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Pediatric optic pathway/hypothalamic gliomas (OPHG) pose challenges in treatment due to their location and proximity to vital structures. Surgical resection plays a key role in the management of OPHG especially when the tumor exhibits mass effect and causes symptoms. However, data regarding outcomes and complications of surgical resection for OPHG remains heterogenous. The authors performed a systematic review on pediatric OPHG in four databases: PubMed, EMBASE, Cochrane Library, and Google Scholar. We included studies that reported on the visual outcomes and complications of OPHG resection. A meta-analysis was performed and reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 26 retrospective studies were included. Seven hundred ninety-seven pediatric patients with OPHG undergoing surgical resection were examined. A diagnosis of NF1 was confirmed in 9.7%. Gross total resection was achieved in 36.7%. Intraorbital optic pathway gliomas showed a significantly higher gross total resection rate compared to those located in the chiasmatic/hypothalamic region (75.8% vs. 9.6%). Postoperatively, visual acuity improved in 24.6%, remained unchanged in 68.2%, and worsened in 18.2%. Complications included hydrocephalus (35.4%), anterior pituitary dysfunction (19.6%), and transient diabetes insipidus (29%). Tumor progression post-resection occurred in 12.8%, through a mean follow-up of 53.5 months. Surgical resection remains an essential strategy for treating symptomatic and large pediatric OPHG and can result in favorable vision outcomes in most patients. Careful patient selection is critical. Patients should be monitored for hydrocephalus development postoperatively and followed up to assess for tumor progression and adjuvant treatment necessity.
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Neoplasias Hipotalâmicas , Complicações Pós-Operatórias , Humanos , Criança , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Hipotalâmicas/cirurgia , Neoplasias Hipotalâmicas/complicações , Glioma/cirurgia , Glioma/complicações , Glioma do Nervo Óptico/cirurgia , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/efeitos adversos , Resultado do Tratamento , Pré-EscolarRESUMO
In patients with drug-resistant epilepsy (DRE) who are not candidates for resective surgery, various thalamic nuclei, including the anterior, centromedian, and pulvinar nuclei, have been extensively investigated as targets for neuromodulation. However, the therapeutic effects of different targets for thalamic neuromodulation on various types of epilepsy are not well understood. Here, we present a 32-year-old patient with multifocal bilateral temporoparieto-occipital epilepsy and bilateral malformations of cortical development (MCDs) who underwent bilateral stereoelectroencephalographic (SEEG) recordings of the aforementioned three thalamic nuclei bilaterally. The change in the rate of interictal epileptiform discharges (IEDs) from baseline were compared in temporal, central, parietal, and occipital regions after direct electrical stimulation (DES) of each thalamic nucleus. A significant decrease in the rate of IEDs (33% from baseline) in the posterior quadrant regions was noted in the ipsilateral as well as contralateral hemisphere following DES of the pulvinar. A scoping review was also performed to better understand the current standpoint of pulvinar thalamic stimulation in the treatment of DRE. The therapeutic effect of neuromodulation can differ among thalamic nuclei targets and epileptogenic zones (EZs). In patients with multifocal EZs with extensive MCDs, personalized thalamic targeting could be achieved through DES with thalamic SEEG electrodes.
