Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 12.027
Filtrar
1.
Molecules ; 26(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34205930

RESUMO

BACKGROUND: Neurotic disturbances, anxiety, neurosis-like disorders, and stress situations are widespread. Benzodiazepine tranquillizers have been found to be among the most effective antianxiety drugs. The pharmacological action of benzodiazepines is due to their interaction with the supra-molecular membrane GABA-a-benzodiazepine receptor complex, linked to the Cl-ionophore. Benzodiazepines enhance GABA-ergic transmission and this has led to a study of the role of GABA in anxiety. The search for anxiolytics and anticonvulsive agents has involved glutamate-ergic, 5HT-ergic substances and neuropeptides. However, each of these well-known anxiolytics, anticonvulsants and cognition enhancers (nootropics) has repeatedly been reported to have many adverse side effects, therefore there is an urgent need to search for new drugs able to restore damaged cognitive functions without causing significant adverse reactions. OBJECTIVE: Considering the relevance of epilepsy diffusion in the world, we have addressed our attention to the discovery of new drugs in this field Thus our aim is the synthesis and study of new compounds with antiepileptic (anticonvulsant) and not only, activity. METHODS: For the synthesis of compounds classical organic methods were used and developed. For the evaluation of biological activity some anticonvulsant and psychotropic methods were used. RESULTS: As a result of multistep reactions 26 new, five-membered heterocyclic systems were obtained. PASS prediction of anticonvulsant activity was performed for the whole set of the designed molecules and probability to be active Pa values were ranging from 0.275 to 0.43. The studied compounds exhibit protection against pentylenetetrazole (PTZ) seizures, anti-thiosemicarbazides effect as well as some psychotropic effect. The biological assays evidenced that some of the studied compounds showed a high anticonvulsant activity by antagonism with pentylenetetrazole. The toxicity of compounds is low and they do not induce muscle relaxation in the studied doses. According to the study of psychotropic activity it was found that the selected compounds have an activating behavior and anxiolytic effects on the models of "open field" and "elevated plus maze" (EPM). The data obtained indicate the anxiolytic (anti-anxiety) activity of the derivatives of pyrimidines, especially pronounced in compounds 6n, 6b, and 7c. The studied compounds increase the latent time of first immobilization on the model of "forced swimming" (FST) and exhibit some antidepressant effect similarly to diazepam. Docking studies revealed that compound 6k bound tightly in the active site of GABAA receptor with a value of the scoring function that estimates free energy of binding (ΔG) at -7.95 kcal/mol, while compound 6n showed the best docking score and seems to be dual inhibitor of SERT transporter as well as 5-HT1A receptor. CONCLUSIONS: Тhe selected compounds have an anticonvulsant, activating behavior and anxiolytic effects, at the same time exhibit some antidepressant effect.


Assuntos
Azepinas/administração & dosagem , Azepinas/síntese química , Pirimidinas/administração & dosagem , Pirimidinas/síntese química , Convulsões/tratamento farmacológico , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/síntese química , Ansiolíticos/química , Ansiolíticos/farmacologia , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/síntese química , Anticonvulsivantes/química , Anticonvulsivantes/farmacologia , Azepinas/química , Azepinas/farmacologia , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Pentilenotetrazol/efeitos adversos , Pirimidinas/química , Pirimidinas/farmacologia , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , Ratos , Receptores de GABA-A/química , Receptores de GABA-A/metabolismo , Convulsões/induzido quimicamente , Convulsões/fisiopatologia
2.
Medicine (Baltimore) ; 100(23): e26241, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34115012

RESUMO

RATIONALE: Todd paralysis (a stroke-like presentation in some patients with epilepsy) caused by limbic encephalitis (LE) is not easily distinguished from acute ischemic stroke by clinicians in the emergency room. PATIENT CONCERNS: We report a contactin-associated protein-like 2-antibody (CASPR2-Ab)-positive patient who presented with atypical LE. DIAGNOSES: CASPR2-Ab-positive LE was the presumed diagnosis. Re-evaluation of cerebrospinal fluid (CSF) samples revealed autoantibodies targeting CASPR2 at an immunoglobulin G titer of 1:1. The clinical presentation of subacute onset seizures, abnormal electroencephalography, hypermetabolism on positron emission tomography, good immunotherapy response, and the presence of specific antibodies in serum supports a diagnosis of autoimmune LE. INTERVENTION: The patient received glucocorticoids (1 g for 3 days and 500 mg for 3 days), immunoglobulin (25 g for 3 days), sodium valproate (1 g for 3 days), and clonazepam (1 mg for 3 days). OUTCOMES: Remission of temporal lobe epilepsy symptoms and cognitive dysfunction was observed. Follow-up analysis of CSF and serological examination were not approved by the patient. His Mini-Mental State Examination score improved to 21/30. Stable remission of symptoms was achieved throughout the follow-up period of 50 days. LESSONS: Autoimmune encephalitis (AE) should be considered in cases of late-onset epilepsy following meningioma peritumoral brain edema and resection. A diagnosis of AE should be considered in patients presenting with stroke-like symptoms if the magnetic resonance imaging abnormality does not match a known vascular territory. Early and correct diagnosis is crucial because immunotherapy is usually effective for this disease.


