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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]

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.)

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).)

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.)

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.)

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: 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.

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.)

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.)

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.)

Objective: The goal of this study was to perform an analysis of a single-center experience with hemispherotomy reoperations for refractory hemispheric pediatric epilepsy due to persistence of seizures after initial surgery. The authors also identify possible anatomical and neurophysiological reasons for hemispherotomy failure, as well as risk factors and surgical options for this subgroup of patients., Methods: A review was performed of the medical records in 18 consecutive cases in which candidates for redo hemispherotomy were treated between 2003 and 2018 at the authors' epilepsy surgery center. Fourteen patients underwent reoperation due to seizure recurrence and were studied herein, whereas in 3 the initial surgical procedure was stopped because of uncontrollable bleeding, and the remaining patient refused to undergo a reoperation in spite of seizure recurrence and went on to have a vagus nerve stimulation device placed., Results: Among the 14 patients whose seizures recurred and in whom reoperations were done, the etiology of epilepsy consisted of 7 cases with malformations of cortical development (50%), 5 cases of Rasmussen encephalitis (35.8%), 1 case of porencephaly (7.1%), and 1 case of Sturge-Weber syndrome (7.1%). Eleven patients had radiological evidence of incomplete disconnection. After reoperation, 6 patients were Engel class IA, 1 was Engel II, 5 were Engel III, and 2 were Engel IV, within a mean follow-up of 48.4 months., Conclusions: Patients with malformations of cortical development have a higher risk of seizure recurrence, and these malformations comprised the main etiology in the reoperation series. Failure of an initial hemispherotomy usually occurs due to incomplete disconnection and needs to be extensively assessed. Outcomes of reoperation are most often favorable, with acceptable complication rates.

Objectives: Recently, defects in the protein kinase mTOR (mammalian target of rapamycin) and its associated pathway have been correlated with hemimegalencephaly (HME). mTOR acts as a central regulator of important physiological cellular functions such as growth and proliferation, metabolism, autophagy, death, and survival. This study was aimed at identifying specific variants in mTOR signaling pathway genes in patients diagnosed with HME., Methods: Using amplicon and whole exome sequencing (WES) of resected brain and paired blood samples from five HME patients, we were able to identify pathogenic mosaic variants in the mTOR pathway genes MTOR , PIK3CA , and DEPDC5 ., Results: These results strengthen the hypothesis that somatic variants in PI3K-Akt-mTOR pathway genes contribute to HME. We also describe one patient presenting with a pathogenic variant on DEPDC5 gene, which reinforces the role of DEPDC5 on cortical structural changes due to mTORC1 hyperactivation. These findings also provide insights into when in brain development these variants occurred. An early developmental variant is expected to affect a larger number of cells and to result in a larger malformation, whereas the same variant occurring later in development would cause a minor malformation., Significance: In the future, numerous somatic variants in known or new genes will undoubtedly be revealed in resected brain samples, making it possible to draw correlations between genotypes and phenotypes and allow for a genetic clinical diagnosis that may help to predict a given patient's outcome., Competing Interests: We thank the support provided by the Research Support Foundation (FAEPA) of the University Hospital of Ribeirão Preto Medical School and the Center of Genomic Medicine, University Hospital, Ribeirão Preto Medical School (CMG/HCFMRP) for patient recruitment and sample preparation. This work was supported by grants from the Howard Hughes Medical Institute (to JGG), and Camila B. Garcia was recipient of a scholarship from the National Support Program for the Health Care of Persons with Disabilities (PRONAS/PCD) and Coordination of Improvement of Higher Education Personnel‐Brazil (CAPES). The authors confirm that they have read the journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (© 2020 The Authors. Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy.)

