Childhood Central Nervous System Research Articles

Emotional Repercussions of Grandparents Facing the Illness and Treatment of Cancer in Pediatric Oncology at a Reference Hospital.

Childhood cancer, especially leukemias and central nervous system tumors, deeply impacts families, requiring important decisions during treatment. Parents, overwhelmed with increasing responsibilities, can rely on the crucial support of grandparents, both in providing significant emotional support and in actively participating in caring for their grandchildren, even if it affects their own daily activities and quality of life. Therefore, we sought to analyze the emotional repercussions of grandparents facing the illness and treatment of cancer. It was based on a qualitative cross-sectional study conducted at a reference hospital of the Unified Health System (SUS) in Pernambuco, Brazil, from December 2023 to February 2024. Data collection was performed through semi-structured and audio-recorded interviews, with participants' consent, transcribed in full, and analyzed using the Bardin technique. Five grandmothers participated in the study, all of them female, aged 52 to 68 years, with a mean age of 61.2 years. The study highlights the importance of grandparents in caring for their grandchildren, emphasizing the emotional challenges present in diagnosis and treatment.

Proton therapy in pediatric neuro-oncology. Potential advantages and the relationship between cost and results

The aim of study: to analyze the accumulated experience and try to identify those clinical situations in which the use of protons will be economically and clinically more effective than photon radiation therapy. Material and methods. The articles devoted to the study of the evaluation and comparison of the effectiveness of proton and photon radiation beams in the treatment of tumors of the central nervous system and published over the past 25 years were searched in the Medline, Embase and the Cochrane Library databases. Results. the analysis of available publications has shown that accelerated protons do not improve survival rates and disease-free rates in all forms of brain tumors compared with photon therapy. However, protons can significantly increase the level of dose distribution conformity and reduce the dose to critical structures (pituitary gland, cochlea, eye lenses, hypothalamus), thus reducing the risk of hearing and visual impairment as well as hormonal and cognitive disorders. All this is critically important for potentially curable malignant tumors, such as medulloblastoma and germinoma, for low malignant potential tumors (grade 1–2 glioma) or tumors with decreased metastatic potential, since proton therapy compared to photon therapy reduces the risk of late side effects that worsen the quality of life of cured children. Conclusion. central nervous system tumors are one of the most common solid malignant neoplasms in children. Radiation therapy (RT) is recognized as an important therapeutic component of treatment and is often used in strategies for multimodal therapy of tumors of the central nervous system in children. Proton radiation therapy is one of the attractive methods of radiotherapy with minimal dose distribution to normal tissues and a decrease in the absorbed dose. The precision of protons reduces the risk of long-term side effects associated with this type of treatment and the induction of secondary malignancies, which is of particular importance for the quality of life.

Registration, incidence patterns, and survival trends of central nervous system tumors among children in Germany 1980-2019: An analysis of 40years based on data from the German Childhood Cancer Registry.

Tumors of the central nervous system (CNS) are the second most common type of pediatric cancer in Germany. We aimed to describe registration practice, incidence, and survival patterns for childhood CNS tumors in Germany for the past 40years. Including all CNS tumor cases in children diagnosed at ages 0-14years registered at the German Childhood Cancer Registry (GCCR) in 1980-2019 (for survival analysis 1980-2016), we calculated age-specific and age-standardized incidence rates (ASIR) over time, average annual percentage changes (AAPC), and 1- and 5-year overall survival. While we observed a pronounced increase in ASIR after the establishment of the GCCR during the 1980s, ASIR for all pediatric CNS tumors combined continued to increase markedly from 28.6 per million in 1990-1999 to 43.3 in 2010-2019 (AAPC=2.7% in 1991-2010, AAPC=0.3% in 2010-2019). The 5-year overall survival from CNS tumors improved from 63% in the 1980s, 70% in the 1990s to 79% in 2010-2016. These improvements have occurred across all age groups. Children diagnosed with ependymomas and choroid plexus tumors experienced the strongest increase (from 54% to 81%). Observed increases in incidence rates for pediatric CNS tumors are likely only partially caused by actual increasing case numbers. The majority is a function of improved registration and, to a minor extent, improvements in diagnostics. Survival from pediatric CNS tumors has, by and large, improved consistently, leading to a growing population of childhood cancer survivors with diverse health biographies and risk of lifelong adverse impact on health and wellbeing.

