Epilepsy is one of the most common neurological diseases, characterized by transient and unprovok... more Epilepsy is one of the most common neurological diseases, characterized by transient and unprovoked events called epileptic seizures. Electroencephalogram (EEG) is an auxiliary method used to perform both the diagnosis and the monitoring of epilepsy. Given the unexpected nature of an epileptic seizure, its prediction would improve patient care, optimizing the quality of life and the treatment of epilepsy. Predicting an epileptic seizure implies the identification of two distinct states of EEG in a patient with epilepsy: the preictal and the interictal. In this paper, we developed two deep learning models called Temporal Multi-Channel Transformer (TMC-T) and Vision Transformer (TMC-ViT), adaptations of Transformer-based architectures for multi-channel temporal signals. Moreover, we accessed the impact of choosing different preictal duration, since its length is not a consensus among experts, and also evaluated how the sample size benefits each model. Our models are compared with fully connected, convolutional, and recurrent networks. The algorithms were patient-specific trained and evaluated on raw EEG signals from the CHB-MIT database. Experimental results and statistical validation demonstrated that our TMC-ViT model surpassed the CNN architecture, state-of-the-art in seizure prediction.
We studied morphologic characteristics of dysmorphic neurons in the hippocampus of seven patients... more We studied morphologic characteristics of dysmorphic neurons in the hippocampus of seven patients with medically intractable TLE and compare histological, clinical, and imaging features with ten TLE patients with classical hippocampal sclerosis without abnormal cells. Such dysmorphic neurons were observed in the hilus of the dentate gyrus and were characterized by giant or misshapen cells with abnormal cytoskeletal structure and atypical dendritic processes that resembled the dysmorphic neurons from cortical dysplasias. Specimens with dysmorphic cells also contained other cytoarchitectural abnormalities including bilamination of the dentate granular cell layer (four out seven cases), and the presence of Cajal-Retzius cells in the dentate gyrus or Ammon's horn (five out seven cases). There were no statistically significant differences regarding the age at onset, duration of epilepsy, and hippocampal asymmetry ratio between patients with or without dysmorphic cells. Nevertheless, it is interesting to note that a higher proportion of patients with dysmorphic neurons continued to present auras after surgery, when compared with patients without those cells.
BACKGROUND Motor cortex stimulation (MCS) is proper as a non-pharmacological therapy for patients... more BACKGROUND Motor cortex stimulation (MCS) is proper as a non-pharmacological therapy for patients with chronic and neuropathic pain (NP). AIMS Investigate if the MCS in the primary motor cortex (M1) produces analgesia and how the MCS could interfere in the MCS-induced analgesia. Also, elucidate if the persistent activation of N-methyl-D-aspartic acid receptor (NMDAr) in the periaqueductal grey matter (PAG) can contribute to central sensitization 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 done low-frequency (20 μA, 100 Hz) during 15 s by a deep brain stimulation (DBS) device. Moreover, M1-treatment with an NMDAr agonist (at 2, 4, and 8 nmol) investigated the effect of chemical stimulation in CCI rats. RESULTS The PAG dorsomedial column (dmPAG) was pretreated with the NMDAr antagonist LY 235959 (at 8 nmol), followed by MCS. The MCS decreased the mechanical allodynia in rats with chronic NP. The M1-treatment with an NMDA agonist at 2 and 8 nmol reduced the mechanical allodynia in CCI rats. Also, dmPAG-pretreatment with LY 235959 at 8 nmol attenuated the mechanical allodynia evoked by MCS. CONCLUSION The M1 cortex NMDA glutamatergic system is involved in the modulation of chronic NP. The analgesic effect of MCS may depend on glutamate signaling by the NMDAr located in the PAG neurons in rodents with chronic neuropathic pain.
Purpose We aimed to analyze the potential for postoperative (PO) medication suspension and reduct... more 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.
Objectives To evaluate how telomere length behaves in adamantinomtous craniopharyngioma (aCP) and... more 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 ...
ObjectiveDrebrins are crucial for synaptic function and dendritic spine development, remodeling, ... more ObjectiveDrebrins 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.MethodsHippocampal 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 colocali...
Background: Meningiomas are the most frequent primary central nervous system (CNS) tumors. Their ... more 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 intr...
Background Chronic constriction injury (CCI) is a model of neuropathic pain induced by four loose... more 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 p...