Objective: Chronic constriction injury (CCI) of the sciatic nerve is a peripheral nerve injury widely used to induce mononeuropathy. This study used machine learning methods to identify the best gait analysis parameters for evaluating peripheral nerve injuries., Methods: Twenty-eight male Wistar rats (weighing 270±10 g), were used in the present study and divided into the following 4 groups: CCI with 4 ligatures around the sciatic nerve (CCI-4L; n=7), a modified CCI model with 1 ligature (CCI-1L; n=7), a sham group (n=7), and a healthy control group (n=7). All rats underwent gait analysis 7 and 28 days postinjury. The data were evaluated using Kinovea and WeKa software (machine learning and neural networks)., Results: In the machine learning analysis of the experimental groups, the pre-swing (PS) angle showed the highest ranking in all 3 analyses (sensitivity, specificity, and area under the receiver operating characteristics curve using the Naive Bayes, k-nearest neighbors, radial basis function classifiers). Initial contact (IC), step length, and stride length also performed well. Between 7 and 28 days after injury, there was an increase in the total course time, step length, stride length, stride speed, and IC, and a reduction in PS and IC-PS. Statistically significant differences were found between the control group and experimental groups for all parameters except speed. Interactions between time after injury and nerve injury type were only observed for IC, PS, and IC-PS., Conclusion: PS angle of the ankle was the best gait parameter for differentiating nonlesions from nerve injuries and different levels of injury.

Background: Training in medical education depends on the availability of standardized materials that can reliably mimic the human anatomy and physiology. One alternative to using cadavers or animal bodies is to employ phantoms or mimicking devices. Styrene-ethylene/butylene-styrene (SEBS) gels are biologically inert and present tunable properties, including mechanical properties that resemble the soft tissue. Therefore, SEBS is an alternative to develop a patient-specific phantom, that provides real visual and morphological experience during simulation-based neurosurgical training., Results: A 3D model was reconstructed and printed based on patient-specific magnetic resonance images. The fused deposition of polyactic acid (PLA) filament and selective laser sintering of polyamid were used for 3D printing. Silicone and SEBS materials were employed to mimic soft tissues. A neuronavigation protocol was performed on the 3D-printed models scaled to three different sizes, 100%, 50%, and 25% of the original dimensions. A neurosurgery team (17 individuals) evaluated the phantom realism as "very good" and "perfect" in 49% and 31% of the cases, respectively, and rated phantom utility as "very good" and "perfect" in 61% and 32% of the cases, respectively. Models in original size (100%) and scaled to 50% provided a quantitative and realistic visual analysis of the patient's cortical anatomy without distortion. However, reduction to one quarter of the original size (25%) hindered visualization of surface details and identification of anatomical landmarks., Conclusions: A patient-specific phantom was developed with anatomically and spatially accurate shapes, that can be used as an alternative for surgical planning. Printed models scaled to sizes that avoided quality loss might save time and reduce medical training costs., Competing Interests: Not applicableFWG is shareholder of Gphantom. All the others disclose no conflict of interest.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Surgical treatment of epilepsy in children often involves brain areas outside the temporal lobe and, therefore, techniques for extratemporal surgery must be included in the armamentarium of epilepsy surgery centers. Nowadays, disconnective procedures are preferable to traditional resective operations because they reduce the rate of complications related to extensive resections while achieving equivalent seizure outcomes. This article describes the practical anatomy and surgical techniques used for temporoparietooccipital (TPO), parietooccipital, and frontal disconnections, as well as the possibility of extending previous lobar disconnections to the whole hemisphere (hemispherotomy)., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Purpose: To evaluate the efficacy of surgery with neuronavigation compared to conventional neurosurgical treatment of epilepsy in terms of safety and seizure outcomes and to assess the quality of the evidence base of neuronavigation in this clinical context., Method: Systematic review using the electronic databases of Cochrane, CRD, PubMed, Embase, SciELO and LILACS in Portuguese, English and Spanish. The [MeSH] terms included "epilepsy" and "neuronavigation"., Eligibility Criteria: Studies assessing surgery with neuronavigation for the surgical treatment of epilepsy or brain injuries associated with epileptic seizures., Results: We identified 28 original articles. All articles yielded scientific evidence of low quality. Outcome data presented in the articles identified was heterogeneous and did not amount to compelling evidence that epilepsy surgery with neuronavigation produces higher rates of seizure control, a reduced need for reoperations, or lower rates of complications or postoperative neurological deficits., Conclusion: We were unable to find any publications providing convincing evidence that neuronavigation improves outcomes of epilepsy surgery. Whilst this does not mean that neuronavigation cannot improve neurosurgical outcomes in this clinical setting, well-designed research studies evaluating the role of neuronavigation are urgently needed., (Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Glioblastoma (GBM) is one of the most aggressive central nervous system tumors with a patient's median survival of <1 year. Polo-like kinases (PLKs) are a family of serine/threonine kinases that have key roles in cell cycle control and DNA-damage response. We evaluated PLK1, 2, 3 and 4 gene expression in 8 GBM cell lines and 17 tumor samples, and analyzed the effect of the PLK1 inhibition on SF188 and T98G GBM cell lines and 13 primary cultures. Our data showed PLK1 overexpression and a variable altered expression of PLK2, 3 and 4 genes in GBM tumor samples and cell lines. Treatments with nanomolar concentrations of BI 2536, BI 6727, GW843682X or GSK461364 caused a significant decrease in GBM cells proliferation. Colony formation was also found to be inhibited (P<0.05), whereas apoptosis rate and mitotic index were significantly increased (P<0.05) after PLK1 inhibition in both GBM cell lines. Cell cycle analysis showed an arrest at G2 (P<0.05) and cell invasion was also decreased after PLK1 inhibition. Furthermore, simultaneous combinations of BI 2536 and temozolomide produced synergistic effects for both the cell lines after 48 h of treatment. Our findings suggest that PLK1 might be a promising target for the treatment of GBMs.