MZ1, a BRD4 inhibitor, exerted its anti-cancer effects by suppressing SDC1 in glioblastoma

BackgroundGlioblastoma (GBM) is a relatively prevalent primary tumor of the central nervous system in children, characterized by its high malignancy and mortality rates, along with the intricate challenges of achieving complete surgical resection. Recently, an increasing number of studies have focused on the crucial role of super-enhancers (SEs) in the occurrence and development of GBM. This study embarks on the task of evaluating the effectiveness of MZ1, an inhibitor of BRD4 meticulously designed to specifically target SEs, within the intricate framework of GBM.MethodsThe clinical data of GBM patients was sourced from the Chinese Glioma Genome Atlas (CGGA) and the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the gene expression data of tumor cell lines was derived from the Cancer Cell Line Encyclopedia (CCLE). The impact of MZ1 on GBM was assessed through CCK-8, colony formation assays, EdU incorporation analysis, flow cytometry, and xenograft mouse models. The underlying mechanism was investigated through RNA-seq and ChIP-seq analyses.ResultsIn this investigation, we made a noteworthy observation that MZ1 exhibited a substantial reduction in the proliferation of GBM cells by effectively degrading BRD4. Additionally, MZ1 displayed a notable capability in inducing significant cell cycle arrest and apoptosis in GBM cells. These findings were in line with our in vitro outcomes. Notably, MZ1 administration resulted in a remarkable decrease in tumor size within the xenograft model with diminished toxicity. Furthermore, on a mechanistic level, the administration of MZ1 resulted in a significant suppression of pivotal genes closely associated with cell cycle regulation and epithelial-mesenchymal transition (EMT). Interestingly, our analysis of RNA-seq and ChIP-seq data unveiled the discovery of a novel prospective oncogene, SDC1, which assumed a pivotal role in the tumorigenesis and progression of GBM.ConclusionIn summary, our findings revealed that MZ1 effectively disrupted the aberrant transcriptional regulation of oncogenes in GBM by degradation of BRD4. This positions MZ1 as a promising candidate in the realm of therapeutic options for GBM treatment.

A Review of Current Perspectives on Motoric Insufficiency Rehabilitation following Pediatric Stroke.

Pediatric stroke (PS) is an injury caused by the occlusion or rupture of a blood vessel in the central nervous system (CNS) of children, before or after birth. Hemiparesis is the most common motoric deficit associated with PS in children. Therefore, it is important to emphasize that PS is a significant challenge for rehabilitation, especially since the consequences may also appear during the child's growth and development, reducing functional capacity. The plasticity of the child's CNS is an important predecessor of recovery, but disruption of the neural network, specific to an immature brain, can have harmful and potentially devastating consequences. In this review, we summarize the complexity of the consequences associated with PS and the possibilities and role of modern rehabilitation. An analysis of the current literature reveals that Constraint-Induced Movement Therapy, forced-use therapy, repetitive transcranial magnetic stimulation, functional electrical stimulation and robot-assisted therapy have demonstrated at least partial improvements in motor domains related to hemiparesis or hemiplegia caused by PS, but they are supported with different levels of evidence. Due to the lack of randomized controlled studies, the optimal rehabilitation treatment is still debatable, and therefore, most recommendations are primarily based on expert consensuses, opinions and an insufficient level of evidence.

Клінічне спостереження тератоми головного мозку новонародженого

A congenital brain tumor is a tumor detected before birth or during the first two months of life. The frequency of congenital brain tumors is extremely low - 0.34 per 1 million newborns, and no more than 1.5% of all neoplasms of the central nervous system in children, but the rapid growth of the tumor and the destruction of normal brain tissue give them a fatal prognosis. Purpose - to expand knowledge on the possibilities of antenatal diagnosis and the features of the management of the early neonatal period of congenital mіalformations based on the clinical observation of fetal brain teratoma. An overview of literature sources is provided on the prevalence of pathology, histological structure (teratomas, neuroepithelial and mesenchymal tumors), features of the clinical course that distinguish them from childhood tumors - mainly supratentorial localization, lack of growth restriction due to the mobility of the bones of the skull, prognosis and tactics of pregnancy and childbirth . Ultrasound examination is the main method of diagnosis of brain tumors, which are visualized in the form of a solid or cystic calcified formation or not, and manifestations of hypervascularization can also be absent or present. The features of the structure and development of the teratoma, which contains cells of all 3 germ layers and has properties of rapid destructive growth, are also described. Hydrocephalus accompanying congenital brain tumors can be caused both by compression of the ventricular system and intracranial hemorrhages. Thanks to modern diagnostic capabilities, most cases are detected in terms of possible termination of pregnancy, in the case of childbirth with such a pathology, in 60% of cases, a cesarean section is used. The given clinical case shows the possibilities of antenatal diagnosis of a brain tumor and even clearly establishing the depth of the lesion, at the same time as the lack of treatment options. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Childhood and Adolescent Central Nervous System Tumours in Spain: Incidence and Survival over 20 Years: A Historical Baseline for Current Assessment.

