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Background: Glioblastoma is the most lethal primary malignant brain tumor. Although considerable progress has been made in the treatment of this aggressive tumor, the clinical outcome for patients remains poor. Histone deacetylases (HDACs) are recognized as promising targets for cancer treatment. In the past several years, HDAC inhibitors (HDACis) have been used as radiosensitizers in glioblastoma treatment. However, no study has demonstrated the status of global HDAC expression in gliomas and its possible correlation to the use of HDACis. The purpose of this study was to evaluate and compare mRNA and protein levels of class I, II and IV of HDACs in low grade and high grade astrocytomas and normal brain tissue and to correlate the findings with the malignancy in astrocytomas.Methods: Forty-three microdissected patient tumor samples were evaluated. The histopathologic diagnoses were 20 low-grade gliomas (13 grade I and 7 grade II) and 23 high-grade gliomas (5 grade III and 18 glioblastomas). Eleven normal cerebral tissue samples were also analyzed (54 total samples analyzed). mRNA expression of class I, II, and IV HDACs was studied by quantitative real-time polymerase chain reaction and normalized to the housekeeping gene beta-glucuronidase. Protein levels were evaluated by western blotting.Results: We found that mRNA levels of class II and IV HDACs were downregulated in glioblastomas compared to low-grade astrocytomas and normal brain tissue (7 in 8 genes, p < 0.05). The protein levels of class II HDAC9 were also lower in high-grade astrocytomas than in low-grade astrocytomas and normal brain tissue. Additionally, we found that histone H3 (but not histone H4) was more acetylated in glioblastomas than normal brain tissue.Conclusion: Our study establishes a negative correlation between HDAC gene expression and the glioma grade suggesting that class II and IV HDACs might play an important role in glioma malignancy. Evaluation of histone acetylation levels showed that histone H3 is more acetylated in glioblastomas than normal brain tissue confirming the downregulation of HDAC mRNA in glioblastomas. [ABSTRACT FROM AUTHOR]

Aim: We aim the isolated and combined effects of sedentary behaviour exposure time and physical activity levels on muscle strength in older adults., Design: This prospective observational cohort study, analytical in nature, using exploratory survey methods and physical performance testing. With 5-year longitudinal follow-up (2015-2020)., Methods: A total of 459 older adults participated in the baseline, with a total of 224 being included/located again in the follow-up. We evaluate muscle strength using handgrip tests and sit-to-stand tests. The international physical activity questionnaire was used to measure physical activity and sedentary behaviour. Generalised Estimation Equations tested both independent and combined effects, reporting results as β coefficients and confidence intervals., Results: Older adults exhibiting low sedentary behaviour displayed enhanced handgrip strength compared to those with high sedentary behaviour. Notably, older adults who were sufficiently active with low sedentary behaviour, sufficiently active with high sedentary behaviour, and insufficiently active with low sedentary behaviour showed increased handgrip strength compared to their counterparts who were insufficiently active with high sedentary behaviour. This trend was consistent for lower limb strength., Conclusion: Interventions that encourage a reduction in sedentary behaviour and an increase in physical activity are essential to maintain muscle strength among older adults., Implications for Practice: The findings of this study underscore the importance of addressing both sedentary behaviour and physical activity levels in clinical interventions aimed at preserving muscle strength in older adults. Routine assessments of physical activity and sedentary behaviour could help tailor personalised exercise programs, potentially enhancing functional independence and reducing the risk of frailty and disability in older patients., Patient or Public Contribution: Patients were involved in the sample of the study., Reporting Method: This study was conducted in accordance with the Strengthening Research in Observational Studies in Epidemiology (STROBE) guidelines., (© 2024 John Wiley & Sons Ltd.)

Introduction: Studies addressing the methylation pattern in adamantinomatous craniopharyngioma (ACP) are lacking., Objective: To identify methylation signatures in ACPs regarding clinical presentation and outcome., Methods: Clinical and pathology data were collected from 35 patients with ACP (54% male; 18.1 years [2-68]). CTNNB1 mutations and methylation profile (MethylationEPIC/Array-Illumina) were analyzed in tumoral DNA. Unsupervised machine learning analysis of this comprehensive methylome sample was achieved using hierarchical clustering and multidimensional scaling. Statistical associations between clusters and clinical features were achieved using the Fisher test and global biological process interpretations were aided by Gene Ontology enrichment analyses., Results: Two clusters were revealed consistently by all unsupervised methods (ACP-1: n = 18; ACP-2: n = 17) with strong bootstrap statistical support. ACP-2 was enriched by CTNNB1 mutations (100% vs 56%, P = .0006), hypomethylated in CpG island, non-CpG Island sites, and globally (P < .001), and associated with greater tumor size (24.1 vs 9.5 cm3, P = .04). Enrichment analysis highlighted pathways on signaling transduction, transmembrane receptor, development of anatomical structures, cell adhesion, cytoskeleton organization, and cytokine binding, and cell type-specific biological processes as regulation of oligodendrocytes, keratinocyte, and epithelial cells differentiation., Conclusion: Two clusters of patients with ACP were consistently revealed by unsupervised machine learning methods, with one of them significantly hypomethylated, enriched by CTNNB1 mutated ACPs, and associated with increased tumor size. Enrichment analysis reinforced pathways involved in tumor proliferation and in cell-specific tumoral microenvironment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To evaluate QOL and caregiver burden of children and teenagers submitted to hemispherotomy for pharmacoresistant epilepsy, by comparing pre and post-surgical intervention data., Materials and Methods: Retrospective analysis of pediatric patients submitted to surgical hemispherotomy before intervention (preOP) and their follow-up at 6 months (6 M PO) and 2 years (2Y PO) after surgery. QOL was evaluated through the Quality of Life in Childhood Epilepsy (QVCE-50) questionnaire and caregiver burden, through the Zarit Burden Interview (ZBI) tool., Results: Twenty-two patients were included in the study. Sixteen patients (72%) were classified as Engel I at 2Y PO follow-up. QVCE-50 scale showed improvement of total QOL at 2Y PO. In relation to QVCE-50-specific domains, there was an improvement in the physical domain and in the cognitive-education a decrease in psychological and a stabilization in social/familiar domain scores. The majority of caregivers classified their burden as mild to moderate, with no PO improvement., Conclusions: Hemispherotomy represents an effective seizure control treatment, as well as it contributes to improvement of QOL, particularly in the physical domain and in spite of children's physical and cognitive limitations. However, no improvement in caregiver burden was observed, probably due to the chronic condition of these patients, which might be worsened by social issues., Competing Interests: Declarations. Ethics approval and consent to participate consent: All procedures were in compliance with research policies and were approved by the Institutional Committee on Human Research (CAAE: 31802620.8.0000.5440). Consent for publication: The correspondent author has read and understood the publishing policy and submits this manuscript in accordance with this policy. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hemispheric epilepsy is quite frequent in children, compared with adults, and encompasses pathological substrates as diverse as hemimegalencephaly, Rasmussen encephalitis, Sturge-Weber syndrome, and porencephaly, among others. These patients most often become pharmacoresistant and thus require surgical management. Although anatomical hemispherectomy is a possibility, the technique that is favored by most epilepsy surgery centers worldwide is functional hemispherotomy, which results in equivalent outcomes with fewer postoperative complications. Therefore, it is essential that pediatric epilepsy neurosurgeons become familiar with these techniques. The present video describes in detail all surgical aspects of the perisylvian hemispherotomy., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication.The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication., (© 2024, The Authors.)