Assuntos
Encefalite Límbica/diagnóstico , Proteínas de Membrana/análise , Meningioma/diagnóstico , Proteínas do Tecido Nervoso/análise , Biomarcadores/análise , Biomarcadores/sangue , Disfunção Cognitiva/etiologia , Humanos , Encefalite Límbica/complicações , Imageamento por Ressonância Magnética/métodos , Masculino , Proteínas de Membrana/sangue , Meningioma/complicações , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/sangue , Paresia/etiologia , Convulsões/etiologia , Convulsões/fisiopatologia , Tomografia Computadorizada por Raios X/métodos
3.
Int J Mol Sci ; 22(11)2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070933

RESUMO

Hippocampal damage after traumatic brain injury (TBI) is associated with late posttraumatic conditions, such as depression, cognitive decline and epilepsy. Mechanisms of selective hippocampal damage after TBI are not well understood. In this study, using rat TBI model (lateral fluid percussion cortical injury), we assessed potential association of immediate posttraumatic seizures and changes in corticosterone (CS) levels with neuroinflammation and neuronal cell loss in the hippocampus. Indices of distant hippocampal damage (neurodegeneration and neuroinflammation) were assessed using histological analysis (Nissl staining, Iba-1 immunohistochemical staining) and ELISA (IL-1ß and CS) 1, 3, 7 and 14 days after TBI or sham operation in male Wistar rats (n = 146). IL-1ß was elevated only in the ipsilateral hippocampus on day 1 after trauma. CS peak was detected on day 3 in blood, the ipsilateral and contralateral hippocampus. Neuronal cell loss in the hippocampus was demonstrated bilaterally; in the ipsilateral hippocampus it started earlier than in the contralateral. Microglial activation was evident in the hippocampus bilaterally on day 7 after TBI. The duration of immediate seizures correlated with CS elevation, levels of IL-1ß and neuronal loss in the hippocampus. The data suggest potential association of immediate post-traumatic seizures with CS-dependent neuroinflammation-mediated distant hippocampal damage.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Corticosterona/sangue , Hipocampo/metabolismo , Microglia/metabolismo , Neurônios/metabolismo , Convulsões/metabolismo , Animais , Biomarcadores/metabolismo , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/fisiopatologia , Contagem de Células , Morte Celular , Modelos Animais de Doenças , Hipocampo/patologia , Hipocampo/fisiopatologia , Inflamação , Interleucina-1beta/biossíntese , Masculino , Microglia/patologia , Neurônios/patologia , Ratos , Ratos Wistar , Convulsões/patologia , Convulsões/fisiopatologia , Fatores de Tempo
4.
Epilepsia Open ; 6(2): 437-442, 2021 06.
Artigo em Inglês | MEDLINE | ID: covidwho-1222614

RESUMO

OBJECTIVE: Hyperventilation (HV) is one of the main and basic activation methods during ambulatory electroencephalogram (EEG), unless medical reasons contraindicate it. During the COVID-19 pandemic, with the high risk of human-to-human infection, local guidelines and recommendations have been developed that suggest not to perform the HV maneuver routinely. Our objective was to characterize patients who present positive HV in an epilepsy center. METHODS: We analyzed retrospectively all the ambulatory EEGs performed during one year in our specialized ambulatory child and adolescent epilepsy center, and describe patients with positive maneuver. RESULTS: A total of 305 EEGs were performed. Patients under 3 years and 11 months were excluded as well as all patients that did not fill up the criteria for epilepsy diagnosis. From the 252 EEGs that were included in the study, 194 EEGs (77%) were classified as abnormal and 58 (23%) as normal. From these same 252 EEGs, 150 EEG finished correctly the HV maneuver. Physiological slowing response was found in 54 EEGs (36%), no changes (negative) in 83 (55%), and abnormal response (positive) in 13 EEGs (9%). The 13 HV-positive EEGs showed 4 patients with an increase of epileptiform activity, 3 patients experienced an increase of basal preregistered abnormal slowing, and 6 EEGs showed trigger of bilaterally synchronous and symmetric 2-4 Hz spike-and-slow wave discharges and absences. None of these last 6 patients needed more than 3 minutes to elicit the paroxysmal discharge. SIGNIFICANCE: Based on these findings and according with other studies, the low positivity and high specificity of the HV maneuver support the idea that HV could be excluded during the COVID-19 pandemic situation, and also reevaluate whether it could be changed to a complementary maneuver, restricted only for cases where absence epilepsy is suspected. Larger studies will be needed to reaffirm this proposal.


