How to become a pediatric neurosurgeon in Latin America: training opportunities, current status, and future challenges.

PURPOSE: To provide an analysis of pediatric neurosurgery educational opportunities in Latin America in order to characterize and evaluate the strengths, weaknesses, and limitations to assume a career in pediatric neurosurgery. METHODS: An online survey was distributed to pediatric neurosurgeons in Latin America to assess aspects of pediatric neurosurgical education, working conditions, and training opportunities. The survey was open to neurosurgeons that treat pediatric patients, whether or not they had completed fellowship training in pediatrics. A descriptive analysis was done with a subgroup analysis stratified the results among certified pediatric neurosurgeons and non-certified pediatric neurosurgeons. RESULTS: In total, 106 pediatric neurosurgeons completed the survey, of whose the vast majority completed their training in a Latin American pediatric neurosurgery program. A total of 19 accredited academic programs in pediatric neurosurgery were found in Latin America distributed in 6 different countries. On average, the pediatric neurosurgical training in America Latina has a duration of 278 years, ranging from 1 to > 6 years. CONCLUSIONS: This study is the first of its kind to review pediatric neurosurgical training in Latin America, in which both pediatric and general neurosurgeons provide neurosurgical care to children in the continent; however, we found that in the majority of the cases, children are treated by certified pediatric neurosurgeons, of whose the vast majority were trained in Latin American programs. On the other hand, we found areas of improvement in the specialty in the continent, including regulation of training opportunities, increased support for funding, and more opportunities for education among all countries.

Can a new noninvasive method for assessment of intracranial pressure predict intracranial hypertension and prognosis?

PURPOSE: Individuals with TBI are at risk of intracranial hypertension (ICH), and monitoring of intracranial pressure (ICP) is usually indicated. However, despite many new noninvasive devices, none is sufficiently accurate and effective for application in clinical practice, particularly in the management of TBIs. This study aimed to compare the noninvasive Brain4Care system (nICP) with invasive ICP (iICP) curve parameters in their ability to predict ICH and functional prognosis in severe TBI. METHODS: Observational, descriptive-analytical, and prospective study of 22 patients between 2018 and 2021, simultaneously monitored with nICP and iICP. The independent variables evaluated were the presence of ICH and functional prognoses. The dependent variables were the P2/P1 pressure ratio metrics, time to peak (TTP), and TTP × P2/P1. RESULTS: We found a good nonlinear correlation between iICP and nICP waveforms, despite a moderate Pearson's linear correlation. The noninvasive parameters of P2/P1, P2/P1 × TTP, and TTP were not associated with outcomes or ICH. The nICP P2/P1 ratio showed sensitivity/specificity/accuracy (%) of 100/0/56.3, respectively for 1-month outcomes and 77.8/22.2/50 for 6-month outcomes. The nICP TTP ratio had values of 100/0/56.3 for 1-month and 99.9/42.9/72.2 for 6-month outcomes. The nICP P2/P1 × TTP values were 100/0/56.3 for 1-month outcomes and 81.8/28.6/61.1 for 6-month outcomes. CONCLUSION: Brain4Care's noninvasive method showed low specificity and accuracy and cannot be used as the sole means of monitoring ICP in patients with severe TBI. Future studies with a larger sample of patients with P2 > P1 and new nICP curve parameters are warranted.

Association between objectively measured physical activity of parents and children: The 2015 Pelotas birth cohort.

OBJECTIVE: The present study aims to verify the association between objectively measured physical activity (PA) of parents and child in the 2015 Pelotas Birth Cohort, a population-based Brazilian birth cohort. METHODS: The main exposures were paternal moderate-to-vigorous PA (MVPA) collected when children were 1-year of age, and maternal MVPA when children were 2-years. The outcome was children's overall PA (ENMO in mg) at 4-years of age. PA was measured using wrist-worn ActiGraph accelerometers during seven complete days. Potential confounders were maternal age, maternal and paternal education, and household asset index. Crude and adjusted analyses were performed using linear regressions. RESULTS: Our analytical sample comprised 1326 children with valid accelerometer data and with both parents. Mean child PA was 48.1 mg, being higher among boys compared with girls (Boys: 50 mg, 95% CI: 49.1; 50.9; Girls: 46 mg, 95% CI: 45.2; 46.8). Children's PA at 4 years was positively associated with maternal MVPA at age 2 years (p < 0.001) and paternal MVPA at age 1 year (p < 0.001). A child with both parents in the highest tertile of unbouted MVPA presented higher overall PA (p = 0.001). Similar results were found for boys; however, for girls, paternal unbouted MVPA was not associated with overall PA. CONCLUSION: Overall, our results showed a positive impact of maternal and parental PA over 4-year-old children acceleration. These findings could be valuable when planning evidence-based interventions and policies to promote PA in young children, providing a broader perspective over the role of parents over children's behavior.

Glomus jugulare in a pediatric patient: case report and literature review.