Objective: To analyze the factors associated with low functional mobility in older adults residing in Alcobaça, BA., Methods: This is an epidemiological survey with a cross-sectional design, conducted in 2015 with 473 older adults (62.4% women; mean age 70.2 ± 8.2 years) from Alcobaça, BA. The interview script addressed sociodemographic characteristics, health, and behavioral aspects. Functional mobility was assessed using the Short Physical Performance Battery (≤6 points). Inferential analyses were conducted using the Mann-Whitney U test and Poisson regression (with robust variance and estimation of prevalence ratios and their respective 95.0% confidence intervals)., Results: The prevalence of low functional mobility was 9.6%, with associated factors including the use of alcoholic beverages (PR = 1.7, 95% CI: 1.01-1.13) and the number of repetitions in elbow flexion (PR = 1.01, 95% CI: 1.01-1.05). Additionally, older adults with low mobility had lower height, thigh circumference, and lower performance in handgrip strength tests, elbow flexion, and flexibility. They also spent more time in sedentary behavior and less time in physical activity compared to older adults with preserved mobility ( p  < 0.05)., Conclusion: Older adults with low mobility exhibit poorer values in anthropometric parameters, lower performance in motor tests, spend less time engaged in physical activities, and more time in sedentary behavior., Competing Interests: The authors declare that there is no conflict of interest., (© 2024 The Author(s). Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.)

Meningomyelocele is one of the most severe forms of neural tube defects (NTDs) and the most frequent structural birth defect of the central nervous system. We assembled the Spina Bifida Sequencing Consortium to identify causes. Exome and genome sequencing of 715 parent-offspring trios identified six patients with chromosomal 22q11.2 deletions, suggesting a 23-fold increased risk compared with the general population. Furthermore, analysis of a separate 22q11.2 deletion cohort suggested a 12- to 15-fold increased NTD risk of meningomyelocele. The loss of Crkl , one of several neural tube-expressed genes within the minimal deletion interval, was sufficient to replicate NTDs in mice, where both penetrance and expressivity were exacerbated by maternal folate deficiency. Thus, the common 22q11.2 deletion confers substantial meningomyelocele risk, which is partially alleviated by folate supplementation.

Purpose: Hydrocephalus is a brain disease prevalent in the pediatric population that presents complex pathophysiology and multiple etiologies. The best treatment is still ventricular shunting. Mechanical obstruction is the most frequent complication, but the resulting pathological effects are still unknown., Objective: Evaluation and comparison of clinical, histopathological, and immunohistochemical aspects in the acute phase of experimental hydrocephalus induced by kaolin, after treatment with adapted shunt, and after shunt obstruction and posterior disobstruction., Methods: Wistar rats aged 7 days were used and divided into 4 groups: control group without kaolin injection (n = 6), untreated hydrocephalic group (n = 5), hydrocephalic group treated with ventriculosubcutaneous shunt (DVSC) (n = 7), and hydrocephalic group treated with shunt, posteriorly obstructed and disobstructed (n = 5). The animals were submitted to memory and spatial learning evaluation through the Morris water maze test. The rats were sacrificed at 28 days of age and histological analysis of the brains was performed with luxol fast blue, in addition to immunohistochemical analysis in order to evaluate reactive astrocytosis, inflammation, neuronal labeling, and apoptotic activity., Results: The group with shunt obstruction had worse performance in memory tests. Reactive astrocytosis was more evident in this group, as was the inflammatory response., Conclusions: Obstruction of the shunt results in impaired performance of behavioral tests and causes irreversible histopathological changes when compared to findings in the group with treated hydrocephalus, even after unblocking the system. The developed model is feasible and efficient in simulating the clinical context of shunt dysfunction., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Epilepsy surgery for pediatric drug-resistant epilepsy has been shown to improve seizure control, enhance patient and family QoL, and reduce mortality. However, diagnostic tools and surgical capacity are less accessible worldwide. The International Society Pediatric Neurosurgery (ISPN) has established a Pediatric Epilepsy Surgery Interest Group (PESIG), aiming to enhance global collaboration in research and educational aspects. The goals of this manuscript are to introduce PESIG and analyze geographical differences of epilepsy surgery and technology availability., Methods: PESIG was established (2022) following an ISPN executive board decision. Using a standardized form, we surveyed the PESIG members, collecting and analyzing data regarding geographical distribution, and availability of various epilepsy treatment-related technologies., Results: Two hundred eighty-two members registered in PESIG from 70 countries, over 6 continents, were included. We categorized the countries by GDP as follows: low, lower-medium, upper-medium, and high income. The most commonly available technology was vagus nerve stimulation 68%. Stereoelectroencephalography was available for 58%. North America had statistically significant greater availability compared to other continents. Europe had greater availability compared to Africa, Asia, and South (Latin) America. Asia had greater availability compared to Africa. High-income countries had statistically significant greater availability compared to other income groups; there was no significant difference between the other income-level subgroups., Conclusion: There is a clear discrepancy between countries and continents regarding access to epilepsy surgery technologies. This strengthens the need for collaboration between neurologists and neurosurgeons from around the world, to enhance medical education and training, as well as to increase technological availability., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We investigated the participation of the nucleus of the tractus solitarius (NTS) in tonic‒clonic seizures and postictal antinociception control mediated by NMDA receptors, the role of NTS GABAergic interneurons and noradrenergic pathways from the locus coeruleus (LC) in these phenomena. The NTS-lateral nucleus reticularis paragigantocellularis (lPGi)-LC pathway was studied by evaluating neural tract tracer deposits in the lPGi. NMDA and GABAergic receptors agonists and antagonists were microinjected into the NTS, followed by pharmacologically induced seizures. The effects of LC neurotoxic lesions caused by DSP-4, followed by NTS-NMDA receptor activation, on both tonic‒clonic seizures and postictal antinociception were also investigated. The NTS is connected to lPGi neurons that send outputs to the LC. Glutamatergic vesicles were found on dendrites and perikarya of GABAergic interneurons in the NTS. Both tonic‒clonic seizures and postictal antinociception are partially dependent on glutamatergic-mediated neurotransmission in the NTS of seizing rats in addition to the integrity of the noradrenergic system since NMDA receptor blockade in the NTS and intrathecal administration of DSP-4 decrease the postictal antinociception. The GABA A receptor activation in the NTS decreases both seizure severity and postictal antinociception. These findings suggest that glutamatergic inputs to NTS-GABAergic interneurons, in addition to ascending and descending noradrenergic pathways from the LC, are critical for the control of both seizures and postictal antinociception., (© 2024. The Author(s).)

