Cerebellar mutism syndrome (CMS) is a potential complication of pediatric posterior fossa tumor (pPFT) resection and may be related to disruption of the dentato-rubro-thalamic tract (DRTT). Intraoperative tractography allows assessment of changes to the DRTT during surgery. We evaluated macro- and microstructural changes of the DRTT by comparing pre- and intraoperative diffusion MRI (dMRI) tractography in patients with pPFT. Pre- and intraoperative T1-weighted and dMRI data were acquired to reconstruct the DRTT, while the arcuate fasciculus (AF) was reconstructed as a control tract. To evaluate macrostructural intraoperative alterations, tract volume and diameter were calculated. Microstructural changes were assessed using fractional anisotropy (FA) and mean diffusivity (MD), both globally and along the tract. Speech disturbances, as a characteristic symptom of CMS, were scored preoperatively and at hospital discharge, based on retrospective neurological reports. In 30 patients (aged > 21 months) with sufficient data quality, intraoperative reductions in tract volumes and diameters were observed (p < 0.05) in the decussating DRTT (d-DRTT) (-45.4% to -10%) and AF (-9.9% to -5.1%), while the non-decussating DRTT (nd-DRTT) remained stable. Right d-DRTT volume loss correlated with ventricular enlargement (r = -0.476, p = 0.022). Whole-tract analyses revealed increased FA in the AF and increased MD in the nd-DRTT and AF. Along-tract analyses demonstrated high variance of the MD in the DRTT cerebellar segments. Patients with postoperative speech disturbances showed higher variance of FA and MD along the DRTT, particularly in the left cerebellar segment. pPFT surgery affected the variation of the DRTT microstructure near the resection cavity, whereas the AF remained relatively stable. Although we did not find significant differences in patients with postoperative speech disturbances, we observed a much higher variability in MD in this group, suggesting a potential effect of DRTT disruption in these symptoms.

Abstract Neonatal encephalopathy (NE) following perinatal hypoxia-ischemia (HI) can lead to a wide range of neurodevelopmental consequences, ranging from mild motor problems to severe cerebral palsy, epilepsy, cognitive impairments, and behavioral issues. There is growing recognition of the long-term effects of NE during childhood, but little is known about the outcomes in adulthood, particularly from the perspective of the individuals affected and their families. Existing research primarily relies on outcome measures from neurodevelopmental assessments, which often fail to capture the lived experiences of those affected, limiting our understanding of the meaning and impact of the consequences of NE on their everyday lives. This paper tells the stories of four adults with varying outcomes following NE due to HI, ranging from largely typical development to cerebral palsy to subtle but significant cognitive challenges. Their narratives demonstrate that the long-term consequences of NE are highly variable and influenced by a complex interaction of medical, social, and environmental factors. They shared experiences of challenges, e.g., memory issues, which significantly affect their lives but are not routinely assessed in neurodevelopmental follow-up. Moreover, their narratives underscore that difficulties may emerge or evolve over time, emphasizing the need for ongoing, individualized care. Importantly, the stories of these adults also show that despite the challenges that they have faced and continue to face, they live fulfilling lives that go beyond what results from developmental assessments may indicate. These insights from lived experience experts emphasize the need for a holistic, patient-centered approach in both research and long-term follow-up care.

Craniosynostosis is a congenital condition characterized by premature fusion of one or more cranial sutures, leading to abnormal head shapes in children. Imaging plays a critical role in diagnosis, surgical planning, and monitoring, with various modalities available for use depending on clinical suspicion and syndromic involvement. The American Academy of Pediatrics recommends a tiered imaging approach based on clinical suspicion. Plain radiographs have limited value when craniosynostosis is strongly suspected; CT scans are reserved for confirmed or high-suspicion cases; and cranial ultrasound is a useful radiation-free screening tool but operator-dependent. The timing of surgical intervention depends on the suture involved and the surgical technique chosen, in discussion with the family. The timing of CT imaging should be discussed with the craniofacial team, as scans performed too early for diagnosis may require repeat imaging before surgery. Early referral to a craniofacial team is advised. Syndromic craniosynostosis often requires additional imaging and may present with brain anomalies like ventriculomegaly, callosal thinning, Chiari I malformations, and venous malformations.