PURPOSE: The jugular and tympanic glomus are rare neoplasms in the general population, being even more uncommon in the pediatric population. There is considerable morbidity associated with both disease and treatment. Treatment is essentially surgical, carried out in recent years in a multidisciplinary manner using preoperative embolization associated with microsurgery and eventually adjuvant radiotherapy. The outcome depends on the location of the lesion and its proximity to noble structures in addition to multidisciplinary monitoring in the postoperative period. METHODS: In this article, a literature review was carried out in the PubMed database, finding reports from 17 patients diagnosed with the disease. Only articles in English were considered. RESULTS: Moreover, we reported a case of a 14-year-old patient diagnosed with jugulotympanic glomus who underwent radical surgical treatment of the lesion. CONCLUSION: This is a rare case of jugulotympanic glomus in a pediatric patient, who underwent surgical treatment associated with multidisciplinary therapy, with a favorable postoperative outcome.

Reversible Bitemporal Hemihypokinetic Pupil Without Hemianopia: A New Chiasmal Sign.

Chiasmal syndromes present mostly with visual problems, such as changes in visual fields, decreased visual acuity, or dyschromatopsia (and classically without pupillary reflex defects). The prototypical bitemporal hemianopia upon visual field testing can easily suggest chiasmal compression due to sellar/suprasellar involvement. However, because of the complexity of the decussation of fibres at the optic chiasm and the presence of anatomical variants, unpredictable visual fields defects can be detected in chiasmal diseases. In some patients, especially in those who have undergone neurosurgical procedures, visual field examination and neuroimaging may not completely reflect the classical pattern of chiasmal visual loss. We describe a novel semiological sign, reporting a patient in which a pupillary bitemporal hemihypokinesia was not accompanied by hemianopia, with the phenomenon being abolished by surgical resection of the causative pituitary macroadenoma. In addition, this finding was an important tool in making the diagnosis.

Prevalence of ideal cardiovascular health in young adults: A birth cohort from southern Brazil.

BACKGROUND: Ideal cardiovascular health (ICH) aims at primordial prevention of cardiovascular diseases in the population. However, there is a lack of research describing ICH in youth from middle-income countries. The aims of this study were to describe the prevalence of ICH at 18- and 22-year-old and to investigate the influence of socioeconomic status. METHODS: The sample consisted of participants from the Pelotas 1993 birth-cohort followed-up at 18- (n = 4,106) and 22-year-old (n = 3,810). Ideal metrics were created for diet, smoking, body mass index, physical activity, blood pressure, total cholesterol, and blood glucose. The presence of 4 or more ideal metrics was defined as ICH. Socioeconomic status was obtained using wealth quintiles calculated with factor analysis based on analysis based on the ownership of household and education. The impact of socioeconomic status on ICH metrics was statistically measured using the slope index of inequality. RESULTS: The prevalence of ICH was 84.5% (95% confidence interval [CI] = 82.7-86.2%) and 84.1% (82.3-85.8%) at 18-year-old and decreased to 61.1% (58.4-63.7%) and 68.7% (66.2-71.2%) at 22-years old, for male and female, respectively. Socioeconomic status influenced ICH and its components differently in males and females. Wealthiest females had ICH prevalence 19 percentage points (pp) (11-27 pp) higher compared to the poorest, whereas poorest males had ICH prevalence 12 pp (1-21 pp) higher compared to the wealthiest. Longitudinal decreases in ICH components were mostly present in the poorest females. CONCLUSIONS: In middle-income countries, the prevalence of ICH is high at 18-year-old and decreases in a 4-year follow-up. Socioeconomic status influences differently individuals' ICH between sexes. Efforts are needed to maintain ICH in youth and different strategies may be required between the social status.

Perillyl alcohol for pediatric TP53- and RAS-mutated SHH-medulloblastoma: an in vitro and in vivo translational pre-clinical study.

PURPOSE: Inhalation of perillyl alcohol (POH) recently emerged as an investigational promising antiglioma strategy. However, little attention has been paid to its therapeutic potential for other brain tumors, especially in the pediatric setting. METHODS: The effects of POH were explored in medulloblastoma cell models belonging to the SHH variant with activation of RAS (ONS-76) or with TP53 mutations (DAOY and UW402), by means of proliferation and invasion assays. Interactions with methotrexate, thiotepa, or ionizing radiation were also assessed. Mice bearing subcutaneous tumors were treated with intraperitoneal injections. Alternatively, animals with intracranial tumors were exposed to intranasal POH alone or combined with radiation. Tumor growth was measured by bioluminescence. Analyses of cytotoxicity to the nasal cavity were also performed, and the presence of POH in the brain, lungs, and plasma was surveyed through chromatography/mass spectrometry. RESULTS: POH decreased cell proliferation and colony formation, with conspicuous death, though the invasive capacity was only affected in the NRAS-mutated cell line. Median-drug effect analysis displayed synergistic combinations with methotrexate. Otherwise, POH showed to be a reasonable radiosensitizer. In vivo, intraperitoneal injection significantly decreased tumor volume. However, its inhalation did not affect orthotopic tumors, neither alone or followed by cranial irradiation. Nasal cavity epithelium showed unimportant alterations, though, no traces of POH or its metabolites were detected in tissue samples. CONCLUSION: POH presents robust in vitro antimedulloblastoma effects and sensitizes cell lines to other conventional therapeutics, reducing tumor volume when administered intraperitoneally. Nevertheless, further improvement of delivery devices and/or drug formulations are needed to better characterize its effectiveness through inhalation.