Background: Rasmussen encephalitis (RE) is characterized by pharmacoresistant epilepsy and progressive neurological deficits concurrent with unilateral hemispheric atrophy. Evidence of an inflammatory autoimmune process has been extensively described in the literature; however, the precise etiology of RE is still unknown. Despite data supporting a beneficial effect of early immunosuppressive and immunomodulatory interventions, surgical disconnection of the affected hemisphere is considered the treatment of choice for these patients. The aim of this study was to report a series of children and adolescents who underwent hemispheric surgery (HS) for the treatment of RE, analyzing their clinical, electrographic, and neuroimaging features pre-operatively, as well as their postoperative status, including seizure and functional outcomes., Methods: All patients with RE who underwent HS in the Epilepsy Surgery Center (CIREP) of the University Hospital of Ribeirão Preto Medical School, between 1995 and 2020 were retrospectively reviewed. Preoperative and postoperative analyses included gender; age at epilepsy onset; seizure semiology; seizure frequency; interictal and ictal electroencephalographic (EEG) findings; age at surgery; duration of epilepsy; surgical complications; duration of follow-up; histopathological findings; and postoperative seizure, cognitive, and functional outcomes., Results: Forty-four patients were evaluated. Mean age at seizure onset and epilepsy duration was 6 years and 2.5 years, respectively. Mean age at surgery was 9 years, with an average follow-up ranging from 3 months to 23 years. All patients presented with severe epilepsy and distinct neurological abnormalities on MRI. Before HS, different degrees of abnormal intellectual performance as well as hemiparesis were seen in 86% and 90%, respectively. Histopathology examination confirmed this diagnosis in 95% patients. At the last follow-up, 68% of patients were seizure free, and 70% were classified as Engel Class I or II. Postoperatively, the cognitive status remained unchanged in 64% of patients. Likewise, the gross motor function remained unchanged in 54% of patients and 74% had functional hand ability after HS., Conclusions: Considering the progressive damage course of RE, hemispheric surgery should be offered to pediatric patients. It has manageable risks and results in good seizure outcome, and the preoperative functional status of these children is often preserved (even when the left hemisphere is involved), thus improving their quality of life., Competing Interests: Declaration of competing interest The authors declare to have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS., Methods: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks., Results: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality., Significance: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background and Aims: The dysgranula parts of the posterior insular cortex (PIC) stimulation (PICS) has been investigated as a new putative cortical target for nonpharmacologic therapies in patients with chronic and neuropathic pain (NP). This work investigates the neural bases of insula neurostimulation-induced antinociception and glutamatergic neurochemical mechanisms recruited by the PICS in animals with neuropathy., Materials and Methods: Male Wistar rats were submitted to the von Frey and acetone tests to assess mechanical and cold allodynia after 21 days of chronic constriction injury (CCI) of the sciatic nerve or Sham procedure ("false operated"). Either the Cascade Blue 3000 MW lysine-fixable dextran (CBD) or the biotinylated dextran amine 3000 MW (BDA) neural tract tracer was microinjected into the PIC. The electrical PICS was performed at a low frequency (20 μA, 100 Hz) for 15 seconds by a deep brain stimulation device. PIC N-methyl-D-aspartate (NMDA) receptors (NMDAR) blockade with the selective antagonist LY235959 (at 2, 4, and 8 nmol/200 nL) followed by PICS was investigated in rats with CCI., Results: PIC sends projections to the caudal pontine reticular nucleus, alpha part of the parvicellular reticular nucleus, dorsomedial tegmental area, and secondary somatosensory cortex (S 2 ). PICS decreased both mechanical and cold allodynia in rats with chronic NP. Blockade of NMDAR in the PIC with LY235959 at 8 nmol attenuated PICS-produced antinociception., Conclusion: Neuroanatomic projections from the PIC to pontine reticular nuclei and S 2 may contribute to chronic NP signaling. PICS attenuates the chronic NP, and the NMDA glutamatergic system in the PIC may be involved in PICS-induced antinociception in rodents with NP conditions., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Neuropathic pain (NP) represents a complex disorder with sensory, cognitive, and emotional symptoms. The medial prefrontal cortex (mPFC) takes critical regulatory roles and may change functionally and morphologically during chronic NP. There needs to be a complete understanding of the neurophysiological and psychopharmacological bases of the NP phenomenon. This study aimed to investigate the participation of the infralimbic division (IFL) of the mPFC in chronic NP, as well as the role of the N-methyl-D-aspartic acid receptor (NMDAr) in the elaboration of chronic NP. Male Wistar rats were submitted to the von Frey and acetone tests to assess mechanical and cold allodynia after 21 days of chronic constriction injury (CCI) of the sciatic nerve or Sham-procedure ("false operated"). Electrical neurostimulation of the IFL/mPFC was performed by low-frequency stimuli (20 μA, 100 Hz) applied for 15 s by deep brain stimulation (DBS) device 21 days after CCI. Either cobalt chloride (CoCl 2 at 1.0 mM/200 nL), NMDAr agonist (at 0.25, 1.0, and 2.0 nmol/200 nL) or physiological saline (200 nL) was administered into the IFL/mPFC. CoCl 2 administration in the IFL cortex did not alter either mechanical or cold allodynia. DBS stimulation of the IFL cortex decreased mechanical allodynia in CCI rats. Chemical stimulation of the IFL cortex by an NMDA agonist (at 2.0 nmol) decreased mechanical allodynia. NMDA at any dose (0.25, 1.0, and 2.0 nmol) reduced the flicking/licking duration in the cold test. These findings suggest that the IFL/mPFC and the NMDAr of the neocortex are involved in attenuating chronic NP in rats., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Groups (Grp) 3 and 4 are aggressive molecular subgroups of medulloblastoma (MB), with high rates of leptomeningeal dissemination. To date, there is still a paucity of biomarkers for these subtypes of MBs. In this study, we investigated the clinical significance and biological functions of Musashi-1 (MSI1) in Grp3 and Grp4-MBs. First, we assessed the expression profile of MSI1 in 59 primary MB samples (15-WNT, 18-SHH, 9-Grp3, and 17-Grp4 subgroups) by qRT-PCR. MSI1 mRNA expression levels were also validated in an additional public dataset of MBs (GSE85217). The ROC curve was used to validate the diagnostic standards of MSI1 expression. Next, the potential correlated cell-cycle genes were measured by RNA-Seq. Cell cycle, cell viability, and apoptosis were evaluated in a Grp3/Grp4 MB cell line after knockdown of MSI1 and cisplatin treatment. We identified an overexpression of MSI1 with a high accuracy to discriminate Grp3/Grp4-MBs from non-Grp3/Grp4-MBs. We identified that MSI1 knockdown not only triggered transcriptional changes in the cell-cycle pathway, but also affected G2/M phase in vitro, supporting the role of knockdown of MSI1 in cell-cycle arrest. Finally, MSI1 knockdown decreased cell viability and sensitized D283-Med cells to cisplatin treatment by enhancing cell apoptosis. Based on these findings, we suggest that MSI1 modulates cell-cycle progression and may play a role as biomarker for Grp3/Grp4-MBs. In addition, MSI1 knockdown combined with cisplatin may offer a potential strategy to be further explored in Grp3/Grp4-MBs., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