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Epilepsia Resistente a Medicamentos , Eletroencefalografia , Pulvinar , Humanos , Adulto , Epilepsia Resistente a Medicamentos/terapia , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletroencefalografia/métodos , Estimulação Encefálica Profunda/métodos , Técnicas Estereotáxicas , Estudo de Prova de Conceito , Tálamo/fisiopatologia , Masculino , Terapia por Estimulação Elétrica/métodosRESUMO
Importance: Guidelines recommend seizure prophylaxis for early posttraumatic seizures (PTS) after severe traumatic brain injury (TBI). Use of antiseizure medications for early seizure prophylaxis after mild or moderate TBI remains controversial. Objective: To determine the association between seizure prophylaxis and risk reduction for early PTS in mild and moderate TBI. Data Sources: PubMed, Google Scholar, and Web of Science (January 1, 1991, to April 18, 2023) were systematically searched. Study Selection: Observational studies of adult patients presenting to trauma centers in high-income countries with mild (Glasgow Coma Scale [GCS], 13-15) and moderate (GCS, 9-12) TBI comparing rates of early PTS among patients with seizure prophylaxis with those without seizure prophylaxis. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) reporting guidelines were used. Two authors independently reviewed all titles and abstracts, and 3 authors reviewed final studies for inclusion. A meta-analysis was performed using a random-effects model with absolute risk reduction. Main Outcome Measures: The main outcome was absolute risk reduction of early PTS, defined as seizures within 7 days of initial injury, in patients with mild or moderate TBI receiving seizure prophylaxis in the first week after injury. A secondary analysis was performed in patients with only mild TBI. Results: A total of 64 full articles were reviewed after screening; 8 studies (including 5637 patients) were included for the mild and moderate TBI analysis, and 5 studies (including 3803 patients) were included for the mild TBI analysis. The absolute risk reduction of seizure prophylaxis for early PTS in mild to moderate TBI (GCS, 9-15) was 0.6% (95% CI, 0.1%-1.2%; P = .02). The absolute risk reduction for mild TBI alone was similar 0.6% (95% CI, 0.01%-1.2%; P = .04). The number needed to treat to prevent 1 seizure was 167 patients. Conclusion and Relevance: Seizure prophylaxis after mild and moderate TBI was associated with a small but statistically significant reduced risk of early posttraumatic seizures after mild and moderate TBI. The small absolute risk reduction and low prevalence of early seizures should be weighed against potential acute risks of antiseizure medications as well as the risk of inappropriate continuation beyond 7 days.
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Anticonvulsivantes , Lesões Encefálicas Traumáticas , Convulsões , Humanos , Lesões Encefálicas Traumáticas/complicações , Anticonvulsivantes/uso terapêutico , Convulsões/prevenção & controle , Convulsões/etiologiaRESUMO
ABSTRACT: Chronic stress induces a group of unrecognized cardiovascular impairments, including elevated hemodynamic variables and vascular dysfunction. Moreover, hydrogen sulfide (H 2 S), a gasotransmitter that regulates the cardiovascular system decreases under chronic stress. Thus, this study assessed the impact of sodium hydrosulfide (NaHS) (H 2 S donor) on chronic restraint stress (CRS)-induced cardiovascular changes. For that purpose, male Wistar rats were restrained for 2 hours a day in a transparent acrylic tube over 8 weeks. Then, body weight, relative adrenal gland weight, serum corticosterone, H 2 S-synthesizing enzymes, endothelial nitric oxide synthetize expression, reactive oxygen species levels, lipid peroxidation, and reduced glutathione-to-oxidized glutathione (GSH 2 :GSSG) ratio were determined in the thoracic aorta. The hemodynamic variables were measured in vivo by the plethysmograph method. The vascular function was evaluated in vitro as vasorelaxant responses induced by carbachol or sodium nitroprusside, and norepinephrine (NE)-mediated vasocontractile responses in the thoracic aorta. CRS increased (1) relative adrenal gland weight; (2) hemodynamic variables; (3) vasoconstrictor responses induced by NE, (4) reactive oxygen species levels, and (5) lipid peroxidation in the thoracic aorta. In addition, CRS decreased (1) body weight; (2) vasorelaxant responses induced by carbachol; (3) GSH content, and (4) GSH 2 :GSSG ratio. Notably, NaHS administration (5.6 mg/kg) restored hemodynamic variables and lipid peroxidation and attenuated the vasoconstrictor responses induced by NE in the thoracic aorta. In addition, NaHS treatment increased relative adrenal gland weight and the GSH 2 :GSSG ratio. Taken together, our results demonstrate that NaHS alleviates CRS-induced hypertension by reducing oxidative stress and restoring vascular function in the thoracic aorta.