Evaluating H3F3A K27M and G34R/V somatic mutations in a cohort of pediatric brain tumors of different and rare histologies.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Effect of High-velocity Resistance Exercise on 24-h Blood Pressure in Hypertensive Older Women.

This study investigated the acute post-exercise effect of high-velocity resistance exercise on ambulatory blood pressure in hypertensive older women. Fourteen volunteers (67.9±5.1 years) performed a high-velocity resistance exercise session (8 exercises using Thera-Band, 3 sets of 6 repetitions as fast as possible in the concentric phase with moderate intensity) and a control session, separated by a 7-10-day period. Ambulatory blood pressure was monitored following 12-h post-sessions and compared between conditions at 1 to 4-h, 5 to 8-h, and 9 to 12-h. Average 24-h ambulatory blood pressure, awake, asleep periods, and blood pressure load were also analyzed. There was a condition by time interaction for systolic ambulatory blood pressure over 12-h post-sessions (P=0.043). It was observed a lower systolic ambulatory blood pressure in the first 4-h period following the high-velocity resistance exercise session compared to the control session (-6.7 mmHg, 95% CI - 11.6 to -1.8 mmHg; P=0.011). No changes were observed for diastolic ambulatory blood pressure over 12-h post-sessions as well as for the other variables analyzed (P>0.05). In summary, a single high-velocity resistance exercise session elicits a post-exercise antihypertensive effect and may be considered as a strategy to acutely improve blood pressure control in hypertensive older women.

Adult giant cerebellar cavernous malformations: case report and review of the literature.

Cavernous malformations are vascular malformations that can occur anywhere in the central nervous system (CNS). Giant cavernous malformations (GCM) are extremely rare in adults, especially in the posterior fossa. Herein, we described a 48-year-old male who presented with vertigo and postural instability for three months. Neuroimaging revealed a 131.15 cm3 heterogeneous midline upper cerebellar lesion. After a suboccipital craniotomy, a gross total resection (GTR) was accomplished. Histopathologic examination revealed a huge cavernous malformation. Only 27 GCM adult cases were reported in the English-based literature. Only two patients had cerebellar lesions and, to the best of our knowledge, this is the first case of cerebellar vermis GCM. We concluded that cerebellar GCM (CGCM) in adults are exceedingly rare and indolent lesions. These lesions can radiologically and clinically mimic neoplastic lesions that have to be considered in the differential diagnosis. GTR is the mainstay of treatment and, whenever possible, should be attempted.

Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course.

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.

High-throughput microRNA profile in adult and pediatric primary glioblastomas: the role of miR-10b-5p and miR-630 in the tumor aggressiveness.

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.

The effect of filum terminale sectioning for Chiari 1 malformation treatment: systematic review.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Midface distraction osteogenesis using a modified external device and 3D virtual simulation: technical note.

INTRODUCTION/BACKGROUND: Distraction osteogenesis (DO) with an external distraction device such as the rigid external distraction frame has become an established method for treating midface hypoplasia in faciocraniosynostosis. It allows for greater advancement of the midface in comparison with traditional Le Fort III osteotomies, associated or not with fronto-orbital osteotomies (Le Fort IV). However, the forward movement of the bone segments may not always be performed obeying an ideal distraction vector, resulting in asymmetries, anterior open bite, and loosening of screws. In addition, the cost of the distraction devices is significant and may preclude their routine use in developing countries. METHOD: We present an alternative device and method for craniofacial advancement in a clinical case of Crouzon's syndrome. RESULTS: A 3D virtual simulation of the distraction vector and a modified external device were used in the current case. CONCLUSION: The alternative external device in this case proved to be safe, effective, and reliable.

Pediatric neurosurgery during the COVID-19 pandemic: update and recommendations from the Brazilian Society of Pediatric Neurosurgery.

OBJECTIVES: Coronavirus 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. METHODS: Pediatric 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. RESULTS: Of 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. CONCLUSIONS: The 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.

MicroRNA profile of pediatric pilocytic astrocytomas identifies two tumor-specific signatures when compared to non-neoplastic white matter.

PURPOSES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: In summary, our data demonstrate that PA harbors at least two distinct miRNA signatures, including a subgroup of patients with NF1/PA lesions.

Decompressive craniectomy for severe traumatic brain injury in children: analysis of long-term neuropsychological impairment and review of the literature.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

Monitoring optic chiasmatic-hypothalamic glioma volumetric changes by MRI in children under clinical surveillance or chemotherapy.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Impact of the Canonical Wnt Pathway Activation on the Pathogenesis and Prognosis of Adamantinomatous Craniopharyngiomas.

CTNNB1 mutations and abnormal ß-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. ß-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. ß-Catenin was positive and aberrantly distributed in 11 out of 14 tumor samples. Stronger ß-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 ß-catenin. These data suggest that Wnt pathway activation contributes to the pathogenesis and prognosis of aCPs.