RESUMO
All tissues undergo continuous reconditioning via the complex orchestration of changes in tissue protein synthesis and breakdown rates. Skeletal muscle tissue has been well studied in this regard, and has been shown to turnover at a rate of 1-2% per day in vivo in humans. Few data are available on protein synthesis rates of other tissues. Because of obvious limitations with regard to brain tissue sampling no study has ever measured brain protein synthesis rates in vivo in humans. Here, we applied stable isotope methodology to directly assess protein synthesis rates in neocortex and hippocampus tissue of six patients undergoing temporal lobectomy for drug-resistant temporal lobe epilepsy (Clinical trial registration: NTR5147). Protein synthesis rates of neocortex and hippocampus tissue averaged 0.17 ± 0.01 and 0.13 ± 0.01%/h, respectively. Brain tissue protein synthesis rates were 3-4-fold higher than skeletal muscle tissue protein synthesis rates (0.05 ± 0.01%/h; P < 0.001). In conclusion, the protein turnover rate of the human brain is much higher than previously assumed.
Assuntos
Encéfalo/fisiopatologia , Epilepsia do Lobo Temporal/patologia , Plasticidade Neuronal/fisiologia , Proteínas/metabolismo , Adulto , Encéfalo/cirurgia , Isótopos de Carbono , Epilepsia do Lobo Temporal/sangue , Epilepsia do Lobo Temporal/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuronavegação , Procedimentos Neurocirúrgicos/métodos , Fenilalanina/metabolismo , Fatores de TempoRESUMO
BACKGROUND: Stereoelectroencephalography (SEEG) is an established diagnostic technique for the localization of the epileptogenic zone in drug-resistant epilepsy. In vivo accuracy of SEEG electrode positioning is of paramount importance since higher accuracy may lead to more precise resective surgery, better seizure outcome and reduction of complications. OBJECTIVE: To describe experiences with the SEEG technique in our comprehensive epilepsy center, to illustrate surgical methodology, to evaluate in vivo application accuracy and to consider the diagnostic yield of SEEG implantations. METHODS: All patients who underwent SEEG implantations between September 2008 and April 2016 were analyzed. Planned electrode trajectories were compared with post-implantation trajectories after fusion of pre- and postoperative imaging. Quantitative analysis of deviation using Euclidean distance and directional errors was performed. Explanatory variables for electrode accuracy were analyzed using linear regression modeling. The surgical methodology, procedure-related complications and diagnostic yield were reported. RESULTS: Seventy-six implantations were performed in 71 patients, and a total of 902 electrodes were implanted. Median entry and target point deviations were 1.54 mm and 2.93 mm. Several factors that predicted entry and target point accuracy were identified. The rate of major complications was 2.6%. SEEG led to surgical therapy of various modalities in 53 patients (69.7%). CONCLUSIONS: This study demonstrated that entry and target point localization errors can be predicted by linear regression models, which can aid in identification of high-risk electrode trajectories and further enhancement of accuracy. SEEG is a reliable technique, as demonstrated by the high accuracy of conventional frame-based implantation methodology and the good diagnostic yield.
Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Eletrodos Implantados/efeitos adversos , Eletroencefalografia/métodos , Complicações Pós-Operatórias/etiologia , Técnicas Estereotáxicas/efeitos adversos , Adolescente , Adulto , Epilepsia Resistente a Medicamentos/diagnóstico , Eletroencefalografia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controleRESUMO
INTRODUCTION: Intensive care management for traumatic brain injury (TBI) patients aims to prevent secondary cerebral damage. Targeted temperature management is one option to prevent cerebral damage, as hypothermia may have protective effects. By conducting a systematic literature review we evaluated: 1) the presence of a temperature difference (gradient) between brain temperature (Tb) and core temperature (Tc) in TBI patients; and 2) clinical factors associated with reported differences. EVIDENCE ACQUISITION: The PubMed database was systematically searched using Mesh terms and key words, and Web of Sciences was assessed for additional article citations. We included studies that continuously and simultaneously measured Tb and Tc in severe TBI patients. The National Institutes of Health (NIH) quality assessment tool for observational cohort and cross-sectional studies was modified to fit the purpose of our study. Statistical data were extracted for further meta-analyses. EVIDENCE SYNTHESIS: We included 16 studies, with a total of 480 patients. Clinical heterogeneity consisted of Tb/Tc measurement site, measurement device, physiological changes, local protocols, and medical or surgical interventions. The studies have a high statistical heterogeneity (I2). The pooled mean temperature gradient between Tb and Tc was +0.14 °C (95% confidence interval: 0.03 to 0.24) and ranged from -1.29 to +1.1 °C. Patients who underwent a decompressive (hemi)craniectomy showed lower Tb values compared to Tc found in three studies. CONCLUSIONS: Studies on Tb and Tc are heterogeneous and show that, on average, Tb and Tc are not clinically significant different in TBI patients (<0.2 °C). Interpretations and interventions of the brain and central temperatures will benefit from standardization of temperature measurements.
Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Humanos , Temperatura , Estudos Transversais , Lesões Encefálicas Traumáticas/cirurgia , Encéfalo/cirurgia , Estudos Observacionais como AssuntoRESUMO
Temporal lobe epilepsy (TLE) is increasingly associated with blood-brain barrier dysfunction and microvascular alterations, yet the pathophysiological link is missing. An important barrier function is exerted by the glycocalyx, a gel-like layer coating the endothelium. To explore such associations, we used intraoperative videomicroscopy to quantify glycocalyx and microcirculation properties of the neocortex and hippocampus of 15 patients undergoing resective brain surgery as treatment for drug-resistant TLE, and 15 non-epileptic controls. Fluorescent lectin staining of neocortex and hippocampal tissue was used for blood vessel surface area quantification. Neocortical perfused boundary region, the thickness of the glycocalyx' impaired layer, was higher in patients (2.64 ± 0.52 µm) compared to controls (1.31 ± 0.29 µm), P < 0.01, indicative of reduced glycocalyx integrity in patients. Moreover, erythrocyte flow velocity analysis revealed an impaired ability of TLE patients to (de-)recruit capillaries in response to changing metabolic demands (R2 = 0.75, P < 0.01), indicating failure of neurovascular coupling mechanisms. Blood vessel quantification comparison between intraoperative measurements and resected tissue showed strong correlation (R2 = 0.94, P < 0.01). This is the first report on in vivo assessment of glycocalyx and microcirculation properties in TLE patients, confirming the pivotal role of cerebrovascular changes. Further assessment of the cerebral microcirculation in relation to epileptogenesis might open avenues for new therapeutic targets for drug-resistant epilepsy.
Assuntos
Epilepsia do Lobo Temporal , Humanos , Epilepsia do Lobo Temporal/cirurgia , Glicocálix , Microcirculação/fisiologia , Barreira Hematoencefálica , CapilaresRESUMO
INTRODUCTION: Resective epilepsy surgery is often seen as a last resort when treating drug-resistant epilepsy. Positive results on quality of life (QoL) and economic benefits after surgery argue for a less restrictive attitude towards epilepsy surgery for drug-resistant epilepsy. QoL and economic benefits are country-dependent. The objective of the Resective Epilepsy Surgery, QUality of life and Economic evaluation (RESQUE) trial is to evaluate the change in QoL before and after epilepsy surgery in Dutch people with drug-resistant epilepsy. The results will form part of an economic evaluation of epilepsy surgery in people with epilepsy (PWE) in The Netherlands. METHODS AND ANALYSIS: A longitudinal prospective multicentre cohort study involving 100 PWE undergoing epilepsy surgery between 2019 and 2025 is being performed in three Dutch academic hospitals. Excluded are PWE who have a lower level of intelligence (TIQ<70) or who do not master the Dutch language. Before surgery and 3, 6, 12 and 24 months after surgery, PWE receive validated online questionnaires (QOLIE-31, EQ-5D, iMCQ and iPCQ) on QoL, cost of care, expectations and satisfaction. Primary outcome is the change in QoL. Secondary outcomes are change in generic QoL, seizure reduction (International League Against Epilepsy Outcome Classification), medical consumption, productivity, the correlation between QoL and seizure reduction and expectation of and satisfaction with the surgery. ETHICS AND DISSEMINATION: The study design has been approved by the Medical Ethics Review Committee (METC) of Maastricht UMC+ (2019-1134) and the Amsterdam UMC (vu). At the time of writing, UMC Utrecht is in the process of considering approval. The study will be conducted according to the Dutch Medical Research Involving Human Subjects Act and the Declaration of Helsinki. The results will be publicly disclosed and submitted for publication in international peer-reviewed scientific journals. There is no veto on publication by the involved parties. TRIAL REGISTRATION: NL8278; Pre-results.
Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Humanos , Estudos de Coortes , Análise Custo-Benefício , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia/cirurgia , Epilepsia/complicações , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Qualidade de Vida , Convulsões , Resultado do TratamentoRESUMO
BACKGROUND: Ganglioglioma (GG) and dysembryoplastic neuroepithelial tumor (DNET) belong to the group of low-grade epilepsy-associated tumors (LEAT) and are the most prevalent tumor types found in patients undergoing epilepsy surgery. Histopathological differentiation between GG and DNET can be difficult on biopsies due to limited tumor tissue. CASE DESCRIPTION: Here, we present a rare case where a low-grade tumor was initially classified as DNET, based on biopsy findings and unfortunately dedifferentiated within 10 years into a glioblastoma multiforme. After gross total resection, the initial tumor was reclassified as GG. CONCLUSION: This case illustrates the diagnostic challenges of LEAT, especially on biopsy material. Therefore, we advocate to counsel for complete resection and histopathological diagnosis utilizing tumor markers to confirm the nature of the tumor and to advice type of follow-up and eventual concurrent treatment.
RESUMO
The glycocalyx is an important constituent of blood vessels located between the bloodstream and the endothelium. It plays a pivotal role in intercellular interactions in neuroinflammation, reduction of vascular oxidative stress, and provides a barrier regulating vascular permeability. In the brain, the glycocalyx is closely related to functions of the blood-brain barrier and neurovascular unit, both responsible for adequate neurovascular responses to potential threats to cerebral homeostasis. An aneurysmal subarachnoid hemorrhage (aSAH) occurs following rupture of an intracranial aneurysm and leads to immediate brain damage (early brain injury). In some cases, this can result in secondary brain damage, also known as delayed cerebral ischemia (DCI). DCI is a life-threatening condition that affects up to 30% of all aSAH patients. As such, it is associated with substantial societal and healthcare-related costs. Causes of DCI are multifactorial and thought to involve neuroinflammation, oxidative stress, neuroinflammation, thrombosis, and neurovascular uncoupling. To date, prediction of DCI is limited, and preventive and effective treatment strategies of DCI are scarce. There is increasing evidence that the glycocalyx is disrupted following an aSAH, and that glycocalyx disruption could precipitate or aggravate DCI. This review explores the potential role of the glycocalyx in the pathophysiological mechanisms contributing to DCI following aSAH. Understanding the role of the glycocalyx in DCI could advance the development of improved methods to predict DCI or identify patients at risk for DCI. This knowledge may also alter the methods and timing of preventive and treatment strategies of DCI. To this end, we review the potential and limitations of methods currently used to evaluate the glycocalyx, and strategies to restore or prevent glycocalyx shedding.
RESUMO
The purpose of this study was to determine a possible association between two GABA transporter (GAT) single-nucleotide polymorphisms (SNPs), rs2697153 G>A in SLC6A1 (GAT-1) and rs2272400 C>T in SLC6A11 (GAT-3), and drug-resistant temporal lobe epilepsy (TLE). DNA was isolated from 138 TLE patients (from the neocortex) and 94 non-epileptic controls (from blood/buccal swaps), and amplified by polymerase chain reaction and subjected to restriction fragment length polymorphism assays. A subgroup of patients with a positive history of febrile seizures (FS+) and traumatic brain injury (TBI+) were investigated in a separate analysis. P values were obtained using the Chi-Square test and Fishers exact test. The GAT-1 SNP was different between patients and controls (p<0.05); the AA genotype was observed in 40% of the cases vs 23% of the controls (p<0.05). Thirty-one patients were FS+ and the GAT-3 CT genotype was observed significantly more frequently in the FS+ group (14%) than in the FS- group (1%; p<0.01). Thirteen patients were TBI+, and genotyping for GAT-1 and GAT-3 in these patients did not result in statistical differences between TBI+ and TBI- groups. The findings suggest that TLE is associated with GAT-1 and GAT-3 SNPs. More specifically, GAT-3 c1572T seems to be associated with TLE in patients with FS+. However, the pathophysiological consequences of these SNPs remain to be elucidated.