Central nervous system (CNS) neoplasms are highly frequent solid tumours in children and adolescents. While some studies have shown a rise in their incidence in Europe, others have not. Survival remains limited. We addressed two questions about these tumours in Spain: (1) Is incidence increasing? and (2) Has survival improved? This population-based study included 1635 children and 328 adolescents from 11 population-based cancer registries with International Classification of Childhood Cancer Group III tumours, incident in 1983-2007. Age-specific and age-standardised (world population) incidence rates (ASRws) were calculated. Incidence time trends were characterised using annual percent change (APC) obtained with Joinpoint. Cases from 1991 to 2005 (1171) were included in Kaplan-Meier survival analyses, and the results were evaluated with log-rank and log-rank for trend tests. Children's survival was age-standardised using: (1) the age distribution of cases and the corresponding trends assessed with Joinpoint; and (2) European weights for comparison with Europe. ASRw 1983-2007: children: 32.7 cases/106; adolescents: 23.5 cases/106. The overall incidence of all tumours increased across 1983-2007 in children and adolescents. Considering change points, the APCs were: (1) children: 1983-1993, 4.3%^ (1.1; 7.7); 1993-2007, -0.2% (-1.9; 1.6); (2) adolescents: 1983-2004: 2.9%^ (0.9; 4.9); 2004-2007: -7.7% (-40; 41.9). For malignant tumours, the trends were not significant. 5-year survival was 65% (1991-2005), with no significant trends (except for non-malignant tumours). CNS tumour incidence in Spain was found to be similar to that in Europe. Rises in incidence may be mostly attributable to changes in the registration of non-malignant tumours. The overall malignant CNS tumour trend was compatible with reports for Southern Europe. Survival was lower than in Europe, without improvement over time. We provide a baseline for assessing current paediatric oncology achievements and incidence in respect of childhood and adolescent CNS tumours.

Acute myelomonoblastic leukemia in children, the particularities of extramedullary infiltration based on a clinical case

Childhood acute myeloidleukemia (AML) represents approximately 5% of childhood malignancies and 15% to 25% of pediatric acute leukemia. The extramedullary manifestation of infiltrating clonal blast populations in a variety of organs and tissues in acute myeloid leukemia (AML) is defined as a distinct entity in the 2016 WHO classification of myeloid neoplasms, myeloid sarcoma The rate of complete remission after induction chemotherapy was lower in patients with extramedullary infiltration, overall survival and event-free survival were not different between patients with and without extramedullary infiltration. Purpose of the study: Presentation of a clinical case of ALM type M4 with the presence of an extramedullary infiltrate in the tissue of the central nervous system in children. Materials and methods: The clinical, paraclinical, imaging data of the patient were studied in parallel with the specialized literature on similar cases. Results: Boy, 5 years old, goes to the doctor with accusations of bilateral palpebral edema, bilateral temporal region edema and bilateral exophthalmos , more pronounced on the left. In the general analysis of the blood: - Hemoglobin - 89 g/l , Leukocytes - 7.2 x 10^9/l; unsegmented neutrophil - 1%; segmented - 18%; lymphocytes - 44%; monocytes - 20%; blast cells - 16%; Platelets - 70 x 10^9/l;VSH - 44 mm/h. During the physical examination: the peripheral lymph nodes are palpable. No signs of central nervous system damage. It is supposed the diagnosis: Acute myeloid leukemia, sarcoma, or neuroblastoma. A medullary puncture: moderately cellular marrow was determined, with blastcells 15.2%. Morphologically, it is more similar to acute myelo-monoblastic leukemia FAB-M4. Computerized Tomography-multiple, hyperdense pathological foci, with localization with inand bilateral extraorbital, associated with exophthalmos. The formation from the sphenoid sinus extends to the nasopharynx , through the pterygopalatine fossa, with narrowing of the lumen and mass effect on the palatine tonsils. Immunophenotyping: CD45-/+ SS low 8% population, CD36+ 6%CD64+ monoblasts 8%, Promonocytes /monocytes – (CD64+/CD14+) 25%.He underwent treatment according to the AML BFM 2004 program with numerous complications, andcranial radiotherapy. At the moment, the child is in morphological remission. Conclusions. The differential diagnosis of hyperdense intracranial masses may include neuroblastoma, meningioma, lymphoma, metastases, or sarcomas. Correct and early diagnosis and initiation of specific treatment are essential to increase the survival rate in cases of acute leukemia in children.

