Treatment of depressed skull fractures with vacuum devices in the neonatal period: A case series.

PURPOSE: The management of depressed skull fractures in infants can be either conservative or surgical. This study aimed to examine the outcomes of management with a negative-pressure vacuum device on depressed skull fractures in newborns. METHODS: Twenty-eight patients (aged 1-6 days) with simple depressed skull fractures underwent skull elevation using negative-pressure vacuum devices. A protocol for nonsurgical management was adopted for infants with such fractures between 2010 and 2023. All patients were initially evaluated with neurological examination and complementary assessments-hematological and coagulation studies, transfontanel transcranial ultrasound, skull radiography, and computed tomography scanning with three-dimensional reconstruction-according to availability and clinical needs. Gentle (negative) extraction pressure was applied with one of several devices (according to institutional availability) for a maximum duration of 60 s; this was performed as soon as possible after diagnosis, preferably within 72 h. Follow-up data, available in the clinical records, were reported. RESULTS: All patients exhibited satisfactory elevation of the depressed bone without associated injuries, except one patient who presented with an associated cephalohematoma which prevented optimal device coupling to generate sufficient vacuum pressure for correction. Neither neurological deficits nor development of epilepsy was noted; normal neurological assessment and oral alimentation tolerance were confirmed within 24 h post procedure. CONCLUSIONS: According to our data, ping-pong skull fracture elevation using the vacuum method is a safe and satisfactory treatment in the neonatal period. Early treatment allows for quick resolution, and in our opinion is the strategy of choice for depressed skull fractures in newborns.

Analysis of long-term family dynamics in mothers who have undergone fetal myelomeningocele surgery using telemedicine: a pilot study.

OBJECTIVE: The aim of this study was to understand the dynamics of families with children with myelomeningocele undergoing intrauterine fetal surgery. METHODS: A retrospective cohort pilot study was carried out with 11 mothers of children who had undergone intrauterine myelomeningocele repair. Participants in this study responded to an electronic questionnaire (via Google Forms), developed by the study authors, that consisted of 22 multiple-choice questions, of which 17 were closed-ended and 5 had a standardized format. RESULTS: The mean (± standard deviation) of the mothers' age was 37.6 (± 3.5) years. The median of gestational age at delivery and birthweight were 34.9 (range, 33 to 36.1) weeks and 2,300 (range, 1,950 to 2,763) g, respectively. The majority of mothers were white (81.8%), had university degree (81.8%), were Catholic (63.6%), and were married (100%). The majority of mothers rated their relationship with their husband, family, and friends as excellent (54.5, 72.7, and 54.5%, respectively). All 11 mothers reported that the newborn with myelomeningocele was born <37 weeks gestation and the birthweight most often<2,500 g. Approximately 64% of the mothers reported that their child required adaptations or had special needs, of which walking aids (50%) and bladder control (50%) were the most common ones. CONCLUSION: Telemedicine proved to be a useful tool in the long-term follow-up of children who underwent intrauterine surgery to correct myelomeningocele.

Resection of the quadrangular lobule of the cerebellum to increase exposure of the cerebellomesencephalic fissure: an anatomical study with clinical correlation.

OBJECTIVE: The lateral aspect of the cerebellomesencephalic fissure frequently harbors vascular pathology and is a common surgical corridor used to access the pons tegmentum, as well as the cerebellum and its superior and middle peduncles. The quadrangular lobule of the cerebellum (QLC) represents an obstacle to reach these structures. The authors sought to analyze and compare exposure of the cerebellar interpeduncular region (CIPR) before and after QLC resection and provide a case series to evaluate its clinical applicability. METHODS: Forty-two sides of human brainstems were prepared with Klingler's method and dissected. The exposure area before and after resection of the QLC was measured and statistically studied. A case series of 59 patients who underwent QLC resection for the treatment of CIPR lesions was presented and clinical outcomes were evaluated at 1-year follow-up. RESULTS: The anteroposterior surgical corridor of the CIPR increased by 10.3 mm after resection of the QLC. The mean exposure areas were 42 mm2 before resection of the QLC and 159.6 mm2 after resection. In this series, ataxia, extrapyramidal syndrome, and akinetic mutism were found after surgery. However, all these cases resolved within 1 year of follow-up. Modified Rankin Scale score improved by 1 grade, on average. CONCLUSIONS: QLC resection significantly increased the exposure area, mainly in the anteroposterior axis. This surgical strategy appears to be safe and may help the neurosurgeon when operating on the lateral aspect of the cerebellomesencephalic fissure.

The long-term effect on functional outcome of endoscopic brainwashing for intraventricular hemorrhage compared to external ventricular drainage alone: A retrospective single-center cohort study.