Introduction: Canonical and non-canonical Wnt pathways are involved in the genesis of multiple tumors; however, their role in pituitary tumorigenesis is mostly unknown., Objective: This study evaluated gene and protein expression of Wnt pathways in pituitary tumors and whether these expression correlate to clinical outcome., Materials and Methods: Genes of the WNT canonical pathway: activating ligands (WNT11, WNT4, WNT5A), binding inhibitors (DKK3, sFRP1), β-catenin (CTNNB1), β-catenin degradation complex (APC, AXIN1, GSK3β), inhibitor of β-catenin degradation complex (AKT1), sequester of β-catenin (CDH1), pathway effectors (TCF7, MAPK8, NFAT5), pathway mediators (DVL-1, DVL-2, DVL-3, PRICKLE, VANGL1), target genes (MYB, MYC, WISP2, SPRY1, TP53, CCND1); calcium dependent pathway (PLCB1, CAMK2A, PRKCA, CHP); and planar cell polarity pathway (PTK7, DAAM1, RHOA) were evaluated by QPCR, in 19 GH-, 18 ACTH-secreting, 21 non-secreting (NS) pituitary tumors, and 5 normal pituitaries. Also, the main effectors of canonical (β-catenin), planar cell polarity (JNK), and calcium dependent (NFAT5) Wnt pathways were evaluated by immunohistochemistry., Results: There are no differences in gene expression of canonical and non-canonical Wnt pathways between all studied subtypes of pituitary tumors and normal pituitaries, except for WISP2, which was over-expressed in ACTH-secreting tumors compared to normal pituitaries (4.8x; p = 0.02), NS pituitary tumors (7.7x; p = 0.004) and GH-secreting tumors (5.0x; p = 0.05). β-catenin, NFAT5 and JNK proteins showed no expression in normal pituitaries and in any of the pituitary tumor subtypes. Furthermore, no association of the studied gene or protein expression was observed with tumor size, recurrence, and progressive disease. The hierarchical clustering showed a regular pattern of genes of the canonical and non-canonical Wnt pathways randomly distributed throughout the dendrogram., Conclusions: Our data reinforce previous reports suggesting no activation of canonical Wnt pathway in pituitary tumorigenesis. Moreover, we describe, for the first time, evidence that non-canonical Wnt pathways are also not mis-expressed in the pituitary tumors.

Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98 th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.

It is clear that sudden unexpected death in epilepsy (SUDEP) is mainly a problem for people with refractory epilepsy, but our understanding of the best way to its prevention is still incomplete. Although the pharmacological treatments available for epilepsies have expanded, some antiepileptic drugs are still limited in clinical efficacy. In the present paper, we described an experience with vagus nerve stimulation (VNS) treatment by opening space and providing the opportunity to implement effective preventative maps to reduce the incidence of SUDEP in children and adolescents with refractory epilepsy.

