Search

Introduction: Hydrocephalus is a multifactorial disease, affecting the dynamics of cerebrospinal fluid (CSF) and leading to severe neurological impairment in children; in spite of the recent advances in hydrocephalus research, it has many physiopathological aspects that still remain poorly understood, especially after treatment. Objectives: To analyze the clinical, radiological, histopathological, and biochemical aspects of kaolin-induced hydrocephalus in an experimental model, both in the acute phase and after shunt treatment, by means of behavioral tests, magnetic resonance imaging (MRI) scans, histopathological studies, and level of inflammatory interleukins in the CSF. Methods: Seven-day-old Wistar rats were used and subdivided into three subgroups: treated hydrocephalic (n = 24), untreated hydrocephalic (n = 17), and controls (n = 5). The hydrocephalic groups underwent cisternal injection of 15% kaolin for induction of hydrocephalus at 7 days of age. The treated group was submitted to a ventricular-subcutaneous shunt (VSCS) 1 week after induction. All animals were euthanized at 21 days of age. They underwent motor function and memory testing as well as brain MRI scans. Histopathological analysis for glial fibrillary acidic protein and Ki-67 was done, and CSF was collected for measurement of IL-1β, IL-6, and TNF-α. Results: The average time to reach the water maze platform was highest in the untreated hydrocephalic group. The magnetization transfer rates were 37.21 and 33.76 before and after shunting, respectively. The mean astrocyte counts were 2.45, 1.36, and 90.5 for shunted, untreated, and control animals, respectively. The mean CSF IL-1β concentrations were 62.3 and 249.6 pg/mL, the average IL-6 levels were 104.2 and 364.7 pg/mL, and the average TNF-α values were 4.9 and 170.5 pg/mL for the treated hydrocephalic group and the untreated group, respectively. Conclusions: Pups treated with a CSF shunt showed better performance on memory tests. VSCS did not revert demyelination caused by hydrocephalus. Likewise, reactive astrocytosis and cell proliferation over the germinal matrix were not reversed after shunting. Hydrocephalic animals had raised levels of inflammatory interleukins, which returned to normal after treatment.

We are deeply saddened by the passing of Dr. William Harkness. A gifted surgeon, a caring clinician, a visionary leader and devoted family man, William left an indelible impression on pediatric neurosurgery and the many people whose lives he touched. Dr. William was educated at Eton School and qualified in medicine in 1979, at the University of Birmingham. His neurosurgical training commenced at the Radcliffe Infirmary, Oxford and later continued in Birmingham. Upon completion of his specialist training in 1991, he was appointed as a consultant neurosurgeon at the National Hospital for Neurology and Neurosurgery, Queen Square and Great Ormond Street Hospital for Sick Children (GOSH), but it was the latter institution that became his professional home as he focused his career on pediatric neurosurgery, establishing a legendary partnership with Dr. Richard Hayward. Dr. William spent a year in North America undergoing training at UCLA, Seattle, Miami and Montreal. He enthusiastically embraced the multidisciplinary team approach, enabling him to establish a world-leading children’s epilepsy surgery service together with Helen Cross at GOSH. While this is where he had his greatest scientific impact, he was a consummate pediatric neurosurgeon who thought deeply and wrote on a wide range of conditions. William was known to be an exceptionally skillful surgeon, with many neurosurgical trainees citing him as the one of the leading technical neurosurgeons they had worked with. He served as clinical lead for pediatric neurosciences at GOSH and led the development of a national plan for epilepsy surgery services in Great Britain. Throughout his career William was an ardent advocate for pediatric neurosurgery, representing the specialty in many forums including the Society of British Neurological Surgeons. Dr. Willian was a participant in the first ever European Society for Pediatric Neurosurgery (ESPN) educational course, where he struck up a legendary friendship with the late Jim Goodrich, he went on to become one of the most sought-after lecturers worldwide, including many Latin American Courses of Pediatric Neurosurgery (LACPN). In ISPN, there are few who have contributed more to the society. Dr. William served as scientific chair, communications chair, treasurer and ultimately president, (2016-2017). Combining his organizational and technical skills, he worked with Jim Johnson to develop InterSurgeon, a web-based platform promoting international collaboration through linking neurosurgeons and related organisations across the world. Supported by among others, the ISPN, UAB and the G4Alliance, InterSurgeon has grown beyond neurosurgery and will be a lasting tribute to William’s vision and drive. Dr. William was also an integral member of the Global Neurosurgery Committee of the World Federation of Neurosurgical Societies (WFNS). He worked tirelessly to propel the field, and always made sure he was available to provide advice and assistance. During his time with the committee, he expanded the knowledge base on global neurosurgery, worked to align the multitude of projects in the field, and improved collaboration amongst neurosurgeons around the world. He married Philippa Lubomirski in 1982. She survives him as do their four children, Fran, Ed, Gabi and Letitia, their grandchildren, Arlo, Joanie, Betsy, Peggy and Ari, and his sister, Nicola. Above all else, we remember William’s devotion to his family most vividly. His beloved wife Philippa, who accompanied him on most of his travels. And his four children, Fran, Ed, Gabi and Letitia, their grandchildren, Arlo, Joanie, Betsy, Peggy and Ari, and his sister, Nicola. We extend our sincere condolences to his family and close friends

Background: Jugular foramen paragangliomas (JFP) treatment represents a challenge for surgeons due to its close relationship with facial nerve (FN), lower cranial nerves (LCN), and internal carotid artery. Due to its hypervascularization, preoperative tumor embolization has been indicated. Methods: Retrospective analysis of the clinical evolution of 26 patients with JFP class C/D previously embolized treated through infratemporal/cervical access without FN transposition. Results: Total and subtotal resections were 50% each, regrowth/recurrence were 25%, and 23%, respectively, and mortality was 3.9%. Postoperatively, 68.4% of patients had FN House and Brackmann (HB) Grades I/II. New FN deficits were 15.4% post embolization and 30.7% postoperatively. Previous FN deficits worsened in 46.1%. Tumor involved the FN in 30.8% and in 62.5% of them these nerves were resected and grafted (60% of them had HB III). Lateral fall, ear murmur, and vertigo improved in all patients. Tinnitus improved in 77.8% and one patient developed tinnitus after surgery. Hearing loss did not improve, eight partial hearing loss remained unchanged and four worsened. New postoperative LCN deficits were 64.3%. Postoperative KPS between 80 and 100 dropped 8.3%. Two patients with secretory paragangliomas with arterial hypertension difficult to control had better postoperative blood pressure control. Conclusion: Although still with significant morbidity due to FN and LCN injuries, the treatment of patients with JFP Fisch C/D has good long-term results. Surgical techniques without FN transposition have less intraoperative nerve damage, lower rates of total resection, and higher recurrence. Preoperative embolization of JFP reduces the intraoperative blood loss but can cause FN deficit.

Extent of resection is one of the major contributing factors for survival of glioblastoma patients. However, before this surgical goal may be contemplated, the patient with suspected glioblastoma must undergo a series of preoperative steps: to confirm this pathology as the most probable clinical hypothesis, to assess the extension of the lesion and the potential involvement of eloquent areas of the brain, as well as to determine the clinical performance status of the patient and have the patient’s and family member’s goals and expectations aligned with surgical options that minimizes risks of poor outcome or functional deficits and increases survival odds. Several surgical adjuncts may contribute in increasing these odds, such as intraoperative imaging (i.e., intraoperative MRI and ultrasound), intraoperative navigation, fluorescent dyes, such as 5-ALA, and finally intraoperative mapping with or without awake craniotomy.