Background: Intraventricular hemorrhage (IVH) is a complex condition with both mechanical and chemical effects, resulting in mortality rates of 50-80%. Recent reports advocate for neuroendoscopic treatment, particularly endoscopic brainwashing (EBW), but long-term functional outcomes remain insufficiently explored. This study aims to outline the step-by-step procedure of EBW as applied in our institution, providing results and comparing them with those of external ventricular drainage (EVD) alone. Methods: We performed a retrospective analysis of adult patients with IVH who underwent EBW and patients submitted to EVD alone at our institution. All medical records were reviewed to describe clinical and radiological characteristics. Results: Although both groups had similar baseline factors, EBW patients exhibited a larger hemoventricle (median Graeb score 25 vs. 23 in EVD, P = 0.03) and a higher prevalence of chronic kidney disease and diabetes. Short-term mortality was lower in EBW (52% and 60% at 1 and 6 months) compared to EVD (80% for both), though not statistically significant (P = 0.06). At one month, 16% of EBW patients achieved a good outcome (Modified Rankin scale < 3) versus none in the EVD group (P = 0.1). In the long term, favorable outcomes were observed in 32% of EBW patients and 11% of EVD patients (P = 0.03), with no significant difference in shunt dependency. Conclusion: Comparing EBW and EVD, patients submitted to the former treatment have the highest modified Graeb scores and, at a long-term follow-up, have better outcomes, demonstrated by the improvement of the patients in the follow-up.

Intracranial non-germinomatous germ cell tumors in children and adolescents: how can the experience from an uppermiddle-income country contribute to the worldwide effort to improve outcomes?

Background: Non-germinomatous germ cell tumors (NGGCT) accounts for one third of intracranial GCT. While the germinoma group have an excellent overall survival, the standard of practice for children with NGGCT is still under evaluation. Aims: Describe the results of the of the Brazilian consortium protocol. Methods: Since 2013, 15 patients with a diagnosis of NGGCT by histopathology and/or serum/cerebrospinal fluid (CSF) tumor markers, ßHCG >200mlU/ml and/or positive alpha-fetoprotein were treated with neoadjuvant chemotherapy with carboplatin, cyclophosphamide and etoposide followed by ventricular radiotherapy (RTV) of 18Gy with boost (32Gy) to the primary site. Metastatic patients underwent craniospinal irradiation (CSI) and "slow responders" to the four initial cycles of CT, to autologous stem cell transplantation (ASCT) followed by CSI. Results: Mean age, 13.1 years. Thirteen males. Primary sites: pineal (n=12), suprasellar (n=2) and bifocal (n=1). Four patients were metastatic at diagnosis. Eight patients had CSF and/or serum alpha-fetoprotein levels > 1,000ng/ml. Tumor responses after chemotherapy demonstrated complete in six cases and partial in seven, with "second-look" surgery being performed in five cases, and two patients presenting viable lesions being referred to ASCT. The main toxicity observed was hematological grades 3/4. Two patients with metastatic disease, one with Down Syndrome and AFP > 1,000ng/ml and the other with choriocarcinoma and pulmonary metastases, developed progressive disease resulting in death, as well as two other patients without evidence of disease, due to endocrinological disorders. Event-free and overall survival at 2 and 5 years were 80% and 72.7%, respectively, with a mean follow-up of 48 months (range, 7-107). Conclusions: Despite the small number of patients, in our series, treatment with six cycles of chemotherapy and RTV with focal boost for localized disease (n=11) and ACST for identified slow responders (n=2) seem to be effective strategies contributing to the overall effort to improve outcomes of this group of patients.

Analysis of long-term family dynamics in mothers who have undergone fetal myelomeningocele surgery using telemedicine: a pilot study

SUMMARY OBJECTIVE: The aim of this study was to understand the dynamics of families with children with myelomeningocele undergoing intrauterine fetal surgery. METHODS: A retrospective cohort pilot study was carried out with 11 mothers of children who had undergone intrauterine myelomeningocele repair. Participants in this study responded to an electronic questionnaire (via Google Forms), developed by the study authors, that consisted of 22 multiple-choice questions, of which 17 were closed-ended and 5 had a standardized format. RESULTS: The mean (± standard deviation) of the mothers' age was 37.6 (± 3.5) years. The median of gestational age at delivery and birthweight were 34.9 (range, 33 to 36.1) weeks and 2,300 (range, 1,950 to 2,763) g, respectively. The majority of mothers were white (81.8%), had university degree (81.8%), were Catholic (63.6%), and were married (100%). The majority of mothers rated their relationship with their husband, family, and friends as excellent (54.5, 72.7, and 54.5%, respectively). All 11 mothers reported that the newborn with myelomeningocele was born <37 weeks gestation and the birthweight most often<2,500 g. Approximately 64% of the mothers reported that their child required adaptations or had special needs, of which walking aids (50%) and bladder control (50%) were the most common ones. CONCLUSION: Telemedicine proved to be a useful tool in the long-term follow-up of children who underwent intrauterine surgery to correct myelomeningocele.