The Role of Molecular Aspects in the Occurrence of Febrile Seizures

Febrile seizures are the result of complex interactions between multiple molecular components in the child's central nervous system, including changes in neurotransmitters, neuronal activity, and the brain's inflammatory response. When a child has a fever, there is an increase in body temperature, which triggers a series of molecular changes in the brain, affecting electrical signaling pathways and triggering characteristic seizures. The literature search process was carried out on various databases (PubMed, Web of Sciences, EMBASE, Cochrane Libraries, and Google Scholar) regarding studies of molecular aspects of febrile seizures. This study follows the preferred reporting items for systematic reviews and meta-analysis (PRISMA) recommendations. An increase in body temperature (fever) is the main trigger for febrile seizures. Fever can result in changes in brain chemistry, including changes in neurotransmitters and inflammatory responses, which can affect the molecular pathways that trigger seizures. Glutamate is the main neurotransmitter that plays a role in triggering seizures. Increased glutamate release during fever can trigger excessive activity in neurons. On the other hand, GABA, a neurotransmitter that plays a role in dampening neuronal activity, may also be involved, and an imbalance between glutamate and GABA may occur during seizures. Genetic factors play a role in susceptibility to febrile seizures. Several genes, such as SCN1A and GABRG2, have been identified as potentially increasing the risk of febrile seizures, especially those of a complex nature. Febrile seizures usually do not cause permanent changes in brain structure. However, in some very rare cases, such as EASIFE, temporary changes in brain structure may occur.

Pediatric low-grade glioma: State-of-the-art and ongoing challenges.

The most common childhood central nervous system (CNS) tumor is pediatric low-grade glioma (pLGG), representing 30%-40% of all CNS tumors in children. Although there is high associated morbidity, tumor-related mortality is relatively rare. pLGG is now conceptualized as a chronic disease, underscoring the importance of functional outcomes and quality-of-life measures. A wealth of data has emerged about these tumors, including a better understanding of their natural history and their molecular drivers, paving the way for the use of targeted inhibitors. While these treatments have heralded tremendous promise, challenges remain about how to best optimize their use, and the long-term toxicities associated with these inhibitors remain unknown. The International Pediatric Low-Grade Glioma Coalition (iPLGGc) is a global group of physicians and scientists with expertise in pLGG focused on addressing key pLGG issues. Here, the iPLGGc provides an overview of the current state-of-the-art in pLGG, including epidemiology, histology, molecular landscape, treatment paradigms, survival outcomes, functional outcomes, imaging response, and ongoing challenges. This paper also serves as an introduction to 3 other pLGG manuscripts on (1) pLGG preclinical models, (2) consensus framework for conducting early-phase clinical trials in pLGG, and (3) pLGG resistance, rebound, and recurrence.