The brainstem is defined as the portion of the neural axis between the diencephalon and the cervical spinal cord. Brainstem gliomas (BSGs) can occur anywhere within this region and account for 10% to 15% of primary pediatric intracranial tumors. The development of neuroimaging allied to the refinement of surgical tools, such as improved magnification and visualization of the surgical field with more powerful surgical microscopes and sources of light, followed by the introduction of ultrasonic aspirator, anesthetic and intraoperative neurophysiological monitoring provided the neurosurgeon with conditions for a much safer surgical management of these tumors. This article reviews the current state of knowledge with regard to tumors arising in the brain stem in children, the therapeutic options available and provides recommendations with regard to management.

Background: Pediatric traumatic brain injury (TBI) is a serious social and economic problem. Emerging countries have 89% of the cases worldwide and lack relevant epidemiological studies on the subject. Objectives: Characterize the demographic, social and economic profiles of the pediatric population suffering TBI in Brazil. Methods: Data on the cases of pediatric TBI in Brazil between 2008 and 2020 were collected through the computer department of the Unified Health System (DATASUS) maintained by the Brazilian Ministry of Health. Results: There are about 28,836 hospital admissions due to pediatric TBI per year and an incidence of 45.11 admissions /100,000/year. The in-hospital mortality rate was 1.47/100,000/year, and the case fatality rate was 3.26%. The average annual cost of hospital expenses was US$ 12.311.759, with the average admission cost having a value of US $417. The 15–19 age group was the most frequently admitted to hospital for pediatric TBI and had the highest number of in- hospital deaths; in addition, more males were affected by this trauma compared to females at a rate of 2.31:1. Ethnic populations that are social minorities are more susceptible to a poor prognosis of TBI. Conclusion: Pediatric TBI should be recognized as an important public health problem in Brazil, as it is responsible for considerable social and economic costs. Public policies that reduce the causes of this type of trauma in the pediatric population are urgently needed in Brazil and other emerging countries.

A scientific journal’s greatest responsibility is to ensure that all contributions accepted for publications are rigorously but fairly reviewed. The Editor-in-Chief and Archives of Pediatric Neurosurgery gratefully acknowledge the qualified and regular collaboration of renowned medical doctors and scientists who kindly devoted their time to constructively review the submitted articles. Their expertise and invaluable assistance contributed to maintain a high scientific standard for APN. We are thus indebted to the Editorial Board members and the following experts who reviewed papers and completed the peer-reviewing process within 2020.

Low back pain (LBP) is a common condition. It is estimated that 84% of adults will present LBP symptoms at some point in their lives. Rarely, however, is LPB an indication of a serious medical condition, requiring further investigation. The treatment of non-specific LBP is based on non-pharmacological strategies, e.g., non-steroidal anti-inflammatory drugs (NSAID) or skeletal muscle relaxants. The use of epidural steroid injection (ESI) or facet joint injections relieves pain originating from degenerative spine disorders or a disk herniation, thereby providing rapid pain improvement, despite considerable long-term outcomes. Although rare, ESI complications can occur, and infections are infrequently described. This paper describes a rare case of an abscess in the psoas muscle, secondary to facet joint lumbar block. We report a male aged between 30 and 40 years old with LBP, who was submitted to a facet joint and ESI. The procedure evolved into a spinal infection of the psoas muscle. In addition, we present a brief literature review on psoas infections after spinal injection. Infection post facet joint lumbar block is very rare, with few publications in the literature. Early detection and the aggressive broad-spectrum antibiotic course must be initiated until adequate cultures are obtained and antibiotics prolong to at least four weeks.

Context: Skull base tumors are varied in children and are particularly challenging to pediatric neurosurgeons, with few papers in the literature describing the evolution, complications, and outcome. The authors evaluated long-term outcomes in children submitted to skull base tumor surgery and performed a literature review. Aims: The aim of this study was to analyze surgical results, complications, and outcomes, on comparison with previous publications. Materials and Methods: A retrospective analysis of children undergoing surgery at a single institution between 2000 and 2018 for lesions of the cranial base was carried out. In addition, a literature review was carried out describing a total of 115 children operated on for skull base tumors. Statistical Analysis: Chi-squared and Fisher’s exact tests were performed to compare the distribution of categorical variables and a nonparametric Mann–Whitney U test was used to perform intergroup comparisons of continuous variables. Results: Seventeen children ranging in age from 8 months to 17 years (mean, 10.9 years) underwent skull base approaches. Tumor types included schwannoma, meningioma, chondroid chordoma, mature teratoma, epidermoid cyst, hemangiopericytoma, rhabdomyosarcoma, myofibroblastic inflammatory tumor, fibromyxoid sarcoma, Crooke’s cell adenoma, ossifying fibroma, osteoblastoma, nasopharyngeal angiofibroma and Ewing’s sarcoma. Gross total resection was achieved in 6 patients (35.3%), 12 patients (70.6%) had benign histology, and 5 patients (29.4%) had a malignant tumor. Transient postoperative cerebrospinal fluid leak affected only one patient. Thirteen children (76.4%) had a residual neurological deficit at last follow-up evaluation. Three (17.6%) surviving patients received adjuvant therapy. The rate of recurrence or lesion progression was 17.6%. Conclusions: Skull base tumors in children present a therapeutic challenge because of their unique pathological composition and can lead to considerable morbidity and mortality in pediatric age.

Glioblastoma (GBM) is the most common primary malignant neoplasm of the central nervous system and, despite the standard therapy; the patients’ prognoses remain dismal. The miRNA expression profiles have been associated with patient prognosis, suggesting that they may be helpful for tumor diagnosis and classification as well as predictive of tumor response to treatment. We described the microRNA expression profile of 29 primary GBM samples (9 pediatric GBMs) and 11 non-neoplastic white matter samples as controls (WM) by microarray analysis and we performed functional in vitro assays on these 2 most differentially expressed miRNAs. Hierarchical clustering analysis showed 3 distinct miRNA profiles, two of them in the GBM samples and a group consisting only of cerebral white matter. When adult and pediatric GBMs were compared to WM, 37 human miRNAs were found to be differentially expressed, with miR-10b-5p being the most overexpressed and miR-630 the most underexpressed. The overexpression of miR-630 was associated with reduced cell proliferation and invasion in the U87 GBM cell line, whereas the inhibition of miR-10b-5p reduced cell proliferation and colony formation in the U251 GBM cell line, suggesting that these miRNAs may act as tumor-suppressive and oncogenic miRNAs, respectively. The present study highlights the distinct epigenetic profiling of adult and pediatric GBMs and underscores the biological importance of mir-10b-5p and miR-630 for the pathobiology of these lethal tumors.