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Sulfeto de Hidrogênio , Sulfetos , Ratos , Animais , Masculino , Espécies Reativas de Oxigênio/metabolismo , Dissulfeto de Glutationa/metabolismo , Dissulfeto de Glutationa/farmacologia , Carbacol/farmacologia , Ratos Wistar , Sulfeto de Hidrogênio/metabolismo , Estresse Oxidativo , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia , Peso CorporalRESUMO
C-phycocyanin (CPC) is a photosynthetic protein found in Arthrospira maxima with a nephroprotective and antihypertensive activity that can prevent the development of hemodynamic alterations caused by chronic kidney disease (CKD). However, the complete nutraceutical activities are still unknown. This study aims to determine if the antihypertensive effect of CPC is associated with preventing the impairment of hemodynamic variables through delaying vascular dysfunction. Twenty-four normotensive male Wistar rats were divided into four groups: (1) sham + 4 mL/kg/d vehicle (100 mM of phosphate buffer, PBS) administered by oral gavage (og), (2) sham + 100 mg/kg/d og of CPC, (3) CKD induced by 5/6 nephrectomy (CKD) + vehicle, (4) CKD + CPC. One week after surgery, the CPC treatment began and was administrated daily for four weeks. At the end treatment, animals were euthanized, and their thoracic aorta was used to determine the vascular function and expression of AT1, AT2, and Mas receptors. CKD-induced systemic arterial hypertension (SAH) and vascular dysfunction by reducing the vasorelaxant response of angiotensin 1-7 and increasing the contractile response to angiotensin II. Also, CKD increased the expression of the AT1 and AT2 receptors and reduced the Mas receptor expression. Remarkably, the treatment with CPC prevented SAH, renal function impairment, and vascular dysfunction in the angiotensin system. In conclusion, the antihypertensive activity of CPC is associated with avoiding changes in the expression of AT1, AT2, and Mas receptors, preventing vascular dysfunction development and SAH in rats with CKD.
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Hipertensão , Insuficiência Renal Crônica , Ratos , Masculino , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Angiotensina II/farmacologia , Angiotensina II/metabolismo , Ficocianina/farmacologia , Ficocianina/uso terapêutico , Ratos Wistar , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Receptor Tipo 1 de Angiotensina , Receptores de Angiotensina , Receptor Tipo 2 de Angiotensina/metabolismoRESUMO
Hydrogen sulfide (H2S) is a gasotransmitter implied in metabolic diseases, insulin resistance, obesity, and type 2 Diabetes Mellitus. This study aimed to determine the effect of chronic administration of sodium hydrosulfide (NaHS; inorganic H2S donor), L-Cysteine (L-Cys; substrate of H2S producing enzymes) and DL-Propargylglycine (DL-PAG; cystathionine-gamma-lyase inhibitor) on the vascular dysfunction induced by insulin resistance in rat thoracic aorta. For this purpose, 72 animals were divided into two main sets that received: 1) tap water (control group; n = 12); and 2) fructose 15% w/v in drinking water [insulin resistance group (IR); n = 60] for 20 weeks. After 16 weeks, the group 2 was divided into five subgroups (n = 12 each), which received daily i. p. injections during 4 weeks of: 1) non-treatment (control); 2) vehicle (phosphate buffer saline; PBS, 1 ml/kg); 3) NaHS (5.6 mg/kg); 4) L-Cys (300 mg/kg); and (5) DL-PAG (10 mg/kg). Hemodynamic variables, metabolic variables, vascular function, ROS levels and the expression of p-eNOS and eNOS were determined. IR induced: 1) hyperinsulinemia; 2) increased HOMA-index; 3) decreased Matsuda index; 4) hypertension, vascular dysfunction, increased ROS levels; 5) increased iNOS, and 6) decreased CSE, p-eNOS and eNOS expression. Furthermore, IR did not affect contractile responses to norepinephrine. Interestingly, NaHS and L-Cys treatment, reversed IR-induced impairments and DL-PAG treatment decreased and increased the HOMA and Matsuda index, respectively. Taken together, these results suggest that NaHS and L-Cys decrease the metabolic and vascular alterations induced by insulin resistance by reducing oxidative stress and activating eNOS. Thus, hydrogen sulfide may have a therapeutic application.