1 Ototoxicity and Cognitive Outcomes among Children Treated for Brain Tumors in Infancy

Objective:Treatment of childhood central nervous system (CNS) tumors can lead to sensorineural hearing loss (SNHL), with prior research indicating associations between SNHL and cognitive difficulties. Infants (0-3 years) treated for CNS tumors are at particular risk for neurocognitive deficits due to increased vulnerability of the developing brain and missed developmental opportunities secondary to prolonged treatment. This study expands upon existing research by examining the association between treatment-related SNHL and later neurocognitive outcomes among infants.Participants and Methods:Serial audiology and neurocognitive assessments were conducted as part of a prospective, multisite, longitudinal trial (SJYC07). Children with newly diagnosed CNS tumors were treated with chemotherapy, with or without focal proton or photon radiation therapy (RT). SNHL was dichotomized based on hearing in the better ear as present versus not present (Chang grade ≥1a vs. <1a). Neurocognitive assessments included intellectual functioning (IQ), and parent ratings of executive functioning and behavioral functioning. Demographic and clinical variables investigated included: sex, age at diagnosis (years), treatment type (chemotherapy only vs. chemotherapy + RT), risk group (low vs. intermediate vs. high), and socioeconomic status (SES, continuous). Logistic regression models were used to identify factors associated with SNHL. Change point longitudinal models were used to examine the effect of each covariate individually and the potential impact of SNHL on trajectories of neurocognitive outcomes.Results:Of 135 patients (median age at diagnosis= 1.5 years), 67% had mild-to-severe SNHL as defined by Chang grade ≥1a at last follow-up. SNHL occurred early after treatment with a 1-year cumulative incidence 63.0% ±4.3%. SNHL was associated with age at diagnosis (p <.001) but not sex, treatment exposure or study risk arm (p >.10). At pretreatment baseline, IQ was associated with age at diagnosis (older age= higher IQ) and SES (higher SES= higher IQ) with a change in the trajectory of IQ after SNHL (stable prior to SNHL and declined 1.46 points/year after SNHL), which was impacted by tumor location (patients with supratentorial tumors stable prior to SNHL and declined 2.84 points/year after SNHL; whereas, patients with infratentorial tumors increased 1.93 points/year prior to SNHL and were stable after SNHL). At pre-treatment baseline, adaptive functioning was associated with age at diagnosis (older age= higher skills) with a change in adaptive functioning after SNHL that varied by age. There was a change in trajectory of attention problems (stable before SNHL and worsening 1.39 points/year after SNHL). SNHL was not associated with parent report of emerging executive functioning.Conclusions:Children with brain tumors experience SNHL and cognitive difficulties early in treatment that can worsen over time. Younger age at diagnosis is associated with greater risk for SNHL and cognitive difficulties. Analyses of the time course between the emergence of SNHL and cognitive late effects suggests even mild SNHL is associated with a clinically signficant decline in IQ and attention problems. These findings have notable implications with respect to refining monitoring guidelines, informing modifications to treatment, advocating for interventions, and helping educate parents, teachers, and providers about the significant impact of mild SNHL.

FRI225 Clinical Course Of Late-onset Adrenal Insufficiency Due To Treatment Of Childhood Acute Lymphoblastic Leukemia

Abstract Disclosure: M. Iwabuchi: None. Background: Some people who were treated for cancer during childhood may develop endocrine problems as because of changes in the function of endocrine system. Acute lymphoblastic leukemia is the most common type of cancer and leukemia in children and components of ALL treatment are induction, consolidation, maintenance, and central nervous system prophylaxis. It is recommended that people who had irradiation in a dose of 40 Gy or higher to the central area of the hypothalamic-pituitary axis should have a blood test done to check the cortisol level and should be done yearly for at least 15 years since this complication can occur many years after irradiation. Clinical Case: A man in his 40s was admitted with symptoms of diarrhea, low-grade fever, and drowsiness. The serum sodium level that caused his symptoms decreased to 100 mEq/L and was adequately corrected. Endocrinological examination confirmed the diagnosis of central adrenal insufficiency. Soon after starting hormonal replacement therapy with hydrocortisone, his general conditions improved. After establishing our relationship, he confessed to having a history of ALL in childhood. According to his medical records at the time, he underwent induction therapy with vincristine-prednisone in 1977, maintenance therapy with 6-mercaptopurine, and radiation therapy to the central nervous system of 25 Gy in 1983. In 2023, 40 years have passed since radiation therapy. He was able to lead a normal life on oral hydrocortisone 20 mg/day without recurrence of adrenal insufficiency. Clinical Lesson: A 40-old male survivor of ALL developed adrenal insufficiency in 30 years after cranial irradiation during childhood. Undiagnosed adrenal insufficiency is often the cause of death. We should consider childhood cancer survivors have the risk of a central adrenal insufficiency. The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers (COG LTFU Guidelines) are a resource for healthcare professionals who provide ongoing care to survivors of pediatric malignancies. The screening recommendations in these guidelines are appropriate for asymptomatic survivors of childhood, adolescent, or young adult cancer presenting for routine exposure-based medical follow-up. It is recommended that people who had irradiation in a dose of 40 Gy or higher to the central area of the hypothalamic-pituitary axis should have a blood test done to check the cortisol level and should be done yearly for at least 15 years since this complication can occur many years after irradiation. This case highlights the importance of long-term follow-up of cancer survivors after irradiation and the delayed presentation of adrenal insufficiency. This is the first report of the subsequent treatment course of late-onset adrenal insufficiency that developed 30 years after irradiation for childhood central nervous system ALL. Presentation: Friday, June 16, 2023