OBJECTIVESCoronavirus disease (COVID-19) is a potentially severe respiratory illness that has threatened humanity globally. The pediatric neurosurgery practice differs from that of adults in that it treats children in various stages of physical and psychological development and contemplates diseases that do not exist in other areas. The aim of this study was to identify the level of knowledge and readiness of the healthcare providers, as well as to evaluate new preventive practices that have been introduced, psychological concerns, and the impact of the COVID-19 pandemic on pediatric neurosurgical units in Brazil.METHODSPediatric neurosurgeons were given an online questionnaire developed by the Brazilian Society of Pediatric Neurosurgery to evaluate the impact of the COVID-19 pandemic on their clinical practice.RESULTSOf a cohort of 110 active members of the Brazilian Society of Pediatric Neurosurgery, 76 completed the survey (69%). Ninety-six percent were aware of the correct use of and indication for the types of personal protective equipment in clinical and surgical practices, but only 73.7% of them had unrestricted access to this equipment. Ninety-eight percent of participants agreed or strongly agreed that the pandemic had affected their pediatric neurosurgical practice. The COVID-19 pandemic interfered with outpatient care in 88% of the centers, it affected neurosurgical activity in 90.7%, and it led to the cancellation of elective neurosurgical procedures in 57.3%. Concerning the impact of COVID-19 on surgical activity, 9.2% of the centers had less than 25% of the clinical practice affected, 46.1% had 26%–50% of their activity reduced, 35.5% had a 51%–75% reduction, and 9.2% had more than 75% of their surgical work cancelled or postponed. Sixty-three percent affirmed that patients had been tested for COVID-19 before surgery. Regarding the impact of the COVID-19 pandemic on the mental health of those interviewed, 3.9% reported fear and anxiety with panic episodes, 7.9% had worsening of previous anxiety symptoms, 60.5% reported occasional fear, 10.5% had sadness and some depressive symptoms, and 2.6% reported depressive symptoms.CONCLUSIONSThe COVID-19 pandemic has posed unprecedented challenges to healthcare services worldwide, including neurosurgical units. Medical workers, pediatric neurosurgeons included, should be aware of safety measures and follow the recommendations of local healthcare organizations, preventing and controlling the disease. Attention should be given to the psychological burden of exposure to SARS-CoV-2 in healthcare workers, which carries a high risk of anxiety and depression.

Context Signs and symptoms of Cushing’s syndrome (CS) overlap with common diseases, such as the metabolic syndrome, obesity, osteoporosis, and depression. Therefore, it can take years to finally diagnose CS, although early diagnosis is important for prevention of complications. Objective The aim of this study was to assess the time span between first symptoms and diagnosis of CS in different populations to identify factors associated with an early diagnosis. Data Sources A systematic literature search via PubMed was performed to identify studies reporting on time to diagnosis in CS. In addition, unpublished data from patients of our tertiary care center and 4 other centers were included. Study Selection Clinical studies reporting on the time to diagnosis of CS were eligible. Corresponding authors were contacted to obtain additional information relevant to the research question. Data Extraction Data were extracted from the text of the retrieved articles and from additional information provided by authors contacted successfully. From initially 3326 screened studies 44 were included. Data Synthesis Mean time to diagnosis for patients with CS was 34 months (ectopic CS: 14 months; adrenal CS: 30 months; and pituitary CS: 38 months; P < .001). No difference was found for gender, age ( Conclusions Time to diagnosis differs for subtypes of CS but not for gender and age. Time to diagnosis remains to be long and requires to be improved.

Somatic mutations on H3 histone are currently considered a genetic hallmark for midline pediatric high-grade gliomas (HGGs). Yet, different tumor histologies have been occasionally described to carry these mutations. Since histone modifications can lead to major epigenetic changes with direct impact on prognosis and treatment, we thought to investigate the occurrence of H3F3A K27M and G34R/V mutations in a cohort of pediatric tumors which included HGGs, low-grade gliomas, ependymomas, medulloblastomas, and a series of rare brain tumor lesions of different histologies. A total of 82 fresh-frozen pediatric brain tumor samples were evaluated. PCR or RT-PCR followed by Sanger sequencing for the exon 2 of H3F3A (containing both K27 and G34 hotspots) were obtained and aligned to human genome. Loss of trimethylation mark (H3K27me3) in H3F3A/K27M-mutant samples was confirmed by immunohistochemistry. We found H3F3A/K27M mutation in 2 out of 9 cases of HGGs; no H3F3A/K27M mutations were detected in low-grade gliomas (27), ependymomas (n = 10), medulloblastomas (n = 21), or a series of rare pediatric brain tumors which included meningiomas, dysembryoplastic neuroepithelial tumors (DNETs), central nervous system (CNS) germ-cell tumors, choroid plexus tumors, cortical hamartoma, subcortical tubers, and schwannomas (n = 15). H3F3A/G34R/V mutation was not observed in any of the samples. Our investigation reinforces the low frequency of H3F3A somatic mutations outside the HGG setting. Interestingly, an atypical focal brainstem glioma carrying H3F3A K27M mutation that showed protracted clinical course with late-onset tumor progression was identified.

Head injury is a significant economic, social, and medical problem in developing countries and remains one of the leading causes of pediatric morbidity and mortality. The association of traumatic brain injury and coagulopathy in children is linked with an increase in mortality and poor functional outcomes. However, its impact on long-term outcome has not been discussed in the literature so far. The aim of this paper was to investigate the effect of coagulopathy diagnosed by routine laboratory tests on neurological outcome following traumatic brain injury in children. A retrospective review was carried out using medical records of children with a traumatic brain injury admitted at a level I trauma center, between January 2013 and December 2016, submitted to any neurosurgical procedures. Statistical analysis was performed accordingly to identify factors predicting unfavorable or favorable outcomes at 1- and 6-month follow-ups. Data regarding age, gender, trauma mechanism, Glasgow Coma Scale at admission and at discharge, highest and lowest stable intracranial pressure, serum glucose and coagulation assessment, radiological findings, and length of stay were analyzed. We identified 66 children with surgical head trauma. Mean age was 10.9 years (ranges from 3 months to 17 years), with male predominance (77.3%). Common mechanisms were road traffic accidents (66.7%), falls (19.7%), and blunt trauma (10.6%). Brain edema was detected in 68.2% of the patients, surgical fractures or intracranial bleeding in 75.8%. ICP monitoring was performed in 24.2% of the patients, and of these, 18.7% underwent consecutive decompressive craniectomy. Mean length of in-patient treatment was 16.3 ± 28.2 days. At 1- and 6-month follow-ups, favorable outcome was detected in 71.2 and 78.7% of the patients, respectively. The mortality rate was 12.1%. Routine coagulation assessments such as prothrombin time, fibrinogen levels, and thrombocyte count upon admission were potential prognostic variables identified. The present study concluded that a trauma-related coagulopathy is an important predictor of unfavorable neurological outcome following TBI in pediatric patients. Initial GCS score, age, and neuroradiological findings, such as severe brain edema and different types of intracranial bleeding, correlated with GOS in the first 6 months following TBI. Sustained intracranial hypertension also predicted unfavorable outcome and death in this series.

Neurocysticercosis (NCC) is an infestation of the nervous system caused by encysted larvae of Taenia solium. NCC is an important acquired cause of epilepsy and other neurological manifestations especially in endemic areas. NCC in children has pleomorphic manifestations depending on the location, number, viability of the cysts, and host response. Even with advancing knowledge of the disease manifestations, many aspects related to diagnosis and treatment, particularly in children, still remain controversial and pose challenges to clinical practice. There is no gold standard test to diagnose NCC and the management recommendations are still emerging. This review provides an overview of diagnosis of NCC in children and its management with special focus on current challenges and future prospects.In developing countries, NCC is important not only because of its frequency but also because of high morbidity and mortality rates associated, especially in cases in which it progresses to increased intracranial pressure. Because of its pleomorphic presentation, NCC should be considered in the differential diagnosis of a number of neurological conditions. Treatment with cysticidal therapy leads to reduction in seizure frequency and a faster resolution of lesions.We have summarized the current approaches to diagnosis and treatment of NCC, recent advances in understanding the biology of NCC, and how one can take advantage of these new insights to formulate the next generation of clinical trials.