Purpose: To investigate the accuracy of 1.0T Magnetic Resonance Imaging (MRI) to measure the ventricular size in experimental hydrocephalus in pup rats., Methods: Wistar rats were subjected to hydrocephalus by intracisternal injection of 20% kaolin (n=13). Ten rats remained uninjected to be used as controls. At the endpoint of experiment animals were submitted to MRI of brain and killed. The ventricular size was assessed using three measures: ventricular ratio (VR), the cortical thickness (Cx) and the ventricles area (VA), performed on photographs of anatomical sections and MRI., Results: The images obtained through MR present enough quality to show the lateral ventricular cavities but not to demonstrate the difference between the cortex and the white matter, as well as the details of the deep structures of the brain. There were no statistically differences between the measures on anatomical sections and MRI of VR and Cx (p=0.9946 and p=0.5992, respectively). There was difference between VA measured on anatomical sections and MRI (p<0.0001)., Conclusion: The parameters obtained through 1.0T MRI were sufficient in quality to individualize the ventricular cavities and the cerebral cortex, and to calculate the ventricular ratio in hydrocephalus rats when compared to their respective anatomic slice.

Purpose: To assess the relationship between the presence of pets in homes of epilepsy patients and the occurrence of sudden unexpected death in epilepsy (SUDEP)., Methods: Parents or relatives of SUDEP patients collected over a ten-year period (2000-2009) in a large epilepsy unit were asked if the patient lived together with any domestic pet at the time of death or not. Patients who did not experience SUDEP served as controls., Results and Conclusions: Eleven out of the 1092 included patients (1%) experienced SUDEP, all with refractory symptomatic epilepsy, but none of them had pets in their homes at the time of death. In contrast, the frequency of pet-ownership in the control group (n=1081) was 61%. According to previous studies there are some indications that human health is directly related to companionship with animals in a way that domestic animals prevent illness and facilitate recovery of patients. Companion animals can buffer reactivity against acute stress, diminish stress perception and improve physical health. These factors may reduce cardiac arrhythmias and seizure frequency, factors related to SUDEP. Companion animals may have a positive effect on well-being, thus improving epilepsy outcome., (Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Epilepsy is the main neurological condition in children and adolescents. Unfortunately patients with medical refractory epilepsy are more susceptible for clinical complications and death. We report a prospectively evaluated cohort of children followed for approximately 10 years. Fifty-three of 1012 patients died. Forty-two patients died due to epilepsy or its clinical complications and the main causes of death were pneumonia (in 16 cases), sepsis (in 9 patients), status epilepticus (in 8 patients). In 11 patients cause of death was sudden unexpected death in epilepsy (SUDEP). Mental retardation was significantly more frequent in patients who did not die from SUDEP. SUDEP may be a significant condition associated with mortality in children and adolescents with epilepsy.

Background: A growing body of evidence has revealed the involvement of epigenetic alterations in the etiology of astrocytomas. In the present study, we aimed to evaluate the association of DNA methylation of histone deacetylase genes (HDAC) with the etiology of astrocytoma, and the implications for epigenetic therapy., Materials and Methods: Methylation of the HDAC4, HDAC5 and HDAC6 genes was assessed in 29 tumor samples (astrocytomas grades I, III, and IV) and in the glioblastoma cell lines U87, U251, U343, SF188, and T98G by methylation-specific quantitative PCR (MSED-qPCR)., Results: Significantly increased methylation of the HDAC5 gene was observed in astrocytomas when compared to non-neoplastic brain samples (p=0.0007) and to glioblastomas cell lines (p=0.001). A heterogenic methylation pattern was evidenced when compared to the glioblastoma cell lines. Distinct effects on methylation and gene expression were observed after in vitro treatment of the different cell lines with decitabine., Conclusion: Our results suggest that abnormal methylation of HDAC genes is involved in the etiology of astrocytomas and indicate that loci-specific epigenetic interindividualities might be associated to the differential responses to treatment with decitabine.

The incidence of sudden unexpected death in epilepsy (SUDEP) has been estimated from 0.5-1.4/1,000 person-years in people with treated epilepsy, and 9/1,000 person-years in candidates for epilepsy surgery. Potential risk factors for SUDEP include: age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure type and winter temperatures. The arrythmogenic side-effect of antiepileptic drugs and seizures may increase the risk of SUDEP. In this report, we describe a patient with prolonged post-ictal tachycardia in EEG video recordings with a typical case of SUDEP: a 16-year-old boy with medically intractable complex partial seizures. Magnetic resonance imaging revealed left mesial temporal sclerosis. During non-invasive video-EEG monitoring, the patient presented a post-ictal heart rate increased for five hours. Two months after video-EEG, he died from SUDEP during a tonic-clonic secondary generalized seizure. The possibility of cardiac involvement in the pathogenesis of SUDEP has been suggested by many studies. Evaluation of this patient with EEG-video monitoring, including measurement of heart rate, contributed to an identification of ictal tachycardia that may have played a role in the SUDEP. Premature mortality seems to be increased in patients with epilepsy, and cardiac abnormalities may be a possible cause of SUDEP.

