.3% for centers contributing data on ≥ 20 patients). A multivariate logistic regression on the full data set showed no significant association between pre-resection surgical hydrocephalus treatment, prone position, ultrasonic aspirator use, EVD use, telovelar approach, complete or near total resection, or treating center and either postoperative CM or CMS. Conclusions: While there was variation in surgical management of midline PF tumors among centers participating in this study, the factors in management that were examined did not predict postoperative CM or CMS. [ABSTRACT FROM AUTHOR]

Purpose: Brainstem lesions comprise 10–20% of all pediatric brain tumors. Over the past years, the benefits of stereotactic biopsy versus the use alone of MRI features to guide treatment have been controversial. Methods: Retrospective study with pediatric patients submitted to stereotactic brainstem biopsies between 2008 and 2018. Demographic, clinical, imaging, and surgical characteristics were recorded, as well as the histological diagnosis, complications, and survival. Predictors of survival were evaluated through Cox regression models after multivariate adjustment. Results: Twenty-six patients (mean age of 8.8 ± 4.3 years and 14 female). Diagnosis was reached on 84.6% (95% CI 65.1–95.6%) of the patients. Glioma was diagnosed on 20 cases (11 high-grade and 9 low-grade lesions). There was no association between age and gender and the dichotomized histological diagnosis. Contrast enhancement, diffuse distribution, invasion of adjacent structures, and remote injury were present on 62.5%, 75.0%, 62.5%, and 25.0% of the cases. Hydrocephalus at admission was present on almost half of the patients (46.2%). Only radiological invasion of adjacent structures had a possible association with high-grade lesions (p = 0.057). Surgical trajectory was trans-cerebellar in most of the cases (79.9%). There were no major complications and only two minor/transitory complications. Poorer survival was independently associated with high-grade lesions (HR 32.14, 95% CI 1.40–735.98, p = 0.030) and contrast enhancement at MRI (HR 36.54, 95% CI 1.40–952.26, p = 0.031). Conclusions: Stereotactic biopsy was safe and allows successful tissue sampling for a definite diagnosis. Poorer survival was independently associated with high-grade and contrast-enhancing lesions. [ABSTRACT FROM AUTHOR]

Background: The most common primary CNS tumor in children is the medulloblastoma, which generally occurs in the posterior fossa and can spread through the CNS and spinal cord. Although the recurrence of renal cell carcinoma as a secondary tumor to neuroblastoma has been reported with successful anti-neoplastic treatment, the rare occurrence of a child who initially had medulloblastoma and then developed translocation renal cell carcinoma has never been reported before. Case presentation: We report the case of a 12-year-old boy who initially presented with complaints of vomiting and headache. An MRI head confirmed the presence of 4 × 4 × 3 cm lesion which was resected completely and histopathology report confirmed the diagnosis of medulloblastoma Grade IV. Four years later, the child came for a follow-up visit and during routine screening, a CT scan showed heterogeneous lesion arising from the lower pole calyx of right kidney. The patient was referred to pediatric surgery for right radical nephrectomy involving the right adrenal gland. The histopathology report was consistent with the diagnosis of translocation renal cell carcinoma. Conclusion: Central nervous system (CNS) tumors remain the leading cause of death among pediatric neoplasms. We advise genetic testing of index cases and the establishment of an international tumor registry for a challenging disease. [ABSTRACT FROM AUTHOR]

