Supratentorial and Infratentorial Ependymoma.

Ependymomas are the third most common intracranial tumor in children, presenting in both the supratentorial and infratentorial compartments. They may present in infants, young children, and adolescents with symptoms depending on size, location, and the age of the patient. The ideal imaging for evaluation and treatment is MRI. This is crucial for preoperative evaluation and planning, as well as postoperative assessment and evaluating the efficacy of treatment. Essentially without exception, aggressive surgery aimed at complete resection is the initial and most important factor in the long-term outcome of all these children. Histopathologic diagnosis for intracranial pediatric ependymoma has been narrowed to grade II and grade III, no longer characterized as classic and anaplastic. Subsequent conformal photon or proton beam irradiation is an established post-surgical therapy, with solid evidence that it benefits survival and offers lower toxicity to the normal brain of the young child. Although chemotherapeutic treatment has not been generally impactful, immunotherapeutic interventions may be on the horizon. Updated molecular subgrouping of ependymoma is changing the post-resection approach of these tumors with regard to both treatment and outcome. Excluding spinal ependymoma and subependymoma, there are four subtypes that are defined by genetic characteristics, two found in the supratentorial compartment, ST-EPN-YAP1 and ST-EPN-ZFTA, and two in the posterior fossa, PF-EPN-A and PF-EPN-B. Younger children harboring ZFTA fusion-positive supratentorial and type A posterior fossa tumors, regardless of histology, tend toward the poorest outcomes. On the contrary, older children with supratentorial YAP1 fusion-positive ependymomas and type B posterior fossa tumors may survive with surgery alone. The paradigm shift regarding the behavior of the various childhood ependymoma subtypes will hopefully lead to targeted, individualized therapies and improved outcomes.

Surgical outcome of sinodural meningiomas.

INTRODUCTION: Meningiomas located in the posterior fossa and involving the sinodural angle at the junction of the transverse and sigmoid sinuses are uncommon and present unique challenges due to their complex anatomical location. Despite their distinctive features, they are frequently categorized with tentorial meningiomas in the literature. MATERIALS AND METHODS: This retrospective study conducted at a tertiary care center involved 64 patients with sinodural meningiomas who underwent surgical treatment between 2010 and 2023. The analysis covered demographics, clinical presentation, radiological characteristics, surgical approaches, histopathological findings, and outcomes. RESULTS: The cohort predominantly comprised females (83 %) with a mean age of 47.64 years. Headache (92.2 %) and gait disturbances (62.5 %) were the most common presenting symptoms. Preoperative imaging showed sinus involvement in 57.8 % of cases, predominating Sindou's type 1 and type 6. Gross total resection (Simpson grades 1-2) was achieved in 40.6 % of cases. Postoperative complications included pseudomeningocele (9.4 %), especially in patients with hydrocephalus. CONCLUSION: Sinodural meningiomas represent a distinct subset of posterior fossa tumors, necessitating meticulous preoperative planning and intraoperative decision-making regarding sinus management. The study underscores the importance of individualized surgical strategies and highlights the role of radiosurgery in managing residual disease effectively.

Posterior Fossa Craniopharyngioma Arising from the Inferior Medullary Velum.

We report the case of a 63-year-old man with a midline posterior fossa tumor and peculiar imaging features where we were unsure of the nature of the lesion preoperatively. Histopathology revealed it to be a craniopharyngioma. It appeared to arise from the inferior medullary velum, a site not described before in the literature. The previous four cases mentioned in literature and speculations on the origins in this uncommon site are discussed.

TULIPs decorate the three-dimensional genome of PFA ependymoma.

Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues. A remarkable feature exclusively present in PFA are type B ultra long-range interactions in PFAs (TULIPs), regions separated by great distances along the linear genome that interact with each other in the 3D nuclear space with surprising strength. TULIPs occur in all PFA samples and recur at predictable genomic coordinates, and their formation is induced by expression of EZHIP. The universality of TULIPs across PFA samples suggests a conservation of molecular principles that could be exploited therapeutically.

Cortical and subcortical structural changes in pediatric patients with infratentorial tumors.