Hydrocephalus is a neurological condition with altered cerebrospinal fluid flow (CSF). The treatment is surgical and the most commonly used procedure is ventricle-peritoneal shunt. However, not all patients can undergo immediate surgery or achieve complete lesion reversal. Neuroprotective measures are valuable in such cases. It was evaluated whether the use of celecoxib, a selective inhibitor of COX-2, associated or not with ventricular-subcutaneous derivation, could offer benefits to the brain structures affected by experimental hydrocephalus. Seven-day-old male Wistar Hannover rats induced by intracisternal injection of kaolin 15% were used, divided into five groups with ten animals each: intact control (C), untreated hydrocephalus (H), hydrocephalus treated with celecoxib 20 mg/kg intraperitoneal (HTC), hydrocephalus treated with shunt (HTS) and hydrocephalus treated with shunt and celecoxib 20 mg/kg intraperitoneal (HTCS). Celecoxib was administered for 21 consecutive days, starting the day after hydrocephalus induction and continuing until the end of the experimental period. The surgery was performed seven days after inducing hydrocephalus. Multiple assessment methods were used, such as behavioral tests (water maze and open field), histological analysis (hematoxylin and eosin), immunohistochemistry (caspase-3, COX-2, and GFAP), and ELISA analysis of GFAP. The results of the behavioral and memory tests indicated that celecoxib improves the neurobehavioral response. The improvement can be attributed to the reduced neuroinflammation (p < 0.05), and astrogliosis (p < 0.05) in different brain regions. In conclusion, the results suggest that celecoxib holds great potential as an adjuvant neuroprotective drug for the treatment of experimental hydrocephalus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Rasmussen Encephalitis (RE) is a rare inflammatory neurodegenerative disease associated with refractory seizures, hemiparesis, and cognitive deterioration, due to lateralized cortical atrophy. Hemispheric surgery (hemispherotomy) is the mainstay of treatment, but its unavoidable motor deficits and lack of long-term data regarding seizure outcomes can make patients and families apprehensive to undergo this procedure. The present study aimed at analyzing the results of surgical treatment for RE from a motor and epilepsy standpoint, and mitigate such concerns., Methods: Clinical and operative data were retrospectively collected from medical records of pharmacoresistant patients treated with functional hemispherectomy at a tertiary reference center for epilepsy surgery, during a 24-year period (1996-2020). Variables such as age of epilepsy onset, seizure semiology, seizure frequency, immunomodulatory therapy, age at surgery, duration of epilepsy, surgical procedures and complications, number of medications used preoperatively and postoperatively were described and statistically analyzed., Results: Forty-three (43) patients were included in this study. Mean age of epilepsy onset was 6.14 years, the average interval between epilepsy onset and hemispherotomy was 2.21 years. and the mean age at surgery was 8.28 years. Thirty patients (69.7%) were Engel I at their last follow-up, of whom 23 (56.4%) were Engel Ia, within a mean follow-up of 11.3 years. Duration of epilepsy, seizure frequency, and age at surgery, among others, did not correlate with seizure outcome, except the use of immunotherapy which led to worse outcomes (p < .05). Also, after surgery, motor functionality was significantly recovered (i.e., most patients returned to their previous status) with time., Significance: This study tackled some issues regarding the surgical treatment of this disease, particularly showing that hemispherotomy is safe and leads to potentially recoverable disability of motor functions while providing high rates of effective and long-lasting seizure control; therefore, early surgical indication should be warranted once medical refractoriness has been established., (© 2023 International League Against Epilepsy.)