Purpose: Effects of tumor location on cognitive performance of patients with brain tumor are controversial: some studies reported higher risks related to supratentorial locations, some to infratentorial locations, and still others did not find any differences. We aimed to address this issue by comparing school-aged children with supratentorial or infratentorial tumor with respect not only to cognitive outcomes but also to the associations between core cognitive domains and academic abilities. Methods: 32 children with infratentorial tumor and 22 with supratentorial tumor participated in the study. To detect relationships among cognitive domains, we tested which neuropsychological variable(s) predicted academic skills, controlling for the effects of radiotherapy and time since diagnosis. Results: Radiotherapy and time since diagnosis, but not tumor location, predicted cognitive outcomes. Radiotherapy negatively influenced attention and executive functioning, as well as reading speed and arithmetic operations accuracy. Unexpectedly, longer time since diagnosis was associated with improvement in attention and reading speed. Tumor location showed an effect on the relationships between core cognitive domains and academic skills: verbal and visual-spatial memory influenced reading and mathematical performance in supratentorial patients; in infratentorial patients, an only effect of visual-spatial memory on mathematical performance was detected. Conclusions: Tumor location seems not to influence cognitive performance, while radiotherapy constitutes a key risk factor for cognitive impairment. Attentional and reading abilities may improve over time, possibly due to the weakening of cancer care effects. Different patterns of cognitive associations seem to characterize supratentorial and infratentorial patients, probably associated with different neuroplastic reorganization processes after tumor occurrence. [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]

Purpose: To compare results from a third (1995–2010) cohort of children with medulloblastoma with two previous series (J Neurosurg 86:13–21, 1997; Arch Dis Child 54:200–203, 1979) to analyse the effects of management changes aimed at improving both overall and event-free survivals (OS and EFS) and functional outcomes. Methods: Review of neuro-oncology and imaging databases and previously published results. Results: There was no statistically significant improvement in the 5-year OS for 104 children diagnosed 1995–2010, 61.5% (95% CI, 52.9, 71.6), compared with 50% of the 80 children presenting 1980–1990 (J Neurosurg 86:13–21, 1997) (difference 11.5%; 95% CI, 2.8, 25.4). Five-year OS for 96 children suitable for risk-stratification was overall 66% (95% CI, 57.9, 75.8); standard risk 77.8% (95% CI, 67.4, 89.7); high risk < 3 years 50.0% (95% CI, 32.3, 77.5); high risk ≥ 3 years 54.5% (95% CI, 37.2, 79.9); 5-year EFS were standard risk 68.5% (95% CI, 57.2, 82.1); high risk < 3 years 40.0% (95% CI, 23.4, 68.4); and high risk ≥ 3 years 36.4% (95% CI, 20.9, 63.2); overall 55.2% (95% CI, 46.1, 66.1). Of 62/63 ≥ 5-year survivor, 9 died later from tumour relapse and 4 from second malignancy. Functional outcomes of 62 of the 63 ≥ 5-year survivors: 67.7% had educational issues requiring remedial input; 18% restricted mobility indoors and outdoors; 59.7% hearing impairment (42% prescribed aids). Conclusions: Comparison of this single-institution series with its predecessor found that revised chemotherapy and RT protocols and greater accuracy of risk stratification did not result in statistically significant improvements in either survival or treatment-related functional disability. Extended (> 5-year) follow-up is essential if 20% of late deaths from relapse and second malignancies are not to be overlooked. [ABSTRACT FROM AUTHOR]

Medulloblastoma and central nervous system (CNS) germ cell tumors are very rare in adults, while they account for 25% and 5% of brain tumors in children, respectively (Pastore et al. Eur J Cancer 42:2064–208, 2006). Pediatric experiences, mostly from randomized and controlled clinical trials, have led to different tailored treatments, based on various risk factors, including histology, and extent of disease. For medulloblastoma, biological features have recently emerged that enable therapies to be scaled down in some cases, or pursued more aggressively in the event of chromosomal and/or genetic alterations (Massimino et al. Crit Rev Oncol Hematol 105:35–51, 2016). Such refinements are still impossible for adult patients due to the lack of similar clinical trials that might provide the same or a different understanding regarding patients' prognosis, long-term survival, quality of life, and acute and late toxicities. This review aims to contribute to the debate on the treatment of adults with these two diseases and promote the creation of broad-based, national and international trials to advance our knowledge in this area and to share the skills between pediatric and adult oncologists as adolescent and young adults (AYA) brain tumor national boards are currently requiring. [ABSTRACT FROM AUTHOR]