Assuntos
Assistência Ambulatorial , COVID-19 , Eletroencefalografia/métodos , Epilepsia Tipo Ausência , Adolescente , Assistência Ambulatorial/métodos , Assistência Ambulatorial/estatística & dados numéricos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Criança , Chile/epidemiologia , Técnicas de Diagnóstico Neurológico/normas , Técnicas de Diagnóstico Neurológico/tendências , Epilepsia Tipo Ausência/diagnóstico , Epilepsia Tipo Ausência/epidemiologia , Epilepsia Tipo Ausência/fisiopatologia , Feminino , Humanos , Hiperventilação , Masculino , Estudos Retrospectivos , SARS-CoV-2 , Convulsões/diagnóstico , Convulsões/fisiopatologia , Sensibilidade e Especificidade
5.
Epilepsy Res ; 174: 106650, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33993018

RESUMO

BACKGROUND AND PURPOSE: Post COVID-19 seizures are relatively rare. The aim of the present study was to estimate the frequency of acute symptomatic seizures among patients with COVID-19 and to discuss possible pathophysiological mechanisms. MATERIAL AND METHODS: Out of 439 cases with COVID-19 that were admitted to Assiut and Aswan University hospitals during the period from 1 June to 10 August 2020, 19 patients (4.3 %) presented with acute symptomatic seizures. Each patient underwent computed tomography (CT) or magnetic resonance imaging (MRI) of the brain and conventional electroencephalography (EEG). Laboratory investigations included: blood gases, complete blood picture, serum D-Dimer, Ferritin, C-reactive protein, renal and liver functions, and coagulation profile. RESULTS: Of the 19 patients, 3 had new onset seizures without underlying pathology (0.68 % out of the total 439 patients); 2 others (0.46 %) had previously diagnosed controlled epilepsy with breakthrough seizures. The majority of cases (14 patients, 3.19 %) had primary pathology that could explain the occurrence of seizures: 5 suffered a post COVID-19 stroke (3 ischemic and 2 hemorrhagic stroke); 6 patients had COVID-related encephalitis; 2 patients were old ischemic stroke patients; 1 patient had a brain tumor and developed seizures post COVID-19. CONCLUSION: acute symptomatic seizure is not a rare complication of post COVID-19 infection. Both new onset seizures and seizures secondary to primary brain insult (post COVID encephalitis or recent stroke) were observed.


Assuntos
COVID-19/epidemiologia , Encefalite Viral/epidemiologia , Epilepsia/epidemiologia , Convulsões/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Anticonvulsivantes/uso terapêutico , Encéfalo/diagnóstico por imagem , COVID-19/fisiopatologia , Egito/epidemiologia , Eletroencefalografia , Epilepsia/tratamento farmacológico , Feminino , Hospitalização , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Convulsões/fisiopatologia , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X
6.
Epilepsia Open ; 6(2): 437-442, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34033234

RESUMO

OBJECTIVE: Hyperventilation (HV) is one of the main and basic activation methods during ambulatory electroencephalogram (EEG), unless medical reasons contraindicate it. During the COVID-19 pandemic, with the high risk of human-to-human infection, local guidelines and recommendations have been developed that suggest not to perform the HV maneuver routinely. Our objective was to characterize patients who present positive HV in an epilepsy center. METHODS: We analyzed retrospectively all the ambulatory EEGs performed during one year in our specialized ambulatory child and adolescent epilepsy center, and describe patients with positive maneuver. RESULTS: A total of 305 EEGs were performed. Patients under 3 years and 11 months were excluded as well as all patients that did not fill up the criteria for epilepsy diagnosis. From the 252 EEGs that were included in the study, 194 EEGs (77%) were classified as abnormal and 58 (23%) as normal. From these same 252 EEGs, 150 EEG finished correctly the HV maneuver. Physiological slowing response was found in 54 EEGs (36%), no changes (negative) in 83 (55%), and abnormal response (positive) in 13 EEGs (9%). The 13 HV-positive EEGs showed 4 patients with an increase of epileptiform activity, 3 patients experienced an increase of basal preregistered abnormal slowing, and 6 EEGs showed trigger of bilaterally synchronous and symmetric 2-4 Hz spike-and-slow wave discharges and absences. None of these last 6 patients needed more than 3 minutes to elicit the paroxysmal discharge. SIGNIFICANCE: Based on these findings and according with other studies, the low positivity and high specificity of the HV maneuver support the idea that HV could be excluded during the COVID-19 pandemic situation, and also reevaluate whether it could be changed to a complementary maneuver, restricted only for cases where absence epilepsy is suspected. Larger studies will be needed to reaffirm this proposal.