Assuntos
Epilepsia do Lobo Temporal/genética , Proteínas da Membrana Plasmática de Transporte de GABA/genética , Convulsões Febris/genética , Adulto , Epilepsia do Lobo Temporal/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Since the International Subarachnoid Aneurysm Trial, coiling has been favored over clipping for intracranial aneurysms, resulting in selection of increasingly complex aneurysm configurations for clipping. We present the outcomes of clipping of aneurysms not suitable for coiling, with transit time flowmetry technology to aid monitoring of intraoperative flow. METHODS: All consecutive patients surgically treated for intracranial aneurysms were included. We assessed intraoperative arterial blood flow in relation to postoperative ischemia and unfavorable outcome (modified Rankin Scale score 3-6), along with radiological occlusion rate, at 6 months and 1 year after surgery. RESULTS: Mortality at 1 year was 7.9%, with a 21.6% rate of an unfavorable outcome. Almost all (96.1%) of patients with unruptured aneurysms had an favorable outcome at 1 year, compared with 71.9% of patients with aneurysmal subarachnoid hemorrhage. Postoperative computed tomography imaging showed an 86.7% occlusion rate and a 7.5% rate of clip-related ischemia. Flow <40% of baseline significantly predicted clip-related ischemia (odds ratio [OR], 5.14; 95% confidence interval [CI], 1.41-8.4; P = 0.012). Clip reposition aided by transit time flowmetry resulted in restored flow >50% above baseline flow in 85.7% of aneurysms. Less than 50% flow from baseline was an independent predictor of unfavorable outcome (OR, 3.85; 95% CI, 1.6-9.0; P = 0.001), along other risk factors. CONCLUSION: In this study of clinical and radiological outcomes of surgically treated cerebral aneurysms not suitable for unassisted coiling, we showed positive results for these challenging aneurysms, aided by transit time flowmetry as a valuable tool, providingquantitative measurements of arterial blood flow to help achieve optimal clip placement and minimizing aneurysm residuals that may be sites of rebleeding. Adequate flow, defined as ≥50% of baseline, greatly reduces the risk of unfavorable outcome.
Assuntos
Aneurisma Roto/cirurgia , Aneurisma Intracraniano/cirurgia , Adulto , Idoso , Aneurisma Roto/mortalidade , Aneurisma Roto/patologia , Angiografia Digital/métodos , Angiografia por Tomografia Computadorizada/métodos , Procedimentos Endovasculares/métodos , Feminino , Humanos , Aneurisma Intracraniano/mortalidade , Aneurisma Intracraniano/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Resultado do TratamentoRESUMO
About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping (ESM) is the gold standard for the identification of "eloquent" areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects. Broadband gamma activity (55-200 Hz) recorded with extraoperative electrocorticography (ECoG) during cognitive tasks may be an alternative to ESM but until now has not proven of definitive clinical value. Considering their role in cognition, the alpha (8-12 Hz) and beta (15-25 Hz) bands could further improve the identification of eloquent cortex. We compared gamma, alpha and beta activity, and their combinations for the identification of eloquent cortical areas defined by ESM. Ten patients with intractable focal epilepsy (age: 35.9 ± 9.1 years, range: 22-48, 8 females, 9 right handed) participated in a delayed-match-to-sample task, where syllable sounds were compared to visually presented letters. We used a generalized linear model (GLM) approach to find the optimal weighting of each band for predicting ESM-defined categories and estimated the diagnostic ability by calculating the area under the receiver operating characteristic (ROC) curve. Gamma activity increased more in eloquent than in non-eloquent areas, whereas alpha and beta power decreased more in eloquent areas. Diagnostic ability of each band was close to 0.7 for all bands but depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient's degree of attention to the stimulus. We show that diagnostic ability can be increased by 3-5% by combining gamma and alpha and by 7.5-11% when gamma and beta were combined. We then show how ECoG power modulation from cognitive testing can be used to map the probability of eloquence in individual patients and how this probability map can be used in clinical settings to optimize ESM planning. We conclude that the combination of gamma and beta power modulation during cognitive testing can contribute to the identification of eloquent areas prior to ESM in patients with refractory focal epilepsy.