Objective: To explore pituitary tumors by methylome and transcriptome signatures in a heterogeneous ethnic population., Methods: In this retrospective cross-sectional study, clinicopathological features, methylome, and transcriptome were evaluated in pituitary tumors from 77 patients (61% women, age 12-72 years) followed due to functioning (FPT: GH-secreting n = 18, ACTH-secreting n = 14) and nonfunctioning pituitary tumors (NFPT, n = 45) at Ribeirao Preto Medical School, University of São Paulo., Results: Unsupervised hierarchical clustering analysis (UHCA) of methylome (n = 77) and transcriptome (n = 65 out of 77) revealed 3 clusters each: one enriched by FPT, one by NFPT, and a third by ACTH-secreting and NFPT. Comparison between each omics-derived clusters identified 3568 and 5994 differentially methylated and expressed genes, respectively, which were associated with each other, with tumor clinical presentation, and with 2017 and 2022 WHO classifications. UHCA considering 11 transcripts related to pituitary development/differentiation also supported 3 clusters: POU1F1-driven somatotroph, TBX19-driven corticotroph, and NR5A1-driven gonadotroph adenomas, with rare exceptions (NR5A1 expressed in few GH-secreting and corticotroph silent adenomas; POU1F1 in few ACTH-secreting adenomas; and TBX19 in few NFPTs)., Conclusion: This large heterogenic ethnic Brazilian cohort confirms that integrated methylome and transcriptome signatures classify FPT and NFPT, which are associated with clinical presentation and tumor invasiveness. Moreover, the cluster NFPT/ACTH-secreting adenomas raises interest regarding tumor heterogeneity, supporting the challenge raised by the 2017 and 2022 WHO definition regarding the discrepancy, in rare cases, between clinical presentation and pituitary lineage markers. Finally, making our data publicly available enables further studies to validate genes/pathways involved in pituitary tumor pathogenesis and prognosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: We aimed to analyze the potential for postoperative (PO) medication suspension and reduction, emphasizing passive withdrawal., Methods: Retrospective study of patients under 18 years old submitted to surgical treatment for pharmacoresistant epilepsy and classified as Engel I during the first year of PO follow-up. Therapeutic management was evaluated through discontinuation or reduction of medications, both in terms of the number of ASM prescribed and in daily maintenance dosages in mg/kg., Results: ASM withdrawal started in the first year PO and occurred in 1.2% of cases, with a significant yearly reduction in the number of ASM during follow-up (p < 0.001). A comparison of the most commonly used ASM in daily mg/kg between the preoperative period (preop) and PO showed a reduction of ASM maintenance dosages during PO. Even though recurrence of seizures was observed 5 years after surgery, 125 patients (85%) were still classified as Engel I, albeit a higher number of ASM per patient was observed. Most patients showed no changes in cognitive and adaptive behavior evaluation between preop and PO, even in those who were able to reduce ASM., Conclusion: Significant reduction observed both in the number and daily maintenance dosages of ASM following each year of PO may be an indirect measure of the effectiveness of epilepsy surgery., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Describe the epidemiological profile and social-economic burden that hydrocephalus patients represent to the national public health system, using data available at the online database of the Brazilian Health Ministry (DataSUS)., Methods: This is a populational study based on descriptive statistics of all clinical and surgical appointments included in the DataSUS database. Data included herein were collected between 2015 and 2021 and subdivided into three main groups, related to hydrocephalus incidence and mortality, hospitalizations, and financial costs., Results: In the study period, 3993 new cases of congenital hydrocephalus were diagnosed, with 6051 deaths overall. The mortality rate in the country was 1.5/100000 live births and the prevalence was 0.374/100000 inhabitants. The number of hospitalizations resulting from treatment procedures and complications of hydrocephalus was 137,880 and there was a reduction of up to 27.2% during the SARS-CoV-2 pandemics concerning previous years. Total costs for hydrocephalus management in the country amounted to 140,610,585.51 dollars., Conclusions: Hydrocephalus has a significant impact on public health budgets and pediatric mortality rates; however, it is probably underestimated, due to the paucity of demographic data and epidemiological studies in Latin America and, specifically, in Brazil. The dataSUS also has several limitations in accessing certain data related to hydrocephalus, making it difficult to have a more assertive understanding of the disease in Brazil. The results of this study provide important guidance for future research projects in clinical and experimental hydrocephalus and also the creation of public policies for better governance and care of hydrocephalus patients., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: People with epilepsy are at an increased risk of experiencing executive dysfunction, particularly those with frontal lobe epilepsy (FLE). The literature has also demonstrated alterations in executive functioning (EF) in patients with temporal lobe epilepsy (TLE). However, few studies have examined the neuropsychological profile of posterior cortex epilepsy (PCE), and little attention has been given to cognitive impairments in the pediatric population with PCE. This study aims to investigate EF performance in children with drug-resistant PCE compared to patients with FLE and TLE., Methods: We analyzed neuropsychological data from 217 patients aged 6-18 years who underwent preoperative evaluation for epilepsy surgery. The EF of patients with PCE was compared to patients with FLE and TLE., Results: There was no significant difference in Full-Scale Intelligence Quotient (FSIQ) means between groups. However, we found a significant effect of brain region on the Coding task, in which patients with PCE and FLE performed worse than those with TLE (p = 0.034). We also observed performance differences between groups on the Stroop test (p = 0.005), with patients with PCE and FLE performing worse than the TLE group., Significance: These findings suggest that children with PCE have alterations in their EF that are similar to the deficits found in FLE compared to patients with TLE. This emphasizes the importance of understanding the neuroanatomy of executive functions and the model of neural networks extending beyond the prefrontal cortex., Competing Interests: Declarations of interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Abstract: A 15-year-old adolescent boy with left body epilepsia partialis continua, hemiparesis, and electroencephalogram abnormalities lateralized to the right hemisphere. MRI finding was small hyperintense signal in the left putamen. 18F-FDG PET showed focal glucose hypermetabolism in the right paracentral lobule and hypometabolism in the inferior right frontal and precentral gyri. One month later, a new MRI showed a hyperintense signal over the paracentral lobule. Biopsy on this region confirmed the diagnosis of Rasmussen encephalitis. This patient finally underwent right hemispherotomy and became seizure free. This case emphasize the PET as an important early tool for the diagnosis of Rasmussen encephalitis., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflicts of interest. The authors gratefully acknowledge financial support from the Center for Interdisciplinary Research on Applied Neurosciences, Provost’s Office for Research, University of São Paulo (grant no. 2011.1.9333.1.3)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The present article describes pathophysiological and clinical aspects of congenital malformations of the cerebral tissue (cortex and white matter) that cause epilepsy and very frequently require surgical treatment. A particular emphasis is given to focal cortical dysplasias, the most common pathology among these epilepsy-related malformations. Specific radiological and surgical features are also highlighted, so a thorough overview of cortical dysplasias is provided., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Hydrocephalus is defined as the accumulation of cerebrospinal fluid in the brain ventricles. The usual treatment of hydrocephalus is surgical (shunt), but not all patients can undergo treatment immediately after diagnosis. Thus, neuroprotective measures were tested to minimize the tissue damage involved. Memantine is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, which has shown a neuroprotective action in neurodegenerative diseases. This study aimed to evaluate the neuroprotective response of memantine in animals treated with or without a ventricular-subcutaneous shunt. Seven-day-old male Wistar rats induced by intracisternal injection of kaolin were used, divided into five groups: intact control (n = 10), hydrocephalic (n = 10), hydrocephalic treated with memantine (20 mg/kg/day) (n = 10), hydrocephalic treated with shunt (n = 10), hydrocephalic treated with shunt and memantine (20 mg/kg/day) (n = 10). Memantine administration was started on the day after hydrocephalus induction and continued until the last day of the experimental period, totaling 21 consecutive days of drug application. The CSF shunt surgery was performed seven days after hydrocephalus induction. Behavioral tests (open field, and modified Morris water maze), histological, and immunohistochemical evaluations were performed. Treatment with memantine resulted in significant improvement (p &lt; 0.05) in sensorimotor development, preservation of spatial memory, reduction of astrocytic reaction in the corpus callosum, cortex, and germinal matrix. When associated with the shunt, it has also been shown to reduce the cell death cascade. It is concluded that memantine is a promising adjuvant drug with beneficial potential for the treatment of lesions secondary to hydrocephalus., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Myelomeningocele (MMC) is the most frequent neural tube defect and is frequently associated (around 80% of cases) with hydrocephalus (HC). Both diseases can have severe clinical consequences, insomuch as they require surgical treatment whose complications are not negligible, either when performed in utero or after birth. Therefore, clinical therapies that could have an impact on the incidence and progression of MMC and HC would be certainly valuable; however, this is not the current picture, and there are no effective pharmacological treatments for such patients to this day., Aim and Methods: Therefore, knowing that an inflammatory process comes associated with these disorders, mostly due to nervous tissue distension, the present article aimed at reviewing the role of corticosteroids in reducing inflammation and thus improving the outcome of patients with HC and MMC, considering the well-established anti-inflammatory effects of CS., Results: The systematic review performed herein has found varying results regarding the role of steroids (even though a positive trend was observed) on the treatment and prevention of hydrocephalus, whereas for MMC., Conclusion: There are many reports demonstrating beneficial effects of CS therapy, from a clinical and histopathological point of view., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Pilocytic astrocytoma is the most frequent pediatric glioma. Despite its overall good prognosis, complete surgical resection is sometimes unfeasible, especially for patients with deep-seated tumors. For these patients, the identification of targetable genetic alterations such as NTRK fusions, raised as a new hope for therapy. The presence of gene fusions involving NTRK2 has been rarely reported in pilocytic astrocytoma. The aim of the present study was to investigate the frequency of NTRK2 alterations in a series of Brazilian pilocytic astrocytomas., Methods: Sixty-nine pilocytic astrocytomas, previously characterized for BRAF and FGFR1 alterations were evaluated. The analysis of NTRK2 alterations was performed using a dual color break apart fluorescence in situ hybridization (FISH) assay., Results: NTRK2 fusions were successfully evaluated by FISH in 62 of the 69 cases. Neither evidence of NTRK2 gene rearrangements nor NTRK2 copy number alterations were found., Conclusions: NTRK2 alterations are uncommon genetic events in pilocytic astrocytomas, regardless of patients' clinicopathological and molecular features., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: To evaluate how telomere length behaves in adamantinomtous craniopharyngioma (aCP) and if it contributes to the pathogenesis of aCPs with and without CTNNB1 mutations., Design: Retrospective cross-sectional study enrolling 42 aCP patients from 2 tertiary institutions., Methods: Clinicopathological features were retrieved from the patient's charts. Fresh frozen tumors were used for RNA and DNA analyses. Telomere length was evaluated by qPCR (T/S ratio). Somatic mutations in TERT promoter (TERTp) and CTNNB1 were detected by Sanger and/or whole-exome sequencing. We performed RNA-Seq to identify differentially expressed genes in aCPs presenting with shorter or longer telomere lengths., Results: Mutations in CTNNB1 were detected in 29 (69%) tumors. There was higher frequency of CTNNB1 mutations in aCPs from patients diagnosed under the age of 15 years (85% vs 15%; P = 0.04) and a trend to recurrent disease (76% vs 24%; P = 0.1). No mutation was detected in the TERTp region. The telomeres were shorter in CTNNB1-mutated aCPs (0.441, IQR: 0.297-0.597vs 0.607, IQR: 0.445-0.778; P = 0.04), but it was neither associated with clinicopathological features nor with recurrence. RNAseq identified a total of 387 differentially expressed genes, generating two clusters, being one enriched for short telomeres and CTNNB1-mutated aCPs., Conclusions: Ctnnb1: mutations are more frequent in children and adolescents and appear to associate with progressive disease. CTNNB1-mutated aCPs have shorter telomeres, demonstrating a relationship between the Wnt/β-catenin pathway and telomere biology in the pathogenesis of aCPs.