Time course of hemispheric cerebral volume after decompressive craniectomy in malignant middle cerebral artery stroke / Evolução temporal do volume hemisférico cerebral após craniectomia descompressiva em infarto maligno de artéria cerebral média

Abstract Background Brain edema is the leading cause of death in patients with malignant middle cerebral artery (MCA) infarction. Midline shift (MLS) has been used as a monohemispheric brain edema marker in several studies; however, it does not precisely measure brain edema. It is now possible to directly measure hemisphere brain volume. Knowledge about the time course of brain edema after malignant middle cerebral artery infarction may contribute to the condition's management. Objective Therefore, our goal was to evaluate the course of brain edema in patients with malignant MCA infarction treated with decompressive craniectomy (DC) using hemispheric volumetric measurements. Methods Patients were selected consecutively from a single tertiary hospital between 2013 and 2019. All patients were diagnosed with malignant middle cerebral artery infarction and underwent a decompressive craniectomy (DC) to treat the ischemic event. All computed tomography (CT) exams performed during the clinical care of these patients were analyzed, and the whole ischemic hemisphere volume was calculated for each CT scan. Results We analyzed 43 patients (197 CT exams). Patients' mean age at DC was 51.72 [range: 42-68] years. The mean time between the ischemic ictus and DC was 41.88 (range: 6-77) hours. The mean time between the ischemic event and the peak of hemisphere volume was 168.84 (95% confidence interval [142.08, 195.59]) hours. Conclusion In conclusion, the peak of cerebral edema in malignant MCA infarction after DC occurred on the 7th day (168.84 h) after stroke symptoms onset. Further studies evaluating therapies for brain edema even after DC should be investigated.

Resumo Antecedentes O edema cerebral é a principal causa de morte em pacientes com infarto maligno de artéria cerebral média. O desvio da linha média tem sido utilizado como marcador de edema cerebral mono-hemisférico em alguns estudos; porém, ele não mede de forma precisa o edema cerebral. Atualmente é possível mensurar diretamente o volume do hemisfério cerebral. O conhecimento sobre a evolução temporal do edema cerebral após infartos malignos da artéria cerebral média pode contribuir para o cuidado clínico desta condição. Objetivo Nosso objetivo é avaliar o edema hemisférico ao longo do tempo, em pacientes com infarto maligno da artéria cerebral média, tratados com craniectomia descompressiva. Métodos Os pacientes foram selecionados de forma consecutiva, em um hospital terciário, entre 2013 e 2019. Todos os pacientes apresentavam diagnóstico de infarto maligno de artéria cerebral média e foram submetidos a craniectomia descompressiva. Todas as tomografias computadorizadas de crânio destes pacientes foram analizadas, e o volume do hemisfério cerebral infartado foi mensurado. Resultados Analisamos 43 pacientes (197 tomografias de crânio). A idade média dos pacientes na craniectomia descompressiva foi 51,72 (42-68) anos. O tempo médio entre o ictus e a craniectomia descompressiva foi 41,88 (6-77) horas. O tempo médio entre o ictus e o pico do volume hemisférico foi 168,84 (142,08-195,59) horas. Conclusão O pico do volume cerebral em pacientes com infarto maligno de artéria cerebral média submetidos a craniectomia descompressiva ocorreu no 7o dia (168,84 horas) após o infarto. Mais estudos avaliando terapêuticas direcionadas ao edema cerebral seriam úteis neste contexto.

In utero myelomeningocele repair and high-risk bladder pattern. a prospective study

ABSTRACT Objectives High-risk bladder pattern can be defined by Urodynamic Evaluation (UE) as overactive bladder with detrusor leak point pressure higher than 40 cmH2O and/or higher filling pressures also above 40 cmH2O. We wanted to evaluate response to treatment in myelomeningocele patients operated in utero in this subgroup. Patients and Methods From our prospective cohort of in utero MMC we have identified patients in the high-risk group. Treatment consisted of anticholinergics (Oxybutynin 0.2 mg/Kg) 2 or 3 times daily in association with CIC. At every UE, patients were reclassified in high-risk or low-risk patterns. Patients not responding were proposed bladder reconstruction or diversion according to age. Results Between 2011 to 2020, we have been following 121 patients and 60 (49.6%) of them were initially categorized as high-risk. The initial UE was performed at a mean age of 7.9 months and detrusor overactivity was found in 83.3% (mean maximum pressure of 76.5cmH20). When evaluating patients with 2 or more UE, we identified 44 patients (follow-up: 36.8months). It was observed in the group of patients who underwent 2 to 5 UE, that response to treatment was validated by the finding of 40% of low-risk bladder patterns in the second UE and between 62% to 64% in the third to the fifth UE. The incidence of surgery was 13.3%. Conclusions Early urological treatment of high-risk bladder pattern was effective in approximately 60%. We reinforce the need to correctly treat every patient with myelomeningocele, in accordance with UE, whether undergoing in utero or postnatal treatment.

Use of Vacuum-suction in Depressed Skull Fractures ­ Case Report and Technical Nuances of Nonoperative Treatment

Up to 20% of victims from skull fractures are represented by the pediatric population, and 50% of these lesions are depressed skull fractures. The treatment is multimodal in nature, ranging from conservative treatment to open surgical repair. The last one is associated, although in a small proportion, to complications, such as infections, hematomas and even death, besides the risks of the anesthetic procedure itself. The authors of the present article present a case report of the successful treatment of a depressed skull fracture in a newborn patient, using the vacuum-suction technique. The use of vacuum-suction may be beneficial for the pediatric patients, as it is a quick, non-invasive procedure, without the need for general anesthesia.

