Background: Despite the established associations between paediatric brain tumour treatment, distress, and post-traumatic stress symptoms (PTSS), neither the treatment nor tumour pathology reliably account for symptom severity at the individual level. This study examined whether treatment-related changes in fronto-limbic white matter (WM), brain tissue thought to support emotion, is associated with additional variance in PTSS beyond the effect of treatment and endorsing having experienced a distressing event. Methods: Thirty-six children and adolescents treated for a posterior fossa brain tumour and 17 typically developing children (TDC) completed a questionnaire assessing whether they had experienced a distressing event and measured PTSS and underwent diffusion tensor imaging. Diffusivity metrics of fronto-limbic tracts and tracts that do not support emotional functioning (control tracts) were obtained. A continuous measure of the physical, cognitive, and emotional strain of therapy (i.e., treatment burden), was estimated using the Neurological Predictor Scale. Partial Least Squares path modelling was used in an exploratory, theory-guided framework to examine statistical associations among treatment burden, distress, WM, and PTSS. Results: Patients demonstrated greater radial diffusivity than TDC across fronto-limbic and control tracts. Fronto-limbic WM was associated with PTSS severity within the subclinical range and mediated the effects of treatment burden on PTSS. The control tract WM was not associated with PTSS. PTSS severity was also associated with endorsing a distressing event. Conclusions: The findings support two indicators associated with dimensional variation in PTSS severity: an expected psychological indicator, through endorsing having experienced a distressing event, and a neurobiological indicator, via treatment-related changes to fronto-limbic WM. These results reflect correlational patterns in subclinical symptoms and should be interpreted as exploratory.

BACKGROUND Negative-pressure hydrocephalus is a rare form of symptomatic ventriculomegaly characterized by subatmospheric intracranial pressure (ICP). It can occur following lumbar puncture (LP) in patients with impaired CSF dynamics and is frequently mistaken for ventriculoperitoneal (VP) shunt malfunction. OBSERVATIONS The authors describe the case of a 9-year-old boy with prior medulloblastoma and a VP shunt who presented with neurological decline following LP. Symptoms transiently improved following a large-volume shunt tap, but ventriculomegaly persisted despite shunt revision. ICP monitoring confirmed negative pressure, consistent with post-LP negative-pressure hydrocephalus. Management with an epidural blood patch, neck wrapping, and shunt valve adjustment resulted in clinical and radiographic improvement, notably without the need for prolonged subatmospheric external ventricular drainage. LESSONS Negative-pressure hydrocephalus should be suspected in patients with a shunt who present with ventriculomegaly, a plausible CSF leak, low-pressure CSF, and poor response to shunt revision. The presence of fourth ventricular obstruction should further heighten suspicion. Effective management involves recognizing altered CSF pressure gradients that mimic high-pressure hydrocephalus, considering epidural blood patch placement to repair CSF leakage, using neck wrapping to augment venous pressure and raise intraventricular pressure to the valve’s opening threshold, and avoiding unnecessary shunt revisions or repeat LPs in susceptible patients. https://thejns.org/doi/10.3171/CASE2654

The interplay between emotion and cognition is essential for understanding behavior and mental health. Emotional and cognitive processes are linked through neural circuits, with brain networks such as the limbic system, default mode network, and executive control network modulating emotional responses and cognitive functions. Disruptions to these networks can impact emotion regulation and executive functioning. Children with acquired brain injuries, including pediatric brain tumor survivors (PBTS), may be especially vulnerable to such disruptions. This study explores how network disruptions affect emotion regulation and executive functioning. Participants included 18 typically developing children, 16 PBTS treated with surgery only, and 19 PBTS treated with surgery and radiation (13.14 ± 2.65 years). Structural connectivity was examined using tractography, and resting state functional connectivity was assessed using magnetoencephalography (MEG). Emotion regulation and executive functioning were measured through the Behavior Rating Inventory of Executive Function and Cambridge Neuropsychological Test Automated Battery. Statistical modeling assessed the impact of connectivity on behavioral outcomes. Compared to healthy controls, PBTS showed greater differences in emotion regulation than executive functioning, structural compromise, and aberrant neural synchrony. No significant differences emerged between PBTS treated with surgery versus radiation. Structural connectivity influenced neural synchrony, emotion regulation, and executive functioning. Emotion regulation and executive functioning were interrelated, with structural compromise resulting in poorer outcomes through disrupted neural synchrony. These findings highlight the critical role of network connectivity in supporting emotion regulation and executive functioning, and underscore the importance of considering these processes as interconnected domains influenced by the organization of brain networks.