Evaluation of Neurofibromatosis Type 1 Associated Optic Pathway Gliomas

Background/Aims: Optic pathway gliomas (OPGs) are low-grade gliomas histologically represented by pilocytic astrocytoma (PA) in 90% of cases, can develop from any part of the visual pathways such as optic nerve, chiasm, optic tract, or optic radiations which frequently involve the hypothalamus. OPGs account for 3–5% of childhood central nervous system (CNS) tumors and about 2% of pediatric glial lesions. OPGs are believed to be the most prevalent intracranial tumor in patients with neurofibromatosis type 1 (NF-1) and can occur in 15–20% of NF-1 cases. The aim of this study is to evaluate the clinical features and treatment response in patients diagnosed with optic glioma and NF-1.
 Methods: All cases diagnosed with OPG and received treatment in the Pediatric Oncology Department, between January 2015 to January 2021 were retrospectively evaluated. Inclusion criteria include children and adolescents with OPG aged between 0 and 18 years. The medical records (gender, age, tumor entity, tumor location) of patients, as well as their treatment history and magnetic resonance imaging (MRI) scans, were examined. The diagnosis of OPG was made clinically and radiologically by the tumor board. The recommendations of the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group were used in the diagnosis and evaluation of treatment response. Patients received intravenous chemotherapy with SIOP LGG 2004 (vincristine- carboplatin) with or without bevacizumab (10 mg/kg, started every 2 weeks), therapy or vinblastine (3 mg/m2, weekly). 
 Results: This study included 27 cases during the study period from January 2015 to January 2021. In this study there were 14 male (51.8 %) and 13 female (48.1 %) patients. The median age was 4.8 (range: 0.5–14.9) years. Biopsy was performed in three patients and the diagnosis was low-grade glioma (pilocytic astrocytoma) for all of them. Chemotherapy was administered to 22 cases in total. Twelve patients received vincristine-carboplatine, 5 patients received vincristine-carboplatin with bevacizumab and 5 patients received vinorelbine. Radiological response was evaluated in all 22 patients at 3 months MRI. No patient had a radiological complete respons, 11 patients (50%) had partial response, 2 patients (9%) presented with a progressive disease, showing an increase in measurements of 35% and 9 patients(40.9%) had stable disease at the 3-month evaluation.
 Conclusions: Systemic and visual problems play a significant role in the selection of treatment for pediatric patients with optic gliomas. An essential treatment option for improving symptoms and reducing tumor size is systemic chemotherapy. A crucial therapy option for enhancing vision is bevacizumab for the patients with NF-associated OPG.

Childhood, adolescent, and adult primary brain and central nervous system tumor statistics for practicing healthcare providers in neuro-oncology, CBTRUS 2015-2019.

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention (CDC) and National Cancer Institute (NCI), is the largest aggregation of histopathology-specific population-based data for primary brain and other central nervous system (CNS) in the US. CBTRUS publishes an annual statistical report which provides critical reference data for the broad neuro-oncology community. Here, we summarize the key findings from the 2022 CBTRUS annual statistical report for healthcare providers. Incidence data were obtained from the CDC's National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology, and End Results Program for 52 central cancer registries (CCRs). Survival data were obtained from 42 NPCR CCRs. All rates are per 100 000 and age-adjusted using the 2000 US standard population. Overall median survival was estimated using Kaplan-Meier models. Survival data for selected molecularly defined histopathologies are from the National Cancer Database. Mortality data are from the National Vital Statistics System. The average annual age-adjusted incidence rate of all primary brain and other CNS tumors was 24.25/100 000. Incidence was higher in females and non-Hispanics. The most commonly occurring malignant and predominately non-malignant tumors was glioblastoma (14% of all primary brain tumors) and meningioma (39% of all primary brain tumors), respectively. Mortality rates and overall median survival varied by age, sex, and histopathology. This summary describes the most up-to-date population-based incidence, mortality, and survival, of primary brain and other CNS tumors in the US and aims to serve as a concise resource for neuro-oncology providers.

Kikuchi–Fujimoto disease associated with the central nervous system in children

AbstractThe clinical data of patients with Kikuchi–Fujimoto disease (KFD) combined with the involvement of the central system is limited, particularly for children. This study aimed to investigate the clinical features and prognosis of KFD associated with the central nervous system in children. We collected the clinical data of patients diagnosed with KFD combined with the involvement of the central system, hospitalized at Children's Hospital of Chongqing Medical University (CHCMU). Furthermore, we summarized the clinical features and outcomes in children by reviewing the published literature. Together with the two patients from CHMCU enrolled in this study, we identified 19 children diagnosed with KFD combined with the involvement of the central nervous system, including eight males and 11 females. The onset age ranges from 6 to 18 years (the median age was 14 and the interquartile range was 9–16). Sixteen patients were diagnosed with aseptic meningitis. Headache (78.9%, 15/19) was the most common symptom. Cerebrospinal fluid pressure was increased in 3 patients (60.0%, 3/5), cell count was elevated in 14 patients (73.7%, 14/19), glucose was decreased in 4 patients (21.0%, 4/19), and protein was elevated in 12 patients (63.1%, 12/19). A total of 9 patients had cranial imaging changes. Electroencephalogram (EEG) was performed on seven patients and 4 patients presented abnormal EEG (57.1%, 4/7). A total of 12 patients received steroid therapy; two were combined with antiepileptic treatment. In children, KFD complicated with the involvement of the central nervous system was rare and aseptic meningitis was the primary manifestation. Most patients had a good prognosis and a few had residual sequelae of neurological damage.

