Essential Management of Pediatric Brain Tumors.

Brain tumors are the most common solid tumors in children and are associated with high mortality. The most common childhood brain tumors are grouped as low-grade gliomas (LGG), high grade gliomas (HGG), ependymomas, and embryonal tumors, according to the World Health Organization (WHO). Advances in molecular genetics have led to a shift from pure histopathological diagnosis to integrated diagnosis. For the first time, these new criteria were included in the WHO classification published in 2016 and has been further updated in the 2021 edition. Integrated diagnosis is based on molecular genomic similarities of the tumor subclasses, and it can better explain the differences in clinical courses of previously histopathologically identical entities. Important advances have also been made in pediatric neuro-oncology. A growing understanding of the molecular-genetic background of tumorigenesis has improved the diagnostic accuracy. Re-stratification of treatment protocols and the development of targeted therapies will significantly affect overall survival and quality of life. For some pediatric tumors, these advances have significantly improved therapeutic management and prognosis in certain tumor subgroups. Some therapeutic approaches also have serious long-term consequences. Therefore, optimized treatments are greatly needed. Here, we discuss the importance of multidisciplinary collaboration and the role of (pediatric) neurosurgery by briefly describing the most common childhood brain tumors and their currently recognized molecular subgroups

Role of fetal surgery in spinal dysraphism

Open spinal dysraphism is a common and clinically challenging organo-genetic malformation. Due to the well-known multi-organ affection with significant implication on the lives of patients and their families, abortion after prenatal diagnosis became reality in most parts of the world. After publication of the Management of Myelomeningocele Study (MOMS) results fetal surgery seems to be a new option and a broad discussion arose regarding advantages and risks of in utero treatment of spina bifida. This paper tries to evaluate objectively the actual state of knowledge and experience. This review article gives a historical overview as well as the experimental and pathophysiological background of fetal surgery in open spinal dysraphism. Additionally clinical follow-up experience of foetoscopically treated patients are presented and discussed. After carefully outweighing all available information on fetal surgery for spina bifida, one has to conclude, in accordance with the MOMS investigators, that in utero surgery cannot be considered a standard option at present time. But there is clear evidence of the hypothesis that early closure of the spinal canal has a positive influence on spinal cord function and severity of Chiari malformation type II, has been proven. A persisting problem is the fetal risk of prematurity and the maternal risk of uterus damage. There is also evidence that due to technical restrictions, fetal closure of the spinal canal bears unsolved problems leading to a higher postnatal incidence of complication surgery. Finally, missing long-term results make a definite evaluation impossible so far. At the moment, fetal surgery in open spinal dysraphism is not a standard of care despite promising results regarding central nervous system protection due to early spinal canal closure. Many technical problems need to be solved in the future in order to make this option a safe and standard one

A 21-year-old female with a third ventricular tumor

A 21-year-old female presented with a 2-months history of tinnitus, vertigo and nausea. On magnetic resonance imaging of the brain, she demonstrated a small contrast-enhancing mass in the posterior part of the third ventricle. Intraoperatively, the tumor showed a close relationship to the choroid plexus of the third ventricle. Histopathology revealed a benign schwannoma of World Health Organization grade I. To our knowledge, only 9 cases of intraventricular Schwann cell tumors have been published so far. Most of these tumors were benign schwannomas, except for 2 cases of malignant peripheral nerve sheath tumors. The tumor of our patient is the first reported schwannoma of the third ventricle. The origin of intraventricular Schwann cell tumors is unknown. They may arise from autonomic perivascular nerves in the choroid plexus or from ectopic neural crest-derived cells. Histologically, intraventricular schwannoma needs to be distinguished from other spindle cell tumors, in particular pilocytic astrocytoma and fibroblastic meningioma

Head circumference - a useful single parameter for skull volume development in cranial growth analysis?