Assuntos
Assistência Ambulatorial , COVID-19 , Eletroencefalografia/métodos , Epilepsia Tipo Ausência , Adolescente , Assistência Ambulatorial/métodos , Assistência Ambulatorial/estatística & dados numéricos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Criança , Chile/epidemiologia , Técnicas de Diagnóstico Neurológico/normas , Técnicas de Diagnóstico Neurológico/tendências , Epilepsia Tipo Ausência/diagnóstico , Epilepsia Tipo Ausência/epidemiologia , Epilepsia Tipo Ausência/fisiopatologia , Feminino , Humanos , Hiperventilação , Masculino , Estudos Retrospectivos , SARS-CoV-2 , Convulsões/diagnóstico , Convulsões/fisiopatologia , Sensibilidade e Especificidade
7.
Nat Commun ; 12(1): 3095, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34035249

RESUMO

The analysis of biomedical signals for clinical studies and therapeutic applications can benefit from embedded devices that can process these signals locally and in real-time. An example is the analysis of intracranial EEG (iEEG) from epilepsy patients for the detection of High Frequency Oscillations (HFO), which are a biomarker for epileptogenic brain tissue. Mixed-signal neuromorphic circuits offer the possibility of building compact and low-power neural network processing systems that can analyze data on-line in real-time. Here we present a neuromorphic system that combines a neural recording headstage with a spiking neural network (SNN) processing core on the same die for processing iEEG, and show how it can reliably detect HFO, thereby achieving state-of-the-art accuracy, sensitivity, and specificity. This is a first feasibility study towards identifying relevant features in iEEG in real-time using mixed-signal neuromorphic computing technologies.


Assuntos
Encéfalo/fisiologia , Eletrocorticografia/métodos , Rede Nervosa/fisiologia , Neurônios/fisiologia , Potenciais de Ação/fisiologia , Algoritmos , Encéfalo/citologia , Eletrocorticografia/instrumentação , Humanos , Modelos Neurológicos , Convulsões/fisiopatologia , Lobo Temporal/fisiopatologia
8.
Int J Mol Sci ; 22(8)2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33920037

RESUMO

Epilepsy, one of the most common neurological disorders worldwide, is characterized by recurrent seizures and subsequent brain damage. Despite strong evidence supporting a deleterious impact on seizure occurrence and outcome severity, stress is an overlooked component in people with epilepsy. With regard to stressor duration and timing, acute stress can be protective in epileptogenesis, while chronic stress often promotes seizure occurrence in epilepsy patients. Preclinical research suggests that chronic stress promotes neuroinflammation and leads to a depressive state. Depression is the most common psychiatric comorbidity in people with epilepsy, resulting in a poor quality of life. Here, we summarize studies investigating acute and chronic stress as a seizure trigger and an important factor that worsens epilepsy outcomes and psychiatric comorbidities. Mechanistic insight into the impact of stress on epilepsy may create a window of opportunity for future interventions targeting neuroinflammation-related disorders.


Assuntos
Epilepsia/fisiopatologia , Inflamação/fisiopatologia , Convulsões/fisiopatologia , Comorbidade , Epilepsia/epidemiologia , Epilepsia/psicologia , Humanos , Inflamação/epidemiologia , Inflamação/psicologia , Masculino , Qualidade de Vida , Convulsões/epidemiologia , Convulsões/psicologia
9.
Ann Neurol ; 89(5): 872-883, 2021 05.
Artigo em Inglês | MEDLINE | ID: covidwho-1148790

RESUMO

OBJECTIVE: The aim was to determine the prevalence and risk factors for electrographic seizures and other electroencephalographic (EEG) patterns in patients with Coronavirus disease 2019 (COVID-19) undergoing clinically indicated continuous electroencephalogram (cEEG) monitoring and to assess whether EEG findings are associated with outcomes. METHODS: We identified 197 patients with COVID-19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns. Multivariate Cox proportional hazards analysis assessed the relationship between EEG patterns and clinical outcomes. RESULTS: Electrographic seizures were detected in 19 (9.6%) patients, including nonconvulsive status epilepticus (NCSE) in 11 (5.6%). Epileptiform abnormalities (either ictal or interictal) were present in 96 (48.7%). Preceding clinical seizures during hospitalization were associated with both electrographic seizures (36.4% in those with vs 8.1% in those without prior clinical seizures, odds ratio [OR] 6.51, p = 0.01) and NCSE (27.3% vs 4.3%, OR 8.34, p = 0.01). A pre-existing intracranial lesion on neuroimaging was associated with NCSE (14.3% vs 3.7%; OR 4.33, p = 0.02). In multivariate analysis of outcomes, electrographic seizures were an independent predictor of in-hospital mortality (hazard ratio [HR] 4.07 [1.44-11.51], p < 0.01). In competing risks analysis, hospital length of stay increased in the presence of NCSE (30 day proportion discharged with vs without NCSE: HR 0.21 [0.03-0.33] vs 0.43 [0.36-0.49]). INTERPRETATION: This multicenter retrospective cohort study demonstrates that seizures and other epileptiform abnormalities are common in patients with COVID-19 undergoing clinically indicated cEEG and are associated with adverse clinical outcomes. ANN NEUROL 2021;89:872-883.