Abstract Background Although targeted therapies for paediatric low-grade gliomas (pLGG) have shown efficacy, comparisons of alteration-specific long-term outcomes between targeted therapies and conventional chemotherapy are lacking. Methods We performed a population-based study of BRAF-altered pLGG treated at relapse with trametinib (for BRAF fused pLGG) or dabrafenib +/- trametinib (BRAF V600E), compared with chemotherapy-treated pLGG. Imaging responses (RAPNO) were assessed by neuroradiologists. Results The initial cohort comprised 267 BRAF fused and 161 BRAF V600E pLGG. Across alterations and lines of therapy, imaging responses for chemotherapy-treated pLGG were similar. Clinician-determined progression-free survival (PFS) was poor and, importantly, equivalent between first/second-line chemotherapy. For BRAF fused pLGG treated with chemotherapy or trametinib, there was a higher objective response rate (>25% reduction) with trametinib – 60% (18/30) versus 36% (8/22) [second-line] versus 39% (22/56) [first-line]. Trametinib yielded significantly more partial responses. Moreover, 56% of tumours refractory/non-responsive to first-line chemotherapy responded to trametinib. These responses translated to superior disease control with 18-month PFS of 91% (n = 34) versus 52% for second-line chemotherapy (n = 27) (p < 0.001). At 3.5 years, PFS for patients who remained on therapy was 82% versus 19% for chemotherapy. These differences narrowed for patients who discontinued trametinib, with 49% progressing within 2 years. Interestingly, disseminated tumours were more likely to progress on therapy – 67% probability at 5 years (p = 0.001). BRAF V600E pLGG treated with targeted therapy (n = 19) also showed superior disease control with 5-year PFS of 82% versus 33% for second-line chemotherapy (n = 9) (p = 0.02). With prolonged treatment times (median 5.5 years [1-10.9]), tumour control persisted – only 16% of patients progressed on therapy. Review of V600E imaging responses is ongoing. Conclusion Acknowledging variation in treatment courses and follow-up, targeted therapy for relapsed BRAF-altered pLGG yields superior tumour control relative to chemotherapy. Ongoing work will help elucidate optimal treatment schedules and long-term functional outcomes.

Response Assessment in Pediatric Neuro-Oncology (RAPNO) is an international working group dedicated to developing standardized recommendations for response assessment in children with central nervous system (CNS) tumors enrolled on clinical trials. This standardization facilitates easier and more reliable comparison of responses across trials. Since the first RAPNO publication in 2013, response guidelines have been issued for medulloblastoma, low-grade glioma (LGG), high-grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), ependymoma, and craniopharyngioma. Many of these guidelines have already been incorporated into clinical trials to evaluate their effectiveness and accuracy. RAPNO has always been predicated on the idea that these consensus recommendations will require updates over time as they are applied in practice given technological advancements, evolving treatment approaches, and growing knowledge of disease pathology. A half-day RAPNO symposium sponsored by the Society of Neuro-Oncology (SNO) was held in San Diego, CA, USA, on May 15, 2025. This event coincided with the 8th Biennial Pediatric Society of Neuro-Oncology meeting. The main objectives were to identify ongoing RAPNO challenges, discuss potential updates, and plan future initiatives across three specific groups: 1) LGG/Craniopharyngioma, 2) HGG/Diffuse Midline Glioma (DMG)/Ependymoma, and 3) Medulloblastoma and other seeding tumors. This manuscript reviews the symposium proceedings and highlights key topics and challenges discussed, as well as outlining future RAPNO initiatives.

Immunotherapy is a rapidly evolving field in pediatric neuro-oncology, using diverse strategies to enhance or initiate an antitumor immune response. Its use has expanded from hematologic malignancies to solid central nervous system (CNS) tumors, creating new diagnostic challenges in neuroimaging, particularly in children. The aim of this review is to summarize current immunotherapeutic strategies for pediatric solid CNS tumors and to discuss their characteristic imaging findings and response patterns, with emphasis on pitfalls in differentiating true progression from treatment‑related inflammatory changes. Across different immunotherapeutic approaches, a major challenge is distinguishing tumor progression from pseudoprogression, immune‑related flare phenomena, and neurotoxicity. Multiparametric imaging combining advanced MRI techniques and metabolic imaging may improve diagnostic specificity; however, validation in children is limited, and existing response frameworks such as iRANO and RAPNO do not specifically address immunotherapy‑related imaging patterns in the pediatric population. Immunotherapy is reshaping the management of pediatric solid CNS tumors, but imaging‑based response assessment remains difficult. There is a pressing need for pediatric‑focused response criteria and standardized imaging strategies that incorporate the unique features of immunotherapy‑related changes in the developing brain.