A realização cie trepanações e craniotomias em pacientes com traumatismo craniencefálico grave com os objetivos de diagnosticar e de drenar hematomas intracranianos era uma prática conhecida de todos os neurocirurgiões antes da angiografia. Posteriormente, ela passou a ser usada com menor freqüência, restrita aos casos de pacientes com traumatismo craniencefálico grave com processos expansivos de evolução rápida, com o objetivo de descomprimir rapidamente o tronco cerebral. Após o advento da tomografia computadorizada, esta prática passou a ser discutível frente à rapidez com que se pode obter o diagnóstico preciso de lesões expansivas intracranianas, extra e intracerebrais. A análise da literatura permite a conclusão que apenas em poucas situações em que o paciente é atendido inicialmente com sinais evolutivos de compressão do tronco cerebral ou quando o paciente necessita de tratamento cirúrgico de emergência por lesões extracranianas, as trepanações exploradoras podem ser justificadas sem tomografia computadorizada.

Hypertrophic olivary degeneration (HOD) is a rare transsynaptic form of degeneration occurring after injury to the dentato-rubro-olivary pathway (“Guillain-Mollaret triangle”). The majority of studies have described HOD resulting from posterior fossa (PF) hemorrhage or infarction. HOD in patients undergoing PF surgery has not been well characterized. These lesions are rare and symptomatic children with HOD are even more uncommon. The purpose of this study was to evaluate HOD that develops after PF operations in children. A literature review was carried out describing 37 pediatric cases of HOD in 13 articles. In addition, two new cases of our own experience were included. HOD is a rare complication related after PF tumors surgery and symptoms may be misdiagnosed with pediatric cerebellar mutism syndrome. Children with HOD usually do not develop palatal tremor but ataxia is common.

Craniopharyngiomas can be a surgical challenge for the pediatric neurosurgeon. Ideally, total removal must be achieved. However, the need to reduce surgical morbidity and preserve quality of life has led to a number of neurosurgical approaches in order to attain this goal. The aim of this article is to present an alternative surgical approach to these lesions and to provide the rationale for this technique. Medical charts and operative records of eight pediatric patients harboring craniopharyngiomas who underwent surgical treatment using a supraorbital eyebrow approach (SOA) were reviewed from 2014 to 2016. Only patients younger than 18 years with a minimum follow-up of 12 months were included in this study. Using pre-operative magnetic resonance (MRI) scans, tumors were classified according to their degree of hypothalamic involvement. The surgical technique is also described in detail. The study group included six males and two females with a mean age of 10 years (range, 2–16 years). The SOA was used successfully in elective surgery of eight craniopharyngiomas. The hypothalamus was displaced by the tumor in three patients and severely involved in five patients. Subtotal resection was undertaken in six patients, whereas gross-total resection was achieved in two. Endoscopic assistance was used after standard microscopic visualization in two out of eight cases. Cosmetic outcomes were excellent, and the complication rate related to the surgical procedure was quite low, apart from diabetes insipidus (which occurred in three out of the eight patients). In one patient, a large subdural collection needed surgery for evacuation. Mean follow-up was 23.2 months (range, 12–36 months). Additionally, no CSF leak or wound infection was identified. The supraorbital eyebrow approach is an alternative route to operate on craniopharyngiomas in properly selected cases of all pediatric age ranges, from infants to teenagers. There is sufficient working space for the endoscope and all instruments, allowing for endoscopic assistance and bimanual surgical technique. Cosmetic results are excellent, and complications related to the approach are minimal.

Medulloblastoma (MB) is a malignant childhood brain tumor which at molecular level is classified into at least four major subtypes: WNT, SHH, group C and group D differing in response to treatment. Previous studies have associated changes in expression levels and activation of certain HOX genes with MB development. In the present study, we investigate the role of HOX genes in two attributes acquired by tumor cells: migration and proliferation potential, as well as, in vivo tumorigenic potential. We analyzed UW402, UW473, DAOY and ONS-76 human pediatric MB cell lines and cerebellum primary cultures. Two-color microarray-based gene expression analysis was used to identify differentially expressed HOX genes. Among the various HOX genes significantly overexpressed in DAOY and ONS-76 cell lines compared to UW402 and UW473 cell lines, HOXA10 and HOXB4 were selected for further analysis. The expression levels of these HOX genes were validated by real-time PCR. A mouse model was used to study the effect of the HOXA10 and HOXB4 genes on the in vivo tumorigenic potential and the in vitro proliferative and migration potential of MB cell lines. Our results show that the inhibition of HOXA10 in DAOY cell line led to increased in vitro cell migration while in vitro cell proliferation or in vivo tumorigenic potential were unaffected. We also observed that induced expression of HOXB4 in the UW473 cell line significantly reduced in vitro cell proliferation and migration capability of UW473 cells with no effect on the in vivo tumorigenicity. This suggests that HOXA10 plays a role in migration events and the HOXB4 gene is involved in proliferation and migration processes of medulloblastoma cells, however, it appears that these genes are not essential for the tumorigenic process of these cells.

The purpose of this study is to evaluate a noninvasive device to assess intracranial pressure wave form in children with hydrocephalus. A prospective and non-experimental descriptive-analytic study was performed. Fifty-six patients were enrolled in this study. They were divided in four groups: group A, children with clinically compensated hydrocephalus; B, surgically treated hydrocephalus; C, patients with acute intracranial hypertension due to hydrocephalus; and D, children without neurological disease (control). Data were collected through the installation of an extracranial deformation sensor, coupled to the children’s scalp, which allowed registration of noninvasive intracranial pressure curves. Parameters obtained were analyzed: P2/P1 ratio, “classification P1 and P2 and P1 slope. P2/P1 index and “classification of P1 and P2” had a sensitivity of 80% and specificity of 100% for predicting intracranial hypertension. “P1 slope” presented no statistical difference. This study showed a useful and noninvasive method for monitoring intracranial pressure, which was able to indicate the intracranial hypertension in children with hydrocephalus and, thus, should be further investigated for clinical applications.

Medulloblastoma (MB) is the most common malignant tumor of the central nervous system (CNS) in children. Despite its relative good survival rates, treatment can cause long time sequels and may impair patients’ lifespan and quality, making the search for new treatment options still necessary. Polo like kinases (PLKs) constitute a five-member serine/threonine kinases family (PLK 1–5) that regulates different stages during cell cycle. Abnormal PLKs expression has been observed in several cancer types, including MB. As gene regulators, miRNAs have also been described with variable expression in cancer. We evaluated gene expression profiles of all PLK family members and related miRNAs (miR-100, miR-126, miR-219, and miR-593*) in MB cell lines and tumor samples. RT-qPCR analysis revealed increased levels of PLK1–4 in all cell lines and in most MB samples, while PLK5 was found underexpressed. In parallel, miR-100 was also found upregulated while miR-129, miR-216, and miR-593* were decreased in MB cell lines. Variable miRNAs expression patterns were observed in MB samples. However, a correlation between miR-100 and PLK4 expression was observed, and associations between miR-100, miR-126, and miR-219 expression and overall and event free survival were also evinced in our cohort. Moreover, despite the lack of association with clinico-pathological features, when comparing primary tumors to those relapsed, we found a consistent decrease on PLK2, miR-219, and miR-598* and an increase on miR-100 and miR-126. Specific dysregulation on PLKs and associated miRNAs may be important in MB and can be used to predict prognosis. Although miRNAs sequences are fundamental to predict its target, the cell type may also be consider once that mRNA repertoire can define different roles for specific miRNA in a given cell.