Assuntos
COVID-19/epidemiologia , COVID-19/fisiopatologia , Eletroencefalografia/tendências , Convulsões/epidemiologia , Convulsões/fisiopatologia , Idoso , COVID-19/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Convulsões/diagnóstico , Resultado do Tratamento
10.
Neural Netw ; 139: 212-222, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33780727

RESUMO

Epilepsy is a neurological brain disorder that affects ∼75 million people worldwide. Predicting epileptic seizures holds great potential for improving the quality of life of people with epilepsy, but seizure prediction solely from the Electroencephalogram (EEG) is challenging. Classical machine learning algorithms and a variety of feature engineering methods have become a mainstay in seizure prediction, yet performance has been variable. In this work, we first propose an efficient data pre-processing method that maps the time-series EEG signals into an image-like format (a "scalogram") using continuous wavelet transform. We then develop a novel convolution module named "semi-dilated convolution" that better exploits the geometry of wavelet scalograms and nonsquare-shape images. Finally, we propose a neural network architecture named "semi-dilated convolutional network (SDCN)" that uses semi-dilated convolutions to solely expand the receptive field along the long dimension (image width) while maintaining high resolution along the short dimension (image height). Results demonstrate that the proposed SDCN architecture outperforms previous seizure prediction methods, achieving an average seizure prediction sensitivity of 98.90% for scalp EEG and 88.45-89.52% for invasive EEG.


Assuntos
Eletroencefalografia/métodos , Redes Neurais de Computação , Convulsões/fisiopatologia , Encéfalo/fisiopatologia , Humanos , Convulsões/diagnóstico , Análise de Ondaletas
11.
Expert Opin Drug Saf ; 20(5): 561-576, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33645379

RESUMO

Introduction: Management of individuals with Dravet Syndrome has evolved significantly over the past 10 years. Progress has been made in understanding the pathophysiology, the long-term outcome and possible consequences of inappropriate therapies, new drugs have been approved by the regulatory authorities and patients and families expressed their needs beyond seizures' control.Areas covered: The authors aimed at providing an overview of the main antiseizure medications used in Dravet syndrome with a particular focus on safety considerations. As the highly active phase of seizures takes place before the age of 5 years, the characteristics of antiseizure medications in infancy and childhood have also been considered due to their impact on antiseizure medication safety.Expert opinion: Recent treatments, evaluated via randomized clinical trials, are promising in terms of efficacy and safety in individuals with DS. However, the balance between expected benefits and risks taken must be accurately assessed on an individual basis. There is a lack of data to understand the needs of patients and families, a major point particularly in this population, where the evaluation of efficacy and safety beyond seizures is difficult due to cognitive delay and behavioral disorders and where this evaluation is coming almost exclusively from caregivers.


Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsias Mioclônicas/tratamento farmacológico , Anticonvulsivantes/efeitos adversos , Pré-Escolar , Epilepsias Mioclônicas/fisiopatologia , Humanos , Lactente , Ensaios Clínicos Controlados Aleatórios como Assunto , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia
12.
Neurology ; 96(18): e2261-e2271, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33722994

RESUMO

OBJECTIVE: To test the hypothesis that glutamate and GABA are linked to the formation of epilepsy networks and the triggering of spontaneous seizures, we examined seizure initiation/propagation characteristics and neurotransmitter levels during epileptogenesis in a translationally relevant rodent model of mesial temporal lobe epilepsy. METHODS: The glutamine synthetase (GS) inhibitor methionine sulfoximine was infused into one of the hippocampi in laboratory rats to create a seizure focus. Long-term video-intracranial EEG recordings and brain microdialysis combined with mass spectrometry were used to examine seizure initiation, seizure propagation, and extracellular brain levels of glutamate and GABA. RESULTS: All seizures (n = 78 seizures, n = 3 rats) appeared first in the GS-inhibited hippocampus of all animals, followed by propagation to the contralateral hippocampus. Propagation time decreased significantly from 11.65 seconds early in epileptogenesis (weeks 1-2) to 6.82 seconds late in epileptogenesis (weeks 3-4, paired t test, p = 0.025). Baseline extracellular glutamate levels were 11.6-fold higher in the hippocampus of seizure propagation (7.3 µM) vs the hippocampus of seizure onset (0.63 µM, analysis of variance/Fisher least significant difference, p = 0.01), even though the concentrations of the major glutamate transporter proteins excitatory amino acid transporter subtypes 1 and 2 and xCT were unchanged between the brain regions. Finally, extracellular GABA in the seizure focus decreased significantly from baseline several hours before a spontaneous seizure (paired t test/false discovery rate). CONCLUSION: The changes in glutamate and GABA suggest novel and potentially important roles of the amino acids in epilepsy network formation and in the initiation and propagation of spontaneous seizures.