RESUMO
BACKGROUND: Temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) is a common pharmaco-resistant epilepsy referred for adult epilepsy surgery. Though associated with prolonged febrile seizures (FS) in childhood, the neurobiological basis for this relationship is not fully understood and currently no preventive or curative therapies are available. DNA methylation, an epigenetic mechanism catalyzed by DNA methyltransferases (DNMTs), potentially plays a pivotal role in epileptogenesis associated with FS. In an attempt to start exploring this notion, the present cross-sectional pilot study investigated whether global DNA methylation levels (5-mC and 5-hmC markers) and DNMT isoforms (DNMT1, DNMT3a1, and DNMT3a2) expression would be different in hippocampal and neocortical tissues between controls and TLE patients with or without a history of FS. RESULTS: We found that global DNA methylation levels and DNMT3a2 isoform expression were lower in the hippocampus for all TLE groups when compared to control patients, with a more significant decrease amongst the TLE groups with a history of FS. Interestingly, we showed that DNMT3a1 expression was severely diminished in the hippocampus of TLE patients with a history of FS in comparison with control and other TLE groups. In the neocortex, we found a higher expression of DNMT1 and DNMT3a1 as well as increased levels of global DNA methylation for all TLE patients compared to controls. CONCLUSION: Together, the findings of this descriptive cross-sectional pilot study demonstrated brain region-specific changes in DNMT1 and DNMT3a isoform expression as well as global DNA methylation levels in human TLE with or without a history of FS. They highlighted a specific implication of DNMT3a isoforms in TLE after FS. Therefore, longitudinal studies that aim at targeting DNMT3a isoforms to evaluate the potential causal relationship between FS and TLE or treatment of FS-induced epileptogenesis seem warranted.
Assuntos
DNA (Citosina-5-)-Metiltransferase 1/genética , DNA (Citosina-5-)-Metiltransferases/genética , Epilepsia do Lobo Temporal/genética , Hipocampo/química , Neocórtex/química , Convulsões Febris/epidemiologia , Estudos de Casos e Controles , Estudos Transversais , Metilação de DNA , DNA Metiltransferase 3A , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Especificidade de Órgãos , Projetos Piloto , Convulsões Febris/genéticaRESUMO
INTRODUCTION: Effective treatment of new-onset headache after craniotomy, especially anterior temporal lobectomy (ATL) and amygdalohippocampectomy for drug-resistant temporal lobe epilepsy, is a challenge. The current practice, acetaminophen combined with opioids is often reported by patients as insufficient and sometimes accompanied by opioid-related adverse effects. Based on expert opinion, anaesthesiologists therefore frequently consider s-ketamine as add-on therapy. This randomised parallel group design trial compares s-ketamine with a placebo as add on medication to a multimodal pain approach. METHODS AND ANALYSIS: In total 62 adult participants, undergoing ATL for drug resistant epilepsy under general anaesthesia, will be randomised to either receive a 0.25 mg/kg bolus followed by a continuous infusion of 0.1 mg/kg/hour of s-ketamine or placebo (0.9% NaCl) starting before incision and continued for 48 hours as an addition to acetaminophen and opioids administered in a patient-controlled analgesia pump. The primary outcome measure is the cumulative postoperative opioid consumption. Patient recruitment started August 2018 and will end in 2021. Secondary outcome measures are postoperative pain intensity scores, psychological parameters, length of hospital stay and adverse events and will be reassessed at 3 and 6 months after surgery, with a baseline measurement preoperatively. All data are collected by researchers who are blinded to the treatment. The data will be analysed by multivariable linear mixed-effects regression. ETHICS AND DISSEMINATION: Ethical approval has been given by the local medical ethical committee (NL61666.068.17). This study will be conducted in accordance with the Dutch Medical Research Involving Human Subjects Act and the Declaration of Helsinki. The results of this trial will be publicly disclosed and submitted for publication in an international peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NTR6480.