PURPOSE: This study aimed to detect supratentorial cortical and subcortical morphological changes in pediatric patients with infratentorial tumors. METHODS: The study included 24 patients aged 4-18 years who were diagnosed with primary infratentorial tumors and 41 age- and gender-matched healthy controls. Synthetic magnetization-prepared rapid gradient echo images of brain magnetic resonance imaging were generated using deep learning algorithms applied to T2-axial images. The cortical thickness, surface area, volume, and local gyrification index (LGI), as well as subcortical gray matter volumes, were automatically calculated. Surface-based morphometry parameters for the patient and control groups were compared using the general linear model, and volumes between subcortical structures were compared using the t-test and Mann-Whitney U test. RESULTS: In the patient group, cortical thinning was observed in the left supramarginal, and cortical thickening was observed in the left caudal middle frontal (CMF), left fusiform, left lateral orbitofrontal, left lingual gyrus, right CMF, right posterior cingulate, and right superior frontal (P < 0.050). The patient group showed a volume reduction in the pars triangularis, paracentral, precentral, and supramarginal gyri of the left hemisphere (P < 0.05). A decreased surface area was observed in the bilateral superior frontal and cingulate gyri (P < 0.05). The patient group exhibited a decreased LGI in the right precentral and superior temporal gyri, left supramarginal, and posterior cingulate gyri and showed an increased volume in the bilateral caudate nucleus and hippocampus, while a volume reduction was observed in the bilateral putamen, pallidum, and amygdala (P < 0.05). The ventricular volume and tumor volume showed a positive correlation with the cortical thickness in the bilateral CMF while demonstrating a negative correlation with areas exhibiting a decreased LGI (P < 0.05). CONCLUSION: Posterior fossa tumors lead to widespread morphological changes in cortical structures, with the most prominent pattern being hypogyria. CLINICAL SIGNIFICANCE: This study illuminates the neurological impacts of infratentorial tumors in children, providing a foundation for future therapeutic strategies aimed at mitigating these adverse cortical and subcortical changes and improving patient outcomes.

Development of Chromosome 1q+ Specific Treatment for Highest Risk Pediatric Posterior Fossa Ependymoma.

PURPOSE: There are no effective treatment strategies for children with highest-risk posterior fossa group A ependymoma (PFA). Chromosome 1q gains (1q+) are present in approximately 25% of newly diagnosed PFA tumors, and this number doubles at recurrence. Seventy percent of children with chromosome 1q+ PFA will die because of the tumor, highlighting the urgent need to develop new therapeutic strategies for this population. EXPERIMENTAL DESIGN: In this study, we utilize 1q+ PFA in vitro and in vivo models to test the efficacy of combination radiation and chemotherapy in a preclinical setting. RESULTS: 5-fluorouracil (5FU) enhances radiotherapy in 1q+ PFA cell lines. Specifically, 5FU increases p53 activity mediated by the extra copy of UCK2 located on chromosome 1q in 1q+ PFA. Experimental downregulation of UCK2 resulted in decreased 5FU sensitivity in 1q+ PFA cells. In in vitro studies, a combination of 5FU, retinoid tretinoin (ATRA), and radiation provided the greatest reduction in cellular proliferation and greatest increase in markers of apoptosis in 1q+ PFA cell lines compared with other treatment arms. Similarly, in vivo experiments demonstrated significant enhancement of survival in mice treated with combination radiation and 5FU and ATRA. CONCLUSIONS: These results are the first to identify a chromosome 1q+ specific therapy approach in 1q+ PFA. Existing phase I studies have already established single-agent pediatric safety and dosages of 5FU and ATRA, allowing for expedited clinical application as phase II trials for children with high-risk PFA.

The long-term impact of irradiation on functional connectivity in brain circuits involved in memory processes after pediatric posterior fossa tumor.