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Diabetes Mellitus Tipo 2 , Sulfeto de Hidrogênio , Hipertensão , Resistência à Insulina , Animais , Ratos , Cistationina gama-Liase/antagonistas & inibidores , Cistationina gama-Liase/metabolismo , Cisteína/farmacologia , Cisteína/uso terapêutico , Cisteína/metabolismo , Diabetes Mellitus Tipo 2/complicações , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/uso terapêutico , Sulfeto de Hidrogênio/metabolismo , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Resistência à Insulina/fisiologia , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de OxigênioRESUMO
Spinal cord stimulation (SCS) restores motor control after spinal cord injury (SCI) and stroke. This evidence led to the hypothesis that SCS facilitates residual supraspinal inputs to spinal motoneurons. Instead, here we show that SCS does not facilitate residual supraspinal inputs but directly triggers motoneurons action potentials. However, supraspinal inputs can shape SCS-mediated activity, mimicking volitional control of motoneuron firing. Specifically, by combining simulations, intraspinal electrophysiology in monkeys and single motor unit recordings in humans with motor paralysis, we found that residual supraspinal inputs transform subthreshold SCS-induced excitatory postsynaptic potentials into suprathreshold events. We then demonstrated that only a restricted set of stimulation parameters enables volitional control of motoneuron firing and that lesion severity further restricts the set of effective parameters. Our results explain the facilitation of voluntary motor control during SCS while predicting the limitations of this neurotechnology in cases of severe loss of supraspinal axons.
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Humans' ability to adapt and learn relies on reflecting on past performance. These experiences form latent representations called internal states that induce movement variability that improves how we interact with our environment. Our study uncovered temporal dynamics and neural substrates of two states from ten subjects implanted with intracranial depth electrodes while they performed a goal-directed motor task with physical perturbations. We identified two internal states using state-space models: one tracking past errors and the other past perturbations. These states influenced reaction times and speed errors, revealing how subjects strategize from trial history. Using local field potentials from over 100 brain regions, we found large-scale brain networks such as the dorsal attention and default mode network modulate visuospatial attention based on recent performance and environmental feedback. Notably, these networks were more prominent in higher-performing subjects, emphasizing their role in improving motor performance by regulating movement variability through internal states.
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Mapeamento Encefálico , Encéfalo , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Aprendizagem , Movimento , Imageamento por Ressonância MagnéticaRESUMO
INTRODUCTION AND IMPORTANCE: Portal biliopathy (PB) is an abnormality of the biliary tree wall due to extrahepatic portal hypertension. Among the complications of portal biliopathy are digestive bleeding, jaundice, and cholangitis. Surgical treatment is an exception when medical management is not possible. CASE PRESENTATION: This is a case series study of four patients with severe PB complications requiring surgical management in our center from 2005 to 2016. Two of them had previous surgical procedures related to portal hypertension. All presented with severe biliary stenosis and recurrent cholangitis, and two also had massive upper gastrointestinal bleeding. Because of endoscopic management failure, a Roux-en-Y hepaticojejunostomy was performed in all cases. Two patients presented morbidity Clavien-Dindo>IIIA, requiring reoperation. During follow-up, no one developed other complications related to PB. DISCUSSION: Surgical treatment for PB complications is a challenge and mainly implies a portosystemic shunt as a first step. When it fails, an alternative is perform a biliodigestive anastomoses, with high risk of bleeding given the prominent collaterals present in the hepatoduodenal pedicle secondary to portal cavernomatosis. CONCLUSION: Our patients after YRGB didn't present new complications due to PB. The surgery could be a definite solution for PB complications. It has only been made for selective cases because it implies high complexity and risk.
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The SEEG methodology has gained favor in North America over the last decade as a means of localizing the epileptogenic zone (EZ) prior to epilepsy surgery. Recently, the application of a robotic stereotactic guidance system for implantation of SEEG electrodes has become more popular in many epilepsy centers. The technique for the use of the robot requires extreme precision in the pre-surgical planning phase and then the technique is streamlined during the operative portion of the methodology, as the robot and surgeon work in concert to implant the electrodes. Herein is detailed precise operative methodology of using the robot to guide implantation of SEEG electrodes. A major limitation of the procedure, namely its heavy reliance on the ability to register the patient to a preoperative volumetric magnetic resonance image (MRI), is also discussed. Overall, this procedure has been shown to have a low morbidity rate and an extremely low mortality rate. The use of a robotic stereotactic guidance system for the implantation of SEEG electrodes is an efficient, fast, safe, and accurate alternative to conventional manual implantation strategies.