Febrile seizures (FS) affect almost 2-5% of children and factors related to an increase susceptibility of children to FS may involve an imbalance of inflammatory cytokines and genetic factors. FS had low morbidity, but may be associated with the occurrence of late chronic epilepsy. Here we describe factors related to FS and its possible correlation with SUDEP.

Individuals with epilepsy are at higher risk of sudden unexpected death in epilepsy (SUDEP), responsible for 7.5% to 17% of all deaths in epilepsy. Many factors are current associated with SUDEP and possible effect of stress and cardiac arrhythmia are still not clear. Sudden death syndrome (SDS) in chickens is a disease characterized by an acute death of well-nourished and seeming healthy Gallus gallus after abrupt and brief flapping of their wings, similar to an epileptic seizure, with an incidence estimated as 0.5 to 5% in broiler chickens. A variety of nutritional and environmental factors have been included: but the exactly etiology of SDS is unknown. Studies had suggested that the hearts of broiler chickens are considerably more susceptible to arrhythmias and stress may induce ventricular arrhythmia and thus, sudden cardiac death. In this way, SDS in Gallus gallus could be an interesting model to study SUDEP.

Objective: To compare the intellectual coefficient (IQ) of three groups of children with epilepsy: 1) medically controlled, 2) medically uncontrolled and 3) surgically controlled., Methods: From December 2007 until July 2008, 98 pediatric patients were selected, with an age range between 6 and 12 years. Neuropsychological assessment included the Wechsler Intelligence Scale for Children-third edition (WISC-III). Results are related to epileptic syndrome, etiology of epilepsy, drug therapy, age at epilepsy onset and epilepsy duration., Results: WISC scores were significantly better in the medically controlled group when compared to the medically uncontrolled group. The medically controlled group performed significantly better in the majority of the WISC subtests when compared to the medically uncontrolled group: vocabulary, arithmetic, comprehension, digit span, picture completion, picture arrangement, and block design. A significantly higher number of idiopathic epilepsy and monotherapy cases was observed in the medically controlled group when compared to the medically uncontrolled group. Surgically controlled children had no significant differences in IQ performance when compared to medically controlled children., Conclusions: Children with good seizure control have higher general, verbal and performed intelligence when compared to children with refractory epilepsy. These results may be influenced by clinical factors such as use of monotherapy, drug type and epileptic syndrome and etiology. Epilepsy surgery can have a positive impact on cognitive performance of children who were free of seizures after surgery.

Genes involved in formation/development of the adenohypophysis, CTNNB1 gene, and microRNAs might be implicated in the craniopharyngioma pathogenesis. The objective of this study is to perform the molecular analysis of HESX1, PROP1, POU1F1, and CTNNB1 genes and evaluate a panel of miRNA expression in craniopharyngioma. We also verified whether the presence of CTNNB1 mutation is associated with clinical findings and miRNA expression. The study included 16 patients with adamantinomatous craniopharyngioma (nine children and seven adults; eight females and eight males; 6-55 years, median 15.5 years). DNA, RNA, and cDNA were obtained from craniopharyngioma and normal pituitaries. DNA was also extracted from peripheral blood of healthy subjects. All genes were amplified by polymerase chain reaction and direct sequenced. Relative quantification of miRNA expression was calculated using the 2(-ΔΔCt) method. We found no mutations in HESX1, PROP1, and POU1F1 genes and four polymorphisms in PROP1 gene which were in Hardy-Weinberg equilibrium and had similar allelic frequencies in craniopharyngioma and controls. We found seven different mutations in CTNNB1 in eight of 16 patients. Younger patients presented more frequently CTNNB1 mutation than adults. We observed hyperexpression of miR-150 (1.7-fold); no different expression of miR-16-1, miR-21, and miR23a; and an underexpression of miR-141, let-7a, miR-16, miR-449, miR-145, miR-143, miR-23b, miR-15a, and miR-24-2 (ranging from -7.5 to -2.5-fold; p = 0.02) in craniopharyngioma. There was no association between tumor size or the recurrence and the presence of CTNNB1mutations. miR-16 and miR-141 were underexpressed in craniopharyngioma presenting CTNNB1 mutations. miR-23a and miR24-2 were hyperexpressed in patients who underwent only one surgery. Mutations or polymorphisms in pituitary transcription factors are unlikely to contribute to the adamantinomatous craniopharyngioma pathogenesis, differently of CTNNB1 mutations. Our data suggest the potential involvement of the deregulation of miRNA expression in the craniopharyngioma pathogenesis and outcome and also that the miRNA could modulate the Wnt signaling pathway in craniopharyngioma tumorigenesis.