PURPOSE: Memory is one of the main specific cognitive domains impaired with attention and processing speed after a pediatric brain tumor. This work explored the long-term impact of radiotherapy in children with posterior fossa tumor (PFT) on brain connectivity in neural circuits involved in memory using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: A total of 20 irradiated and 15 non-irradiated PFT survivors, and 21 healthy controls, prospectively included in the IMPALA study (NCT04324450), performed memory tests assessing episodic, procedural, and working memories and were subjected to an rs-fMRI. We manually contoured main structures involved in memory to explore connectivity at rest in a seed-to-voxel analysis. The groups were compared and differences in connectivity were correlated with behavioral scores and irradiation doses. RESULTS: The performance of all mnesic tasks was lower in PFT survivors with a greater alteration in working and episodic memory in irradiated patients. Irradiated survivors had atypical connectivities in all memory circuits compared to controls and in cortico-caudate and cortico-cerebellar circuits compared to non-irradiated survivors. Non-irradiated survivors had only atypical connectivities in the cortico-cerebellar circuits compared to controls. In irradiated survivors, atypical connectivities in cortico-hippocampal circuits were linked with episodic memory scores and dose of irradiation to the left hippocampus and in cortico-striatal circuits with procedural memory scores and dose of irradiation to the striatum. CONCLUSION: The results of this study highlight that irradiation has a long-term impact on brain connectivity in brain circuits involved in memory after pediatric PFT with a specific radiation-dose effect in supratentorial structures.

Posterior fossa tumors in children: current insights.

While in adults most intracranial tumors develop around the cerebral hemispheres, 45 to 60% of pediatric lesions are found in the posterior fossa, although this anatomical region represents only 10% of the intracranial volume. The latest edition of the WHO classification for CNS tumors presented some fundamental paradigm shifts that particularly affected the classification of pediatric tumors, also influencing those that affect posterior fossa. Molecular biomarkers play an important role in the diagnosis, prognosis, and treatment of childhood posterior fossa tumors and can be used to predict patient outcomes and response to treatment and monitor its effectiveness. Although genetic studies have identified several posterior fossa tumor types, differing in terms of their location, cell of origin, genetic mechanisms, and clinical behavior, recent management strategies still depend on uniform approaches, mainly based on the extent of resection. However, significant progress has been made in guiding therapy decisions with biological or molecular stratification criteria and utilizing molecularly targeted treatments that address specific tumor biological characteristics. The primary focus of this review is on the latest advances in the diagnosis and treatment of common subtypes of posterior fossa tumors in children, as well as potential therapeutic approaches in the future.   Conclusion: Molecular biomarkers play a central role, not only in the diagnosis and prognosis of posterior fossa tumors in children but also in customizing treatment plans. They anticipate patient outcomes, measure treatment responses, and assess therapeutic effectiveness. Advances in neuroimaging and treatment have significantly enhanced outcomes for children with these tumors. What is Known: • Central nervous system tumors are the most common solid neoplasms in children and adolescents, with approximately 45 to 60% of them located in the posterior fossa. • Multimodal approaches that include neurosurgery, radiation therapy, and chemotherapy are typically used to manage childhood posterior fossa tumors What is New: • Notable progress has been achieved in the diagnosis, categorization and management of posterior fossa tumors in children, leading to improvement in survival and quality of life.

Impact of a pediatric posterior fossa tumor and its treatments on motor procedural learning.

INTRODUCTION: Posterior fossa tumor (PFT) survivors have difficulty learning new skills. Procedural memory is a skill learning system that allows, through training, the automatization of procedures and progressive improvement of performance. It underlies most of the motor procedures in everyday life that we perform automatically, such as riding a bike or writing. Motor procedural memory is divided into two components: motor sequence learning involving mainly cortico-striatal networks, and motor adaptation involving mainly cortico-cerebellar networks. The aim of this work was to explore the impact of a tumor and its treatment during childhood on procedural learning hypothesizing that sequence learning would be impaired in PFT survivors who have been treated with radiotherapy, whereas motor adaptation would be impaired in all PFT survivors. METHOD: 22 irradiated survivors of PFT, 17 non-irradiated survivors and 21 healthy controls from the IMPALA study (NCT04324450) performed a motor sequence learning task and a motor adaptation task. Doses received by striatal and cerebellar structures were reported from the initial dosimetry plans. RESULTS: Sequence learning was preserved in both tumor groups, but at the individual level 7/22 irradiated, and 4/17 non-irradiated participants failed to learn the motor sequence. Motor adaptation was impaired in both tumor groups, predominantly in the irradiated group. CONCLUSION: This study sheds new light on the long-term impact of PFT treatments in childhood on a rarely-studied part of memory, which is perceptual-motor procedural learning. Our results suggest that the cerebellum and striatum could be considered as organs at risk with regard to procedural learning.

Spatial transcriptomic analysis delineates epithelial and mesenchymal subpopulations and transition stages in childhood ependymoma.