Minimally invasive lumbar arthrodesis and percutaneous pedicle screws: a systematic review / Artrodese lombar minimamente invasiva e parafusos pediculares percutâneos: revisão sistemática / Artrodesis lumbar mínimamente invasiva y tornillos pediculares percutáneos: revisión sistemática

ABSTRACT A systematic review of the literature was performed in order to organize, evaluate, and select evidences available about the safety and efficacy of minimally invasive percutaneous arthrodesis with percutaneous pedicle screws in the treatment of patients with degenerative disc disease (and other spinal pathologies) as compared to conventional arthrodesis. PubMed, EMBASE and Cochrane Library databases were consulted to locate clinical trials and case reports/case series published in English between 2014 and 2019. After selection according to the inclusion/exclusion criteria, 21 of the 197 articles identified were chosen for a complete reading and used for the present review. Although the level of evidence of most of the studies included made the demonstration of efficacy and superiority among the surgical techniques reviewed difficult, the findings related to the minimally invasive procedure indicate a safe and reliable approach for the treatment of lumbar diseases. Level of evidence II; Systematic review of literature.

RESUMO A revisão sistemática da literatura foi realizada com o objetivo de organizar, avaliar e selecionar evidências a respeito da segurança e eficácia da artrodese percutânea minimamente invasiva com parafusos pediculares percutâneos no tratamento de pacientes com doença degenerativa de disco (e outras patologias da coluna), em comparação com a artrodese convencional. Foram consultadas as bases de dados PubMed, EMBASE e Biblioteca Cochrane para localizar ensaios clínicos e relatos/séries de casos publicados em inglês entre 2014 e 2019. Dentre 197 estudos identificados, depois de seleção usando critérios de inclusão/exclusão, 21 artigos foram escolhidos para leitura na íntegra e usados na presente revisão. Apesar do nível de evidência da maioria dos estudos incluídos dificultar a demonstração de eficácia e superioridade entre as técnicas cirúrgicas revisadas, os achados referentes ao procedimento minimamente invasivo apontam para uma abordagem segura e confiável para o tratamento de doenças lombares. Nível de evidência II; Revisão sistemática da literatura.

RESUMEN La revisión sistemática de la literatura fue realizada con el objetivo de organizar, evaluar y seleccionar evidencias al respecto de la seguridad y eficacia de la artrodesis percutánea mínimamente invasiva con tornillos pediculares en el tratamiento de pacientes con enfermedad degenerativa de disco (y otras patologías de la columna) en comparación con la artrodesis convencional. Fueron consultadas las bases de datos PubMed, EMBASE y Biblioteca Cochrane para localizar ensayos clínicos y relatos/series de casos publicados en inglés entre 2014 y 2019. Entre 197 estudios identificados, después de selección usando criterios de inclusión/exclusión, fueron escogidos 21 artículos para lectura integral y usados en la presente revisión. A pesar de que el nivel de evidencia de la mayoría de los estudios incluidos dificulte la demostración de eficacia y superioridad entre las técnicas quirúrgicas revisadas, los hallazgos referentes al procedimiento mínimamente invasivo apuntan hacia un abordaje seguro y confiable para el tratamiento de enfermedades lumbares. Nivel de evidencia II; Revisión sistemática de la literatura.

Management of Chiari I Deformity in Children and Adolescents: A Report from the Consensus Taskforce of the Brazilian Society of Pediatric Neurosurgery

Much controversy remains on the current management of Chiari I deformity (CID) in children, with many clinical, surgical and ethic-legal implications. The Brazilian Society of Pediatric Neurosurgery (SBNPed, in the Portuguese acronym) has put together a panel of experts to analyze updated published data on the medical literature about this matter and come up with several recommendations for pediatric neurosurgeons and allied health professionals when dealing with CID. Their conclusions are reported herein, along with the respective scientific background.

The natural history of patients with acute disc herniation: a series of 150 cases / A história natural de pacientes com herniação discal aguda: uma série de 150 casos / La historia natural de pacientes con herniación discal aguda: una serie de 150 casos

ABSTRACT Objective This study aims to analyze the characteristics of patients with acute lumbar/sciatic disc herniation who underwent conservative, pain block procedures and surgical treatment, in order to better understand the natural history of herniations and their surgical indications, as well as the impact of hernia volume. Methods We analyzed 150 patients with a diagnosis of acute lumbar disc herniation. The treatments considered were: conservative, infiltration/pain block procedures and microdiscectomy. For seven patients who were surgically treated, the lumbar sequestrectomy volume was submitted to pathological analysis. Results Of the 150 patients, 80% were treated conservatively; 15.31% were treated with pain block procedures and 4.66% underwent microdiscectomy. The mean age of the surgical group was 42.5 years, and 57.1% of the patients were men. Most of the hernias were at L5-S1 (55.5%), and 77.7% were on the left side. All patients had presented significant lumbar pain or sciatica for a long period prior to the surgery. The Lasègue sign was present in all patients. Of the total number of patients, 85.7% presented hypoesthesia and 42.8% presented focal motor deficits, among other findings. The mean hernia volume was 9.6 cm3. Conclusions Unresponsiveness to conservative treatment is an important indication for surgery. The clinical manifestations in patients with a lumbar/sciatic hernia can be very diverse, as can the disc herniation volume, so these are not good indicators for surgery. Level of evidence IV; Case series