Abstract Background In the era of molecular characterization and targeted therapies for paediatric low-grade gliomas (pLGG), it is essential to understand the role of driver alterations in determining responses and long-term outcomes for upfront chemotherapy. Methods We performed a population-based study of pLGG treated with upfront chemotherapy. Chemotherapy responses (RAPNO) were assessed by expert neuroradiologists. Results We analyzed 247 BRAF fused, 139 BRAF V600E, and 188 NF1 pLGG (median follow-up 8.2 years). Incompletely resected BRAF-altered pLGG could be stratified into 3 groups based on location and need for chemotherapy/radiation: hemispheric/cerebellar (25% BRAF fused and 10% BRAF V600E treated by 5 years), midline (59% & 56%), and optic pathway (92% & 79%) (p < 0.002). All disseminated pLGG required treatment. The objective response rates (>25% reduction) to chemotherapy were 39% (22/56) for BRAF fused, 20% (3/15) for V600E, and 32% (12/38) for NF1. Interestingly, BRAF fused responders had superior clinician-determined progression-free survival (PFS) relative to initially stable tumours (p = 0.0041). Dismal long-term control was observed for BRAF fused (n = 73) and V600E (n = 22) pLGG with 15-year PFS of 16% and 22% (p = 0.5953), contrasting 49% for NF1 (n = 51) (p < 0.0001). Strikingly, all V600E pLGG in patients <7 y.o. progressed within 3 years (p = 0.0063). V600E optic pathway gliomas also fared poorly with 4-year PFS of 8%, versus 34% for BRAF fused (p = 0.0721) versus 73% for NF1 (p < 0.0001). Despite superior PFS for NF1 optic pathway glioma patients, 49% had profound or worse visual impairment at last follow-up, versus 23% for BRAF fused (p = 0.0441). Imaging review revealed further >25% shrinkage beyond the chemotherapy period in 16% of BRAF fused and 27% of NF1 tumours, with 91% showing best response at > 5 years. Conclusion This study provides important driver alteration-specific information on long-term pLGG tumour control and patient outcomes. Insights from these observations can inform trial design and comparison with targeted therapies.

Abstract Background Risk factors for poor social adjustment after brain tumor treatment are not well established. Prior work implicates age, sex, treatment factors, and inhibitory control performance. However, it’s unknown whether functional and structural brain connectivity within inhibitory control networks can help explain social outcomes after treatment. Methods Using magnetoencephalography, the Go/No-Go task, diffusion-weighted imaging, and the Pediatric Quality of Life (PedsQL) questionnaire, we quantified differences in inhibitory control, supporting brain connectivity, and social adjustment between children treated for brain tumors (n = 15) and typically developing controls (TDC; n = 11). Results Relative to TDC, children treated for brain tumors showed significantly (1) reduced low gamma neural communication between networks important for inhibitory control, indexed by lower weighted phase lag indices (wPLI); (2) disrupted white matter microstructure between these networks, indexed by lower intra-axonal and higher extra-axonal diffusivity metrics; and (3) lower parent-reported social adjustment based on the PedsQL. In robust regressions across participants, poorer social adjustment was associated with female sex, more treatments and complications, reduced low gamma wPLI underlying inhibitory control within key networks, and more diffuse white matter damage. Groups did not significantly differ in Go/No-Go performance, and performance was not related to social outcomes. Conclusions These findings suggest that both specific perturbations to functional connectivity within inhibitory control networks and broad damage to structural connectivity contribute to social difficulties after brain tumor treatment. These results provide preliminary evidence that measures of network connectivity could inform approaches for identifying children at greatest risk of social difficulties and guiding prioritization of supports.