Assuntos
Encéfalo/metabolismo , Rede Nervosa/metabolismo , Neurotransmissores/metabolismo , Convulsões/metabolismo , Animais , Encéfalo/fisiopatologia , Eletroencefalografia/métodos , Ácido Glutâmico/metabolismo , Masculino , Rede Nervosa/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Roedores , Convulsões/fisiopatologia , Ácido gama-Aminobutírico/metabolismo
13.
Ann Neurol ; 89(5): 872-883, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33704826

RESUMO

OBJECTIVE: The aim was to determine the prevalence and risk factors for electrographic seizures and other electroencephalographic (EEG) patterns in patients with Coronavirus disease 2019 (COVID-19) undergoing clinically indicated continuous electroencephalogram (cEEG) monitoring and to assess whether EEG findings are associated with outcomes. METHODS: We identified 197 patients with COVID-19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns. Multivariate Cox proportional hazards analysis assessed the relationship between EEG patterns and clinical outcomes. RESULTS: Electrographic seizures were detected in 19 (9.6%) patients, including nonconvulsive status epilepticus (NCSE) in 11 (5.6%). Epileptiform abnormalities (either ictal or interictal) were present in 96 (48.7%). Preceding clinical seizures during hospitalization were associated with both electrographic seizures (36.4% in those with vs 8.1% in those without prior clinical seizures, odds ratio [OR] 6.51, p = 0.01) and NCSE (27.3% vs 4.3%, OR 8.34, p = 0.01). A pre-existing intracranial lesion on neuroimaging was associated with NCSE (14.3% vs 3.7%; OR 4.33, p = 0.02). In multivariate analysis of outcomes, electrographic seizures were an independent predictor of in-hospital mortality (hazard ratio [HR] 4.07 [1.44-11.51], p < 0.01). In competing risks analysis, hospital length of stay increased in the presence of NCSE (30 day proportion discharged with vs without NCSE: HR 0.21 [0.03-0.33] vs 0.43 [0.36-0.49]). INTERPRETATION: This multicenter retrospective cohort study demonstrates that seizures and other epileptiform abnormalities are common in patients with COVID-19 undergoing clinically indicated cEEG and are associated with adverse clinical outcomes. ANN NEUROL 2021;89:872-883.


Assuntos
COVID-19/epidemiologia , COVID-19/fisiopatologia , Eletroencefalografia/tendências , Convulsões/epidemiologia , Convulsões/fisiopatologia , Idoso , COVID-19/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Convulsões/diagnóstico , Resultado do Tratamento
14.
Nat Commun ; 12(1): 1423, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658509

RESUMO

In the mammalian hippocampus, adult-born granule cells (abGCs) contribute to the function of the dentate gyrus (DG). Disruption of the DG circuitry causes spontaneous recurrent seizures (SRS), which can lead to epilepsy. Although abGCs contribute to local inhibitory feedback circuitry, whether they are involved in epileptogenesis remains elusive. Here, we identify a critical window of activity associated with the aberrant maturation of abGCs characterized by abnormal dendrite morphology, ectopic migration, and SRS. Importantly, in a mouse model of temporal lobe epilepsy, silencing aberrant abGCs during this critical period reduces abnormal dendrite morphology, cell migration, and SRS. Using mono-synaptic tracers, we show silencing aberrant abGCs decreases recurrent CA3 back-projections and restores proper cortical connections to the hippocampus. Furthermore, we show that GABA-mediated amplification of intracellular calcium regulates the early critical period of activity. Our results demonstrate that aberrant neurogenesis rewires hippocampal circuitry aggravating epilepsy in mice.


Assuntos
Epilepsia/fisiopatologia , Hipocampo/fisiopatologia , Neurogênese/fisiologia , Animais , Cálcio/metabolismo , Clozapina/análogos & derivados , Clozapina/farmacologia , Modelos Animais de Doenças , Eletroencefalografia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurogênese/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Pilocarpina/farmacologia , Retroviridae/genética , Convulsões/fisiopatologia , Ácido gama-Aminobutírico/metabolismo
15.
Int J Mol Sci ; 22(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33668718

RESUMO

BACKGROUND: Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE. METHODS: Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus. RESULTS: The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1ß levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity.