Assuntos
Acetaminofen/uso terapêutico , Analgésicos não Narcóticos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Epilepsia/cirurgia , Cefaleia/tratamento farmacológico , Ketamina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Método Duplo-Cego , Combinação de Medicamentos , Cefaleia/etiologia , Humanos , Procedimentos Neurocirúrgicos/efeitos adversos , Dor Pós-Operatória/etiologia , Assistência Perioperatória , Resultado do TratamentoRESUMO
BACKGROUND: We present a case of orbital compartment syndrome (OCS) leading to monocular irreversible blindness following a pterional craniotomy for clipping of an anterior communicating artery aneurysm. OCS is an uncommon but vision-threatening entity requiring urgent decompression to reduce the risk of permanent visual loss. Iatrogenic orbital roof defects are a common finding following pterional craniotomies. However, complications related to these defects are rarely reported. CASE DESCRIPTION: A 65-year-old female who underwent an anterior communicating artery clipping via a pterional approach 4 days before developed proptosis, ocular movement paresis, and irreversible visual impairment following an orthopedic surgery. Computed tomography images revealed an intraorbital cerebrospinal fluid (CSF) collection, which was evacuated via an acute recraniotomy. The next day, proptosis and intraorbital CSF collection on computed tomography images reoccurred and an oral and maxillofacial surgeon evacuated the collection via a blepharoplasty incision and blunt dissection. In addition, the patient was treated with acetazolamide and an external lumbar CSF drainage during 12 days. Hereafter, the CSF collection did not reoccur. Unfortunately, monocular blindness was persistent. We hypothesize the CSF collection occurred due to the combination of a postoperative orbital roof defect and a temporarily increased intracranial pressure during the orthopedic surgery. CONCLUSION: We plead for more awareness of this severe complication after pterional surgeries and emphasize the importance of 1) strict ophthalmologic examination after pterional craniotomies in case of intracranial pressure increasing events, 2) immediate consultation of an oral and maxillofacial surgeon, and 3) consideration of CSF-draining interventions since symptoms are severely invalidating and irreversible within a couple of hours.
Assuntos
Cegueira/diagnóstico por imagem , Síndromes Compartimentais/diagnóstico por imagem , Craniotomia/efeitos adversos , Órbita/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Doença Aguda , Idoso , Cegueira/etiologia , Síndromes Compartimentais/etiologia , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Complicações Pós-Operatórias/etiologia , Osso Esfenoide/diagnóstico por imagem , Osso Esfenoide/cirurgiaRESUMO
BACKGROUND: The regulation of cerebral arterial vasomotor tone involves several mechanisms. The role of sympathetic nerves and the adrenergic neurotransmitter, noradrenaline (NA), has been the subject of debate for decades. Moreover, the specific role of endothelin-1 (ET-1) in cerebral arterial vasoconstriction has not been elucidated to date. In this study, we evaluated the contribution of NA and ET-1 to cerebral artery vasoconstriction. METHODS: Arterial responses of rat middle cerebral arteries, and human pial cerebral arteries to cumulative concentrations of NA and ET-1, and to Electrical Field Stimulation (EFS), were evaluated. To assess the role of NA and ET-1 when EFS was applied, experiments were performed in the presence of adrenergic, neurogenic, and endothelin-1 receptor modulators. RESULTS: We found that vasoconstriction of cerebral arteries following EFS requires the application of exogenous NA, whereas neither EFS nor NA alone induced vasoconstriction. The observed vasoconstriction was abolished by α-adrenoreceptor antagonist, catecholamine-release inhibitor, blockade of the perivascular neurons, and by the endothelin-2 receptor antagonist (BQ123). CONCLUSION: Based on our results, cerebral artery vasoconstriction requires simultaneous neurogenic and adrenergic activation and is ET-1 dependent. We hypothesize that NA modulates the release of ET-1. Upon release, ET-1 binds to the ETA-receptor on smooth muscle cells inducing cerebral artery vasoconstriction.