Objective: Brain tumors are the second most common pediatric malignancy and the most common cause of cancer-related mortality and morbidities. Major advances in terms of surgery, radiation, and chemotherapy have led to better outcomes in developed countries. Delayed diagnosis, advanced disease at presentation, late referrals, nosocomial infections, delays to radiotherapy, and poor support services are the major reasons for poorer outcomes in developing countries. Little is known about the profile of brain tumors in Pakistan. This study aims to evaluate the epidemiology, management, and clinical outcomes of children with brain tumors in Pakistan in a single tertiary care center. Methods/materials: All children (0–16 years) with primary CNS tumors from 2004 to 2014 at Aga Khan University Hospital were reviewed retrospectively for clinical data, demographics, radiological findings, management, and outcome. Results: One hundred seventy-five children were included in the study. Male to female ratio was 1.4:1. Most of the patients were in 5–10 years age group (38.9%). Most common presenting complains were headache 115 (65.7%) and vomiting 100 (57.1%). Predominant site was infratentorial 93 (53%). Glial tumors were 105 (60%) followed by embryonal 40(22.9%), craniopharyngiomas 25 (14.3%), and germ cell 1 (0.6%). Astrocytomas (25.7%) were the most common glial tumors while medulloblastoma (15.4%) was the most common embryonal tumor. Majority of the patients underwent surgical resection (78.8%). Radiation was given to 47 (26.8%) patients. A half of the patients, 89 (50%), were lost to follow-up. Forty-two (24%) patients expired, 20 (11.4%) are alive with residual disease while 15 patients (8.5%) were cured with no evidence of recurrence and regular follow-ups. Conclusion: This is the only study from Pakistan showing demographics of the childhood brain tumors. Significant improvement needs to be made for timely diagnosis, early referrals, and collaborated team efforts with multidisciplinary tumor board to improve outcome. [ABSTRACT FROM AUTHOR]

Background: Recent studies on medulloblastomas (MB) suggest that a large fraction of tumors appearing as late recurrence turn out to be secondary malignancies, e.g., malignant gliomas, after thorough molecular investigation. Results: Here, we report of a patient with a group 4 MB that developed a distant recurrence after more than 18 years. The recurrent tumor was confirmed by histology and genome-wide DNA methylation profiling. Conclusion: Our case not only illustrates the potential of very late recurrences after seemingly cured group 4 MB, but also illustrates that detailed molecular analyses are indispensable in patients with a history of a previous malignancy. [ABSTRACT FROM AUTHOR]

Medulloblastoma is the most common malignant brain tumor in children. Approximately 30% of children with medulloblastoma will progress or relapse despite being treated. New therapies have been proposed in recent years, including high-dose chemotherapy, immunotherapy, and targeted therapy. However, the best treatment for these patients remains unclear, and in this situation prognosis is poor. Oral etoposide has been used as a single agent or in combination for treating relapsed brain tumors since the 1990s. We report an 8-year-old patient with recurrent metastatic medulloblastoma who had an excellent response after treatment with oral etoposide, maintaining a great quality of life. As clinicians, we must always try to include our patients in clinical trials; however, when this is not possible, we should not forget that "old drugs" such as oral etoposide may work in some patients, with a good response of the tumor, and what is most important, providing the patient with a good quality of life. [ABSTRACT FROM AUTHOR]

Radiation-associated aneurysms are rare, difficult to treat, and associated with high morbidity and mortality when ruptured, compared with aneurysms unrelated to radiation treatment. We present a 16-year-old patient with a radiation-induced intracranial aneurysm arising from the left posterior inferior cerebellar artery (PICA), 10 years following radiotherapy for medulloblastoma. The patient successfully underwent endovascular coil embolization of the parent artery across the neck of the aneurysm. CT angiography and MRI in the days following the procedure demonstrated maintained flow in the anterior and lateral medullary PICA segments with no brainstem infarct. [ABSTRACT FROM AUTHOR]