Purpose Hemispherectomy is an effective treatment option for pharmacoresistant epilepsy. Neverthe... more Purpose Hemispherectomy is an effective treatment option for pharmacoresistant epilepsy. Nevertheless, when high cortical functions are at risk during the presurgical evaluation, especially for older children, and for the left hemisphere, despite good seizure outcome, the anticipated decrease of cognitive functions may prevent a decision to perform surgery. The objective of this study is to report the cognitive outcome, based on verbal and performance intelligence skills, in a series of older children and adolescents who underwent left hemispherectomy, analyzing the risks (residual cognitive deficit) and benefits (seizure reduction) of surgery. Methods We retrospectively analyzed pre-and postoperative clinical and neuropsychological data from our patients who underwent left hemispherectomy, aged between 6 and 18 years. Results We included 15 patients, with a mean follow-up of 3.1 years, 12 patients (80%) were Engel I, and the other three were classified as Engel II, III, and IV. Nine patients were tested by Wechsler Scales of Intelligence; postsurgically all but one kept the same intellectual levels; verbal intelligence quotient (VIQ) remained unchanged in 13 and improved in one, whereas performance intelligence quotient (PIQ) decreased in four patients. Both Total Vineland and communication scores of Vineland Adaptive Behavior Scales were obtained in six patients: in all, scores were classified as deficient adaptive functioning pre-and postoperatively, remaining unchanged. Conclusion The evaluation of the remaining intellectual abilities after left hemispherectomy in older children and adolescents is useful to discuss the risks and benefits of this surgery, enabling better and safer decisions regarding surgical indications and timing.
OBJECTIVEThe goal of this study was to perform an analysis of a single-center experience with hem... more OBJECTIVEThe 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.METHODSA 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.RESULTSAmong the 14 patients whose seizures recurred and in whom ...
ObjectivesRecently, defects in the protein kinase mTOR (mammalian target of rapamycin) and its as... more ObjectivesRecently, 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.MethodsUsing 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.ResultsThese 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 insig...
Introduction: Hydrocephalus is a multifactorial disease, affecting the dynamics of cerebrospinal ... more Introduction: Hydrocephalus is a multifactorial disease, affecting the dynamics of cerebrospinal fluid (CSF) and leading to severe neurological impairment in children; in spite of the recent advances in hydrocephalus research, it has many physiopathological aspects that still remain poorly understood, especially after treatment. Objectives: To analyze the clinical, radiological, histopathological, and biochemical aspects of kaolin-induced hydrocephalus in an experimental model, both in the acute phase and after shunt treatment, by means of behavioral tests, magnetic resonance imaging (MRI) scans, histopathological studies, and level of inflammatory interleukins in the CSF. Methods: Seven-day-old Wistar rats were used and subdivided into three subgroups: treated hydrocephalic (n = 24), untreated hydrocephalic (n = 17), and controls (n = 5). The hydrocephalic groups underwent cisternal injection of 15% kaolin for induction of hydrocephalus at 7 days of age. The treated group was submi...
Background. As the survival of preterm infants has increased significantly, germinal matrix hemor... more Background. As the survival of preterm infants has increased significantly, germinal matrix hemorrhage (GMH) has become an important public health issue. Nevertheless, treatment strategies for the direct neuronal injury are still scarce. The present study aims to analyze the neuroprotective properties of cannabidiol in germinal matrix hemorrhage. Methods. 112 Wistar rat pups (P7) were submitted to an experimental collagenase induced model of GMH. Inflammatory response and neuronal death were analyzed both at the perilesional area as at the distant ipsilateral CA1 hippocampal area. Immunohistochemistry for GFAP and caspase 3 was used. The ipsilateral free water content was assessed for stimation of cerebral edema, and neurodevelopment and neurofunctional tests were conducted. Results. Reduction of reactive astrocytosis was observed both in the perilesional area 24 hours and 14 days after the hemorrhage lesion (p < 0.001) and in the Stratum oriens of the ipsilateral hippocampal CA1 14 days after the hemorrhage lesion (p < 0.05) in the treated groups. Similarly, there was a reduction in the number of Caspase 3-positive astrocytes in the perilesional area in the treated groups 24 hours after the hemorrhage lesion (p < 0.001). Finally, we found a significant increase in the weight of the rats treated with cannabidiol. Conclusion. The treatment of GMH with cannabidiol significantly reduced the number of apoptotic cells and reactive astrocytes in the perilesional area and the ipsilateral hippocampus. In addition, this response was sustained 14 days after the hemorrhage. These results corroborate our hypothesis that cannabidiol is a potential neuroprotective agent in the treatment of germinal matrix hemorrhage.