BACKGROUND: The diverse cellular constituents of childhood brain tumor ependymoma, recently revealed by single cell RNA-sequencing, may underly therapeutic resistance. Here we use spatial transcriptomics to further advance our understanding of the tumor microenvironment, mapping cellular subpopulations to the tumor architecture of ependymoma posterior fossa subgroup A (PFA), the commonest and most deadly childhood ependymoma variant. METHODS: Spatial transcriptomics data from intact PFA sections was deconvoluted to resolve the histological arrangement of neoplastic and non-neoplastic cell types. Key findings were validated using immunohistochemistry, in vitro functional assays and outcome analysis in clinically-annotated PFA bulk transcriptomic data. RESULTS: PFA are comprised of epithelial and mesenchymal histological zones containing a diversity of cellular states, each zone including co-existing and spatially distinct undifferentiated progenitor-like cells; a quiescent mesenchymal zone population, and a second highly mitotic progenitor population that is restricted to hypercellular epithelial zones and that is more abundant in progressive tumors. We show that myeloid cell interaction is the leading cause of mesenchymal transition in PFA, occurring in zones spatially distinct from hypoxia-induced mesenchymal transition, and these distinct EMT-initiating processes were replicated using in vitro models of PFA. CONCLUSIONS: These insights demonstrate the utility of spatial transcriptomics to advance our understanding of ependymoma biology, revealing a clearer picture of the cellular constituents of PFA, their interactions and influence on tumor progression.

Application of Apparent Diffusion Coefficient Histogram Metrics for Differentiation of Pediatric Posterior Fossa Tumors : A Large Retrospective Study and Brief Review of Literature.

PURPOSE: This study aimed to evaluate the application of apparent diffusion coefficient (ADC) histogram analysis to differentiate posterior fossa tumors (PFTs) in children. METHODS: A total of 175 pediatric patients with PFT, including 75 pilocytic astrocytomas (PA), 59 medulloblastomas, 16 ependymomas, and 13 atypical teratoid rhabdoid tumors (ATRT), were analyzed. Tumors were visually assessed using DWI trace and conventional MRI images and manually segmented and post-processed using parametric software (pMRI). Furthermore, tumor ADC values were normalized to the thalamus and cerebellar cortex. The following histogram metrics were obtained: entropy, minimum, 10th, and 90th percentiles, maximum, mean, median, skewness, and kurtosis to distinguish the different types of tumors. Kruskal Wallis and Mann-Whitney U tests were used to evaluate the differences. Finally, receiver operating characteristic (ROC) curves were utilized to determine the optimal cut-off values for differentiating the various PFTs. RESULTS: Most ADC histogram metrics showed significant differences between PFTs (p < 0.001) except for entropy, skewness, and kurtosis. There were significant pairwise differences in ADC metrics for PA versus medulloblastoma, PA versus ependymoma, PA versus ATRT, medulloblastoma versus ependymoma, and ependymoma versus ATRT (all p < 0.05). Our results showed no significant differences between medulloblastoma and ATRT. Normalized ADC data showed similar results to the absolute ADC value analysis. ROC curve analysis for normalized ADCmedian values to thalamus showed 94.9% sensitivity (95% CI: 85-100%) and 93.3% specificity (95% CI: 87-100%) for differentiating medulloblastoma from ependymoma. CONCLUSION: ADC histogram metrics can be applied to differentiate most types of posterior fossa tumors in children.

Motor Functioning and Intelligence Quotient in Paediatric Survivors of a Fossa Posterior Tumor Following a Multidisciplinary Rehabilitation Program.

BACKGROUND: Short- and long-term consequences after treatment for childhood fossa posterior tumors are extensively reported in the literature; however, papers highlighting physical function throughout rehabilitation and its correlation with Intelligence Quotient (IQ) are sparse. This study aims to describe the physical functioning and IQ of these survivors, their progression during rehabilitation, and the association with histopathological tumor classification. Additionally, the correlation between gross motor functioning and cognitive functioning was investigated. METHODS: This retrospective single-center cohort study included 56 children (35 (62.5%) males and 21 (37.5%) females, with an average age of 6.51 years (SD 4.13)) who followed a multidisciplinary program at the Child Rehabilitation Centre, Ghent University Hospital in the period from 2005 to 2020. Descriptive statistical analysis was performed with the use of non-parametric tests and linear regression to determine the relationship between gross motor functioning and IQ. RESULTS: This report shows impaired motor and intelligence performance in children with a fossa posterior tumor. Although multidisciplinary rehabilitation is beneficial, it is not able to counteract the further decline of several motor skills and intelligence during oncological treatment, more specifically in children with a medulloblastoma. A correlation between gross motor function and total IQ was found. CONCLUSION: Pediatric survivors of a fossa posterior tumor experience impaired physical and intellectual functions, with more decline during oncological treatment despite simultaneous multidisciplinary rehabilitation.