Assuntos
Artérias Cerebrais/fisiologia , Endotelina-1/farmacologia , Norepinefrina/farmacologia , Receptor Cross-Talk/fisiologia , Receptores de Endotelina/fisiologia , Vasoconstrição/fisiologia , Adulto , Idoso , Animais , Artérias Cerebrais/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Endogâmicos WKY , Receptor Cross-Talk/efeitos dos fármacos , Receptores de Endotelina/agonistas , Vasoconstrição/efeitos dos fármacos , Adulto JovemRESUMO
OBJECTIVE: Dystrophin is part of a protein complex that connects the cytoskeleton to the extracellular matrix. In addition to its role in muscle tissue, it functions as an anchoring protein within the central nervous system such as in hippocampus and cerebellum. Its presence in the latter regions is illustrated by the cognitive problems seen in Duchenne Muscular Dystrophy (DMD). Since epilepsy is also supposed to constitute a comorbidity of DMD, it is hypothesized that dystrophin plays a role in neuronal excitability. Here, we aimed to study brain dystrophin distribution and expression in both, human and experimental temporal lobe epilepsy (TLE). METHOD: Regional and cellular dystrophin distribution was evaluated in both human and rat hippocampi and in rat cerebellar tissue by immunofluorescent colocalization with neuronal (NeuN and calbindin) and glial (GFAP) markers. In addition, hippocampal dystrophin levels were estimated by Western blot analysis in biopsies from TLE patients, post-mortem controls, amygdala kindled (AK)-, and control rats. RESULTS: Dystrophin was expressed in all hippocampal pyramidal subfields and in the molecular-, Purkinje-, and granular cell layer of the cerebellum. In these regions it colocalized with GFAP, suggesting expression in astrocytes such as Bergmann glia (BG) and velate protoplasmic astrocytes. In rat hippocampus and cerebellum there were neither differences in dystrophin positive cell types, nor in the regional dystrophin distribution between AK and control animals. Quantitatively, hippocampal full-length dystrophin (Dp427) levels were about 60% higher in human TLE patients than in post-mortem controls (p < 0.05), whereas the level of the shorter Dp71 isoform did not differ. In contrast, AK animals showed similar dystrophin levels as controls. CONCLUSION: Dystrophin is ubiquitously expressed by astrocytes in the human and rat hippocampus and in the rat cerebellum. Hippocampal full-length dystrophin (Dp427) levels are upregulated in human TLE, but not in AK rats, possibly indicating a compensatory mechanism in the chronic epileptic human brain.
RESUMO
PURPOSE: To determine hippocampal expression of neuronal GABA-transporter (GAT-1) and glial GABA-transporter (GAT-3) in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). METHODS: Hippocampal sections were immunohistochemically stained for GABA-transporter 1 and GABA-transporter-3, followed by quantification of the immunoreactivity in the hilus by optical density measurements. GABA-transporter 3 positive hilar cells were counted and GABA-transporter protein expression in sections that included all hippocampal subfields was quantified by Western blot. RESULTS: The hilar GABA-transporter 1 expression of patients with severe hippocampal sclerosis was about 7% lower compared to that in the mild hippocampal sclerosis/control group (p<0.001). The hilar GABA-transporter 3 expression was about 5% lower in the severe hippocampal sclerosis group than in the mild hippocampal sclerosis/control group (non-significant). Also, severe hippocampal sclerosis samples contained 34% less (non-significant) GABA-transporter 3 positive cells compared to that of controls. Protein expression as assessed by Western blot showed that GABA-transporter 1 was equally expressed in mild and severe hippocampal sclerosis samples, whereas GABA-transporter 3 was reduced by about 62% in severe hippocampal sclerosis samples (p<0.0001). CONCLUSION: These data confirm that GABA-transporter expression is spatially and isoform-specific reduced and GABA-transporter 3 positive cell numbers are unchanged in hippocampal sclerosis. Implications for the use of GABAergic antiepileptic therapies in hippocampal sclerosis vs non-hippocampal sclerosis patients remain to be studied.