Using the pilocarpine model of epilepsy, we investigated the effects of alcohol consumption on the frequency of seizures in animals with epilepsy as well the underlying a possible association between alcohol intake and sudden unexpected death in epilepsy (SUDEP) occurrence. Rats were divided randomly into two groups: (A) rats with epilepsy and (B) rats with epilepsy that received a daily dose of ethanol solution (350 mg kg(-1), i.p.) for 30 days. The basal frequency of seizures observed in the A and B groups during the first 30 days were 3.4+/-1.5 and 3.2+/-1.9 seizures per week per animal, respectively. In B group, it was observed a significant seizure increase (11.6+/-5.3) during the first 2 weeks of alcohol administration and quite interesting, one rat died suddenly after a generalized tonic-clonic seizure during this period. We concluded in our experimental study that exist a possible association between alcohol abuse and SUDEP occurrence.

Unlabelled: People with epilepsy are more likely to die prematurely and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). Several studies have reported a moderate or high seizure frequency among SUDEP cases and SUDEP is considered rare in patients in remission., Method: We reviewed the occurrence of SUDEP in our epilepsy unit over an 8-year period to identify a potential association between seizure frequency and SUDEP occurrence in children with epilepsy., Results: From 835 patients evaluated, 12 had suffered SUDEP and nearly all of the SUDEP cases in our children are related to chronic uncontrolled epilepsy (daily--50.0%, two to four/week--41.7%, monthly--8.3%)., Conclusion: SUDEP is not a rare event in children and increased mortality was recorded in those individuals who had not responded to pharmacologic treatment. Improved seizure control seems to be one of the most important measures to prevent SUDEP.

Epilepsy is the commonest serious neurological disorder and individuals with epilepsy are at higher risk of death than the general population and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures play a potential role. The ultimate goal of SUDEP research is to develop methods to prevent it and nutritional aspects such as omega-3 fatty acid deficiency may have an interesting role in this scenario. Omega-3 fatty acids reduce the risk of cardiovascular mortality and are important for treating or preventing some neurological diseases, including epilepsy. A dietary modification or nutritional supplements increasing the ingestion of omega-3 fatty acids may help to ''save the brain'.

Autism spectrum disorders (ASD) are neurodevelopment disorders that cause severe and pervasive impairment in socialization, communication, and behavior. Although the availability of antipsychotic treatment in ASD has expanded, we will be very careful with side effects of these pharmacological agents. Following this reasoning, emerging data indicate that some antipsychotics may be associated with cardiovascular adverse events (e.g., QT interval prolongation), suggesting that this could be correlated to sudden death. Quite interesting, substantial evidence from epidemiological and case-control studies indicates that omega-3 reduces the risk of cardiovascular mortality, particularly sudden cardiac death. In accordance to the above mentioned findings, as omega-3 fatty acids per se have a direct cardiovascular protective role, our paper hypothesized that omega-3 fatty acids supplementation in ASD patients treated with atypical antipsychotic drugs may reduce cardiac arrhythmias and hence sudden cardiac death.