2015 IEEE 28th International Symposium on Computer-Based Medical Systems, 2015
This report aimed at promoting communication among project participants (hospital personnel and m... more This report aimed at promoting communication among project participants (hospital personnel and medical residents), increasing autonomy in decision-making during surgical planning. The steps taken for neuro navigation on a head model produced by additive manufacturing were analyzed for quality and risk assessment. Danger related to each navigation step, expected event sequence, dangerous situation and damage were pinpointed. User involvement was required from each project participant. After technical description of model preparation (filling and target deployment), the following steps were described: 1. Biomodel fixation, 2. T1-weighted image acquisition, 3. Target planning, 4. Stereotactic procedure, 5. Tomography acquisition, 6. Accuracy verification, 7. Disassembly. Error sources were identified and standardized procedures were established. A series of proposals were listed to assure quality and reproducibility. We concluded that accuracy can be improved as materials and procedures used for stereotaxy are optimized.
Journal of Neuropathology & Experimental Neurology, 2015
Up to 20% of patients with pilocytic astrocytoma (PA) experience a poor outcome. BRAF alterations... more Up to 20% of patients with pilocytic astrocytoma (PA) experience a poor outcome. BRAF alterations and Fibroblast growth factor receptor 1 (FGFR1) point mutations are key molecular alterations in Pas, but their clinical implications are not established. We aimed to determine the frequency and prognostic role of these alterations in a cohort of 69 patients with PAs. We assessed KIAA1549:BRAF fusion by fluorescence in situ hybridization and BRAF (exon 15) mutations by capillary sequencing. In addition, FGFR1 expression was analyzed using immunohistochemistry, and this was compared with gene amplification and hotspot mutations (exons 12 and 14) assessed by fluorescence in situ hybridization and capillary sequencing. KIAA1549:BRAF fusion was identified in almost 60% of cases. Two tumors harbored mutated BRAF. Despite high FGFR1 expression overall, no cases had FGFR1 amplifications. Three cases harbored a FGFR1 p.K656E point mutation. No correlation was observed between BRAF and FGFR1 alterations. The cases were predominantly pediatric (87%), and no statistical differences were observed in molecular alterationsYrelated patient ages. In summary, we confirmed the high frequency of KIAA1549:BRAF fusion in PAs and its association with a better outcome. Oncogenic mutations of FGFR1, although rare, occurred in a subset of patients with worse outcome. These molecular alterations may constitute alternative targets for novel clinical approaches, when radical surgical resection is unachievable.
Resumo A Engenharia Clínica é uma área com atuação nos Estabelecimentos Assistenciais de Saúde, d... more Resumo A Engenharia Clínica é uma área com atuação nos Estabelecimentos Assistenciais de Saúde, desenvolvendo atividades baseadas nos conhecimentos de engenharia e de gerenciamento aplicadas às tecnologias de saúde. Nesse contexto, este trabalho relata os impactos econômicos da aplicação de técnicas de gestão em Engenharia Clínica num hospital público brasileiro de grande porte e referência em alta complexidade-Hospital de Clínicas da Universidade Federal de Uberlândia. Trata-se de uma pesquisa quantitativa, onde foram consideradas questões econômicas e de qualidade, suportada por pesquisa documental. O levantamento de dados baseou-se em relatórios e documentos administrativos do hospital do período de 2001 a 2010, referentes a recursos humanos, indicadores de serviços, indicadores de qualidade, custos com peças e contratos. Dentre os resultados encontrados, destaca-se a redução de aproximadamente 20% nas manutenções corretivas e sua estabilização ao longo do tempo, mesmo em face de um elevado aumento do parque tecnológico da instituição. No montante global de gastos com contratos, observou-se uma redução de cerca de 65% no período avaliado. A economia gerada pela gestão em Engenharia Clínica para a instituição foi de aproximadamente R$ 2 milhões em 2010, e a economia acumulada no período de 2001 a 2010 foi de R$ 7,6 milhões. Concluiu-se, que a gestão em Engenharia Clínica na instituição possibilitou uma redução significativa nos custos por meio da formação e capacitação de uma equipe própria, da redução dos custos com contratos e melhor planejamento das manutenções. Tais resultados demonstram a importância de um serviço de Engenharia Clínica para a melhor gestão de custos e das tecnologias em hospitais, sejam eles públicos ou privados. Palavras-chave Gestão hospitalar, Tecnologias em saúde, Custos, Manutenção. Economic evaluation of implementing a service of Clinical Engineering in a Brazilian public hospital Abstract Clinical Engineering is an important area for health care facilities, capable of applying engineering and management techniques to improve health technologies. In this context, this paper reports the economic impacts of the application of clinical engineering management techniques in a large Brazilian public hospital, which is also a reference for high complexity medical procedures-General Hospital of the Federal University of Uberlândia. The discussion is supported by a quantitative documentary research, which took into account not only the economic aspects, but also the quality of the service provided. The survey was based on reports and administrative documents from 2001 to 2010, related to human resources, service and quality indicators, costs of parts and contracts. Among the findings, it was observed a reduction of approximately 20% in corrective maintenance and their stabilization over time, even as the technological park of the institution increased. As for the overall amount of cost with contracts, there was a reduction of approximately 65% during the period.