BACKGROUND:Neonates with critical congenital heart disease (CCHD) are at risk for long-term cognitive impairments, including memory deficits. We aimed to assess the incidence and timing of mammillary body (MB) injury, critical memory structures, in neonates with CCHD and explore its association with cognitive outcome at 2 years of age. METHODS:We included neonates who underwent surgery with cardiopulmonary bypass in the first 6 weeks of life. Pre- and postoperative cerebral magnetic resonance imaging were reviewed for MB injury, defined as signal change on T1-, T2-, or diffusion-weighted imaging, or atrophy. Cognitive outcomes at 2 years were measured using the Dutch Bayley Scales of Infant and Toddler Development, Third Edition. RESULTS:A total of 96 neonates were included. MB injury was present in 5% preoperatively and 61% postoperatively (P < 0.001). It was not related to other acquired brain lesions. Preoperative MB injury occurred more frequently in neonates with younger postmenstrual age at birth (P = 0.002) and those who developed low cardiac output syndrome before surgery (P = 0.030). Similarly, new postoperative MB injury was associated with younger postmenstrual age at surgery (P = 0.002) as well as perioperative low cardiac output syndrome (P = 0.033). No significant differences in cognitive index scores emerged between children with neonatal MB injury and those without. CONCLUSIONS:MB injury is frequent in neonatal CCHD, predominantly postoperatively, and is associated with low cardiac output syndrome and younger postmenstrual age. The relationship between neonatal MB injury and cognitive and memory outcomes later in life warrants further study.

Background Hypoxic–ischemic (HI) brain injury due to perinatal asphyxia causes long‐term neurological morbidity in newborns. HI affects brain areas including the cortex, hippocampus, and basal ganglia. More recently the mammillary bodies (MBs), critical for memory, were also shown to be affected in patients, despite treatment with therapeutic hypothermia (TH). Here we characterized the kinetics and extent of MB damage in an established neonatal HI mouse model and evaluated the therapeutic potential of TH or a novel regenerative intervention: intranasal mesenchymal stem cell (MSC) therapy. Methods HI was induced in 9‐day‐old mouse pups; structural and cellular MB damage was assessed at days 1 to 3 and day 28 post HI by immunohistochemistry. For TH, mice were placed at 32 °C for 3 hours directly post HI, and MB damage was assessed at day 10. For MSC therapy, mice received intranasally 0.5×10 6 MSCs at day 10 post HI and MB damage was assessed at day 28 post HI. Results At days 1 to 3 post HI, mice showed cell death, microglia activation, and early gliosis in the ipsilateral MB. Glial scarring was still present at day 28 post HI with concomitant ipsilateral MB atrophy. Additionally, HI induced mammillothalamic tract atrophy and reduced the expression of calbindin + but not parvalbumin + cells. While TH and intranasal MSCs both reduced the HI‐induced cortical/hippocampal lesions, neither treatment reduced MB damage. Conclusions Our novel findings demonstrate early onset and long‐lasting MB damage in a neonatal HI mouse model, mirroring newborn patients. TH and MSCs therapy failed to protect the MBs, highlighting the importance for future research into treatment strategies to protect or repair this vulnerable structure.

OBJECTIVE:To compare the neurodevelopmental outcome at 18-24 months, 5-6 years, and 8-10 years of age among children who received therapeutic hypothermia (TH) for neonatal encephalopathy (NE) following perinatal asphyxia. STUDY DESIGN:A retrospective, multicenter cohort study was performed in children with NE treated with TH at 2 level III neonatal intensive care units between January 2008 and December 2015, with neurodevelopmental testing at 18-24 months (visit 1), 5-6 years (visit 2), and 8-10 years (visit 3). Motor, cognitive, and behavioral scores, derived from standardized neurodevelopmental tests, were converted to Z-scores and compared across the visits using linear mixed modeling. RESULTS:Seventy-seven children were analyzed. In linear mixed modeling, motor Z-scores decreased nonlinearly throughout the follow-up visits, being lower among children with a lower total IQ at 8-10 years and deep gray matter injury on neonatal brain magnetic resonance imaging. Cognitive Z-scores decreased among children with mammillary body abnormalities on neonatal magnetic resonance imaging, and were significantly lower in children with a lower gestational age and lower socioeconomic status. Z-scores indicating internalizing behavioral problems increased linearly (visit 1: median -0.7, IQR 1.4; visit 2: median -0.5, IQR 1.2; visit 3: median -0.1, IQR 1.5). CONCLUSIONS:Motor, cognitive, and behavioral Z-scores significantly worsened from 2 to 8-10 years among children who received TH for NE, highlighting the importance of long-term developmental surveillance.