Context: MicroRNAs (miRNAs) are small noncoding RNAs, functioning as antisense regulators of gene expression by targeting mRNA and contributing to cancer development and progression. More than 50% of miRNA genes are located in cancer-associated genomic regions or in fragile sites of the genome., Objective: The aim of the study was to analyze the differential expression of let-7a, miR-15a, miR-16, miR-21, miR-141, miR-143, miR-145, and miR-150 in corticotropinomas and normal pituitary tissue and verify whether their profile of expression correlates with tumor size or remission after treatment., Material and Methods: ACTH-secreting pituitary tumor samples were obtained during transphenoidal surgery from patients with Cushing disease and normal pituitary tissues from autopsies. The relative expression of miRNAs was measured by real-time PCR using RNU44 and RNU49 as endogenous controls. Relative quantification of miRNA expression was calculated using the 2(-DeltaDeltaCt) method., Results: We found underexpression of miR-145 (2.0-fold; P = 0.04), miR-21 (2.4-fold; P = 0.004), miR-141 (2.6-fold; P = 0.02), let-7a (3.3-fold; P = 0.003), miR-150 (3.8-fold; P = 0.04), miR-15a (4.5-fold; P = 0.03), miR-16 (5.0-fold; P = 0.004), and miR-143 (6.4-fold; P = 0.004) in ACTH-secreting pituitary tumors when compared to normal pituitary tissues. There were no differences between miRNA expression and tumor size as well as miRNA expression and ratio of remission after surgery, except in patients presenting lower miR-141 expression who showed a better chance of remission., Conclusion: Our results support the possibility that altered miRNA expression profile might be involved in corticotrophic tumorigenesis. However, the lack of knowledge about miRNA target genes postpones full understanding of the biological functions of down-regulated or up-regulated miRNAs in corticotropinomas.

Cadherins are cell-to-cell adhesion molecules that play an important role in the establishment of adherent-type junctions by mediating calcium-dependent cellular interactions. The CDH1 gene encodes the transmembrane glycoprotein E-cadherin which is important in maintaining homophilic cell-cell adhesion in epithelial tissues. E-cadherin interacts with catenin proteins to maintain tissue architecture. Structural defects or loss of expression of E-cadherin have been reported as a common feature in several human cancer types. This study aimed to evaluate the expression of E-cadherin and their correlation with clinical features in microdissected brain tumor samples from 81 patients, divided into 62 astrocytic tumors grades I to IV and 19 medulloblastomas, and from 5 white matter non-neoplasic brain tissue samples. E-cadherin (CDH1) gene expression was analyzed by quantitative real-time polymerase chain reaction. Mann-Whitney, Kruskal-Wallis, Kaplan-Meir, and log-rank tests were performed for statistical analyses. We observed a decrease in expression among pathological grades of neuroepithelial tumors. Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than did neuroepithelial tumors. Expression of E-cadherin gene was higher in astrocytic than embryonal tumors (P = 0.0168). Low-grade malignancy astrocytomas (grades I-II) showed higher CDH1 expression than did high-grade malignancy astrocytomas (grades III-IV) and medulloblastomas (P < 0.0001). Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than grade I malignancy astrocytomas, considered as benign tumors (P = 0.0473). These results suggest that a decrease in E-cadherin gene expression level in high-grade neuroepithelial tumors may be a hallmark of malignancy in dedifferentiated tumors and that it may be possibly correlated with their progression and dissemination.

We describe the relative frequency, clinical features, neuroimaging and pathological results, and outcome after pharmacological or surgical intervention for a series of pediatric patients with temporal lobe epilepsy (TLE) from an epilepsy center in Brazil. The medical records of children younger than 12 years with features strongly suggestive of TLE were reviewed from January 1999 to June 1999. Selected children were evaluated regarding clinical, EEG, and magnetic resonance imaging (MRI) investigation and divided into three groups according to MRI: group 1 (G1, N = 9), patients with hippocampal atrophy; group 2 (G2, N = 10), patients with normal MRI, and group 3 (G3, N = 12), patients with other specific temporal lesions. A review of 1732 records of children with epilepsy revealed 31 cases with TLE (relative frequency of 1.79%). However, when the investigation was narrowed to cases with intractable seizures that needed video-EEG monitoring (N = 68) or epilepsy surgery (N = 32), the relative frequency of TLE increased to 19.11 (13/68) and 31.25% (10/32), respectively. At the beginning of the study, 25 of 31 patients had a high seizure frequency (80.6%), which declined to 11 of 31 (35.5%) at the conclusion of the study, as a consequence of pharmacological and/or surgical therapy. This improvement in seizure control was significant in G1 (P < 0.05) and G3 (P < 0.01) mainly due to good postsurgical outcome, and was not significant in G2 (P > 0.1, McNemar's test). These results indicate that the relative frequency of TLE in children was low, but increased considerably among cases with pharmacoresistant seizures. Patients with specific lesions were likely to undergo surgery, with good postoperative outcomes.