Objective: In mesial temporal lobe epilepsy (MTLE), the rate of correct seizure lateralization of... more Objective: In mesial temporal lobe epilepsy (MTLE), the rate of correct seizure lateralization of ictal semiology and ictal EEG is better for patients with unilateral interictal spikes (UIS) than for patients with bilateral interictal spikes (BIS), possibly due to rapid seizure propagation patterns associated with bilateral epileptogenesis. In this study, the authors investigated if ictal SPECT is a reliable diagnostic test for both UIS and BIS patients.Methods: Video-EEG recording was used as the gold standard to examine the accuracy of ictal SPECT and its relationship with interictal and ictal EEG. Ninety-three consecutive patients with MTLE associated with hippocampal sclerosis were included in the analysis. Ictal SPECT was considered accurate if two blinded observers independently lateralized the scan correctly.Results: Ictal SPECT correctly lateralized 75 (80.6%) of 93 scans. The rate of correct seizure lateralization was 87.6% for the UIS group and only 55.0% for the BIS group...
Epilepsy is one of the most common neurological diseases, characterized by transient and unprovok... more Epilepsy is one of the most common neurological diseases, characterized by transient and unprovoked events called epileptic seizures. Electroencephalogram (EEG) is an auxiliary method used to perform both the diagnosis and the monitoring of epilepsy. Given the unexpected nature of an epileptic seizure, its prediction would improve patient care, optimizing the quality of life and the treatment of epilepsy. Predicting an epileptic seizure implies the identification of two distinct states of EEG in a patient with epilepsy: the preictal and the interictal. In this paper, we developed two deep learning models called Temporal Multi-Channel Transformer (TMC-T) and Vision Transformer (TMC-ViT), adaptations of Transformer-based architectures for multi-channel temporal signals. Moreover, we accessed the impact of choosing different preictal duration, since its length is not a consensus among experts, and also evaluated how the sample size benefits each model. Our models are compared with fully connected, convolutional, and recurrent networks. The algorithms were patient-specific trained and evaluated on raw EEG signals from the CHB-MIT database. Experimental results and statistical validation demonstrated that our TMC-ViT model surpassed the CNN architecture, state-of-the-art in seizure prediction.
We studied morphologic characteristics of dysmorphic neurons in the hippocampus of seven patients... more We studied morphologic characteristics of dysmorphic neurons in the hippocampus of seven patients with medically intractable TLE and compare histological, clinical, and imaging features with ten TLE patients with classical hippocampal sclerosis without abnormal cells. Such dysmorphic neurons were observed in the hilus of the dentate gyrus and were characterized by giant or misshapen cells with abnormal cytoskeletal structure and atypical dendritic processes that resembled the dysmorphic neurons from cortical dysplasias. Specimens with dysmorphic cells also contained other cytoarchitectural abnormalities including bilamination of the dentate granular cell layer (four out seven cases), and the presence of Cajal-Retzius cells in the dentate gyrus or Ammon's horn (five out seven cases). There were no statistically significant differences regarding the age at onset, duration of epilepsy, and hippocampal asymmetry ratio between patients with or without dysmorphic cells. Nevertheless, it is interesting to note that a higher proportion of patients with dysmorphic neurons continued to present auras after surgery, when compared with patients without those cells.