Updates in the classification of ependymal neoplasms: The 2021 WHO Classification and beyond.

Ependymal neoplasms occur at all ages and encompass multiple tumor types and subtypes that develop in the supratentorial compartment, the posterior fossa, or the spinal cord. Clinically, ependymomas represent a very heterogeneous group of tumors from rather benign subependymomas to very aggressive and often deadly childhood ependymomas of the posterior fossa. Newly identified biological markers and classification schemes, e. g. based on global DNA methylation profiling, have led to the definition of 10 types of ependymal tumors and an improved prediction of patients' outcome by applying the new classification system. While the exact genetic basis for several ependymoma types still remains unclear, the knowledge about ependymoma driving events has significantly increased within the last decade and contributed to a classification based on molecular characteristics and localization rather than histological features alone. Convincing evidence is now pointing towards gene fusions involving ZFTA or YAP1 causing the development of supratentorial ependymomas. Also, H3, EZHIP, or TERT mutations have been detected in a fraction of infratentorial ependymal tumors. Finally, MYCN amplifications have recently been identified in spinal ependymomas, in addition to the previously known mutations in NF2. This review summarizes how recent findings regarding biology, molecular tumor typing, and clinical outcome have impacted the classification of ependymomas as suggested by the updated 2021 WHO CNS tumor classification system. We focus on changes compared to the previous classification of 2016 and discuss how a formal grading could evolve in the future and guide clinicians to treat ependymoma patients.

Meta-Analysis of Apparent Diffusion Coefficient in Pediatric Medulloblastoma, Ependymoma, and Pilocytic Astrocytoma.

BACKGROUND: Medulloblastoma, ependymoma, and pilocytic astrocytoma are common pediatric posterior fossa tumors. These tumors show overlapping characteristics on conventional MRI scans, making diagnosis difficult. PURPOSE: To investigate whether apparent diffusion coefficient (ADC) values differ between tumor types and to identify optimum cut-off values to accurately classify the tumors using different performance metrics. STUDY TYPE: Systematic review and meta-analysis. SUBJECTS: Seven studies reporting ADC in pediatric posterior fossa tumors (115 medulloblastoma, 68 ependymoma, and 86 pilocytic astrocytoma) were included following PubMed and ScienceDirect searches. SEQUENCE AND FIELD STRENGTH: Diffusion weighted imaging (DWI) was performed on 1.5 and 3 T across multiple institution and vendors. ASSESSMENT: The combined mean and standard deviation of ADC were calculated for each tumor type using a random-effects model, and the effect size was calculated using Hedge's g. STATISTICAL TESTS: Sensitivity/specificity, weighted classification accuracy, balanced classification accuracy. A P value < 0.05 was considered statistically significant, and a Hedge's g value of >1.2 was considered to represent a large difference. RESULTS: The mean (± standard deviation) ADCs of medulloblastoma, ependymoma, and pilocytic astrocytoma were 0.76 ± 0.16, 1.10 ± 0.10, and 1.49 ± 0.16 mm2 /sec × 10-3 . To maximize sensitivity and specificity using the mean ADC, the cut-off was found to be 0.96 mm2 /sec × 10-3 for medulloblastoma and ependymoma and 1.26 mm2 /sec × 10-3 for ependymoma and pilocytic astrocytoma. The meta-analysis showed significantly different ADC distributions for the three posterior fossa tumors. The cut-off values changed markedly (up to 7%) based on the performance metric used and the prevalence of the tumor types. DATA CONCLUSION: There were significant differences in ADC between tumor types. However, it should be noted that only summary statistics from each study were analyzed and there were differences in how regions of interest were defined between studies. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

Comparison of neuropsychological functioning in pediatric posterior fossa tumor survivors: Medulloblastoma, low-grade astrocytoma, and healthy controls.