Introduction: Intraoperative electrocorticography (ECoG) can be performed in cases of temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS). However, its significance and correlation with surgical outcome are still controversial., Objectives: To analyze the electrophysiological characteristics of temporal lobe structures during ECoG of patients with TLE-HS, with emphasis on the comparison between pre- and post-resection recordings and surgical outcome., Patients and Methods: Seventeen patients with refractory TLE-HS submitted to corticoamigdalohipocampectomy were included in the study. Clinical variables included age at the onset, duration of epilepsy and seizure outcome. The post-operative follow-up ranged from 24 to 36 months. According to outcome subjects were divided in two subgroups: (A) individuals free of seizures (Engel 1A), and (B) individuals not-free of seizures (Engel 1B-IV). Four patterns of ECoG findings were identified: isolated discharges; high frequency spikes (HFS); continuous discharges; combination of isolated discharges and HFS. According to predominant topography ECoG was classified as mediobasal, lateral (or neocortical), mediobasal and lateral., Results: The progressive removal of the temporal pole and the hippocampus was associated with significant decrease of neocortical spikes. No correlation between clinical variables and seizure outcome was observed. Patients who only had isolated spikes on intraoperative ECoG presented a statistical trend for excellent surgical control. Patients who presented temporal pole blurring on MRI also had better post-surgical seizure outcome., Conclusions: This study showed that out of diverse clinical and laboratory variables, only isolated discharges on intraoperative ECoG and temporal pole blurring on MRI predicted excellent post-surgical seizure outcome. However, other studies with larger number of patients are still necessary to confirm these findings.

Neocortical development is a highly complex process encompassing cellular proliferation, neuronal migration and cortical organization. At any time this process can be interrupted or modified by genetic or acquired factors causing malformations of cortical development (MCD). Epileptic seizures are the most common type of clinical manifestation, besides developmental delay and focal neurological deficits. Seizures due to MCD are frequently pharmacoresistant, especially those associated to focal cortical dysplasia (FCD). Surgical therapy results have been reported since 1971, however, currently available data from surgical series are still limited, mainly due to small number of patients, distinct selection of candidates and surgical strategies, variable pathological diagnosis and inadequate follow-up. This study addresses the possibilities of seizure relief following resection of focal cortical dysplasia, and the impact of presurgical evaluation, extent of resection and pathological findings on surgical outcome. We included 41 patients, 22 adults and 19 children and adolescents, with medically intractable seizures operated on from 1996 to 2002. All were submitted to standardized presurgical evaluation including high-resolution MRI, Video-EEG monitoring and ictal SPECT. Post-surgical seizure outcome was classified according to Engel's schema. Univariate and multivariate analysis were performed. Fifteen patients had temporal and 26 extratemporal epilepsies. Of the total 26 patients (63.4%) reached seizure-free status post-operatively. There was no correlation between outcome and age at surgery, duration of epilepsy, frequency of seizures, and pathological findings. There was, however, a clear correlation with topography of FCD (temporal versus extratemporal) and regional ictal EEG onset, on univariate as well as multivariate analysis.

Purpose: We sought to analyze the contralateral volumes of the temporal pole, posterior segment of the temporal lobe, amygdala, hippocampus, and parahippocampal gyrus in patients with temporal lobe epilepsy (TLE) due to histologically proven mesial temporal lobe sclerosis (MTLS), seizure free for >or=4 years of postsurgical follow-up., Methods: Forty-six (23 male) TLE patients, operated on between 1996 and 2001, with histopathologic diagnosis of MTLS, and a postsurgical follow-up of >or=4 years, had their temporal lobe structures manually segmented, measured, and compared with those of 23 normal volunteers, paired as groups for sex, age, and handedness., Results: The mean volumes of the contralateral temporal pole, hippocampus, and parahippocampal gyrus in TLE patients were significantly lower than those in controls., Conclusions: MRI volumetric data show that the damage in TLE due to MTS may be more widespread and bilateral, even in patients with unilateral TLE by clinical and neurophysiological criteria. Our results are relevant to the discussion of epileptogenic mechanisms in TLE.