Intracranial Pressure Evaluation in Swine During Full-Endoscopic Lumbar Spine Surgery.

BACKGROUND: Neurological complications during full-endoscopic spine surgery (FESS) might be attributed to intracranial pressure (ICP) increase due to continuous saline infusion (CSI). Understanding CSI and ICP correlation might modify irrigation pump usage. This study aimed to evaluate invasive ICP during interlaminar FESS; correlate ICP with irrigation pump parameters (IPPs); evaluate ICP during saline outflow occlusion, commonly used to control bleeding and improve the surgeon's view; and, after durotomy, simulate accidental dural tear. METHODS: Five swine were monitored, submitted to total intravenous anesthesia, and positioned ventrally. A parenchymal catheter was installed through a skull burr for ICP monitoring. Lumbar interlaminar FESS was performed until exposure of neural structures. CSI was used within progressively higher IPPs (A [60 mm Hg, 350 mL/minute] to D [150 mm Hg, 700 mL/minute]), and ICP was documented. During each IPP, different situations were grouped: intact dura with open channels (A1-D1) or occlusion test (A2-D2); dural tear with open channels (Ax1-Dx1) or occlusion test (Ax2-Dx2). ICP <20 mm Hg was defined as safe. RESULTS: Basal average ICP was 8.1 mm Hg. Adjustment in total intravenous anesthesia or suspension of tests was necessary due to critical ICP or animal discomfort. It was safe to operate with all IPPs with opened drainage channels (A1-D1) even with dural tear (Ax1-Dx1). Several occlusion tests (A2-D2, Ax2-Dx2) caused ICP increase (e.g., 86.1 mm Hg) influenced by anesthetic state and hemodynamics. CONCLUSIONS: During FESS, CSI might critically raise ICP. Keeping drainage channels open, with ideal anesthetic state, ICP remains safe even with high IPPs, despite dural tear. Drainage occlusions can quickly raise ICP, being even more severe with higher IPPs. Total intravenous anesthesia may protect from ICP increase and may allow longer drainage occlusion or higher IPPs.

Two year follow-up of distal unruptured intracranial aneurysms treated with a surface modified flow diverter under prasugrel monotherapy.

BACKGROUND: A new generation of modified surface flow diverters (FDs) and monotherapy using new antiplatelets may reduce both ischemic and hemorrhagic complications during the treatment of intracranial aneurysms. Previous preliminary safety analysis of distal unruptured intracranial aneurysms treated with the FD p48 MW HPC (phenox-Wallaby, Bochum, Germany) under antiplatelet monotherapy with prasugrel showed promising results. However, the long term outcomes of distal intracranial aneurysms treated with FDs under antiplatelet monotherapy are not known. METHODS: This was a single center, prospective, pivotal, open single arm study. The primary (safety) endpoint was absence of any new neurological deficits after treatment until the 24 month follow-up. The primary (efficacy) endpoint was the incidence of complete aneurysm occlusion 24 months after treatment. The secondary (efficacy) endpoints were any incidence of aneurysm dome reduction 24 months after treatment. RESULTS: 21 patients harboring 27 distal aneurysms of the anterior circulation were included. No patient had neurologic deficits in the time from treatment to the 24 month follow-up. Complete aneurysm occlusion occurred in 20 (74%) of 27 aneurysms at the 24 month follow-up. Four aneurysms (14.8%) had dome reduction, and three aneurysms (11.1%) remained unchanged. CONCLUSIONS: In this pilot trial, treatment of distal unruptured intracranial aneurysms with an FD under monotherapy with prasugrel, followed by monotherapy with aspirin, appeared to be safe and effective. Randomized studies with long term follow-up are needed to confirm these results.

Epidemiological study of paediatric traumatic brain injury in Brazil.