RESUMO Objetivo O presente estudo tem como objetivo analisar as características dos pacientes com hérnia de disco lombar/ciática aguda que passaram por procedimentos conservadores, procedimentos de bloqueio de dor e tratamento cirúrgico, a fim de melhor entender a história natural das hérnias e suas indicações cirúrgicas, assim como o impacto do volume da hérnia. Métodos Analisamos 150 pacientes diagnosticados com hérnia de disco lombar aguda. Os tratamentos considerados foram: tratamento conservador, procedimentos para bloqueio da dor/infiltração e microdiscectomia. Para sete pacientes tratados cirurgicamente, o volume de sequestrectomia lombar foi enviado para análise patológica. Resultados Dos 150 pacientes analisados, 80% foram tratados de modo conservador, 15,31% com procedimentos de bloqueio da dor e 4,66% com microdiscectomia. A idade média do grupo submetido à cirurgia foi 42,5 anos, sendo que 57,1% dos pacientes eram homens. A maior parte das hérnias estavam localizadas em L5-S1 (55,5%) e 77,7% das hérnias estavam no lado esquerdo. Todos os pacientes apresentaram significativa dor lombar ou ciática por um longo período antes da cirurgia. O sinal de Lasègue estava presente em todos pacientes. Do número total de pacientes, 85,7% apresentaram hipoestesia e 42,8% apresentaram déficits motores focais, entre outros achados. O volume médio das hérnias foi 9,6 cm3. Conclusões A falta de resposta ao tratamento conservador é uma importante indicação para cirurgia. As manifestações clínicas dos pacientes com hérnia lombar/ciática podem ser muito diversas, assim como o volume da hérnia de disco, portanto, esses não são bons indicadores para cirurgia. Nível de evidência IV; Série de casos.

RESUMEN Objetivo El presente estudio tiene como objetivo analizar las características de los pacientes con hernia de disco lumbar/ciática aguda que pasaron por procedimientos conservadores, procedimientos de bloqueo de dolor y tratamiento quirúrgico, a fin de entender mejor la historia natural de las hernias y sus indicaciones quirúrgicas, así como el impacto del volumen de la hernia. Métodos Analizamos a 150 pacientes diagnosticados con hernia de disco lumbar aguda. Los tratamientos considerados fueron: conservador, procedimientos para bloqueo de dolor/infiltraci ón y microdiscectom ía . Para siete pacientes tratados quirúrgicamente, el volumen de secuestrectomía lumbar fue enviado para análisis patológico. Resultados De los 150 pacientes analizados, 80% fue tratado de modo conservador, 15,31% con procedimientos de bloqueo de dolor y 4,66% con microdiscectomía. La edad promedio del grupo sometido a cirugía fue de 42,5 años, siendo que 57,1% de los pacientes eran hombres. La mayor parte de las hernias estaban localizadas en L5-S1 (55,5%) y 77,7% de las hernias estaban en el lado izquierdo. Todos los pacientes presentaron dolor lumbar o ciático significativo por un largo período antes de la cirugía. La señal de Lasègue estaba presente en todos los pacientes. Del número total de pacientes, 85,7% de los pacientes present ó hipostesia y 42,8% present ó déficit s motores focales, entre otros hallazgos. El volumen promedio de las hernias fue de 9,6 cm3. Conclusiones La falta de respuesta al tratamiento conservador es una importante indicación para la cirugía. Las manifestaciones clínicas de los pacientes con hernia lumbar/ciática pueden ser muy diversas, así como el volumen de la hernia de disco, por lo tanto, é stos no son buenos indicadores para cirugía. Nivel de evidencia IV; Serie de casos.

Intravenous grafts of human amniotic fluid-derived stem cells reduce behavioral deficits in experimental ischemic stroke

Amniotic fluid has been investigated as new cell source for stem cells in the development of future cell-based transplantation. This study reports isolation of viable human amniotic fluid-derived stem cells, labeled with multimodal iron oxide nanoparticles, and its effect on focal cerebral ischemia–reperfusion injury in Wistar rats. Middle cerebral artery occlusion of 60 min followed by reperfusion for 1 h, 6 h, and 24 h was employed in the present study to produce ischemia and reperfusion-induced cerebral injury in rats. Tests were employed to assess the functional outcome of the sensorimotor center activity in the brain, through a set of modified neurological severity scores used to assess motor and exploratory capacity 24 h, 14, and 28 days after receiving cellular therapy via tail vein. In our animal model of stroke, transplanted cells migrated to the ischemic focus, infarct volume decreased, and motor deficits improved. Therefore, we concluded that these cells appear to have beneficial effects on the ischemic brain, possibly based on their ability to enhance endogenous repair mechanisms.