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Epilepsia , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Eletrodos Implantados , Técnicas Estereotáxicas , Epilepsia/cirurgia , Imageamento Tridimensional , Eletroencefalografia/métodosRESUMO
OBJECTIVE: Posttraumatic epilepsy (PTE) develops in as many as one third of severe traumatic brain injury (TBI) patients, often years after injury. Analysis of early electroencephalographic (EEG) features, by both standardized visual interpretation (viEEG) and quantitative EEG (qEEG) analysis, may aid early identification of patients at high risk for PTE. METHODS: We performed a case-control study using a prospective database of severe TBI patients treated at a single center from 2011 to 2018. We identified patients who survived 2 years postinjury and matched patients with PTE to those without using age and admission Glasgow Coma Scale score. A neuropsychologist recorded outcomes at 1 year using the Expanded Glasgow Outcomes Scale (GOSE). All patients underwent continuous EEG for 3-5 days. A board-certified epileptologist, blinded to outcomes, described viEEG features using standardized descriptions. We extracted 14 qEEG features from an early 5-min epoch, described them using qualitative statistics, then developed two multivariable models to predict long-term risk of PTE (random forest and logistic regression). RESULTS: We identified 27 patients with and 35 without PTE. GOSE scores were similar at 1 year (p = .93). The median time to onset of PTE was 7.2 months posttrauma (interquartile range = 2.2-22.2 months). None of the viEEG features was different between the groups. On qEEG, the PTE cohort had higher spectral power in the delta frequencies, more power variance in the delta and theta frequencies, and higher peak envelope (all p < .01). Using random forest, combining qEEG and clinical features produced an area under the curve of .76. Using logistic regression, increases in the delta:theta power ratio (odds ratio [OR] = 1.3, p < .01) and peak envelope (OR = 1.1, p < .01) predicted risk for PTE. SIGNIFICANCE: In a cohort of severe TBI patients, acute phase EEG features may predict PTE. Predictive models, as applied to this study, may help identify patients at high risk for PTE, assist early clinical management, and guide patient selection for clinical trials.
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Lesões Encefálicas Traumáticas , Epilepsia Pós-Traumática , Humanos , Estudos de Casos e Controles , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico , Epilepsia Pós-Traumática/diagnóstico , Epilepsia Pós-Traumática/etiologia , Eletroencefalografia , Escala de Coma de GlasgowRESUMO
OBJECTIVE: To develop a new method to quantify visually-enhanced vestibulo-ocular reflex (VVOR) gain, in patients with vestibular function loss, that is mathematically suitable given the nature of the test, and determine the reliability of the method by comparing results with those of the gold standard, the video head impulse test (vHIT). MATERIALS AND METHODS: We developed a new method for VVOR gain quantification and conducted a cross-sectional study in patients diagnosed with vestibular function loss and controls, all participants undergoing both a VVOR test and a vHIT. We measured VVOR gain with three different methods: area under the curve (AUC), slope regression, and a Fourier method (VVORAUC , VVORSP , and VVORFR , respectively); and compared these gain values with vHIT gain calculated using the AUC method. RESULTS: Overall, 111 patients were included: 29 healthy subjects and 82 patients with vestibular function loss. Intraclass correlation coefficients (ICC(1,1)) between gain from the gold standard and each of the VVOR gain methods were: 0.68 (CI: 0.61-0.75) for VVORAUC , 0.66 (CI: 0.58-0.73) for VVORSP and 0.71 (CI: 0.64-0.77) for VVORFR . No interference was found between VVOR gain calculation methods and potentially influential variables considered (p ≥ 0.98). CONCLUSION: The new method for quantifying VVOR gain showed good concordance with the vHIT method. LEVEL OF EVIDENCE: 2: Individual cross-sectional studies with consistently applied reference standard and blinding (Diagnosis) Laryngoscope, 133:3554-3563, 2023.
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Reflexo Vestíbulo-Ocular , Vestíbulo do Labirinto , Humanos , Estudos Transversais , Reprodutibilidade dos Testes , Teste do Impulso da Cabeça/métodosRESUMO
Cerebral white matter lesions prevent cortico-spinal descending inputs from effectively activating spinal motoneurons, leading to loss of motor control. However, in most cases, the damage to cortico-spinal axons is incomplete offering a potential target for new therapies aimed at improving volitional muscle activation. Here we hypothesized that, by engaging direct excitatory connections to cortico-spinal motoneurons, stimulation of the motor thalamus could facilitate activation of surviving cortico-spinal fibers thereby potentiating motor output. To test this hypothesis, we identified optimal thalamic targets and stimulation parameters that enhanced upper-limb motor evoked potentials and grip forces in anesthetized monkeys. This potentiation persisted after white matter lesions. We replicated these results in humans during intra-operative testing. We then designed a stimulation protocol that immediately improved voluntary grip force control in a patient with a chronic white matter lesion. Our results show that electrical stimulation targeting surviving neural pathways can improve motor control after white matter lesions.