Objective: This report detailed four cases of tumor recurrence in the subfrontal region after cerebellar medulloblastoma resection without local relapse and explored the causes of recurrence. In addition, a case-based update and insight into the entity is attempted.Methods: All four patients received cerebellar medulloblastoma resection and postoperative radiotherapy. They were admitted to our hospital when they were found to have a recurrent tumor in the subfrontal region of the anterior skull base. All four patients received re-resection of the tumor, which was confirmed to be recurrent medulloblastoma by postoperative pathological results.Results: All patients received local radiotherapy and temozolomide chemotherapy after recurrent tumor resection. They all died due to multiple organ failure resulting from tumor metastasis to other sites or tumor regrowth within 2 years after the second operation.Conclusion: Medulloblastoma metastasize to the subfrontal region and develop a homogenous recurrence is rare. Underdosage of radiation, a gravity-related sanctuary effect, surgical position, and perioperative hydrocephalus management might be factors contributing to this supratentorial meningeal recurrence. A better prevention of tumor recurrence might be achieved by extensive microsurgical tumor resection in the initial operation and by minimizing the need for a permanent V-P shunt in the treatment of perioperative hydrocephalus as well as by administering full-dose radiotherapy to the region of the cribriform plate in the subfrontal area. [ABSTRACT FROM AUTHOR]

Medulloblastoma is a congenital brain tumor which can be associated with different congenital anomalies. However, coincidence of cerebellar medulloblastoma with sacral agenesis has not been reported so far. A variety of genetic and/or environmental predisposing factors have been proposed for both diseases. Herein, an unprecedented coincidence of these two conditions is presented. A neonate was born with lumbosacral agenesis, paraplegia, and atrophic legs, and he developed medulloblastoma with three ventricular hydrocephalus 3 years later. Different aspects regarding the embryology and etiology of both ailments are discussed, assuming the possibility that the same genetic and/or environmental risk factors may have played a part in both conditions. [ABSTRACT FROM AUTHOR]

Background and importance: Giant cavernous malformations (GCM) are low flow, angiographically occult vascular lesions, with a diameter >4 cm. Cerebellar GCMs are extremely rare, with only seven cases reported based on English literature. These lesions are most commonly seen in the pediatric age group, which is known to have an increased risk of hemorrhage, being surgery clearly recommended. Clinical presentation: An 18-month-old girl presented with a 6-month history of cervical torticollis and upper extremities clumsiness. An MRI revealed a 57 × 46 × 42 mm multi-cystic, left cerebellar hemisphere mass, showing areas of hemorrhages and cysts with various stages of thrombus. There was no enhancement with contrast. Cerebral angiography ruled out an arteriovenous malformation. She underwent a left paramedian occipital craniotomy, and macroscopic gross total resection was accomplished. Histopathologic examination was consistent with a cavernous malformation. After surgery, the patient had no new neurological deficit and an uneventful postoperative recovery. Follow-up MRI confirmed total removal of the lesion. Conclusion: Cerebellar GCMs in children are symptomatic lesions, which prompt immediate surgical treatment. These are rare lesions, which can radiologically and clinically mimic a tumor with bleed, having to be considered in the differential diagnosis of neoplastic lesions. Cerebellar GCMs might be suspected in the presence of large hemorrhagic intra-axial mass with 'bubbles of blood,' multi-cystic appearance, surrounded by hemosiderin ring, fluid-fluid levels, and accompanying edema-mass effect. Careful radiological study provides a preoperative diagnosis, but its confirmation requires histopathological examination. Complete surgical removal should be attempted when possible. [ABSTRACT FROM AUTHOR]

Purpose: Seizure outcome after treatment for pediatric patients with arteriovenous malformations (AVMs) has been rarely described in the literature. The aim of this study was to determine the risk factors for seizure presentation in pediatric AVM patients and the predictors for seizure control following treatment. Methods: We searched our characteristics of seizures associated with brain arteriovenous malformations prospectively maintained AVM database at Beijing Tiantan Hospital and identified 198 pediatric patients with brain AVMs between the year 2009 and 2014. Seizure presentation, patient characteristics, AVM features, treatment modalities, and postoperative outcomes, especially post-treatment seizure control were collected. Univariate and multivariate logistic regression analyses were applied to determine the risk factors for seizure presentation as well as the predictors for seizure control. Results: Before initiation of any treatments, 63 (31.8 %) of the overall 198 patients presented with seizure. According to multivariate analyses, larger AVM size, frontal AVM location, and history of prior hemorrhage were significantly associated with seizure presentation (all p < 0.05). For patients with pre-treatment seizure presentation, good seizure outcome was achieved in 73.8 %. AVM obliteration, short-period history of seizure, and short duration for seizure onset were independent predictors of good seizure outcome in the multivariate analysis. For the 135 patients without seizures at presentation, the overall rate of de novo seizures was 4.4 %. Conclusion: In pediatric patients with brain AVMs, prior hemorrhage, larger AVM size, and frontal lobe location may predict subsequent seizures. Highest seizure control can be achieved by complete obliteration of the AVMs with microsurgical resection. [ABSTRACT FROM AUTHOR]