In paediatric oncology, imaging biomarkers play an increasing role in diagnostic imaging and research. They can be used for prediction, detection, staging, and grading of diseases, as well as for assessment of response to treatment. Imaging biomarkers are complementary to tissue-based biomarkers, enabling a more personalised approach in oncology care. In this white paper by the European Society of Paediatric Radiology (ESPR) Oncology Taskforce and European Association of Nuclear Medicine (EANM) Paediatrics Committee, an overview is given of the current knowledge on the use of imaging biomarkers in general and per tumour group.

BACKGROUND/PURPOSE:Radiation-induced contrast enhancement (RICE) has been identified as a metric of subclinical toxicity. The aim of this study was to develop a normal tissue complication probability (NTCP) model for RICE after proton therapy in paediatric patients with posterior fossa tumours. MATERIALS AND METHODS:Paediatric patients (n = 75) treated with proton radiotherapy (49.6-59.4 Gy (RBE)), focally or in combination with craniospinal axis irradiation, were included. Follow-up magnetic resonance imaging scans were evaluated for RICE. Dose (D), dose multiplied by dose-averaged linear energy transfer (D⋅LETd), organ at risk association, RICE association and age data were extracted to construct a multivariable logistic regression model to predict RICE in voxels. NTCP was calculated using univariable logistic regression with RICE status as the dependent variable and the expected number of RICE voxels as the independent variable. RESULTS:A total of 60 RICE lesions were identified in 23 patients (30.7 %), of which 36 (60 %) were located in the brainstem, primarily the pons. We observed an increased density of RICE voxels in regions with a combination of high D (38.32-55.94 Gy) and medium-to-high LETd (1.89-6.00 keV/µm) values. In addition, younger age and the anatomical location in the pons were identified as independent risk factors for RICE. The NTCP model's optimism corrected area under the receiver operating characteristic curve (AUC) was 0.79, and the Brier score was 0.16. CONCLUSION:We developed models to predict RICE in paediatric patients. The RICE probability at the voxel- and patient-level increased with D and D⋅LETd, younger age and within the brainstem pons.

Intraoperative fiber tractography can help neurosurgeons in localizing eloquent tracts potentially displaced by tumors. In pediatric posterior fossa tumor (pPFT) patients, disturbances to the eloquent dentato-rubro-thalamic tract (DRTT) might contribute to cerebellar mutism syndrome. This study investigates the effect of fiber tractography parameters on DRTT reconstruction in pre- and intraoperative settings. T1-weighted and diffusion MRI data were acquired from ten pPFT patients and two healthy volunteers. The patients were scanned pre- and intraoperatively. The DRTT was reconstructed using multiple fiber orientation distribution (FOD) and angle thresholds. An expert panel evaluated tract reconstructions to identify optimal parameters in our dataset. The corticospinal tract (CST) served as a control. Relative tract volumes of the DRTT and the CST were calculated. Diffusion MRI data were sufficient for reliable DRTT reconstruction in healthy volunteers. In most pPFT patients, an FOD of 0.01 and a 60° angle threshold were evaluated as optimal for DRTT reconstruction in our dataset. Preoperative DRTT reconstructions showed more reconstructed streamlines and larger relative volumes, particularly in non-decussating tracts. CST reconstructions remained consistent across both timepoints. DRTT reconstruction is feasible in pPFT patients before and during surgery. However, inter-subject variability suggests that some patients may require adjusted thresholds for optimal results.

Paediatric high-grade gliomas (pedHGGs) are highly invasive brain tumours accounting for approximately 15 % of all central nervous system (CNS) tumours in children and adolescents. The outcome for these tumours is generally poor with 5-year survival rates of less than 20 %. Despite improved biological insights into pedHGGs and the promise of more effective therapies, little progress has been made in the effective treatment and the outcome of these tumours over the last four decades. Much of the evidence for the use of chemotherapy in pedHGGs is extrapolated from adult data, and the evidence for its use in the paediatric population is still weak. This guideline was written by members of the SIOPE HGG Working Group as part of the European Standard Clinical Practice (ESCP) Project. The guideline aims to integrate available evidence-based and expert opinion-based information to assist healthcare professionals in the management of pedHGGs and in an attempt to provide equity in healthcare reflecting the varying resources of each European country.