Symptomatic Chiari type I malformation (CM) is treated with posterior fossa decompression with/ without duroplasty. Few authors suggested cerebellar tonsil caudal migration due to a supposed “caudal traction” of cranial nerve structures in a so-called occult tethered cord syndrome. For these authors, filum terminale (FT) sectioning may improve CM symptoms. The objective of this review is to evaluate the effect of FT sectioning on the treatment of CM. Using the PRISMA guidelines for systematic reviews, we reviewed studies to evaluate patient’s outcomes with CM who underwent FT sectioning. The MINORS instrument was used for methodological quality assessment. The included studies’ levels of evidence (LOE) were classified according to the Oxford Centre of Evidence-Based Medicine. Two studies from the same group of authors were included. We cannot assure if the cited cases in the first study were also included in their latter published study. The described results suggest that outcomes were not collected in a standardized fashion. Outcomes are described vaguely as a percentage of improvement. Case series samples were small and included not only patients with CM but also patients with scoliosis and syringomyelia. The MINORS score reported that both studies had low methodological quality. Both included studies were classified as level 4 of evidence. There is no scientific support for filum terminale sectioning in patients with CM without evidence of tethered cord. This procedure may be considered experimental and should be validated in a strict criterion of inclusion clinical trial comparing outcomes in posterior fossa decompression.

The effectiveness of decompressive craniectomy (DC) in the context of neurocritical care in adult patients has been recently under debate. The aim of our study was to evaluate the impact of decompressive craniectomy in severe traumatic brain injury (TBI) in children, focusing on short and long-term neurological and neuropsychological outcomes. Retrospective review of the medical records of children admitted at a level I trauma center, between January 2012 and December 2015, submitted to DC due to severe TBI. Additionally, an extensive review of literature on this subject was carried out. Sixteen patients underwent DC for TBI at our institution during the evaluated period. 62.5% were males and the mean age was 12 years. Road traffic accident (RTA) was the main mechanism of trauma (62.5%). Average Glasgow Coma Scale (GCS) at admission was 5.2, whereas 75% of the patients presented with pathological pupillary reaction. Initial computed tomography (CT) showed skull fractures in 62.5% and acute subdural hemorrhage (ASH) in 56.3% of the patients. The mean intracranial pressure (ICP) was 27.2 mmHg prior to surgery, and the mean time window between admission and DC was 36.3 h. Unilateral DC was performed in 68.8% of the cases. The average Glasgow Outcome Scale (GOS) at 6-month follow-up was 3.7, whereas 70% of the survivors presented good recovery (GOS 4–5). Abnormal pupillary reaction at hospital admission increased 3-fold the risk of long-term neuropsychological disturbances. Follow-up evaluation revealed cognitive abnormality in 55.6% of the patients. The overall mortality at 6-month follow-up was 37.5%. The present study indicates towards a potential benefit of DC in children with severe TBI; nevertheless, our data demonstrated a high incidence of neuropsychological impairment in the long-term follow-up. Psychological and cognitive assessment should be computed in prognosis evaluation in future prospective studies.

Background Endoscopic spinal surgery is becoming quite popular, and the pursuit of a training model to improve surgeons' skills is imperative to overcome the limited availability of human cadavers. Our goal was to determine whether the porcine spine could be a representative model for learning and practicing interlaminar percutaneous endoscopic lumbar procedures (IL-PELPs). Methods Lumbar and cervical segments of the porcine cadaver spine were used for the IL-PELP. We have described the technical notes on the difficulties of the procedure and the relevant anatomical features. To endorse the porcine cadaver for this procedure, 5 neurosurgeons underwent 1 day of training and completed a survey. Results The porcine lumbar spine has small interlaminar windows, and laminectomy is necessary, mimicking the translaminar approaches for higher human lumbar spine levels. The porcine cervical spine has wide and high interlaminar windows and mimics the human L5-S1 interlaminar approach. Entering the spinal canal with the working sheath and endoscope and training the rotation maneuver to access the disc space is only possible in the lumbar segment. It was possible to perform flavectomy and to identify and dissect the dural sac and nerve root in both the lumbar and cervical spine. The neurosurgeons considered the porcine model of good operability and, although different, possible to apply in humans. Conclusions The porcine spine is an effective and representative model for learning and practicing IL-PELPs. Although the described anatomical differences should be known, they did not interfere in performing the main surgical steps and maneuvers for IL-PELPs in the porcine model.

Next-generation sequencing platforms are routinely used for molecular assignment due to their high impact for risk stratification and prognosis in medulloblastomas. Yet, low and middle-income countries still lack an accurate cost-effective platform to perform this allocation. TaqMan Low Density array (TLDA) assay was performed using a set of 20 genes in 92 medulloblastoma samples. The same methodology was assessed in silico using microarray data for 763 medulloblastoma samples from the GSE85217 study, which performed MB classification by a robust integrative method (Transcriptional, Methylation and cytogenetic profile). Furthermore, we validated in 11 MBs samples our proposed method by Methylation Array 450 K to assess methylation profile along with 390 MB samples (GSE109381) and copy number variations. TLDA with only 20 genes accurately assigned MB samples into WNT, SHH, Group 3 and Group 4 using Pearson distance with the average-linkage algorithm and showed concordance with molecular assignment provided by Methylation Array 450 k. Similarly, we tested this simplified set of gene signatures in 763 MB samples and we were able to recapitulate molecular assignment with an accuracy of 99.1% (SHH), 94.29% (WNT), 92.36% (Group 3) and 95.40% (Group 4), against 97.31, 97.14, 88.89 and 97.24% (respectively) with the Ward.D2 algorithm. t-SNE analysis revealed a high level of concordance (k = 4) with minor overlapping features between Group 3 and Group 4. Finally, we condensed the number of genes to 6 without significantly losing accuracy in classifying samples into SHH, WNT and non-SHH/non-WNT subgroups. Additionally, we found a relatively high frequency of WNT subgroup in our cohort, which requires further epidemiological studies. TLDA is a rapid, simple and cost-effective assay for classifying MB in low/middle income countries. A simplified method using six genes and restricting the final stratification into SHH, WNT and non-SHH/non-WNT appears to be a very interesting approach for rapid clinical decision-making. Electronic supplementary material The online version of this article (10.1186/s40478-019-0681-y) contains supplementary material, which is available to authorized users.