Hydrocephalus is characterized by the accumulation of CSF within the cerebral ventricles and the subarachnoid space. Ventricular volume can progressively increase and generate serious damage to the nervous system, with cerebral hypoxia/ischemia as one of the most important factors involved. Hyperbaric oxygen therapy (HBOT) improves oxygen supply to tissues, which can reduce the progression of lesions secondary to ventricular enlargement. We evaluated whether HBOT associated with CSF diversion can promote neuroprotective effects to structures damaged by ventriculomegaly and understand its role. Seven-day-old male Wistar Hannover rats submitted to hydrocephalus by intracisternal injection of 15% kaolin were used. The animals were divided into six groups, with ten animals in each: control, control associated with hyperbaric therapy, hydrocephalic without treatment, hydrocephalic treated with hyperbaric oxygen therapy, hydrocephalic treated with CSF deviation, and hydrocephalic treated with hyperbaric oxygen therapy associated with CSF deviation. To assess the response to treatment, behavioral tests were performed such as modified Morris water maze and object recognition, evaluation by transcranial ultrasonography, histology by Hematoxylin-Eosin and Luxol Fast Blue, immunohistochemistry for GFAP, Ki-67, Caspase-3, COX-2, NeuN and SOD1, and biochemical ELISA assay for GFAP and MBP. The results show that the association of treatments exerts neuroprotective effects such as neurobehavioral improvement, preservation of periventricular structures, antioxidant effect, and reduction of damage resulting from ischemia and the neuroinflammatory process. We conclude that HBOT has the potential to be used as an adjuvant treatment to CSF deviation surgery in experimental hydrocephalus., (Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.)