BACKGROUND: Neuropsychological comparison of medulloblastoma (MB) and cerebellar low-grade astrocytoma (LGA) survivors to controls can clarify treatment-related neurocognitive late effects. While both brain tumor groups undergo surgery to the posterior fossa, children with MB additionally receive craniospinal irradiation with boost and chemotherapy. This study provides an updated comparison of neuropsychological functioning in these two groups and examines effects of demographic risk factors upon outcomes. PROCEDURE: Forty-two children (16 MB, nine LGA, and 17 controls) completed measures of intellectual functioning, verbal learning/memory, visual-motor integration, and fine-motor functioning. The effects of age at diagnosis, time since diagnosis, gender, fatigue, and social status on neuropsychological functioning were examined. RESULTS: MB survivors demonstrated the worst neurocognitive late effects, but they were less severe and extensive than in prior studies. LGA survivors' mean scores were below normative expectations in working memory, processing speed, and fine-motor functioning. In this overall sample, processing speed difficulties were independent of fine-motor functioning and fatigue. Higher parental education was associated with better intellectual functioning, working memory, delayed recall, and visual-motor integration. Neuropsychological function was not associated with gender, age at diagnosis, or time since diagnosis. CONCLUSION: The results support that contemporary treatment approaches with craniospinal irradiation plus boost and chemotherapy confer the greatest risk for late effects, while surgical resection is associated with subtle but important neurocognitive difficulties. Ultimately, this study furthers our understanding of factors impacting neuropsychological function in pediatric MB and LGA survivors and contributes to empirical support for close monitoring and targeted interventions into survivorship.

Differentiation of paediatric posterior fossa tumours by the multiregional and multiparametric MRI radiomics approach: a study on the selection of optimal multiple sequences and multiregions.

OBJECTIVE: To evaluate the diagnostic performance of a radiomics model based on multiregional and multiparametric MRI to classify paediatric posterior fossa tumours (PPFTs), explore the contribution of different MR sequences and tumour subregions in tumour classification, and examine whether contrast-enhanced T1 weighted (T1C) images have irreplaceable added value. METHODS: This retrospective study of 136 PPFTs extracted 11,958 multiregional (enhanced, non-enhanced, and total tumour) features from multiparametric MRI (T1- and T2 weighted, T1C, fluid-attenuated inversion recovery, and diffusion-weighted images). These features were subjected to fast correlation-based feature selection and classified by a support vector machine based on different tasks. Diagnostic performances of multiregional and multiparametric MRI features, different sequences, and different tumoral regions were evaluated using multiclass and one-vs-rest strategies. RESULTS: The established model achieved an overall area under the curve (AUC) of 0.977 in the validation cohort. The performance of PPFTs significantly improved after replacing T1C with apparent diffusion coefficient maps added into the plain scan sequences (AUC from 0.812 to 0.917). When oedema features were added to contrast-enhancing tumour volume, the performance did not significantly improve. CONCLUSION: The radiomics model built by multiregional and multiparametric MRI features allows for the excellent distinction of different PPFTs and provides valuable references for the rational adoption of MR sequences. ADVANCES IN KNOWLEDGE: This study emphasized that T1C has limited added value in predicting PPFTs and should be cautiously adopted. Selecting optimal MR sequences may help guide clinicians to better allocate acquisition sequences and reduce medical costs.

The feasibility and efficacy of short-term visual-motor training in pediatric posterior fossa tumor survivors.