Brain cell type specific proteomics approach to discover pathological mechanisms in the childhood CNS disorder mucolipidosis type IV.

Mucolipidosis IV (MLIV) is an ultra-rare, recessively inherited lysosomal disorder resulting from inactivating mutations in MCOLN1, the gene encoding the lysosomal cation channel TRPML1. The disease primarily affects the central nervous system (CNS) and manifests in the first year with cognitive and motor developmental delay, followed by a gradual decline in neurological function across the second decade of life, blindness, and premature death in third or fourth decades. Brain pathology manifestations in MLIV are consistent with hypomyelinating leukodystrophy with brain iron accumulation. Presently, there are no approved or investigational therapies for MLIV, and pathogenic mechanisms remain largely unknown. The MLIV mouse model, Mcoln1-/- mice, recapitulates all major manifestations of the human disease. Here, to better understand the pathological mechanisms in the MLIV brain, we performed cell type specific LC-MS/MS proteomics analysis in the MLIV mouse model and reconstituted molecular signatures of the disease in either freshly isolated populations of neurons, astrocytes, oligodendrocytes, and neural stem cells, or whole tissue cortical homogenates from young adult symptomatic Mcoln1-/- mice. Our analysis confirmed on the molecular level major histopathological hallmarks of MLIV universally present in Mcoln1-/- tissue and brain cells, such as hypomyelination, lysosomal dysregulation, and impaired metabolism of lipids and polysaccharides. Importantly, pathway analysis in brain cells revealed mitochondria-related alterations in all Mcoln1-/- brain cells, except oligodendrocytes, that was not possible to resolve in whole tissue. We also report unique proteome signatures and dysregulated pathways for each brain cell population used in this study. These data shed new light on cell-intrinsic mechanisms of MLIV and provide new insights for biomarker discovery and validation to advance translational studies for this disease.

Perturbations in neural stem cell function during a neurotropic viral infection in juvenile mice.

Viral infections of the central nervous system (CNS) often cause worse neurological outcomes in younger hosts. Throughout childhood, the brain undergoes extensive development and refinement to produce functional neural networks. Network function is maintained partly with the help of neural stem cells (NSCs) that replace neuronal and glia subtypes in the two neurogenic niches of the brain (the hippocampus and subventricular zone). Accumulating evidence suggests that viruses disrupt NSC function in adulthood and infancy, but the in vivo impact of childhood infections on acute and long-term NSC function is unknown. Using a juvenile mouse model of measles virus (MeV) infection, where only mature neurons in the brain are infected, we defined the effects of the antiviral immune response on NSCs from juvenile to adult stages of life. We found that (a) virus persists in the brains of survivors despite an anti-viral immune response; (b) NSC numbers decrease dramatically during early infection, but ultimately stabilize in adult survivors; (c) infection is associated with mild apoptosis throughout the juvenile brain, but NSC proliferation is unchanged; (d) the loss of NSC numbers is dependent upon the stage of NSC differentiation; and (e) immature neurons increase early during infection, concurrent with depletion of NSC pools. Collectively, we show that NSCs are exquisitely sensitive to the inflammatory microenvironment created during neuron-restricted MeV infection in juveniles, responding with an early loss of NSCs but increased neurogenesis. These studies provide insight into potential cellular mechanisms associated with long-term neurological deficits in survivors of childhood CNS infections.

Treatments associated with all-cause mortality among children with primary brain and central nervous system tumors: a retrospective cohort study from the SEER database.