Assuntos
Anticonvulsivantes/uso terapêutico , Inflamação/patologia , Lacosamida/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , Topiramato/uso terapêutico , Animais , Anticonvulsivantes/farmacologia , Biomarcadores/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/fisiopatologia , Interleucina-1beta/metabolismo , Lacosamida/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pilocarpina , Ratos Wistar , Convulsões/fisiopatologia , Estado Epiléptico/fisiopatologia , Topiramato/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
16.
Int J Mol Sci ; 22(4)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33672922

RESUMO

The identification of improved medical countermeasures against exposure to chemical warfare nerve agents (CWNAs), a class of organophosphorus compounds, is dependent on the choice of animal model used in preclinical studies. CWNAs bind to acetylcholinesterase and prevent the catalysis of acetylcholine, causing a plethora of peripheral and central physiologic manifestations, including seizure. Rodents are widely used to elucidate the effects of CWNA-induced seizure, albeit with a caveat: they express carboxylesterase activity in plasma. Carboxylesterase, an enzyme involved in the detoxification of some organophosphorus compounds, plays a scavenging role and decreases CWNA availability, thus exerting a protective effect. Furthermore, species-specific amino acid differences in acetylcholinesterase confound studies that use oximes or other compounds to restore its function after inhibition by CWNA. The creation of a human acetylcholinesterase knock-in/serum carboxylesterase knockout (C57BL/6-Ces1ctm1.1LocAChEtm1.1Loc/J; a.k.a KIKO) mouse may facilitate better modeling of CWNA toxicity in a small rodent species. The current studies characterize the effects of exposure to soman, a highly toxic CWNA, and evaluate the efficacy of anti-seizure drugs in this newly developed KIKO mouse model. Data demonstrate that a combination of midazolam and ketamine reduces seizure duration and severity, eliminates the development of spontaneous recurrent seizures, and protects certain brain regions from neuronal damage in a genetically modified model with human relevance to organophosphorus compound toxicity. This new animal model and the results of this study and future studies using it will enhance medical countermeasures development for both defense and homeland security purposes.


Assuntos
Acetilcolinesterase/metabolismo , Carboxilesterase/metabolismo , Modelos Animais de Doenças , Contramedidas Médicas , Soman/toxicidade , Acetilcolinesterase/genética , Anestésicos/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Carboxilesterase/genética , Substâncias para a Guerra Química/toxicidade , Humanos , Ketamina/farmacologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Midazolam/farmacologia , Convulsões/induzido quimicamente , Convulsões/fisiopatologia , Convulsões/prevenção & controle
17.
J Clin Neurophysiol ; 38(2): 112-123, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33661787

RESUMO

SUMMARY: High-density EEG (HD-EEG) recordings use a higher spatial sampling of scalp electrodes than a standard 10-20 low-density EEG montage. Although several studies have demonstrated improved localization of the epileptogenic cortex using HD-EEG, widespread implementation is impeded by cost, setup and interpretation time, and lack of specific or sufficient procedural billing codes. Despite these barriers, HD-EEG has been in use at several institutions for years. These centers have noted utility in a variety of clinical scenarios where increased spatial resolution from HD-EEG has been required, justifying the extra time and cost. We share select scenarios from several centers, using different recording techniques and software, where HD-EEG provided information above and beyond the standard low-density EEG. We include seven cases where HD-EEG contributed directly to current clinical care of epilepsy patients and highlight two novel techniques which suggest potential opportunities to improve future clinical care. Cases illustrate how HD-EEG allows clinicians to: case 1-lateralize falsely generalized interictal epileptiform discharges; case 2-improve localization of falsely generalized epileptic spasms; cases 3 and 4-improve localization of interictal epileptiform discharges in anatomic regions below the circumferential limit of standard low-density EEG coverage; case 5-improve noninvasive localization of the seizure onset zone in lesional epilepsy; cases 6 and 7-improve localization of the seizure onset zone to guide invasive investigation near eloquent cortex; case 8-identify epileptic fast oscillations; and case 9-map language cortex. Together, these nine cases illustrate that using both visual analysis and advanced techniques, HD-EEG can play an important role in clinical management.


Assuntos
Mapeamento Encefálico/métodos , Eletroencefalografia/métodos , Epilepsia/diagnóstico por imagem , Epilepsia/fisiopatologia , Adolescente , Adulto , Idoso , Mapeamento Encefálico/tendências , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Criança , Eletrodos/tendências , Eletroencefalografia/tendências , Feminino , Previsões , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Couro Cabeludo/diagnóstico por imagem , Couro Cabeludo/fisiopatologia , Convulsões/diagnóstico por imagem , Convulsões/fisiopatologia , Adulto Jovem
18.
J Clin Neurophysiol ; 38(2): 87-91, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33661784

RESUMO

SUMMARY: Recording of interictal epileptiform discharges to classify the epilepsy syndrome is one of the most common indications for ambulatory EEG. Ambulatory EEG has superior sampling compared with standard EEG recordings and advantages in terms of cost-effectiveness and convenience compared with a prolonged inpatient EEG study. Ambulatory EEG allows for EEG recording in all sleep stages and transitional states, which can be very helpful in capturing interictal epileptiform discharges. In the absence of interictal epileptiform discharges or in patients with atypical events, the characterization of an epilepsy syndrome may require recording of the habitual events. Diagnostic ambulatory EEG can be a useful alternative to inpatient video-EEG monitoring in a selected number of patients with frequent events who do not require medication taper or seizure testing for surgical localization.