Head computed tomography (CT) plays a key diagnostic role in assessing anatomically visible cerebral injury, monitoring the development of edema and ischemia, and, in some diseases, assisting in the prediction of outcome. More specifically, after a cardiac arrest, head CT imaging will reveal the impact of global hypoxic-ischemic injury. In adults, some have shown that the gray-white matter ratio (GWR) calculated with Hounsfield units (HU) may be valuable for prognostication. Few studies have investigated their use in the pediatric population, and even fewer have considered age and maturation in their analyses.The objective of this study was to evaluate pediatric normal controls and report their HU and GWR values for use in future studies. Non-contrast head CT scans of children without neurological diseases were used. HU values were measured using predefined regions of interest and the circular dots method. GWR was estimated with 12 different formulas. Analyses were stratified by age (<2 and ≥ 2 years).We analyzed 42 scans. HU in the caudate nucleus, cortical gray matter, and brain parenchyma were lower in younger (n = 18) compared to older children ≥2 years (n = 24). No HU differences between the age groups were measured in the putamen, thalamus, and white matter. GWR calculated with basal ganglia (caudate nucleus + putamen) and cortical gray matter was lower in the younger group.Head CT measurements of HU and GWR change with age in children under 2 years. This feature was most relevant in gray matter areas. Future studies should evaluate which GWR formulas are most effective in assessing the severity of global hypoxic ischemic encephalopathy after cardiac arrest in the pediatric population.

Published in 2021, the 5th edition of the World Health Organization central nervous system tumor classification introduced major changes to the categorization of pediatric brain and spinal cord tumors. Greater focus has been placed on the integration of molecular genetics, highlighting its emerging importance in the diagnosis, prognostication, and targeted therapy of these tumors. New molecularly defined tumors, reclassification of existing tumors, and revised nomenclature are discussed in this article, and subsequent articles provide further information on this new central nervous system tumor landscape in pediatric neuroradiology.

Objectives: The gray-white matter ratio is used to estimate tissue edema on head computed tomography scans in cardiac arrest research. This rapid review aimed to determine whether gray-white matter ratio values differed between studies that included children and adults. We hypothesized that brain maturity affects myelination and, consequently, age would alter the range of the gray-white matter ratio. Methods: We searched PubMed from 2000 to 2025. Studies were selected if they included children or adult patients with cardiac arrest and reported gray-white matter ratio values relative to neurologic outcome groups or to normal controls. We summarized the studies and explored how gray-white matter values trended with age, gray-white matter ratio equations, timing of image acquisition during the post-resuscitation phase, and neurologic outcome groups. Results: We retrieved five studies in children and 40 in adults. Regions of interest and equations used to measure gray-white matter ratio varied between studies, but most included the basal ganglia. The gray-white matter ratio was generally lower in poor-outcome groups than in good-outcome groups. In children with good outcomes, gray-white matter ratio values were similar to those of adults with poor outcomes. The gray-white matter ratio values were lower in younger children than in older children and adults. We did not find a consistent relationship between gray-white matter ratio values and the elapsed time from cardiac arrest to image acquisition. Conclusions: This review revealed varying gray-white matter ratios between children and adults in cardiac arrest studies, underscoring the importance of accounting for age when evaluating gray-white matter ratios in pediatric cardiac arrest populations. Gray-white matter ratio values were dependent on the regions of interest included in the equations. Readers should be aware of these sources of variation when comparing studies that use the gray-white matter ratio as a biomarker of hypoxic-ischemic injury in cardiac arrest. Future work is warranted to optimize the use of the gray-white matter ratio in pediatric cardiac arrest research.

Congenital brain tumors (CBTs) are neoplasms detected during fetal life or early neonatal life. These are exceedingly rare and account for 0.5% to 1.5% of all pediatric brain tumors. CBTs are histologically distinct and clinically more aggressive than other pediatric brain tumors. Advances and increased availability of neuroimaging has enabled early and accurate detection of these lesions and associated complications, allowing clinicians to manage pregnancy and neonatal care and better plan and prepare for interventions in advance. In this article, we provide an overview of the incidence, pathogenesis, and clinical presentation of some common CBTs along with their imaging manifestations.

Recurrence is the most common cause of late mortality in pediatric brain tumor survivors. However, it is unclear how long such patients should be monitored with periodic neuroimaging. Therefore, we investigated the utility of neuroimaging surveillance for recurrence ≥5 years post diagnosis in survivors of pediatric medulloblastoma and ependymoma. We conducted a retrospective study of survivors of medulloblastoma or ependymoma treated between 2000 and 2017. Eligible survivors were disease-free 5 years after diagnosis and underwent magnetic resonance imaging surveillance ≥5 years after diagnosis. Medulloblastoma survivors with a history of recurrence <5 years after diagnosis were excluded. Of 302 children diagnosed in the study period, 129 met inclusion criteria (89 medulloblastoma/40 ependymoma; 77 (59.7%) male; median age at diagnosis 6 years (range < 1-13); median time from diagnosis to last scan 134 months (61-283)). Four medulloblastoma patients had late recurrent disease, one of which was detected on routine neuroimaging (asymptomatic). All medulloblastoma patients with late recurrence died, except for one previously unirradiated patient who was disease-free 29 months after recurrence. Nine ependymoma patients had late recurrence of which 7 were detected on routine neuroimaging. Six out of seven asymptomatic late recurrent ependymoma patients remain alive with a median time after recurrence of 45.5 months (range: 3-121). Both symptomatic patients died. Among ependymoma survivors, asymptomatic detection of late recurrence by surveillance neuroimaging was associated with better survival than symptomatic detection, supporting the continuation of surveillance for at least 10 years after diagnosis. The benefit of prolonged surveillance in medulloblastoma survivors remains uncertain.