Assuntos
Epilepsia do Lobo Temporal/metabolismo , Proteínas da Membrana Plasmática de Transporte de GABA/metabolismo , Hipocampo/metabolismo , Adolescente , Adulto , Autopsia , Criança , Pré-Escolar , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/cirurgia , Feminino , Hipocampo/patologia , Hipocampo/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Esclerose , Transmissão Sináptica , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Health care-related adverse events (HCRAEs), which should not be confused with (blameworthy) medical errors, are common; they can lead to hospital admissions and can have grave consequences. Although they are sometimes potentially preventable, information is lacking on HCRAEs leading to admission to different departments. AIM: This study aimed to gain insight into the incidence, type, severity, and preventability of HCRAEs (including adverse drug events) leading to hospitalization to the departments of internal medicine, surgery, orthopedics, neurology, and neurosurgery. Further, we explore if there are differences regarding these HCRAEs between these departments. METHODS: We retrospectively evaluated the medical records of all patients admitted through the emergency department (ED) in a 6-month period to the departments of internal medicine, surgery, orthopedics, neurology, and neurosurgery. All patients admitted because of HCRAEs were included. RESULTS: More than one-fifth (21.8%; range 12.0%-47.8%) of all admissions to the 5 departments were due to a HCRAE. Half (49.9%) of these HCRAEs were medication-related and 30.5% were procedure-related. In 6.5% of patients, the HCRAE led to permanent disability and another 4.4% of patients died during hospitalization. HCRAEs treated by internists and neurologists were usually medication-related, whereas HCRAEs treated by surgeons, orthopedic surgeons, and neurosurgeons were usually procedure-related. CONCLUSION: Hospital admissions to different departments are often caused by HCRAEs, which sometimes lead to permanent disability or even death. Gaining insight into similarities and differences in HCRAEs occurring in different specialties is a starting point for improving clinical outcomes.
Assuntos
Departamentos Hospitalares , Hospitalização , Erros Médicos , Especialização , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Países Baixos , Estudos Retrospectivos , Adulto JovemRESUMO
The purpose of this prospective observational study was to investigate the relation between the frequency of critical neuromonitoring parameters (brain tissue pO2, (PtiO2) < or = 10 mmHg, intracranial pressure (ICP) > 20 mmHg, cerebral perfusion pressure (CPP) < or = 70 mmHg) and outcome after severe aneurysmal subarachnoid hemorrhage (SAH). In a prospective study on 42 patients monitoring of ICP, CPP, and PtiO2 (in the area at risk for vasospasm) was performed. All patients were primarily classified as Hunt and Hess grade 4 or with secondary deterioration to this grade. Relative proportions of PtiO2 < or = 10 mmHg (n = 42), ICP > 20 mmHg (n = 25) and CPP < or = 70 mmHg (n = 23) were derived from multimodal neuromonitoring data sets for different time intervals, i.e. 1. the total monitoring time; 2. the total monitoring time without the last two monitoring days; 3. the second last monitoring day; and 4. the last monitoring day. Patients were divided into nonsurvivors (GOS = 1) and survivors (GOS = 3-5). For the total monitoring time, significant differences in the relative proportion of critical values were found for all neuromonitoring parameters (p < 0.05). The detailed analysis of consecutive time intervals revealed significantly increased proportions of critical values in nonsurvivors for all neuromonitoring parameters during the last day only. Additionally, ICP > 20 mmHg was significantly more frequent during the second last day (p < 0.01). For other time periods no differences were observed. We conclude, that critical neuromonitoring values are not early predictors of nonsurvival in patients suffering from severe SAH.
Assuntos
Encéfalo/metabolismo , Monitorização Fisiológica/métodos , Oxigênio/metabolismo , Hemorragia Subaracnóidea/metabolismo , Adulto , Cuidados Críticos , Humanos , Pressão Intracraniana , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/mortalidade , Tomografia Computadorizada por Raios XRESUMO
Intraosseous cavernous hemangiomas of the skull are rare lesions for which the origin is unclear. The authors present a case in which there was a radiologically documented history of trauma preceding the development of a hemangioma in the frontal bone. In a review of the literature the authors found 83 cases of skull hemangiomas, and 43% of the lesions were located in the frontal bone. In 25% of these lesions, previous trauma was reported anamnestically. The present case and radiological findings related to it suggest a causal relationship between trauma and the development of intraosseous hemangioma.