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BACKGROUND: Hepatolithiasis is a prevalent disease in Asia but rare in Western countries. An increasing number of cases have been reported in Latin America. Liver resection has been proposed as a definitive treatment for complete stone clearance. The aim of this study was to evaluate the postoperative outcomes of liver resection for the treatment of hepatolithiasis in 2 large hepatobiliary reference centers from South America. METHODS: We conducted a retrospective descriptive analysis from patients with hepatolithiasis who underwent liver resection between November 1986 and December 2018, in 2 Latin-American centers in Chile and Brazil. RESULTS: One hundred forty-nine patients underwent liver resection for hepatolithiasis (72 in Chile, 77 in Brazil). The mean age was 49 years and most patients were female (62.4%). Hepatolithiasis was localized in the left lobe (61.7%), right lobe (24.2%), and bilateral lobe (14.1%). Bilateral lithiasis was associated with higher incidence of preoperative and postoperative cholangitis (81% vs 46.9% and 28.6% vs 6.1%) and need for hepaticojejunostomy (52.4%). In total, 38.9% of patients underwent major hepatectomy and 14.1% were laparoscopic. The postoperative stone clearance was 100%. The 30-day morbidity and mortality rates were 30.9% and 0.7%, respectively. Cholangiocarcinoma was seen in 2 specimens, and no postoperative malignancy were seen after a median follow-up of 38 months. Fourteen patients (9.4%) had intrahepatic stones recurrence. CONCLUSIONS: Liver resection is an effective and definitive treatment for patients with hepatolithiasis. Bilateral hepatolithiasis was associated with perioperative cholangitis, the need for hepaticojejunostomy, and recurrent disease. Resection presents a high rate of biliary tree stone clearance and excellent long-term results, with low recurrence rates and low risk of malignancy.
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Neoplasias dos Ductos Biliares , Colangite , Cálculos Biliares , Litíase , Hepatopatias , Humanos , Pessoa de Meia-Idade , Hepatopatias/epidemiologia , Hepatopatias/cirurgia , Hepatopatias/complicações , Litíase/cirurgia , Estudos Retrospectivos , Hepatectomia/métodos , América Latina/epidemiologia , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Cálculos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Neoplasias dos Ductos Biliares/cirurgia , Colangite/cirurgiaRESUMO
Hydrogen sulfide (H2S) is a unique signaling molecule that, along with carbon monoxide and nitric oxide, belongs to the gasotransmitters family. H2S is endogenously synthesized by enzymatic and non-enzymatic pathways. Three enzymatic pathways involving cystathionine-γ-lyase, cystathionine-ß-synthetase, and 3-mercaptopyruvate sulfurtransferase are known as endogenous sources of H2S. This gaseous molecule has recently emerged as a regulator of many systems and physiological functions, including the cardiovascular system where it controls the vascular tone of small arteries. In this context, H2S leads to vasorelaxation by regulating the activity of vascular smooth muscle cells, endothelial cells, and perivascular nerves. Specifically, H2S modulates the functionality of different ion channels to inhibit the autonomic sympathetic outflow-by either central or peripheral mechanisms-or to stimulate perivascular sensory nerves. These mechanisms are particularly relevant for those pathological conditions associated with impaired neuromodulation of vascular tone. In this regard, exogenous H2S administration efficiently attenuates the increased activity of the sympathetic nervous system often seen in patients with certain pathologies. These effects of H2S on the autonomic sympathetic outflow will be the primary focus of this review. Thereafter, we will discuss the central and peripheral regulatory effects of H2S on vascular tone. Finally, we will provide the audience with a detailed summary of the current pathological implications of H2S modulation on the neural regulation of vascular tone.