BACKGROUND Motor cortex stimulation (MCS) is proper as a non-pharmacological therapy for patients... more BACKGROUND Motor cortex stimulation (MCS) is proper as a non-pharmacological therapy for patients with chronic and neuropathic pain (NP). AIMS Investigate if the MCS in the primary motor cortex (M1) produces analgesia and how the MCS could interfere in the MCS-induced analgesia. Also, elucidate if the persistent activation of N-methyl-D-aspartic acid receptor (NMDAr) in the periaqueductal grey matter (PAG) can contribute to central sensitization 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 done low-frequency (20 μA, 100 Hz) during 15 s by a deep brain stimulation (DBS) device. Moreover, M1-treatment with an NMDAr agonist (at 2, 4, and 8 nmol) investigated the effect of chemical stimulation in CCI rats. RESULTS The PAG dorsomedial column (dmPAG) was pretreated with the NMDAr antagonist LY 235959 (at 8 nmol), followed by MCS. The MCS decreased the mechanical allodynia in rats with chronic NP. The M1-treatment with an NMDA agonist at 2 and 8 nmol reduced the mechanical allodynia in CCI rats. Also, dmPAG-pretreatment with LY 235959 at 8 nmol attenuated the mechanical allodynia evoked by MCS. CONCLUSION The M1 cortex NMDA glutamatergic system is involved in the modulation of chronic NP. The analgesic effect of MCS may depend on glutamate signaling by the NMDAr located in the PAG neurons in rodents with chronic neuropathic pain.
Purpose We aimed to analyze the potential for postoperative (PO) medication suspension and reduct... more 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.
Objectives To evaluate how telomere length behaves in adamantinomtous craniopharyngioma (aCP) and... more 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 ...
ObjectiveDrebrins are crucial for synaptic function and dendritic spine development, remodeling, ... more ObjectiveDrebrins 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.MethodsHippocampal 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 colocali...
Background: Meningiomas are the most frequent primary central nervous system (CNS) tumors. Their ... more 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 intr...
Background Chronic constriction injury (CCI) is a model of neuropathic pain induced by four loose... more 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 p...
Purpose Hemispherectomy is an effective treatment option for pharmacoresistant epilepsy. Neverthe... more Purpose Hemispherectomy is an effective treatment option for pharmacoresistant epilepsy. Nevertheless, when high cortical functions are at risk during the presurgical evaluation, especially for older children, and for the left hemisphere, despite good seizure outcome, the anticipated decrease of cognitive functions may prevent a decision to perform surgery. The objective of this study is to report the cognitive outcome, based on verbal and performance intelligence skills, in a series of older children and adolescents who underwent left hemispherectomy, analyzing the risks (residual cognitive deficit) and benefits (seizure reduction) of surgery. Methods We retrospectively analyzed pre-and postoperative clinical and neuropsychological data from our patients who underwent left hemispherectomy, aged between 6 and 18 years. Results We included 15 patients, with a mean follow-up of 3.1 years, 12 patients (80%) were Engel I, and the other three were classified as Engel II, III, and IV. Nine patients were tested by Wechsler Scales of Intelligence; postsurgically all but one kept the same intellectual levels; verbal intelligence quotient (VIQ) remained unchanged in 13 and improved in one, whereas performance intelligence quotient (PIQ) decreased in four patients. Both Total Vineland and communication scores of Vineland Adaptive Behavior Scales were obtained in six patients: in all, scores were classified as deficient adaptive functioning pre-and postoperatively, remaining unchanged. Conclusion The evaluation of the remaining intellectual abilities after left hemispherectomy in older children and adolescents is useful to discuss the risks and benefits of this surgery, enabling better and safer decisions regarding surgical indications and timing.
OBJECTIVEThe goal of this study was to perform an analysis of a single-center experience with hem... more OBJECTIVEThe 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.METHODSA 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.RESULTSAmong the 14 patients whose seizures recurred and in whom ...
ObjectivesRecently, defects in the protein kinase mTOR (mammalian target of rapamycin) and its as... more ObjectivesRecently, 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.MethodsUsing 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.ResultsThese 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 insig...