BACKGROUND: Pediatric posterior fossa tumor (PFT) survivors experience a range of cognitive and motor impairments that require timely rehabilitation of these functions. In Russia, rehabilitation services are only just beginning to be formed; therefore, it is necessary to test rehabilitation protocols for children surviving cancer. AIM: To evaluate the efficacy of short-term cognitive and motor training (CMT) aimed on visual-motor integration in PFT survivors using training devices. DESIGN: "Single center" quasi randomized controlled experiment. SETTING: Outpatients of the Russkoe Pole Rehabilitation Center. POPULATION: The 63 children cancer survivors between the ages of 6 and 17 years. METHODS: The baseline level of cognitive and motor functions was assessed in all participants. Then the sample of patients split into two subgroups of equal sex, age, and diagnosis. The intervention subgroup received six sessions of CMT for two weeks, and the other subgroup underwent 'empty' two weeks with no intervention. Reassessment of motor and cognitive functions was conducted in all participants. Then the subgroups changed: the first subgroup underwent 'empty' two weeks, and the second subgroup completed the CMT, and further reassessment was provided. RESULTS: The primary results demonstrate an increase in gross and fine motor skills, motor coordination, visual-motor integration, and visual processing after CMT. Secondary results show that the age at onset is an important factor in the subsequent decline in cognitive, motor functions, and eye movements. Children with medulloblastoma perform worse on motor tests than children with astrocytoma. A tumor in the IV ventricle is the most harmful, and a tumor in the cerebellar hemispheres is the least harmful to a child's cognitive and motor development. CONCLUSIONS: This study shows the effectiveness of a short-term CMT program for children who survived PFT. The study also found that cognitive, motor, and visual-motor functions are affected by the tumor's localization, malignancy, and the child's age at onset. CLINICAL REHABILITATION IMPACT: Short-term rehabilitation methods can be useful in pediatric oncological practice. Reconstruction of cognitive functions can occur during the training of more "simple" functions, such as hand-eye integration. The study makes a significant contribution to the methods of short-term rehabilitation in children who survived cancer.

Transcriptional profiling of paediatric ependymomas identifies prognostically significant groups.

The majority of supratentorial ependymomas in children contain oncogenic fusions, such as ZFTA-RELA or YAP1-MAMLD1. In contrast, posterior fossa (PF) ependymomas lack recurrent somatic mutations and are classified based on gene expression or methylation profiling into group A (PFA) and group B (PFB). We have applied a novel method, NanoString nCounter Technology, to identify four molecular groups among 16 supratentorial and 50 PF paediatric ependymomas, using 4-5 group-specific signature genes. Clustering analysis of 16 supratentorial ependymomas revealed 9 tumours with a RELA fusion-positive signature (RELA+), 1 tumour with a YAP1 fusion-positive signature (YAP1+), and 6 not-classified tumours. Additionally, we identified one RELA+ tumour among historically diagnosed CNS primitive neuroectodermal tumour samples. Overall, 9 of 10 tumours with the RELA+ signature possessed the ZFTA-RELA fusion as detected by next-generation sequencing (p = 0.005). Similarly, the only tumour with a YAP1+ signature exhibited the YAP1-MAMLD1 fusion. Among the remaining unclassified ependymomas, which did not exhibit the ZFTA-RELA fusion, the ZFTA-MAML2 fusion was detected in one case. Notably, among nine ependymoma patients with the RELA+ signature, eight survived at least 5 years after diagnosis. Clustering analysis of PF tumours revealed 42 samples with PFA signatures and 7 samples with PFB signatures. Clinical characteristics of patients with PFA and PFB ependymomas corroborated the previous findings. In conclusion, we confirm here that the NanoString method is a useful single tool for the diagnosis of all four main molecular groups of ependymoma. The differences in reported survival rates warrant further clinical investigation of patients with the ZFTA-RELA fusion.

A multimodal approach to the study of children treated for posterior fossa tumor: A review of the literature and a pilot study.

OBJECTIVE: The aims of the present study were: (1) to review the literature on long-lasting cognitive sequelae in children treated for Posterior Fossa Tumor and (2) to investigate anatomic functional relations in a case series of 7 children treated for PFT using magnetic resonance imaging (MRI) post-processing methods. METHODS: We retrospectively analyzed MRIs of children who underwent complete surgical resection of PFT and performed extensive neuropsychological evaluation. Tumor, ventricular volumes, and VPS insertion site were drawn on T1 volumetric MRI scans and normalized to a pediatric template. Children showed worse performances on tasks tapping executive functions, memory, visuo-motor precision, and expressive language. RESULTS: Volumes of interest related to these functions showed a maximum overlap on the left vermis and the lateral ventricle enlargement, except for impaired narrative fluency -which was associated with left lateral ventricle enlargement- and narrative memory -which was related to the right vermis and the enlarged fourth ventricle. CONCLUSION: Results suggest that anatomic functional relations in children treated for PFT are related to a combination of different pathophysiological factors.