New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X

EPNs comprise a heterogeneous group of neuroepithelial tumors, accounting for about 10% of all intracranial tumors in children and up to 30% of brain tumors in those younger than 3 years. Actually, the pattern therapy for low-grade EPNs includes complete surgical resection followed by radiation therapy. Total surgical excision is often not possible due to tumor location. The aim of this study was to evaluate, for the first time, the anti-tumor activity of Amblyomin-X in 4 primary cultures derived from pediatric anaplastic posterior fossa EPN, Group A (anaplastic, WHO grade III) and one primary culture of a high grade neuroepithelial tumor with MN1 alteration, which was initially misdiagnosed as EPN: i) by in vitro assays: comparisons of temozolomide and cisplatin; ii) by intracranial xenograft model. Amblyomin-X was able to induce cell death in EPN cells in a more significant percentage compared to cisplatin. The cytotoxic effects of Amblyomin-X were not detected on hFSCs used as control, as opposed to cisplatin-treatment, which promoted a substantial effect in the hAFSCs viability. TEM analysis showed ultrastructural alterations related to the process of cell death: mitochondrial degeneration, autophagosomes and aggregate-like structures. MRI and histopathological analyzes demonstrated significant tumor mass regression. Our results suggest that Amblyomin-X has a selective effect on tumor cells by inducing apoptotic cell death and may be a therapeutic option for Group AEPNs.

Tropism of mesenchymal stem cell toward CD133+ stem cell of glioblastoma in vitro and promote tumor proliferation in vivo

Background Previous studies have demonstrated remarkable tropism of mesenchymal stem cells (MSCs) toward malignant gliomas, making these cells a potential vehicle for delivery of therapeutic agents to disseminated glioblastoma (GBM) cells. However, the potential contribution of MSCs to tumor progression is a matter of concern. It has been suggested that CD133+ GBM stem cells secrete a variety of chemokines, including monocytes chemoattractant protein-1 (MCP-1/CCL2) and stromal cell-derived factor-1(SDF-1/CXCL12), which could act in this tropism. However, the role in the modulation of this tropism of the subpopulation of CD133+ cells, which initiate GBM and the mechanisms underlying the tropism of MSCs to CD133+ GBM cells and their effects on tumor development, remains poorly defined. Methods/results We found that isolated and cultured MSCs (human umbilical cord blood MSCs) express CCR2 and CXCR4, the respective receptors for MCP-1/CCL2 and SDF-1/CXCL12, and demonstrated, in vitro, that MCP-1/CCL2 and SDF-1/CXC12, secreted by CD133+ GBM cells from primary cell cultures, induce the migration of MSCs. In addition, we confirmed that after in vivo GBM tumor establishment, by stereotaxic implantation of the CD133+ GBM cells labeled with Qdots (705 nm), MSCs labeled with multimodal iron oxide nanoparticles (MION) conjugated to rhodamine-B (Rh-B) (MION-Rh), infused by caudal vein, were able to cross the blood-brain barrier of the animal and migrate to the tumor region. Evaluation GBM tumors histology showed that groups that received MSC demonstrated tumor development, glial invasiveness, and detection of a high number of cycling cells. Conclusions Therefore, in this study, we validated the chemotactic effect of MCP-1/CCL2 and SDF-1/CXCL12 in mediating the migration of MSCs toward CD133+ GBM cells. However, we observed that, after infiltrating the tumor, MSCs promote tumor growth in vivo probably by release of exosomes. Thus, the use of these cells as a therapeutic carrier strategy to target GBM cells must be approached with caution.

Intravenous grafts of human amniotic fluid-derived stem cells reduce behavioral deficits in experimental ischemic stroke

Amniotic fluid has been investigated as new cell source for stem cells in the development of future cell-based transplantation. This study reports isolation of viable human amniotic fluid-derived stem cells, labeled with multimodal iron oxide nanoparticles, and its effect on focal cerebral ischemia–reperfusion injury in Wistar rats. Middle cerebral artery occlusion of 60 min followed by reperfusion for 1 h, 6 h, and 24 h was employed in the present study to produce ischemia and reperfusion-induced cerebral injury in rats. Tests were employed to assess the functional outcome of the sensorimotor center activity in the brain, through a set of modified neurological severity scores used to assess motor and exploratory capacity 24 h, 14, and 28 days after receiving cellular therapy via tail vein. In our animal model of stroke, transplanted cells migrated to the ischemic focus, infarct volume decreased, and motor deficits improved. Therefore, we concluded that these cells appear to have beneficial effects on the ischemic brain, possibly based on their ability to enhance endogenous repair mechanisms.