The neuroprotective effect of Edaravone in young hydrocephalic rats associated with a CSF derivation system was evaluated. The drug has already been shown to be beneficial in experimental hydrocephalus, but the combination of this drug with shunt surgery has not yet been investigated. Fifty-seven-day-old Wistar rats submitted to hydrocephalus by injection of kaolin in the cisterna magna were used and divided into five groups: control (n = 10), hydrocephalic (n = 10), hydrocephalic treated with Edaravone (20 mg/kg/day) (n = 10), hydrocephalic treated with shunt (n = 10) and hydrocephalic treated with shunt and Edaravone (n = 10). Administration of the Edaravone was started 24 h after hydrocephalus induction (P1) and continued until the experimental endpoint (P21). The CSF shunt surgery was performed seven days after hydrocephalus induction (P7). Open-field tests, histological evaluation by hematoxylin and eosin, immunohistochemistry by Caspase-3 and GFAP, and ELISA biochemistry by GFAP were performed. Edaravone reduced reactive astrogliosis in the corpus callosum and germinal matrix (p < 0.05). When used alone or associated with CSF shunt surgery, the drug decreased the cell death process (p < 0.0001) and improved the morphological aspect of the astroglia (p < 0.05). The results showed that Edaravone associated with CSF bypass surgery promotes neuroprotection in young hydrocephalic rats by reducing reactive astrogliosis and decreasing cell death., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Cognitive functioning in epileptic syndromes has been widely explored in patients with temporal lobe epilepsy (TLE), but few studies have investigated the neuropsychological profile in posterior cortex epilepsy (PCE). In this study, we investigated the presurgical intellectual profile of children and adolescents with drug-resistant PCE., Methods: Children and adolescents diagnosed with PCE (n = 25) participated in this study. The data were obtained from medical records, with assessments carried out between the years 2003 and 2019. To compare the intellectual profile, we also included patients diagnosed with frontal (n = 26) and temporal lobe epilepsy (n = 40). The Wechsler Intelligence Scales were used for the assessment of general intelligence., Results: There was an effect of the brain region on the Working Memory Index (p < 0.01), in which patients with TLE had significantly higher scores than groups with FLE (p < 0.01) and PCE (p < 0.05). We also demonstrated that patients with PCE tended to perform worse in the Processing Speed Index than patients with TLE (p = 0.055). The Full-Scale Intelligence Quotient, Verbal Comprehension, and Perceptual Reasoning indexes did not differ among the brain regions., Conclusions: Children and adolescents with PCE demonstrated significant impairment in working memory and processing speed. The pattern of cognitive dysfunction in PCE was similar to that observed in FLE, which expands the evidence of the involvement of frontoparietal networks on cognitive proficiency., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Motor cortex stimulation (MCS) is proper as a non-pharmacological therapy for patients with chronic and neuropathic pain (NP)., Aims: This work aims to investigate if the MCS in the primary motor cortex (M 1 ) produces analgesia and how the MCS could interfere in the MCS-induced analgesia. Also, to elucidate if the persistent activation of N-methyl-d-aspartic acid receptor (NMDAr) in the periaqueductal grey matter (PAG) can contribute to central sensitisation of the NP., Methods: Male Wistar rats were submitted to the von Frey test to evaluate the mechanical allodynia after 21 days of chronic constriction injury (CCI) of the sciatic nerve. The MCS was performed with low-frequency (20 μA, 100 Hz) currents during 15 s by a deep brain stimulation (DBS) device. Moreover, the effect of M 1 -treatment with an NMDAr agonist (at 2, 4, and 8 nmol) was investigated in CCI rats. The PAG dorsomedial column (dmPAG) was pretreated with the NMDAr antagonist LY 235959 (at 8 nmol), followed by MCS., Results: The MCS decreased the mechanical allodynia in rats with chronic NP. The M 1 -treatment with an NMDA agonist at 2 and 8 nmol reduced the mechanical allodynia in CCI rats. In addition, dmPAG-pretreatment with LY 235959 at 8 nmol attenuated the mechanical allodynia evoked by MCS., Conclusion: The M 1 cortex glutamatergic system is involved in the modulation of chronic NP. The analgesic effect of MCS may depend on glutamate signaling recruitting NMDAr located on PAG neurons in rodents with chronic NP., (Copyright © 2021. Published by Elsevier B.V.)

Myelomeningocele (MMC), the commonest type of spina bifida (SB), occurs due to abnormal development of the neural tube and manifest as failure of the complete fusion of posterior arches of the spinal column, leading to dysplastic growth of the spinal cord and meninges. It is associated with several degrees of motor and sensory deficits below the level of the lesion, as well as skeletal deformities, bladder and bowel incontinence, and sexual dysfunction. These children might develop varying degrees of neuropsychomotor delay, partly due to the severity of the injuries that affect the nervous system before birth, partly due to the related cerebral malformations (notably hydrocephalus-which may also lead to an increase in intracranial pressure-and Chiari II deformity). Traditionally, MMC was repaired surgically just after birth; however, intrauterine correction of MMC has been shown to have several potential benefits, including better sensorimotor outcomes (since exposure to amniotic fluid and its consequent deleterious effects is shortened) and reduced rates of hydrocephalus, among others. Fetal surgery for myelomeningocele, nevertheless, would not have been made possible without the development of experimental models of this pathological condition. Hence, the aim of the current article is to provide an overview of the animal models of MMC that were used over the years and describe how this knowledge has been translated into the fetal treatment of MMC in humans., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on "ultra-early" epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months., Methods: To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications., Results: Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19-104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1-3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections)., Significance: Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age., (© 2021 International League Against Epilepsy.)

Background: Meningiomas are the most frequent primary central nervous system (CNS) tumors. Their geographical and ethnic characteristics need to be known, in order to enable rational treatment., Objective: To investigate clinical and epidemiological aspects in a series of patients with meningiomas., Methods: Retrospective analysis on the demographic profile, location and histopathology of 993 patients with meningiomas (768 operated and 225 not operated)., Results: Meningiomas represented 43.8% of the primary CNS tumors; 6.8% were multiple tumors (14.7% with neurofibromatosis 2) and 0.6% were radiation-induced tumors. The mean ages were 53.0 and 63.9 years for operated and non-operated patients and the female/male ratios were 3.2:1 and 6.3:1. Diagnosis was made later among females. The peak incidences were in the 6th and 7th decades respectively for operated and non-operated patients. The incidence was low at early ages and higher among patients aged 70+ years. The meningiomas were intracranial in 96.5% and most were WHO grade I (88.9%) and transitional. In the spinal canal (3.5%), they occurred mainly in the dorsal region (all grade I; mostly transitional). The racial distribution was 1.0% in Asian-Brazilians, 87% in Caucasians and 12% in African-Brazilians. 83.4% and 51.6% of the patients were estimated to be recurrence-free at 10 and 20 years, and the mortality rate was 3%., Conclusions: Most of the demographic data were similar to what has been observed in other western centers. Differences were higher incidence of meningiomas, female and older predominance in non-operated patients, predominance in Caucasian, and higher association with neurofibromatosis 2.