Introduction: Hydrocephalus is a multifactorial disease, affecting the dynamics of cerebrospinal ... more Introduction: Hydrocephalus is a multifactorial disease, affecting the dynamics of cerebrospinal fluid (CSF) and leading to severe neurological impairment in children; in spite of the recent advances in hydrocephalus research, it has many physiopathological aspects that still remain poorly understood, especially after treatment. Objectives: To analyze the clinical, radiological, histopathological, and biochemical aspects of kaolin-induced hydrocephalus in an experimental model, both in the acute phase and after shunt treatment, by means of behavioral tests, magnetic resonance imaging (MRI) scans, histopathological studies, and level of inflammatory interleukins in the CSF. Methods: Seven-day-old Wistar rats were used and subdivided into three subgroups: treated hydrocephalic (n = 24), untreated hydrocephalic (n = 17), and controls (n = 5). The hydrocephalic groups underwent cisternal injection of 15% kaolin for induction of hydrocephalus at 7 days of age. The treated group was submi...
Background. As the survival of preterm infants has increased significantly, germinal matrix hemor... more Background. As the survival of preterm infants has increased significantly, germinal matrix hemorrhage (GMH) has become an important public health issue. Nevertheless, treatment strategies for the direct neuronal injury are still scarce. The present study aims to analyze the neuroprotective properties of cannabidiol in germinal matrix hemorrhage. Methods. 112 Wistar rat pups (P7) were submitted to an experimental collagenase induced model of GMH. Inflammatory response and neuronal death were analyzed both at the perilesional area as at the distant ipsilateral CA1 hippocampal area. Immunohistochemistry for GFAP and caspase 3 was used. The ipsilateral free water content was assessed for stimation of cerebral edema, and neurodevelopment and neurofunctional tests were conducted. Results. Reduction of reactive astrocytosis was observed both in the perilesional area 24 hours and 14 days after the hemorrhage lesion (p < 0.001) and in the Stratum oriens of the ipsilateral hippocampal CA1 14 days after the hemorrhage lesion (p < 0.05) in the treated groups. Similarly, there was a reduction in the number of Caspase 3-positive astrocytes in the perilesional area in the treated groups 24 hours after the hemorrhage lesion (p < 0.001). Finally, we found a significant increase in the weight of the rats treated with cannabidiol. Conclusion. The treatment of GMH with cannabidiol significantly reduced the number of apoptotic cells and reactive astrocytes in the perilesional area and the ipsilateral hippocampus. In addition, this response was sustained 14 days after the hemorrhage. These results corroborate our hypothesis that cannabidiol is a potential neuroprotective agent in the treatment of germinal matrix hemorrhage.
2015 IEEE 28th International Symposium on Computer-Based Medical Systems, 2015
This report aimed at promoting communication among project participants (hospital personnel and m... more This report aimed at promoting communication among project participants (hospital personnel and medical residents), increasing autonomy in decision-making during surgical planning. The steps taken for neuro navigation on a head model produced by additive manufacturing were analyzed for quality and risk assessment. Danger related to each navigation step, expected event sequence, dangerous situation and damage were pinpointed. User involvement was required from each project participant. After technical description of model preparation (filling and target deployment), the following steps were described: 1. Biomodel fixation, 2. T1-weighted image acquisition, 3. Target planning, 4. Stereotactic procedure, 5. Tomography acquisition, 6. Accuracy verification, 7. Disassembly. Error sources were identified and standardized procedures were established. A series of proposals were listed to assure quality and reproducibility. We concluded that accuracy can be improved as materials and procedures used for stereotaxy are optimized.
Journal of Neuropathology & Experimental Neurology, 2015
Up to 20% of patients with pilocytic astrocytoma (PA) experience a poor outcome. BRAF alterations... more Up to 20% of patients with pilocytic astrocytoma (PA) experience a poor outcome. BRAF alterations and Fibroblast growth factor receptor 1 (FGFR1) point mutations are key molecular alterations in Pas, but their clinical implications are not established. We aimed to determine the frequency and prognostic role of these alterations in a cohort of 69 patients with PAs. We assessed KIAA1549:BRAF fusion by fluorescence in situ hybridization and BRAF (exon 15) mutations by capillary sequencing. In addition, FGFR1 expression was analyzed using immunohistochemistry, and this was compared with gene amplification and hotspot mutations (exons 12 and 14) assessed by fluorescence in situ hybridization and capillary sequencing. KIAA1549:BRAF fusion was identified in almost 60% of cases. Two tumors harbored mutated BRAF. Despite high FGFR1 expression overall, no cases had FGFR1 amplifications. Three cases harbored a FGFR1 p.K656E point mutation. No correlation was observed between BRAF and FGFR1 alterations. The cases were predominantly pediatric (87%), and no statistical differences were observed in molecular alterationsYrelated patient ages. In summary, we confirmed the high frequency of KIAA1549:BRAF fusion in PAs and its association with a better outcome. Oncogenic mutations of FGFR1, although rare, occurred in a subset of patients with worse outcome. These molecular alterations may constitute alternative targets for novel clinical approaches, when radical surgical resection is unachievable.