Tumor predisposition syndromes (TPS) are inherited cancer syndromes linked to approximately 10% of all cancers and up to 20% pediatric central nervous system (CNS) tumors. TPS manifest with characteristic patterns of neoplasms throughout the body and require targeted, region-specific imaging for surveillance. Advances in cancer genomics have allowed options for therapies targeting specific molecular pathways. This article highlights CNS imaging features of TPS, with additional insights into the underlying genomic alterations that lead to their development.

Published in 2021, the fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) introduced new molecular criteria for tumor types that commonly occur in either pediatric or adult age groups. Adolescents and young adults (AYAs) are at the intersection of adult and pediatric care, and both pediatric -type and adult -type CNS tumors occur at that age. Mortality rates for AYAs with CNS tumors have increased by 0.6% per year for males and 1% per year for females from 2007 to 2016. To best serve patients, it is crucial that both pediatric and adult radiologists who interpret neuroimages are familiar with the various pediatric- and adult -type brain tumors and their typical imaging morphologic characteristics. Gliomas account for approximately 80% of all malignant CNS tumors in the AYA age group, with the most common types observed being diffuse astrocytic and glioneuronal tumors. Ependymomas and medulloblastomas also occur in the AYA population but are seen less frequently. Importantly, biologic behavior and progression of distinct molecular subgroups of brain tumors differ across ages. This review discusses newly added or revised gliomas in the fifth edition of the CNS WHO classification, as well as other CNS tumor types common in the AYA population.

AIM:To evaluate the ability of blood-biomarkers, clinical examination, electrophysiology, or neuroimaging, assessed within 14 days from return of circulation to predict good neurological outcome in children following out- or in-hospital cardiac arrest. METHODS:Medline, EMBASE and Cochrane Trials databases were searched (2010-2023). Sensitivity and false positive rates (FPR) for good neurological outcome (defined as either 'no, mild, moderate disability or minimal change from baseline') in paediatric survivors were calculated for each predictor. Risk of bias was assessed using the QUIPS tool. RESULTS:Thirty-five studies (2974 children) were included. The presence of any of the following had a FPR < 30% for predicting good neurological outcome with moderate (50-75%) or high (>75%) sensitivity: bilateral reactive pupillary light response within 12 h; motor component ≥ 4 on the Glasgow Coma Scale score at 6 h; bilateral somatosensory evoked potentials at 24-72 h; sleep spindles, and continuous cortical activity on electroencephalography within 24 h; or a normal brain MRI at 4-6d. Early (≤12 h) normal lactate levels (<2mmol/L) or normal s100b, NSE or MBP levels predicted good neurological outcome with FPR rate < 30% and low (<50%) sensitivity. All studies had moderate to high risk of bias with timing of measurement, definition of test, use of multi-modal tests, or outcome assessment heterogeneity. CONCLUSIONS:Clinical examination, electrophysiology, neuroimaging or blood-biomarkers as individual tests can predict good neurological outcome after cardiac arrest in children. However, evidence is often low quality and studies are heterogeneous. Use of a standardised, multimodal, prognostic algorithm should be studied and is likely of added value over single modality testing.

Glioneuronal tumors (GNTs) are an expanding group of primary CNS neoplasms, commonly affecting children, adolescents and young adults. Most GNTs are relatively indolent, low-grade, WHO grade I lesions. In the pediatric age group, GNTs have their epicenter in the cerebral cortex and present with seizures. Alterations in the mitogen-activated protein kinase (MAPK) pathway, which regulates cell growth, are implicated in tumorigenesis. Imaging not only plays a key role in the characterization and pre-surgical evaluation of GNTs but is also crucial role in follow-up, especially with the increasing use of targeted inhibitors and immunotherapies. In this chapter, we review the clinical and imaging perspectives of common pediatric GNTs.