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Gasotransmissores , Sulfeto de Hidrogênio , Humanos , Sulfeto de Hidrogênio/metabolismo , Células Endoteliais/metabolismo , Gasotransmissores/metabolismo , Neurotransmissores/farmacologia , Transdução de SinaisRESUMO
OBJECTIVE: In mesial temporal lobe epilepsy (MTLE), the ideal surgical approach to achieve seizure freedom and minimize morbidity is an unsolved question. Selective approaches to mesial temporal structures often result in suboptimal seizure outcomes. The authors report the results of a pilot study intended to evaluate the clinical feasibility of using an endoscopic anterior transmaxillary (eATM) approach for minimally invasive management of MTLEs. METHODS: The study is a prospectively collected case series of four consecutive patients who underwent the eATM approach for the treatment of MTLE and were followed for a minimum of 12 months. All participants underwent an epilepsy workup and surgical care at a tertiary referral comprehensive epilepsy center and had medically refractory epilepsy. The noninvasive evaluations and intracranial recordings of these patients confirmed the presence of anatomically restricted epileptogenic zones located in the mesial temporal structures. Data on seizure freedom at 1 year, neuropsychological outcomes, diffusion tractography, and adverse events were collected and analyzed. RESULTS: By applying the eATM technique and approaching the far anterior temporal lobe regions, mesial-basal resections of the temporal polar areas and mesial temporal structures were successfully achieved in all patients (2 with left-sided approaches, 2 with right-sided approaches). No neurological complications or neuropsychological declines were observed. All 4 patients achieved Engel class Ia outcome up to the end of the follow-up period (19, 15, 14, and 12 months). One patient developed hypoesthesia in the left V2 distribution but there were no other adverse events. The low degree of white matter injury from the eATM approach was analyzed using high-definition fiber tractography in 1 patient as a putative mechanism for preserving neuropsychological function. CONCLUSIONS: The described series demonstrates the feasibility and potential safety profile of a novel approach for medically refractory MTLE. The study affirms the feasibility of performing efficacious mesial temporal lobe resections through an eATM approach.
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Epilepsia do Lobo Temporal , Epilepsia , Humanos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/cirurgia , Estudos de Viabilidade , Projetos Piloto , Resultado do Tratamento , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/cirurgia , Hipocampo/cirurgiaRESUMO
Eye tracking and other behavioral measurements collected from patient-participants in their hospital rooms afford a unique opportunity to study natural behavior for basic and clinical translational research. We describe an immersive social and behavioral paradigm implemented in patients undergoing evaluation for surgical treatment of epilepsy, with electrodes implanted in the brain to determine the source of their seizures. Our studies entail collecting eye tracking with other behavioral and psychophysiological measurements from patient-participants during unscripted behavior, including social interactions with clinical staff, friends, and family in the hospital room. This approach affords a unique opportunity to study the neurobiology of natural social behavior, though it requires carefully addressing distinct logistical, technical, and ethical challenges. Collecting neurophysiological data synchronized to behavioral and psychophysiological measures helps us to study the relationship between behavior and physiology. Combining across these rich data sources while participants eat, read, converse with friends and family, etc., enables clinical-translational research aimed at understanding the participants' disorders and clinician-patient interactions, as well as basic research into natural, real-world behavior. We discuss data acquisition, quality control, annotation, and analysis pipelines that are required for our studies. We also discuss the clinical, logistical, and ethical and privacy considerations critical to working in the hospital setting.
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Encéfalo , Comportamento Social , Humanos , PrivacidadeRESUMO
Sensory input flow is central to voluntary movements. For almost a century, GABA was believed to modulate this flow by inhibiting sensory axons in the spinal cord to sculpt neural inputs into skilled motor output. Instead, here we show that GABA can also facilitate sensory transmission in monkeys and consequently increase spinal and cortical neural responses to sensory inputs challenging our understanding of generation and perception of movement.
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Traditional methods to access subcortical structures involve the use of anatomical atlases and high precision stereotaxic frames but suffer from significant variations in implantation accuracy. Here, we leveraged the use of the ROSA One(R) Robot Assistance Platform in non-human primates to study electrophysiological interactions of the corticospinal tract with spinal cord circuits. We were able to target and stimulate the corticospinal tract within the internal capsule with high accuracy and efficiency while recording spinal local field potentials and multi-unit spikes. Our method can be extended to any subcortical structure and allows implantation of multiple deep brain stimulation probes at the same time. Clinical Relevance- Our method will allow us to elucidate further roles of the corticospinal tract and its interactions with other processing centers in intact animals and in motor syndromes in the future.