© Springer-Verlag GmbH Germany, part of Springer Nature 2019., The "isomorphic subtype of diffuse astrocytoma" was identified histologically in 2004 as a supratentorial, highly differentiated glioma with low cellularity, low proliferation and focal diffuse brain infiltration. Patients typically had seizures since childhood and all were operated on as adults. To define the position of these lesions among brain tumours, we histologically, molecularly and clinically analysed 26 histologically prototypical isomorphic diffuse gliomas. Immunohistochemically, they were GFAP-positive, MAP2-, OLIG2- and CD34-negative, nuclear ATRX-expression was retained and proliferation was low. All 24 cases sequenced were IDH-wildtype. In cluster analyses of DNA methylation data, isomorphic diffuse gliomas formed a group clearly distinct from other glial/glio-neuronal brain tumours and normal hemispheric tissue, most closely related to paediatric MYB/MYBL1-altered diffuse astrocytomas and angiocentric gliomas. Half of the isomorphic diffuse gliomas had copy number alterations of MYBL1 or MYB (13/25, 52%). Gene fusions of MYBL1 or MYB with various gene partners were identified in 11/22 (50%) and were associated with an increased RNA-expression of the respective MYB-family gene. Integrating copy number alterations and available RNA sequencing data, 20/26 (77%) of isomorphic diffuse gliomas demonstrated MYBL1 (54%) or MYB (23%) alterations. Clinically, 89% of patients were seizure-free after surgery and all had a good outcome. In summary, we here define a distinct benign tumour class belonging to the family of MYB/MYBL1-altered gliomas. Isomorphic diffuse glioma occurs both in children and adults, has a concise morphology, frequent MYBL1 and MYB alterations and a specific DNA methylation profile. As an exclusively histological diagnosis may be very challenging and as paediatric MYB/MYBL1-altered diffuse astrocytomas may have the same gene fusions, we consider DNA methylation profiling very helpful for their identification., This study was supported by an International League against Epilepsy (ILAE) Grant to D. Capper. I. Blumcke was supported by the European Union (FP6 DESIRE Grant Agreement #602531). M. Mittelbronn would like to thank the Luxembourg National Research Fund (FNR) for the support (FNR PEARL P16/BM/11192868 grant). K. Ligon is funded by the Paediatric Low Grade Astrocytoma Foundation and NCI R01CA215489. T. Jacques is funded by The Brain Tumour Charity, Children with Cancer UK, Great Ormond Street Hospital Children’s Charity, Cancer Research UK, the Olivia Hodson Cancer Fund and the National Institute of Health Research. T. Jacques’s work is partly funded by the NIHR GOSH BRC. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. We thank the biomedical scientists in the Division of Neuropathology, the National Hospital for Neurology and Neurosurgery (NHNN) for excellent technical assistance. We also thank clinicians and neuropathologists for referring cases for molecular analysis. Part of the study was funded by the National Institute for Health Research to UCLH Biomedical research centre (BRC399/NS/RB/101410). S. Brandner and Z. Jaunmuktane are also supported by the Department of Health’s NIHR Biomedical Research Centre’s funding scheme. Additional funding was provided by the Brain Tumour Charity (UK) for the Everest Centre for Paediatric Low-Grade Brain Tumour Research

Depressed skull fracture, also referred to as a “ping-pong ball” or “pond” fracture in neonates, is a common sign of traumatic brain injury in paediatric patients. The main causes of depressed skull fractures include labour and obstetric trauma in newborns and direct head trauma in older children. Skull depression rarely resolves spontaneously, and the surgical options include open cranioplasty and percutaneous microscrew elevation, among others. The use of negative pressure as a technique for fracture reduction has been described in a few papers. Here, we present a case-based review along with an illustrative case of depressed skull fracture reduced using the suction cup method via negative pressure. In addition, a Systematic Literature Review was performed to evaluate the safety of applying this procedure. The suction cup method is a feasible method to reduce depressed skull fracture in children, with minimum complications and no apparent long-term impairments.

Medulloblastoma (MB) is the most common solid tumor among pediatric patients and corresponds to 20 % of all pediatric intracranial tumors in this age group. Its treatment currently involves significant side effects. Epigenetic changes such as DNA methylation may contribute to its development and progression. DNA methyltransferase (DNMT) inhibitors have shown promising anticancer effects. The agent Zebularine acts as an inhibitor of DNA methylation and shows low toxicity and high efficacy, being a promising adjuvant agent for anti-cancer chemotherapy. Several studies have reported its effects on different types of tumors; however, there are no studies reporting its effects on MB. We analyzed its potential anticancer effects in four pediatric MB cell lines. The treatment inhibited proliferation and clonogenicity, increased the apoptosis rate and the number of cells in the S phase (p

Germinomas represent the most frequent tumour type in the pineal region. However, the synchronous involvement of the suprasellar region, frequently termed bifocal intracranial germinoma (BFG) is quite rare. A literature search identified a further of 48 pediatric cases with a median age of 12.9 years. BFG is known to be highly radiosensitive. We presented a clinical case of pediatric bifocal germinoma. A 14-year-old boy presented with clinical features of progressive headaches since three months associated with vomits. MR showed two distinct lesions in the pineal and suprasellar regions. Neuroaxis spine MR was normal. Tumor markers for germ cell tumors from blood and cerebrospinal fluid were within the normal range. An endoscopic procedure was performed to treat the hydrocephalus (endoscopic third ventriculostomy) and, in the same procedure the suprasellar lesion was biopsied and the histology revealed a germinoma. She received chemotherapy and a focal radiotherapy covering the sites of primary disease and the ventricular system. Three months after the completion of treatment, the patient achieved a complete clinical and radiological response, which was maintained during the 5-years follow-up period. The optimum management of primary intracranial pineal and suprasellar (bifocal) germinomas still remains controversial. The definition as either localized or disseminated disease has major implications on required treatment and its associated late morbidity. Prospective studies with large cooperative groups worldwide and consensus meetings may reduce uncertainties regarding available management options.

OBJECTIVEThe main objective of neurosurgery is to establish safe and reliable surgical techniques. Medical technology has advanced during the 21st century, enabling the development of increasingly sophisticated tools for preoperative study that can be used by surgeons before performing surgery on an actual patient. Laser-printed models are a robust tool for improving surgical performance, planning an operative approach, and developing the skills and strategy to deal with uncommon and high-risk intraoperative difficulties. Practice with these models enhances the surgeon’s understanding of 3D anatomy but has some limitations with regard to tactile perception. In this study, the authors aimed to develop a preoperative planning method that combines a hybrid model with augmented reality (AR) to enhance preparation for and planning of a specific surgical procedure, correction of metopic craniosynostosis, also known as trigonocephaly.METHODSWith the use of imaging data of an actual case patient who underwent surgical correction of metopic craniosynostosis, a physical hybrid model (for hands-on applications) and an AR app for a mobile device were created. The hybrid customized model was developed by using analysis of diagnostic CT imaging of a case patient with metopic craniosynostosis. Created from many different types of silicone, the physical model simulates anatomical conditions, allowing a multidisciplinary team to deal with different situations and to precisely determine the appropriate surgical approach. A real-time AR interface with the physical model was developed by using an AR app that enhances the anatomic aspects of the patient’s skull. This method was used by 38 experienced surgeons (craniofacial plastic surgeons and neurosurgeons), who then responded to a questionnaire that evaluated the realism and utility of the hybrid AR simulation used in this method as a beneficial educational tool for teaching and preoperative planning in performing surgical metopic craniosynostosis correction.RESULTSThe authors developed a practice model for planning the surgical cranial remodeling used in the correction of metopic craniosynostosis. In the hybrid AR model, all aspects of the surgical procedure previously performed on the case patient were simulated: subcutaneous and subperiosteal dissection, skin incision, and skull remodeling with absorbable miniplates. The pre- and postoperative procedures were also carried out, which emphasizes the role of the AR app in the hybrid model. On the basis of the questionnaire, the hybrid AR tool was approved by the senior surgery team and considered adequate for educational purposes. Statistical analysis of the questionnaire responses also highlighted the potential for the use of the hybrid model in future applications.CONCLUSIONSThis new preoperative platform that combines physical and virtual models may represent an important method to improve multidisciplinary discussion in addition to being a powerful teaching tool. The hybrid model associated with the AR app provided an effective training environment, and it enhanced the teaching of surgical anatomy and operative strategies in a challenging neurosurgical procedure.