Abstract Background The measurement of maximal head circumference is a standard procedure in the examination of childrens’ cranial growth and brain development. The objective of the study was to evaluate the validity of maximal head circumference to cranial volume in the first year of life using a new method which includes ear-to-ear over the head distance and maximal cranial length measurement. Methods 3D surface scans for cranial volume assessment were conducted in this method comparison study of 44 healthy Caucasian children (29 male, 15 female) at the ages of 4 and 12 months. Results Cranial volume increased from measurements made at 4 months to 12 months of age by an average of 1174 ± 106 to 1579 ± 79 ml. Maximal cranial circumference increased from 43.4 ± 9 cm to 46.9 ± 7 cm and the ear-to ear measurement increased from 26.3 ± 21 cm to 31.6 ± 18 cm at the same time points. There was a monotone association between maximal head circumference (HC) and increase in volume, yet a backwards inference from maximal circumference to the volume had a predictive value of only 78% (adjusted R2). Including the additional measurement of distance from ear to ear strengthened the ability of the model to predict the true value attained to 90%. The addition of the parameter skull length appeared to be negligible. Conclusion The results demonstrate that for a distinct improvement in the evaluation of a physiological cranial volume development, the additional measurement of the ear-to ear distance using a measuring tape is expedient, and, especially for cases with pathological skull changes, such as craniosynostosis, ought to be conducted

Childhood supratentorial ependymomas with fusion: an entity with characteristic clinical, radiological, cytogenetic and histopathological features

Ependymoma with YAP1‐MAMLD1 fusion is a rare, recently described supratentorial neoplasm of childhood, with few cases published so far. We report on 15 pediatric patients with ependymomas carrying YAP1‐MAMLD1 fusions, with their characteristic histopathology, immunophenotype and molecular/cytogenetic, radiological and clinical features. The YAP1‐MAMLD1 fusion was documented by RT‐PCR/Sanger sequencing, and tumor genomes were studied by molecular inversion probe (MIP) analysis. Significant copy number alterations were identified by GISTIC (Genomic Identification of Significant Targets in Cancer) analysis. All cases showed similar histopathological features including areas of high cellularity, presence of perivascular pseudo‐rosettes, small to medium‐sized nuclei with characteristic granular chromatin and strikingly abundant cells with dot‐like cytoplasmic expression of epithelial membrane antigen. Eleven cases presented features of anaplasia, corresponding to WHO grade III. MRI showed large supratentorial multinodular tumors with cystic components, heterogeneous contrast enhancement, located in the ventricular or periventricular region. One of two variants of YAP1‐MAMLD1 fusions was detected in all cases. The MIP genome profiles showed balanced profiles, with focal alterations of the YAP1 locus at 11q22.1–11q21.2 (7/14), MAMLD1 locus (Xp28) (10/14) and losses of chromosome arm 22q (5/14). Most patients were female (13/15) and younger than 3 years at diagnosis (12/15; median age, 8.2 months). Apart from one patient who died during surgery, all patients are alive without evidence of disease progression after receiving different treatment protocols, three without postoperative further treatment (median follow‐up, 4.84 years). In this to date, largest series of ependymomas with YAP1‐MAMLD1 fusions we show that they harbor characteristic histopathological, cytogenetic and imaging features, occur mostly in young girls under 3 years and are associated with good outcome. Therefore, this genetically defined neoplasm should be considered a distinct disease entity. The diagnosis should be confirmed by demonstration of the specific fusion. Further studies on large collaborative series are warranted to confirm our findings

Diagnosis and treatment of Chiari malformation type 1 in children : the International Consensus Document

Chiari malformation type 1 (CM1) is a rare condition where agreed classification and treatment are still missing. The goal of this study is to achieve a consensus on the diagnosis and treatment of CM1 in children. A multidisciplinary panel formulated 57 provisional statements based on a review of the literature. Thirty-four international experts (IE) participated in a Delphi study by independently rating each statement on a 4-point Likert scale ("strongly disagree," "disagree," "agree," "strongly agree"). Statements that were endorsed ("agree" or "strongly agree") by < 75% of raters were re-formulated, or new statements were added, and another Delphi round followed (up to a maximum of three). Thirty-five IE were contacted and 34 agreed to participate. A consensus was reached on 30/57 statements (52.6%) after round 1. Three statements were added, and one removed. After round 2, agreement was reached on 56/59 statements (94.9%). Finally, after round 3, which took place during the 2019 Chiari Consensus Conference (Milan, Italy), agreement was reached on 58/59 statements (98.3%) about four main sections (Definition and Classification, Planning, Surgery, Isolated Syringomyelia). Only one statement did not gain a consensus, which is the "definition of radiological failure 24 month post-surgery." The consensus document consists of 58 statements (24 on diagnosis, 34 on treatment), serving clinicians and researchers following children with CM1. There is a clear need for establishing an international network and registry and to promote collaborative studies to increase the evidence base and optimize the long-term care of this patient populatio