Assuntos
Eletroencefalografia/classificação , Eletroencefalografia/métodos , Síndromes Epilépticas/classificação , Síndromes Epilépticas/diagnóstico , Monitorização Ambulatorial/classificação , Monitorização Ambulatorial/métodos , Adulto , Análise Custo-Benefício , Síndromes Epilépticas/fisiopatologia , Feminino , Humanos , Masculino , Convulsões/classificação , Convulsões/diagnóstico , Convulsões/fisiopatologia , Fases do Sono/fisiologia
19.
J Clin Neurophysiol ; 38(2): 101-111, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33661786

RESUMO

SUMMARY: Long-term video-EEG monitoring has been the gold standard for diagnosis of epileptic and nonepileptic events. Medication changes, safety, and a lack of recording EEG in one's habitual environment may interfere with diagnostic representation and subsequently affect management. Some spells defy standard EEG because of ultradian and circadian times of occurrence, manifest nocturnal expression of epileptiform activity, and require classification for clarifying diagnostic input to identify optimal treatment. Some patients may be unaware of seizures, have frequent events, or subclinical seizures that require quantification before optimal management. The influence on antiseizure drug management and clinical drug research can be enlightened by long-term outpatient ambulatory EEG monitoring. With recent governmental shifts to focus on mobile health, ambulatory EEG monitoring has grown beyond diagnostic capabilities to target the dynamic effects of medical and nonmedical treatment for patients with epilepsy in their natural environment. Furthermore, newer applications in ambulatory monitoring include additional physiologic parameters (e.g., sleep, detection of myogenic signals, etc.) and extend treatment relevance to patients beyond seizure reduction alone addressing comorbid conditions. It is with this focus in mind that we direct our discussion on the present and future aspects of using ambulatory EEG monitoring in the treatment of patients with epilepsy.


Assuntos
Gerenciamento Clínico , Eletroencefalografia/tendências , Epilepsia/diagnóstico , Epilepsia/terapia , Monitorização Ambulatorial/tendências , Eletroencefalografia/métodos , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/terapia , Epilepsia/fisiopatologia , Feminino , Humanos , Masculino , Monitorização Ambulatorial/métodos , Convulsões/diagnóstico , Convulsões/fisiopatologia , Convulsões/terapia , Sono/fisiologia
20.
Toxicol Appl Pharmacol ; 415: 115429, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33524447

RESUMO

The zebrafish is extensively used as a model organism for studying several disorders of the central nervous system (CNS), including epilepsy. Some antiseizure drugs (ASDs) have been shown to produce discrepant results in larvae and adults zebrafish, therefore, their anticonvulsant efficacy in subsequent stages of the pentylenetetrazole (PTZ)-induced seizures should be more precisely characterized. The purpose of this study was to investigate behavioral effects of five classic ASDs: valproate (VPA), phenytoin (PHT), carbamazepine (CBZ), diazepam (DZP), and phenobarbital (PB) administered intraperitoneally (i.p.) in the PTZ-induced seizure test in adult zebrafish. We determined the time of maximal effect and the dose-response relationship of the studied ASDs. Furthermore, we assessed changes in the locomotor activity and the anxiety-like behavior in the color preference test. Moreover, drug concentrations in zebrafish homogenates were examined. VPA, DZP, and PB significantly increased the seizure latency at three subsequent stages of seizures (SI-SIII). PHT produced the anticonvulsant-like effect at SI and SII, while CBZ was effective at SII and SIII. Only DZP decreased zebrafish locomotor activity. A strong anxiolytic-like effect was observed after administration of PHT and PB. A weak anxiolytic-like effect occurred after treatment with VPA and DZP. The HPLC analysis showed the average concentrations of the studied ASDs in the fish body during the maximum anticonvulsant activity of each drug. Our results confirm the advantages of using zebrafish with the mature CNS over larval models and its utility to investigate some neuropharmacological properties of the tested drugs.


Assuntos
Ansiolíticos/farmacologia , Anticonvulsivantes/farmacologia , Ansiedade/prevenção & controle , Comportamento Animal/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Convulsões/prevenção & controle , Fatores Etários , Animais , Ansiolíticos/metabolismo , Anticonvulsivantes/metabolismo , Ansiedade/fisiopatologia , Ansiedade/psicologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/fisiopatologia , Percepção de Cores/efeitos dos fármacos , Visão de Cores/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Locomoção/efeitos dos fármacos , Masculino , Pentilenotetrazol , Convulsões/induzido quimicamente , Convulsões/fisiopatologia , Fatores de Tempo , Peixe-Zebra/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...