A 12 years old boy presented with strabismus, left third nerve palsy (ptosis, mydriasis, downward and abducted eye), and vertical conjugate gaze paresis. A brain magnetic resonance image revealed a brainstem solid cystic tumor in the mesencephalic tegmentum, with compression of the aqueduct of Sylvius and associated supratentorial ventriculomegaly. The patient underwent an interhemispheric transcallosal transchoroidal approach for a subtotal resection of the mesencephalic periaqueductal lesion. The pathology report was a low grade neuroepithelial tumor. The patient evolved with no new neurological deficits.

Pilocytic astrocytoma (PA) is a low-grade neoplasm frequently found in childhood. PA is characterized by slow growth and a relatively good prognosis. Genetic mechanisms such as activation of MAPK, BRAF gene deregulation and neurofibromatosis type 1 (NF1) syndrome have been associated with PA development. Epigenetic signature and miRNA expression profile are providing new insights about different types of tumor, including PAs. In the present study we evaluated global miRNA expression in 16 microdissected pediatric PA specimens, three NF1-associated PAs and 11 cerebral white matter (WM) samples by the microarray method. An additional cohort of 20 PAs was used to validate by qRT-PCR the expression of six miRNAs differentially expressed in the microarray data. Unsupervised hierarchical clustering analysis distinguished one cluster with nine PAs, including all NF1 cases and a second group consisting of the WM samples and seven PAs. Among 88 differentially expressed miRNAs between PAs and WM samples, the most underexpressed ones regulate classical pathways of tumorigenesis, while the most overexpressed miRNAs are related to pathways such as focal adhesion, P53 signaling pathway and gliomagenesis. The PAs/NF1 presented a subset of underexpressed miRNAs, which was also associated with known deregulated pathways in cancer such as cell cycle and hippo pathway. In summary, our data demonstrate that PA harbors at least two distinct miRNA signatures, including a subgroup of patients with NF1/PA lesions.

Pott’s puffy tumor is a rare and severe complication of frontal sinusitis, characterized by the progressive swelling of the frontal soft tissues secondary to a subperiosteal abscess. Radiological imaging with ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) are important diagnostic tools in establishing diagnosis and treatment planning. Early surgery along with intravenous antibiotics are required in order to achieve a good recovery. The authors report a case of Pott’s puffy tumor in an obese 14-year-old male, with a previous history of asthma and a chronic use of steroids, treated with neurosurgical debridement followed by a combined course of intravenous (IV) and oral antibiotics, who had a favorable outcome upon long-term follow-up. In addition, a brief review of the current medical literature was performed for a discussion on the diagnostic and therapeutic features of this pathology.

Primary idiopathic intracranial hypertension (PIIH) in children is rare and has a poorly understood pathophysiology. It is characterized by raised intracranial pressure (ICP) in the absence of an identified brain lesion. Diagnosis is usually confirmed by the measurement of a high cerebrospinal fluid (CSF) opening pressure and exclusion of secondary causes of intracranial hypertension. Refractory PIIH may lead to severe visual impairment. The purpose of this study was to evaluate a cranial morcellation decompression (CMD) technique as a new surgical alternative to stabilize intracranial pressure in PIIH. A literature review was carried out, disclosing only 7 pediatric cases of PIIH treated with surgical skull expansion. In addition, we describe here one case of our own experience treated by CMD. CMD surgery is a safe and effective option to control refractory PIIH in selected patients.

Optic pathway gliomas represent 5% of pediatric brain tumors and are typically low-grade lesions. Because of their unpredictable clinical course, adequate treatment approaches have been controversial, involving surveillance, surgery, chemotherapy, and radiotherapy. In this study, we use volumetric imaging to compare evolution of optic chiasmatic-hypothalamic gliomas (OCHG) treated with and without chemotherapy, analyzing tumor volume variation during the overall period. A total of 45 brain MRI were retrospectively analyzed for 14 patients with OCHG. Volumetric assessment of the lesions was performed by a neuroradiologist, using software DISPLAY. OCHG patients were allocated into two groups: group 1 (n = 8) who underwent chemotherapy and group 2 (n = 6) who did not receive chemotherapy. Outcome analysis was performed comparing tumor volume evolution of these two groups. The results showed a reduction of 4.4% of the volume of the lesions for group 1 after the end of chemotherapy, with an increase of 5.3% in volume in the late follow-up examination. For group 2, we found a slight reduction (5%) of the overall volume of the lesions, both with no statistical significance (p > 0.05). From the limited series analyzed in this study, no significant differences were observed in relation to the volume change of lesions treated or not treated with chemotherapy. Larger prospective clinical trials are needed to better evaluate the effect of chemotherapy and radiological response of OCHG.

Background: Genetic and epigenetic modifications are closely related to tumor initiation and progression and can provide guidance for understanding tumor functioning, potentially leading to the discovery of new therapies. Studies have associated hypoxia-related genes to tumor progression and chemo/radioresistance in brain tumors. Information on the expression profile of hypoxiarelated genes in pediatric medulloblastoma, although scarce, may reveal relevant information that could support treatment decisions. Objective: Our study focused on evaluation the of CA9, CA12, HIF1A, EPAS1, SCL2A1 and VEGF genes in 41 pediatric fresh-frozen medulloblastoma sample. Additionally, we analyzed the effect of hypoxia and normoxia in the pediatric medulloblastoma cell-line UW402. Furthermore, we assessed the effects of HIF1A knockdown in cell-proliferation and methylation levels of genes related to hypoxia, apoptosis and autophagy. Method: qPCR was performed to evaluate mRNA levels, and Western blot to confirm HIF1A silencing in both patient samples and cell line. Pyrosequencing was performed to asses the methylation levels after HIF1A knockdown in the UW402 cell line. Results: A higher HIF1A mRNA level was observed in MB patients when compared to the cerebellum (non-tumor match). In UW402 MB cell-line, chemically induced hypoxic resulted in an increase of mRNA levels of HIF1A, VEGF, SCL2A1 and CA9 genes. Additionally, HIF1A knockdown induced a decrease in the expression of hypoxia related genes and a decrease of 30% in cell proliferation was also observed. Also, a significant increase in the methylation of ATG16L1 promoter and decrease in the methylation of EPAS1 promoter were observed after HIF1A knockdown. Conclusion: HIF1A knockdown in medulloblastoma cells lead to decreased cellular proliferation, suggesting that HIF1A can be a potential therapeutic target to be explored in the medulloblastoma. However, the mechanisms behind HIF1A protein stabilization and function are very complex and more data need to be generated to potentially use HIF1A as a therapeutical target.