BACKGROUND AND PURPOSE:Diffuse astrocytoma, MYB- or MYBL1-altered (DA-MYB) is a new tumor type in the family of pediatric-type diffuse low-grade gliomas and is genetically related to angiocentric glioma. Imaging features of DA-MYB, are less well-known. During our clinical work, in a subset of our patients, we identified a relatively characteristic imaging pattern consisting of a large, diffuse, hemispheric tumor with displaced central vessels, which we termed the "fireworks sign." Therefore, the purpose of this work was to describe the frequency of this sign and any additional imaging characteristics in a large patient cohort. MATERIALS AND METHODS:This international retrospective study included 40 patients from 7 countries. We recorded clinical, genetic, and standard radiologic features, focusing on the presence of the fireworks sign but also on the presence or absence of a mismatch between T2WI and FLAIR and a FLAIR rim, which have both been reported in these patients. RESULTS:Most tumors were unilateral and located in the cerebral hemispheres (most frequently in the parietal, temporal, and frontal lobes), hypointense on T1WI, and hyperintense on T2WI. No tumor showed diffusion restriction. The fireworks sign was present in 16 patients. Other features included the T2 FLAIR mismatch (24 cases), FLAIR rim (18 cases), necrosis (5 cases), and enhancement (5 cases). Tumor volume was significantly associated with the fireworks sign (P = .01) and T2 FLAIR mismatch (P = .005). CONCLUSIONS:Imaging features of DA-MYB in children are variable, and the fireworks sign was identified only in a subset of patients. It was usually present in patients with large hemispheric tumors but was also observed in brainstem lesions. Diffusion restriction was consistently absent and enhancement infrequent. A T2 FLAIR mismatch was seen in >50% of patients.

Aims: Embryonal tumours with PLAGL1 or PLAGL2 amplification (ET, PLAGL) show substantial heterogeneity regarding their clinical characteristics and have been treated inconsistently, resulting in diverse outcomes. In this study, we aimed to evaluate the clinical behaviour of ET, PLAGL and elucidate their response pattern across the different applied treatment regimens. Methods: We conducted an in-depth retrospective analysis of clinical and serial imaging data of 18 patients with ET, PLAGL (nine each of PLAGL1 and PLAGL2 amplified). Results: Patients with PLAGL1-amplified tumours (ET, PLAGL1) had fewer relapses (3/9), while PLAGL2-amplified tumours (ET, PLAGL2) were prone to early relapse or progression (8/9) and to distant, leptomeningeal and intraventricular relapses. Progression-free survival differed significantly between the subtypes (log-rank test, p = 0.0055). Postoperative treatment included chemotherapy (n = 17, various protocols), alone (n = 8) or combined with radiotherapy (n = 9). Responses to chemotherapy were observed in both subtypes, and incomplete resection was not associated with inferior survival. All three survivors with ET, PLAGL2 were treated with induction and high-dose chemotherapy with (n = 1—low-dose CSI and boost) or without (n = 2) radiotherapy, whereas five patients with less intensive chemotherapy relapsed. All six survivors with ET, PLAGL1 were treated with conventional chemotherapy regimens, with (n = 4—local radiotherapy n = 3; CSI and boost n = 1) or without (n = 2) radiotherapy. Two patients with ET, PLAGL1 relapsed after 8 years. Conclusions: Adjuvant therapy should be considered for all ET, PLAGL patients: Patients with ET, PLAGL2 might benefit from intensified chemotherapy regimens. In contrast, patients with ET, PLAGL1 showed superior outcomes without high-dose chemotherapy or craniospinal irradiation.