Resumo A Engenharia Clínica é uma área com atuação nos Estabelecimentos Assistenciais de Saúde, d... more Resumo A Engenharia Clínica é uma área com atuação nos Estabelecimentos Assistenciais de Saúde, desenvolvendo atividades baseadas nos conhecimentos de engenharia e de gerenciamento aplicadas às tecnologias de saúde. Nesse contexto, este trabalho relata os impactos econômicos da aplicação de técnicas de gestão em Engenharia Clínica num hospital público brasileiro de grande porte e referência em alta complexidade-Hospital de Clínicas da Universidade Federal de Uberlândia. Trata-se de uma pesquisa quantitativa, onde foram consideradas questões econômicas e de qualidade, suportada por pesquisa documental. O levantamento de dados baseou-se em relatórios e documentos administrativos do hospital do período de 2001 a 2010, referentes a recursos humanos, indicadores de serviços, indicadores de qualidade, custos com peças e contratos. Dentre os resultados encontrados, destaca-se a redução de aproximadamente 20% nas manutenções corretivas e sua estabilização ao longo do tempo, mesmo em face de um elevado aumento do parque tecnológico da instituição. No montante global de gastos com contratos, observou-se uma redução de cerca de 65% no período avaliado. A economia gerada pela gestão em Engenharia Clínica para a instituição foi de aproximadamente R$ 2 milhões em 2010, e a economia acumulada no período de 2001 a 2010 foi de R$ 7,6 milhões. Concluiu-se, que a gestão em Engenharia Clínica na instituição possibilitou uma redução significativa nos custos por meio da formação e capacitação de uma equipe própria, da redução dos custos com contratos e melhor planejamento das manutenções. Tais resultados demonstram a importância de um serviço de Engenharia Clínica para a melhor gestão de custos e das tecnologias em hospitais, sejam eles públicos ou privados. Palavras-chave Gestão hospitalar, Tecnologias em saúde, Custos, Manutenção. Economic evaluation of implementing a service of Clinical Engineering in a Brazilian public hospital Abstract Clinical Engineering is an important area for health care facilities, capable of applying engineering and management techniques to improve health technologies. In this context, this paper reports the economic impacts of the application of clinical engineering management techniques in a large Brazilian public hospital, which is also a reference for high complexity medical procedures-General Hospital of the Federal University of Uberlândia. The discussion is supported by a quantitative documentary research, which took into account not only the economic aspects, but also the quality of the service provided. The survey was based on reports and administrative documents from 2001 to 2010, related to human resources, service and quality indicators, costs of parts and contracts. Among the findings, it was observed a reduction of approximately 20% in corrective maintenance and their stabilization over time, even as the technological park of the institution increased. As for the overall amount of cost with contracts, there was a reduction of approximately 65% during the period.
Objective: In mesial temporal lobe epilepsy (MTLE), the rate of correct seizure lateralization of... more Objective: In mesial temporal lobe epilepsy (MTLE), the rate of correct seizure lateralization of ictal semiology and ictal EEG is better for patients with unilateral interictal spikes (UIS) than for patients with bilateral interictal spikes (BIS), possibly due to rapid seizure propagation patterns associated with bilateral epileptogenesis. In this study, the authors investigated if ictal SPECT is a reliable diagnostic test for both UIS and BIS patients.Methods: Video-EEG recording was used as the gold standard to examine the accuracy of ictal SPECT and its relationship with interictal and ictal EEG. Ninety-three consecutive patients with MTLE associated with hippocampal sclerosis were included in the analysis. Ictal SPECT was considered accurate if two blinded observers independently lateralized the scan correctly.Results: Ictal SPECT correctly lateralized 75 (80.6%) of 93 scans. The rate of correct seizure lateralization was 87.6% for the UIS group and only 55.0% for the BIS group...
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Papers by Helio Machado