Introduction: An appropriate surgical approach for posterior fossa lesions is to start tumor removal from areas with a defined plane to where tumor is infiltrating the brainstem or peduncles. This surgical approach minimizes risk of damage to eloquent areas. Although magnetic resonance imaging (MRI) is the current standard preoperative imaging obtained for diagnosis and surgical planning of pediatric posterior fossa tumors, it offers limited information on the infiltrative planes between tumor and normal structures in patients with medulloblastomas. Because medulloblastomas demonstrate diffusion restriction on apparent diffusion coefficient map (ADC map) sequences, we investigated the role of ADC map in predicting infiltrative and non-infiltrative planes along the brain stem and/or cerebellar peduncles by medulloblastomas prior to surgery. Methods: Thirty-four pediatric patients with pathologically confirmed medulloblastomas underwent surgical resection at our facility from 2004 to 2012. An experienced pediatric neuroradiologist reviewed the brain MRIs/ADC map, assessing the planes between the tumor and cerebellar peduncles/brain stem. An independent evaluator documented surgical findings from operative reports for comparison to the radiographic findings. The radiographic findings were statistically compared to the documented intraoperative findings to determine predictive value of the test in identifying tumor infiltration of the brain stem cerebellar peduncles. Results: Twenty-six patients had preoperative ADC mapping completed and thereby, met inclusion criteria. Mean age at time of surgery was 8.3 ± 4.6 years. Positive predictive value of ADC maps to predict tumor invasion of the brain stem and cerebellar peduncles ranged from 69 to 88 %; negative predictive values ranged from 70 to 89 %. Sensitivity approached 93 % while specificity approached 78 %. Conclusions: ADC maps are valuable in predicting the infiltrative and non-infiltrative planes along the tumor and brain stem interface in medulloblastomas. Inclusion and evaluation of ADC maps in preoperative evaluation can assist in surgical resection planning in patients with medulloblastoma. [ABSTRACT FROM AUTHOR]

Introduction: Confusion has surrounded the description of post-operative mutism and associated morbidity in pediatric patients with cerebellar tumors for years. The heterogeneity of definitions and diagnostic features has hampered research progress within the field, and to date, no international guidelines exist on diagnosis, prevention, treatment, or follow-up of this debilitating condition. An international group of clinicians and researchers from multiple relevant disciplines recently formed a cohesive panel to formulate a new working definition and agree upon standardized methods for diagnosis and follow-up. Methods: Consensus was obtained using the modified nominal group technique, involving four rounds of online Delphi questionnaires interspersed with a structured consensus conference with lectures, group work, and open discussion sessions. Results: A new, proposed definition of 'post-operative pediatric CMS' was formed, preliminary recommendations for diagnostic and follow-up procedures were created, two working groups on a new scoring scale and risk prediction and prevention were established, and areas were identified where further information is needed. Discussion: The consensus process was motivated by desire to further research and improve quality of life for pediatric brain tumor patients. The Delphi rounds identified relevant topics and established basic agreement, while face-to-face engagement helped resolve matters of conflict and refine terminology. The new definition is intended to provide a more solid foundation for future clinical and research work. It is thought as a consensus for moving forward and hopefully paves the way to developing a standard approach to this challenging problem with the advent of better scoring methods and ultimate goal of reducing the risk of CMS. [ABSTRACT FROM AUTHOR]