New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X

EPNs comprise a heterogeneous group of neuroepithelial tumors, accounting for about 10% of all intracranial tumors in children and up to 30% of brain tumors in those younger than 3 years. Actually, the pattern therapy for low-grade EPNs includes complete surgical resection followed by radiation therapy. Total surgical excision is often not possible due to tumor location. The aim of this study was to evaluate, for the first time, the anti-tumor activity of Amblyomin-X in 4 primary cultures derived from pediatric anaplastic posterior fossa EPN, Group A (anaplastic, WHO grade III) and one primary culture of a high grade neuroepithelial tumor with MN1 alteration, which was initially misdiagnosed as EPN: i) by in vitro assays: comparisons of temozolomide and cisplatin; ii) by intracranial xenograft model. Amblyomin-X was able to induce cell death in EPN cells in a more significant percentage compared to cisplatin. The cytotoxic effects of Amblyomin-X were not detected on hFSCs used as control, as opposed to cisplatin-treatment, which promoted a substantial effect in the hAFSCs viability. TEM analysis showed ultrastructural alterations related to the process of cell death: mitochondrial degeneration, autophagosomes and aggregate-like structures. MRI and histopathological analyzes demonstrated significant tumor mass regression. Our results suggest that Amblyomin-X has a selective effect on tumor cells by inducing apoptotic cell death and may be a therapeutic option for Group AEPNs.

Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology

Background: Ependymoma (EPN), the third most common pediatric brain tumor, is a central nervous system (CNS) malignancy originating from the walls of the ventricular system. Surgical resection followed by radiation therapy has been the primary treatment for most pediatric intracranial EPNs. Despite numerous studies into the prognostic value of histological classification, the extent of surgical resection and adjuvant radiotherapy, there have been relatively few studies into the molecular and cellular biology of EPNs. Results: We elucidated the ultrastructure of the cultured EPN cells and characterized their profile of immunophenotypic pluripotency markers (CD133, CD90, SSEA-3, CXCR4). We established an experimental EPN model by the intracerebroventricular infusion of EPN cells labeled with multimodal iron oxide nanoparticles (MION), thereby generating a tumor and providing a clinically relevant animal model. MRI analysis was shown to be a valuable tool when combined with effective MION labeling techniques to accompany EPN growth. Conclusions: We demonstrated that GFAP/CD133+CD90+/CD44+ EPN cells maintained key histopathological and growth characteristics of the original patient tumor. The characterization of EPN cells and the experimental model could facilitate biological studies and preclinical drug screening for pediatric EPNs. Methods: In this work, we established notoriously challenging primary cell culture of anaplastic EPNs (WHO grade III) localized in the posterior fossa (PF), using EPNs obtained from 1 to 10-year-old patients (n = 07), and then characterized their immunophenotype and ultrastructure to finally develop a xenograft model.

Perfil Nutricional de Crianças Portadoras de Tumores Cerebrais com Síndrome Diencefálica ou Síndrome de Russell recebendo Dieta Enteral / Nutritional Profile of Children with Brain Tumor with Diencephalic Syndrome or Russell Syndrome receiving Enteral Diet / Perfil Nutricional de Niños Portadores de Tumores Cerebrales con Síndrome diencefálico o Síndrome de Russell recibiendo dieta Enteral

Introdução: a síndrome diencefálica é uma doença pediátrica rara, decorrente de tumores hipotalâmicos, caracterizada por failure to thrive. Objetivo: descrever o estado nutricional e a terapia nutricional por meio de sonda nasoenteral de pacientes com tumores cerebrais com a síndrome diencefálica. Método:sete pacientes foram acompanhados de julho/1999 a abril/2002 e analisados retrospectivamente, usando os escores-z de peso para idade (P/i), peso para estatura (P/e) e estatura para idade (e/i) no diagnóstico da desnutrição. todos foram avaliados por meio de composição corporal: prega cutânea triciptal (Pct) e circunferências do braço e muscular do braço (cB e cMB) e receberam alimentação por sonda nasoenteral ou gastrostomia após o diagnóstico da neoplasia. Resultados: a idade variou de 2 meses a 13 anos, cinco do sexo masculino. a duração média da nutrição enteral foi de 7 meses (1,1-18,5) após o diagnóstico, sem diferença estatística significante na evolução dos escores-z, apesar do aumento nas médias de P/i (-4,42 para -3,50) e P/e (-3,06 para -1,99), e dos indicadores de composição corporal (Pct: 2,85 para 4,88; cB: 9,81 para 11,84 e cMB: 8,91 para 10,31). Houve redução na média da e/i, caracterizando o atraso no crescimento dessas crianças. Conclusão: a nutrição enteral demonstrou garantir a oferta nutricional e recuperar em parte os indicadores nutricionais de desnutrição aguda; principalmente a gordura corporal, mais do que massa magra. entretanto, manteve-se o déficit de crescimento, agravado na maioria dos casos. a terapia nutricional deve ser implantada durante o tratamento oncológico, assegurando sua continuidade.