Purposes: Demonstrate that transcranial ultrasonography (TUS) scanning is viable and useful as a diagnostic method in experimental hydrocephalus, as well as to compare measurements of cerebral and ventricular width obtained from TUS scans of hydrocephalic rats with post-mortem anatomical specimens, aiming for the development of accurate criteria to establish ventricular enlargement and progression of hydrocephalus subsequently., Methods: Thirty-five male Wistar rats were used. Following hydrocephalus induction, they underwent a transcranial ultrasound scan to measure cerebral and ventricular dimensions, in the fourth and 21 post-induction days. By the end of the experiments, measurements obtained from TUS scans were compared with actual values as seen in the post-mortem specimens of each animal., Results: Ventricular dilation could be clearly visualized in hydrocephalic animals. We performed intraclass correlation coefficient and linear regression analyses that have demonstrated a precise correlation between measurements of TUS scans and post-mortem specimens; we have found a similarity of 0,95 for the cerebral diameter and 0,97 for ventricular width., Conclusions: Transcranial ultrasonography is a useful and reliable diagnostic tool for experimental hydrocephalus; also, it can be used to assess the progression of ventriculomegaly in animal models of hydrocephalus.

Background: Chronic constriction injury (CCI) is a model of neuropathic pain induced by four loose ligatures around the sciatic nerve. This work aimed to investigate the sensory, affective, cognitive, and motor changes induced by an adaptation of the CCI model by applying a single ligature around the sciatic nerve., Methods: Mechanical allodynia was measured from day 1 to day 28 postsurgery by the von Frey test. The beam walking test (BWT) was conducted weekly until 28 days after surgery. Anxiety- and depression-like behaviors, and cognitive performance were assessed through the open field (OF), forced swimming (FS), and novel object recognition (NOR) tests, respectively, 21 days after surgery., Results: The two CCI models, both Bennett and Xie's model (four ligatures of the sciatic nerve) and a modification of it (one ligature), induced mechanical allodynia, increased immobility in the FS, and reduced recognition index in the NOR. The exploratory behavior and time spent in the central part of the arena decreased, while the defensive behavior increased in the OF. The animals subjected to the two CCI models showed motor alterations in the BWT; however, autotomy was observed only in the group with four ligatures and not in the group with a single ligature., Conclusions: Overall these results demonstrate that our adapted CCI model, using a single ligature around the sciatic nerve, induces sensory, affective, cognitive, and motor alterations comparable to the CCI model with four ligatures without generating autotomy. This adaptation to the CCI model may therefore represent an appropriate and more easily performed model for inducing neuropathic pain and study underlying mechanisms and effective treatments., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

Background: Selective dorsal rhizotomy (SDR) is one of the surgical alternatives for treating spasticity, especially in children with spastic diplegia secondary to cerebral palsy (CP). It is becoming increasingly used, and the results of this operation need to be further highlighted., Aim: The main objective of this article was to present the results of such surgical procedure in a cohort of a specialized center, with a particular focus on a quantitative analysis (goniometry)., Materials and Methods: Retrospective review of the medical records and gait analyses of a cohort of 34 patients diagnosed with CP submitted to elective SDR at our institution, in a period of 6 years, was carried out. All patients underwent a thorough clinical and neurological assessment, gait analysis at a dedicated laboratory, and magnetic resonance imaging of whole neuro-axis., Statistical Analysis: For continuous quantitative variables (goniometric angles and muscle tone), a t -student test was used. A scatterplot regression analysis was used for the comparison of modified Ashworth scale (mAS) scores and goniometry measurements., Results and Conclusion: In a mean follow-up of 3.2 years, SDR provides a measurable and consistent improvement in the motor function of spastic patients, as per range of motion and tonus scales, with low complication rates. It also allows for patients to reduce their use of muscle relaxants, even though their global mobility does not change significantly. Therefore, it should be considered for CP patients who suffer with the deleterious effects of spasticity., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Pediatric Neurosciences.)

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.

Objective: Drebrins are crucial for synaptic function and dendritic spine development, remodeling, and maintenance. In temporal lobe epilepsy (TLE) patients, a significant hippocampal synaptic reorganization occurs, and synaptic reorganization has been associated with hippocampal hyperexcitability. This study aimed to evaluate, in TLE patients, the hippocampal expression of drebrin using immunohistochemistry with DAS2 or M2F6 antibodies that recognize adult (drebrin A) or adult and embryonic (pan-drebrin) isoforms, respectively., Methods: Hippocampal sections from drug-resistant TLE patients with hippocampal sclerosis (HS; TLE, n = 33), of whom 31 presented with type 1 HS and two with type 2 HS, and autopsy control cases (n = 20) were assayed by immunohistochemistry and evaluated for neuron density, and drebrin A and pan-drebrin expression. Double-labeling immunofluorescences were performed to localize drebrin A-positive spines in dendrites (MAP2), and to evaluate whether drebrin colocalizes with inhibitory (GAD65) and excitatory (VGlut1) presynaptic markers., Results: Compared to controls, TLE patients had increased pan-drebrin in all hippocampal subfields and increased drebrin A-immunopositive area in all hippocampal subfields but CA1. Drebrin-positive spine density followed the same pattern as total drebrin quantification. Confocal microscopy indicated juxtaposition of drebrin-positive spines with VGlut1-positive puncta, but not with GAD65-positive puncta. Drebrin expression in the dentate gyrus of TLE cases was associated negatively with seizure frequency and positively with verbal memory. TLE patients with lower drebrin-immunopositive area in inner molecular layer (IML) than in outer molecular layer (OML) had a lower seizure frequency than those with higher or comparable drebrin-immunopositive area in IML compared with OML., Significance: Our results suggest that changes in drebrin-positive spines and drebrin expression in the dentate gyrus of TLE patients are associated with lower seizure frequency, more preserved verbal memory, and a better postsurgical outcome., (© 2020 International League Against Epilepsy.)