Cancer predisposition syndromes (CPSs) are a group of inherited disorders that significantly increase the risk of developing various cancers, ranging from infancy through adulthood. CPSs account for about 10% of the pediatric cancers, and they represent a major cause of morbidity and mortality in affected children. The inheritance pattern and the variable penetrance influence the age of onset and the clinical course, resulting in substantial variation in presentation, even within a single family. Early recognition of CPSs is crucial, as timely diagnosis allows for health surveillance, preventive interventions, and genetic counselling for patients and their families. Guidelines and surveillance programs have been developed to identify at-risk patients and coordinate long-term care. This review focuses on the most common CPSs associated with pediatric cancers, with particular emphasis on the involvement of the head and neck region. For each syndrome, we provide a background summary including its genetics and clinical manifestations, followed by a detailed description of characteristic head and neck imaging findings. Illustrative case examples are then presented to demonstrate the spectrum of clinical and imaging features. It highlights imaging features to assist providers reading these studies in the early identification of all possible pathological manifestations in these syndromes. Key CPSs covered include retinoblastoma, Li-Fraumeni syndrome, neurofibromatosis type 1, DICER1 syndrome, rhabdoid tumor predisposition syndrome, Gorlin-Goltz syndrome, hereditary paraganglioma-pheochromocytoma syndrome, constitutional mismatch repair deficiency syndrome, and neuroblastoma predisposition syndrome.

Background:Increasing survival rates in pediatric brain tumor patients highlight the importance of understanding treatment-related neurodevelopmental consequences. The posterior fossa is a primary site for many of these tumors, which are treated with surgery, chemotherapy, and/or radiation therapy that could impact brain function and structure. This retrospective longitudinal study examines changes in subcortical brain structures of pediatric posterior fossa tumor patients over five years post-diagnosis and compares patients who were treated for low- and high-grade tumors. Methods:We analyzed 558 T1-weighted (T1w) brain MR images of 57 pediatric posterior fossa tumor patients (mean age at diagnosis = 9.65 (SD 4.06), 44 % female). There were 39 patients with a low-grade tumor treated with surgery and/or chemotherapy and 18 patients with a high-grade tumor treated with surgery, chemotherapy, and radiation treatment. Volumes of the globus pallidus, caudate, putamen, nucleus accumbens, amygdala, thalamus and hippocampus were calculated using SPM CAT12 (Statistical Parametric Mapping Computational Anatomy Toolbox). Linear mixed effect models were estimated to study the association between volumetric changes and time for these 7 subcortical structures. Results:Significant interactions between time and group were shown in the hippocampus (β = -0.06, SE = 0.02, p < .001) and globus pallidus (β = 0.01, SE = 0.00, p = .016). Patients treated for low-grade tumors exhibited increasing hippocampal volume over time, while those treated for high-grade tumors experienced a decline. In the globus pallidus, volume decreased over time for the low-grade tumor group but remained stable for the high-grade tumor group. Patients with a history of hydrocephalus had smaller thalamic (β = -0.40, SE = 0.14, p = .004) and hippocampal (β = -0.31, SE = 0.12, p = .012) volumes. Younger age at diagnosis was associated with smaller putamen and thalamus, and male sex was associated with larger volumes of the putamen, nucleus accumbens and amygdala. Conclusions:These findings suggest that children who received treatment for low- or high-grade tumors had different subcortical volumes over time, which may be related to treatment, complications, or demographic factors such as age and sex. These results suggest that while brain tumor treatment primarily aims to cure patients, it may inevitably affect neural development and may contribute to a range of cognitive, behavioral, and emotional long-term deficits. This emphasizes the need for long-term monitoring and prospective longitudinal studies into structural and functional brain changes after treatment for pediatric brain tumor.

Neurodegeneration with brain iron accumulation (NBIA) refers to a group of rare genetic disorders characterized by abnormal iron deposition in the basal ganglia and brainstem due to impaired iron homeostasis. Disease severity and manifestations vary according to the underlying genetic mutation and age of presentation; however, most subtypes share progressive neurological features such as dystonia, Parkinsonism, spasticity, cognitive decline, and intellectual disability. In this review, we first outline the physiological role of iron in the central nervous system, emphasizing its importance for neurotransmitter synthesis, myelination, and mitochondrial metabolism, and discuss how disruption of homeostatic mechanisms may lead to ferroptosis and neuronal injury. We then explore the role of neuroimaging in the diagnosis of NBIA, with a focus on MRI as the modality of choice. Finally, we provide an overview of the clinical and imaging features of the major NBIA subtypes, highlighting both shared characteristics and distinctive patterns. Covered NBIA include primary disorders of iron metabolism, such as neuroferritinopathy and aceruloplasminemia, and secondary disorders with disrupted iron regulation, including Pantothenate Kinase-Associated Neurodegeneration, Phospholipase A2 Group VI-Associated Neurodegeneration, Mitochondrial Membrane Protein-Associated Neurodegeneration, Beta-Propeller Protein-Associated Neurodegeneration, Fatty Acid Hydroxylase-Associated Neurodegeneration, Coenzyme A Synthetase Protein-Associated Neurodegeneration, Woodhouse-Sakati syndrome, and Kufor-Rakeb Disease. By integrating genetics, pathophysiology, and imaging, this review aims to improve recognition of NBIA and support comprehensive clinical management.