Background: Traumatic brain injury (TBI) has a high economic and social impact on the family dynamics, particularly among children. High-quality and comprehensive epidemiological studies about TBI in this population are limited worldwide, specifically in Latin America. Therefore, this study aimed to elucidate the epidemiology of TBI among children in Brazil and its effects on the public health system. Methods: This epidemiological (cohort) retrospective study collected data from the Brazilian healthcare database between 1992 and 2021. Results: The mean annual volume of hospital admission (HA) due to TBI in Brazil was 29,017. Moreover, the incidence of TBI in the paediatric population was 45.35 admissions per 100,000 inhabitants/year. Furthermore, approximately 941 paediatric hospital deaths per year were caused by TBI, with an in-hospital lethality rate of 3.21%. The average annual financial transfer for TBI was 12,376,628 USD, and the mean cost per admission was 417 USD. In addition, the mean length of hospital stay was 4.2 days. Notably, the length of stay in the hospital was longer among males, Afro-Brazilians patients and individuals aged 15-19 years. Conclusion: Paediatric TBI is an important public health issue worldwide with high social and economic costs. The incidence of paediatric TBI in Brazil is similar to that in developing countries. Moreover, male predominance (2.3:1) was observed in relation paediatric TBI. Notably, during the pandemic, the incidence of paediatric HA has decreased. To the best of our knowledge, this is the first epidemiological study that specifically evaluates paediatric TBI in Latin America.

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.

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.

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.

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.

Surgical management of embolized jugular foramen paragangliomas without facial nerve transposition: Experience of a public tertiary hospital in Brazil.

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.

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.

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.

Treatment of distal unruptured intracranial aneurysms using a surface-modified flow diverter under prasugrel monotherapy: a pilot safety trial.

BACKGROUND: Flow diverters (FDs) are effective in the treatment of carotid aneurysms. Compared with carotid aneurysms, the treatment of distal intracranial aneurysms with FDs has been associated with a relatively high incidence of complications. Low thrombogenic modified-surface FDs may reduce ischemic complications and allow for the use of a single antiplatelet medication. The aim of this study was to assess the safety and efficacy of the p48 MW HPC Flow Modulation Device (Phenox GmbH, Bochum, Germany) to treat distal intracranial aneurysms used in combination with prasugrel monotherapy. METHODS: This was a single-center, prospective, pivotal, open, single-arm study. Patients were included in this study from December 2019 to September 2020. The primary endpoints were the incidence of any neurologic deficit after treatment until 1 month of follow-up, defined as National Institutes of Health Stroke Scale (NIHSS) ≥1, and the incidence of acute ischemic lesions in magnetic resonance imagin (MRI) images 48 hours after treatment. The secondary endpoint was the rate of complete occlusion of the aneurysms at the 1-month follow-up. RESULTS: Twenty-one patients harboring 27 distal aneurysms of the anterior circulation were included. Mean age was 57.8 (SD 9.7) years, and 16 patients were female (80%). No patient had neurologic symptoms at the 1-month follow-up. Four patients (20%) had asymptomatic acute brain ischemic lesions on MRI. Complete aneurysm occlusion occurred in 9/27 (33.3%) aneurysms at the 1-month follow-up. CONCLUSION: In this pilot safety trial, treatment of distal intracranial aneurysms with p48 MW HPC under monotherapy with prasugrel appeared to be safe.

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.

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.

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.

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.

Arsenic Trioxide exerts cytotoxic and radiosensitizing effects in pediatric Medulloblastoma cell lines of SHH Subgroup.

We evaluated the potential effects of ATO in different pediatric SHH-MB cell lines (ONS-76: TP53-wild type; DAOY and UW402: TP53-mutated). MB cell lines molecular subgroup was confirmed and TP53 mutations were validated. Cell viability, clonogenicity and apoptosis were evaluated after ATO treatment at different concentrations (1-16 µM) alone or combined with irradiation doses (0.5, 1, 2 and 4 Gy). Rad51 and Ku86 proteins were evaluated by WB. ATO treatment reduced cell viability for all SHH-MB cell lines. Significant decrease of clonogenic capacity and higher apoptosis rates were also observed after ATO exposure, being cell death more pronounced (>70%) for the SHH-MB TP53-mutated. Combined treatment of ATO with irradiation also reduced colonies formation in UW402 tumor cells, which was independent of DNA damage repair proteins Rad51 and Ku86. In silico analyses suggested that a set of genes from cell cycle and p53 pathways are differentially expressed in SHH tumor subtypes, suggesting that cell lines may respond to therapies according to the gene expression profiles. Herein, we showed ATO cytotoxicity in pediatric SHH cell lines, with marked radiosensitizing effect for the MB-SHH TP53-mutated cells. These results highlight the potential of ATO, alone or in combination with radiotherapy, supporting further clinical investigations.