CTNNB1 mutations and abnormal β-catenin distribution are associated with the pathogenesis of adamantinomatous craniopharyngioma (aCP). We evaluated the expression of the canonical Wnt pathway components in aCPs and its association with CTNNB1 mutations and tumor progression. Tumor samples from 14 aCP patients and normal anterior pituitary samples from eight individuals without pituitary disease were studied. Gene expression of Wnt pathway activator (WNT4), inhibitors (SFRP1, DKK3, AXIN1, and APC), transcriptional activator (TCF7), target genes (MYC, WISP2, and, CDH1), and Wnt modulator (TP53) was evaluated by qPCR. β-Catenin, MYC, and WISP2 expression was determined by immunohistochemistry (IHC). The transcription levels of all genes studied, except APC, were higher in aCPs as compared to controls and TCF7 mRNA levels correlated with CTNNB1 mutation. CDH1 mRNA was overexpressed in tumor samples of patients with disease progression in comparison to those with stable disease. β-Catenin was positive and aberrantly distributed in 11 out of 14 tumor samples. Stronger β-catenin immunostaining associated positively with tumor progression. MYC positive staining was found in 10 out of 14 cases, whereas all aCPs were negative for WISP2. Wnt pathway genes were overexpressed in aCPs harboring CTNNB1 mutations and in patients with progressive disease. Recurrence was associated with stronger staining for β-catenin. These data suggest that Wnt pathway activation contributes to the pathogenesis and prognosis of aCPs.

Medulloblastoma (MB) is the most common solid tumor among pediatric patients and corresponds to 20 % of all pediatric intracranial tumors in this age group. Its treatment currently involves significant side effects. Epigenetic changes such as DNA methylation may contribute to its development and progression. DNA methyltransferase (DNMT) inhibitors have shown promising anticancer effects. The agent Zebularine acts as an inhibitor of DNA methylation and shows low toxicity and high efficacy, being a promising adjuvant agent for anti-cancer chemotherapy. Several studies have reported its effects on different types of tumors; however, there are no studies reporting its effects on MB. We analyzed its potential anticancer effects in four pediatric MB cell lines. The treatment inhibited proliferation and clonogenicity, increased the apoptosis rate and the number of cells in the S phase (p

A 6 year-old boy presented with progressive decrease of visual acuity in his left eye. Neurological examination revealed a left third nerve palsy. His ophthalmological assessment showed left amaurosis and right temporal hemianopia. Head magnetic resonance scans revealed a suprasellar parachiasmatic lesion causing compression of optic chiasm. The boy underwent a supraorbital craniotomy through a left eyebrow incision; gross total resection was achieved. Postoperatively, the patient was neurologically stable, with visual improvement and no additional neurological deficits. Pathology confirmed the diagnosis of craniopharyngioma.

Objective To describe an atypical clinical and radiological presentation of a brainstem epidermoid cyst in a child and to provide a review of the medical literature on brainstem epidermoid cysts in children. Material and method Review of medical records and operative notes of an unusual case of a patient with a brainstem epidermoid cyst. MEDLINE literature search using the terms brainstem, epidermoid cyst and children. Results Gross total resection of the cyst was achieved. The patient had an uneventful recovery. Conclusion Epidermoid cysts are rare tumors of the brain and children. The management of these tumors can be quite challenging. A good clinical and neuroradiological evaluation pre-operatively is fundamental for a successful surgical treatment. Surgical resection should be as radical as possible without putting the patient's neurological status into risk.

Cavernous hemangioma (CH) is a sporadic vascular malformation occurring either as an autosomal dominant condition or as a well-known complication of radiation exposure. Medulloblastoma is a primitive neuroectodermal tumor common in children and currently treated with surgical resection, chemotherapy, and radiotherapy. Neurofibromatosis is the most common single-gene disorder of the central nervous system. Posterior fossa malignant tumors in the context of neurofibromatosis type I (NF1) are very infrequent. This is the first documented case of an unusual metachronous occurrence of non-radiation-induced CH and medulloblastoma in a child with NF1 phenotype. We report the case of a 13-month-old boy with cafι-au-lait skin lesions associated with NF1-like phenotype who underwent surgical resection of a single CH in the temporal lobe due to recurrent seizures. Four years later he presented with signs of raised intracranial pressure associated with a posterior fossa tumor and hydrocephalus, thus requiring gross total resection of the lesion. Histological analysis revealed a medulloblastoma. After being treated with radiotherapy and chemotherapy, he achieved total remission. Six years later a massive recurrence of the tumor was observed and the child eventually died. The interest in this case lies in the rarity of NF1-like phenotype associated with a non-radiation-induced brain CH and medulloblastoma in a child.

Objective: The treatment of hydrocephalus in children with endoscopic third ventriculostomy (ETV) has particular features and is associated with different success rates (SR). The aim of this study was to identify putative factors that could influence the outcome of ETV in children. Methods: Clinical data of 114 consecutive patients under 18 years of age who underwent 116 consecutive ETVs from January 2000 to January 2010 were reviewed. Data were analyzed with regards to clinical and radiological SR. The actual long-term SR was compared to that predicted by the ETV Success Score (ETVSS) model. Results: The study group included 49 males (43%) and 65 females (57%) with a mean age of 6.17 ± 1.02 years (ranging from 11 days to 18 years) at surgery. Concerning the etiology of hydrocephalus, tumors and aqueductal stenosis (AS) were the most frequently observed, with each occurring in 33 cases (29%), followed by malformations in 24 (21%), cystic lesions in 6 (5%) and other etiologies in 18 patients (16%). The overall SR at the first ETV attempt was 80% (91/114), compared to 74.8% (variance 14.35, 95% CI 69.37-78.22) predicted by the ETVSS. Regarding age, SR was 58% in patients under 6 months of age, 65% in children between 6 months and 1 year, and 86% in children older than 1 year. SR for AS and hydrocephalus associated with posterior fossa tumors were 88 and 90%, respectively. Unsatisfactory results were related to previous intraventricular hemorrhage and infection. The overall complication rate in this series was 13%. Conclusion: ETV is safe and effective in children. In this series, the age of the patient and etiology of hydrocephalus were related to SR. Also, the ETVSS was accurate to predict outcome. In a long-term follow-up, surgical experience was statistically significant in reducing complications.

Radiol Bras. 2015 Set/Out;48(5):333–340http://dx.doi.org/10.1590/0100-3984.2014.0078Chordoid glioma of the third ventricleGlioma cordoide do terceiro ventriculoFigure 1. Axial MRI T2-weighted ( A) and coronal FLAIR ( B) sequences reveal a slightly hyperintense, well-defined hypothalamic/third ventricular tumor (arrows), withperilesional vasogenic edema (arrowheads). C: Axial MRI T1-weighted sequence reveals a predominantly isointense tumor (arrow). D: Gadolinium-enhanced sagittal MRIT1-weighted sequence reveals the tumor with uniform contrast enhancement (arrow).REFERENCES1. Reis F, Schwingel R, Nascimento FBP. Central nervous system lym-phoma: iconographic essay. Radiol Bras. 2013;46:110–6.2. Barreira Junior AK, Moura FC, Monteiro MLR. Linfoma nao-Hodgkinbilateral do seio cavernoso como manifestacao inicial da sindrome deimunodeficiencia adquirida: relato de caso. Arq Bras Oftalmol. 2011;74:130–1.3. Osborn AG. Encefalo de Osborn. Imagem, patologia e anatomia. PortoAlegre, RS: Artmed; 2014.4. Rocha AJ, Vedolin L, Mendonca RA. Encefalo. Serie CBR. Sao Paulo,SP: Elsevier; 2012.Arthur Henrique de Aquino Dultra