Abstract:Background Children with posterior fossa tumors (PFTs) are at risk of long-term neurocognitive deficits, yet the impact of tumor grade and treatment intensity on cortical development remains poorly understood. The aim of this study was to determine whether cortical thickness trajectories differ between children with low- versus high-grade PFTs and whether radiation dose influences cortical development in medulloblastoma patients. Methods:We conducted a retrospective longitudinal study of 55 children (37 low-grade, 18 high-grade medulloblastoma) diagnosed between 2018 and 2020. A total of 406 T1-weighted MRI scans acquired up to five years post-diagnosis were processed using CAT12 in SPM12 to estimate cortical thickness. Vertex-wise linear mixed-effects models assessed cortical thickness changes over time, adjusting for age at diagnosis, sex, and hydrocephalus. Within the high-grade group, we evaluated the effect of craniospinal irradiation (CSI) dose (23.4 vs. ≥36 Gy) on cortical development. Results:Children with low-grade tumors showed significant bilateral cortical thinning over time, consistent with typical neurodevelopment. In contrast, medulloblastoma patients treated with surgery, chemotherapy, and radiation therapy showed relative cortical stability across follow-up. Significant group-by-time interactions were observed, with low-grade patients demonstrating greater cortical thinning in parietal, temporal, and occipital regions. No significant differences in cortical trajectories were found between high- and standard-dose CSI subgroups. Conclusions:Cortical development trajectories in pediatric PFT survivors differ by tumor grade and treatment intensity. While low-grade patients exhibit expected maturational thinning, cortical stability in high-grade patients may reflect disrupted neurodevelopment. These findings underscore the need for longitudinal neuroimaging in pediatric neuro-oncology survivorship care.

Purpose The incidence of proton therapy (PT)-related imaging changes in the central nervous system, and associated symptoms, varies widely in literature. The aim of this study was to assess imaging changes after implementation of intensity modulated pencil beam scanning in a national cohort of pediatric posterior fossa (PF) tumors. Methods and Materials All pediatric PF tumor patients treated in the Netherlands with PT between June 2018 and December 2022 were analyzed. Patients receiving reirradiation or a combination with photon therapy were excluded. Imaging changes were defined as new contrast enhancement on T1-weighted images or abnormal signal on T2-weighted imaging in the brain parenchyma or spinal cord, outside of the tumor bed and within the irradiated area. Associated symptoms were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Results Seventy-seven PF patients (median age, 7.0 years) were analyzed. Median follow-up was 25 months and prescribed dose 54 GyE (range, 49.6-59.4 GyE). At 12 months post-PT, a cumulative incidence rate of 33% contrast enhancement and 47% T2-weighted imaging changes was observed. Of all patients, 15% experienced any neurological symptoms related to these imaging changes, grade ≥2 symptoms were observed in 9%. The imaging changes were predominantly transient. Younger children, especially those aged <5 years, had a significantly higher risk of developing imaging changes (hazard ratio, 8.64; 95% CI, 3.60-20.74) and symptoms (hazard ratio, 6.97; 95% CI, 1.80-26.99). Prescribed dose ≥59.4 GyE and higher cerebellar D0.1cc and D10% were associated with an increased risk of imaging changes and associated symptoms. Conclusions The initial experience of PT for pediatric PF tumors in the Netherlands demonstrates post-PT contrast enhancement with associated symptoms in 15% of the patients, and an increased risk in patients aged <5 years and patients with a prescribed dose ≥59.4 GyE.