Evidence on treatment modalities and survival in childhood primary brain and central nervous system (CNS) tumors remains contradictory, with previous studies often lacking sufficient patient cohort sizes to assess the differences in histological subtypes. This cohort study based on a large population investigated the effects of various treatments on the mortality of patients with different histological types of primary brain and CNS tumors from the Surveillance, Epidemiology, and End Results (SEER) database. Data of demography, primary tumor site, histology, tumor grade and treatments from all pediatric patients with primary brain and CNS tumors were extracted in this retrospective cohort. The outcomes were overall, 1-, 5-, and 10-year all-cause mortality. Multivariate Cox proportional hazards models were to explore the associations of treatment with overall, 1-, 5-, and 10-year all-cause mortality, with hazard ratios (HRs) and 95% confidence intervals (CIs). Totally 10,994 children were included, with the mean age at diagnosis of 7.3 years, and the median follow-up time of 5.0 years. Of which, 2,003 (18.2%) were diffuse astrocytoma, 3,188 (29.0%) were embryonal tumors, and 3,691 (33.5%) were malignant glioma. Then 4,333 (39.41%) children died during the follow-up. For diffuse astrocytomas and malignant gliomas, patients who received all other treatments were associated with overall, 1-, 5- and 10-year all-cause mortality compared to those only received resection. Embryonal tumors patients receiving resection with radiation only and those receiving resection with both chemotherapy and radiation were associated with lower odds of overall, 1-, 5- and 10-year all-cause mortality compared to patients who only received resection. For ependymal tumors, no surgery/only biopsy with chemotherapy, resection with chemotherapy only, resection with both chemotherapy and radiation, and other treatments had increased risks of overall all-cause mortality compared with resection. The risk of 1-year all-cause mortality increased in ependymal tumors with treatment involving resection and radiation. However, resection with both chemotherapy and radiation was not significantly associated with the 1- nor 5-year all-cause mortality. Resection may be recommended for children with diffuse astrocytoma, ependymal tumors, and malignant glioma, while resection with radiotherapy or chemoradiation may be recommended for children with embryonal tumors.

Neurocutaneous Syndromes, Perinatal Factors, and the Risk of Childhood Cancer in Sweden

Neurocutaneous syndromes are associated with cancer predisposition and sometimes associated with perinatal factors. A better understanding of the association between neurocutaneous syndromes, perinatal factors, and childhood cancer is key for earlier cancer detection. To evaluate the association of neurocutaneous syndromes and perinatal factors with childhood cancer risk in a cohort of Swedish children. In this nationwide cohort study, all children and adolescents up to age 20 years, from 1973 to 2015, were identified through the Swedish National Medical Birth Register (MBR), provided they had information on both biological parents. Analyses were conducted from April 2021 through May 2023. Diagnoses of neurocutaneous syndromes were obtained from the MBR, National Patient Register, and Cause of Death register. Perinatal factors (birth weight, gestational age, birth weight by gestational age, 5-minute Apgar score, and head circumference) were obtained from the MBR. Childhood cancer risk (<20 years at diagnosis; identified from the National Cancer Register), including leukemia, lymphoma, and central nervous system (CNS) tumors. Among 4 173 108 included children (2 143 133 [51.4%] male, median [IQR] follow-up 20 [9.7-20] years), 1783 had neurofibromatosis type 1 (NF1), 444 tuberous sclerosis, 63 von Hippel-Lindau disease, and 39 ataxia-telangiectasia. An increased cancer risk was observed among children with any neurocutaneous syndrome (HR, 34.9; 95% CI, 30.8-39.6) and was particularly pronounced for CNS tumors (HR, 111.7; 95% CI, 96.8-128.8), except among children with ataxia-telangiectasia, where the increased risk was associated with lymphomas (HR, 233.1; 95% CI, 75.0-724.1). Leukemia risk was increased only among children with NF1 (HR, 4.1; 95% CI, 1.7-9.8). Several perinatal factors, including high birth weight, being born large for gestational age, preterm birth, low 5-minute Apgar score, and large head circumference had lesser associations with childhood cancer. Adjusting for neurocutaneous syndromes did not affect these associations. In this nationwide cohort study, neurocutaneous syndromes were associated with an increased risk of childhood cancer, especially CNS tumors. Several perinatal factors had lesser associations with childhood cancer, independently of the presence of neurocutaneous syndromes. Other biological mechanisms likely underlie the association between perinatal factors and childhood cancer.

Resolution of the Scientific and Practical Conference with international participation “Targeted and immunotherapy of tumors of the central nervous system in children” (St. Petersburg, March 31, 2023, Almazov National Medical Research Center of the Ministry of Health of Russia)

Resolution of the Scientific and Practical Conference with international participation “Targeted and immunotherapy of tumors of the central nervous system in children” (St. Petersburg, March 31, 2023, Almazov National Medical Research Center of the Ministry of Health of Russia)