Object: Most pediatric patients that present with a posterior fossa tumor have concurrent hydrocephalus. There is significant debate over the best management strategy of hydrocephalus in this situation. The objectives of this paper were to review the pathophysiology model of posterior fossa tumor hydrocephalus, describe the individual risks factors of persistent hydrocephalus, and discuss the current management options. Specifically, the debate over preresection cerebrospinal fluid diversion is discussed. Results: Only 10-40 % demonstrate persistent hydrocephalus after posterior fossa tumor resection. It appears that young age, moderate to severe hydrocephalus, transependymal edema, the presence of cerebral metastases, and tumor pathology (medulloblastoma and ependymoma) on presentation predict postresection or persistent hydrocephalus. The Canadian Preoperative Prediction Rule for Hydrocephalus (CPPRH), a validated prediction model, can be used to stratify patients at point of first contact into high and low risk for persistent hydrocephalus. Conclusions: A protocol is proposed for managing hydrocephalus that utilizes the CPPRH. Low-risk patients can be monitored conservatively with or without an intraoperative extraventricular drain, while high-risk patients require the use of an intraoperative extraventricular drain, higher postoperative hydrocephalus surveillance, and even consideration for a preoperative endoscopic third ventriculostomy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to investigate the spectrum of underlying disease in children with torticollis. Methods: We investigated the spectrum of underlying disease and to evaluate the clinical features of the children presented with torticollis in the last 2 years. Results: Of the 20 children (13 girls and 7 boys with the mean age of 8 years, ranging 2 months-12 years), eight of them have craniospinal pathologies (cerebellar tumors in three, exophytic brain stem glioma, eosinophilic granuloma of C2 vertebra, neuroenteric cyst of the spinal cord, Chiari type 3 malformation, arachnoid cysts causing brainstem compression, and cerebellar empyema), followed by osseous origin in five (congenital vertebral anomalies including hemivertebrae, blocked vertebra, and segmentation anomalies), two muscular torticollis (soft tissue inflammation due to subclavian artery catheterization, myositis ossificans with sternocleidomastoid muscle atrophy), and ocular (congenital cataract and microphthalmia), Sandifer syndrome, paroxysmal torticollis, retropharyngeal abscess each in one patients were detected. Ten patients underwent surgery; two patients received medical therapy for reflux and benign paroxysmal torticollis; and one patient with torticollis due to muscle spasm and soft tissue inflammation was treated with physiotherapy. Conclusions: Various underlying disorders from relatively benign to life-threatening conditions may present with torticollis. The first step should be always a careful and complete physical examination, which must include all systems. Imaging must be performed for ruling out underlying life-threatening diseases in children with torticollis, particularly, if acquired neurological symptoms exist. Besides craniospinal tumors, ophthalmological problems and central nervous system infections should also be kept in mind. Moreover, early diagnosis of these disorders will reduce mortality and morbidity. Therefore, alertness of clinicians in pediatric and pediatric neurosurgery practice must be increased about this alert symptom. [ABSTRACT FROM AUTHOR]

Purpose: The aims of this paper are to describe the morphological alterations within an infant craniofacial skeleton caused by an orbital tumor and present how the bone reacts in contact with a spreading tumor mass. Methods: A study was performed on the dry skull of a child at the age of approximately 2 years. Morphological alterations of the craniofacial skeleton were analysed by visual inspection, and the intracranial cavity was examined with the aid of a digital camera. Subsequently, the skull was examined using computed tomography. Results: The skull was identified as having unilateral symptoms of orbital destruction caused by a malignant tumor, probably retinoblastoma or rhabdomyosarcoma. The left orbit and surrounding bones showed extensive malformation caused by the invading tumor. Profound deformities were also observed in the nasal cavity, which was partially occluded by the collapsed medial wall of the left orbit. The tumor extended to the wall of the orbit, spread out of the orbit, penetrated to the anterior cranial fossa, and probably invaded the brain. Conclusions: Extensive pathological cranial destruction and possible metastases to inner organs suggest that the orbital tumor was the cause of death. Anatomical alterations observed in the craniofacial skeleton indicate a highly aggressive character of the orbital tumor. [ABSTRACT FROM AUTHOR]