Introduction:diencephalic syndrome is a rare disorder of infancy characterized by profound emaciation with failure to thrive. The majority of cases of the syndrome are due to low grade gliomas of the anterior hypothalamus or optic nerve. Objective:to report the nutritional status and efficacy of nutritional support in patients with brain tumors that developed the russell's syndrome. Method:seven patients were retrospectively evaluated by means of z-score of the weight for age (W/a), weight for height (W/H) and height for age (H/a) nutritional status index, for protein-energy malnutrition diagnosis. They were evaluated by means of triceps skinfold thickness (tsFt), arm circumferences (ac) and muscle arm circumferences (Mac) and received enteral nutrition, by nasoenteral tube or gastrostomy at cancer diagnostic. Results: The ages ranged from 2 months to 13 years, five children were males. Mean of the nutritional support was 7 months (1.1-18.5 months) after diagnostic, without statistical differences in z-scores evolution, but there are increase in averages of the W/a (-4,42 to -3,50) and W/H (-3,06 to -1,99), and body composition indicators (tsFt): 2.85 to 4.88, ac: 9.81 to 11.84 and Mac: 8.91 to 10.31). There was decreased in average of H/a, evidencing the growth arrest of these children. Conclusion:enteral feeding has been shown to guarantee nutritional supply and to partially recover nutritional indicators of acute malnutrition; especially body fat, rather than lean mass. However, the growth deficit was not corrected, being aggravated in most cases. nutritional support should be implanted during oncological treatment, ensuring its maintenance.

Introducción:el síndrome diencefalica es una enfermedad pediátrica rara, derivada de tumores de la región hipotalámica, caracterizada por failure to thrive. Objetivo: describir condiciones nutricionales y terapia nutricional de pacientes con tumores cerebrales com síndrome diencefalica y nutrición enteral. Método: siete pacientes fueron acompañados de julio/1999 a abril/2002 y analizados retrospectivamente, usando el score-Z de peso para edad (P/i), peso para estatura (P/e) y estatura para edad (e/i) para el diagnóstico de la desnutrición. todos fueron evaluados por composición corporal (pliegue cutáneo triciptal y circunferencias del brazo y muscular del brazo). los pacientes recibieron nutrición enteral por sonda o gastrostomía, luego del diagnóstico de cancer. Resultados:la edad varía de 2 meses a 13 años, cinco del sexo masculino. la duración media de la nutrición enteral fue de 7 meses (1,1-18,5) después del diagnóstico. no hubo diferencia estadística en la evolución nutricional, a pesar del aumento en P/i (-4,42 a -3,50) y P/e (-3,06 a -1,99), así como en la composición corporal (Pct: 2,85 a 4,88, cB: 9,81 a 11,84 y cMB: 8,91 para 10.31). Hubo una reducción de e/i, caracterizando el retraso en el crecimiento. Conclusión:la nutrición enteral demostró garantizar la oferta nutricional.e la recuperación parcial de la desnutrición aguda, principalmente grasa corporal, más que masa magra, sin respuesta al déficit en el crecimiento, que se agravó en casi todos los casos. la terapia nutricional debe ser implantada durante el tratamiento oncológico, asegurando su continuidad.

The Importance of Student Leagues on Medical Training in Neurosurgery and Residency Choice

Introdução Distúrbios neurológicos e neurocirúrgicos são altamente prevalentes no Brasil. O atendimento inicial é realizado por médicos generalistas, o que demonstra a importância dos estudos práticos e teóricos em neurologia e neurocirurgia nos cursos de graduação em medicina. Objetivos Descrever a escolha da especialidade médica dos formandos da Liga Acadêmica de Neurocirurgia da Escola Paulista de Medicina (LNC-EPM) e mapear a composição dos cursos de neurologia e/ou neurocirurgia e a presença de ligas acadêmicas dessas disciplinas nas escolas médicas do Brasil. Métodos Levantamento pessoal ou por rede social com todos os membros da liga de neurocirurgia da EPM de 2007 a 2015 quanto a conclusão do curso e a residência escolhida. Envio de um formulário online para todas as escolas médicas cadastradas no Conselho Federal de Medicina (CFM). Resultados e Discussão Cinquenta e sete graduandos de medicina já participaram da LNC-EPM, sendo que 45 já concluíram a graduação, 6 fizeram neurocirurgia e 5 neurologia. Conseguimos respostas de 128 das 173 escolas médicas cadastradas no CFM. Um total de 91% das escolas respondeu que possuem curso de neurologia estruturado. Esses cursos dividem-se em: 32 exclusivamente teóricos, com 12 abordando a neurocirurgia; 84 teórico-práticos, com 51 abordando a neurocirurgia. Apenas 19% das faculdades apresentam curso próprio estruturado de neurocirurgia, sendo que metade destes é apenas teórico. Um total de 66% das universidades tem liga acadêmica das disciplinas citadas. Conclusão Nota-se que a presença de ligas acadêmicas de neurologia e neurocirurgia em 66% das escolas médicas brasileiras é, muitas vezes, usada para suprir conhecimento teórico-prático que deveria ser abordado na graduação. Infelizmente, apenas 9,5% das escolas tem curso teórico-prático próprio de neurocirurgia na grade curricular, um fato que é preocupante devido à alta prevalência das doenças neurológicas na população.