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1.
Nat Commun ; 12(1): 4839, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376673

RESUMO

The ability to maintain a sequence of items in memory is a fundamental cognitive function. In the rodent hippocampus, the representation of sequentially organized spatial locations is reflected by the phase of action potentials relative to the theta oscillation (phase precession). We investigated whether the timing of neuronal activity relative to the theta brain oscillation also reflects sequence order in the medial temporal lobe of humans. We used a task in which human participants learned a fixed sequence of pictures and recorded single neuron and local field potential activity with implanted electrodes. We report that spikes for three consecutive items in the sequence (the preferred stimulus for each cell, as well as the stimuli immediately preceding and following it) were phase-locked at distinct phases of the theta oscillation. Consistent with phase precession, spikes were fired at progressively earlier phases as the sequence advanced. These findings generalize previous findings in the rodent hippocampus to the human temporal lobe and suggest that encoding stimulus information at distinct oscillatory phases may play a role in maintaining sequential order in memory.


Assuntos
Potenciais de Ação/fisiologia , Epilepsia/fisiopatologia , Aprendizagem/fisiologia , Neurônios/fisiologia , Ritmo Teta/fisiologia , Adolescente , Adulto , Epilepsia/diagnóstico , Feminino , Hipocampo/citologia , Hipocampo/fisiologia , Humanos , Masculino , Modelos Neurológicos , Neurônios/citologia , Estimulação Luminosa/métodos , Lobo Temporal/citologia , Lobo Temporal/fisiologia , Adulto Jovem
2.
Biochemistry (Mosc) ; 86(6): 641-656, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34225588

RESUMO

The review discusses molecular and cellular mechanisms common to the temporal lobe epileptogenesis/epilepsy and depressive disorders. Comorbid temporal lobe epilepsy and depression are associated with dysfunction of the hypothalamic-pituitary-adrenocortical axis. Excessive glucocorticoids disrupt the function and impair the structure of the hippocampus, a brain region key to learning, memory, and emotions. Selective vulnerability of the hippocampus to stress, mediated by the reception of glucocorticoid hormones secreted during stress, is the price of the high functional plasticity and pleiotropy of this limbic structure. Common molecular and cellular mechanisms include the dysfunction of glucocorticoid receptors, neurotransmitters, and neurotrophic factors, development of neuroinflammation, leading to neurodegeneration and loss of hippocampal neurons, as well as disturbances in neurogenesis in the subgranular neurogenic niche and formation of aberrant neural networks. These glucocorticoid-dependent processes underlie altered stress response and the development of chronic stress-induced comorbid pathologies, in particular, temporal lobe epilepsy and depressive disorders.


Assuntos
Transtorno Depressivo/metabolismo , Epilepsia/metabolismo , Glucocorticoides/metabolismo , Hipocampo/metabolismo , Estresse Psicológico , Animais , Transtorno Depressivo/fisiopatologia , Emoções , Epilepsia/complicações , Epilepsia/fisiopatologia , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/fisiopatologia , Glucocorticoides/fisiologia , Hipocampo/fisiopatologia , Humanos , Inflamação , Aprendizagem , Memória
3.
Clin Neurophysiol ; 132(9): 2248-2250, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34275732

RESUMO

Restructuring of healthcare services during the COVID-19 pandemic has led to lockdown of Epilepsy Monitoring Units (EMUs) in many hospitals. The ad-hoc taskforce of the International League Against Epilepsy (ILAE) and the International Federation of Clinical Neurophysiology (IFCN) highlights the detrimental effect of postponing video-EEG monitoring of patients with epilepsy and other paroxysmal events. The taskforce calls for action to continue functioning of Epilepsy Monitoring Units during emergency situations, such as the COVID-19 pandemic. Long-term video-EEG monitoring is an essential diagnostic service. Access to video-EEG monitoring of the patients in the EMUs must be given high priority. Patients should be screened for COVID-19, before admission, according to the local regulations. Local policies for COVID-19 infection control should be adhered to during the video-EEG monitoring. In cases of differential diagnosis where reduction of antiseizure medication is not required, consider home video-EEG monitoring as an alternative in selected patients.


Assuntos
COVID-19/prevenção & controle , Controle de Doenças Transmissíveis/normas , Eletroencefalografia/normas , Epilepsia/diagnóstico , Acesso aos Serviços de Saúde/normas , Neurofisiologia/normas , COVID-19/epidemiologia , Controle de Doenças Transmissíveis/métodos , Consenso , Eletroencefalografia/métodos , Epilepsia/epidemiologia , Epilepsia/fisiopatologia , Humanos , Internacionalidade , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Neurofisiologia/métodos
4.
Expert Opin Drug Metab Toxicol ; 17(9): 1075-1090, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34310255

RESUMO

INTRODUCTION: The present evidence indicates that approximately 70% of patients with epilepsy can be successfully treated with antiepileptic drugs (AEDs). A significant proportion of patients are not under sufficient control, and pharmacoresistant epilepsy is clearly associated with poor quality of life and increased morbidity and mortality. There is a great need for newer therapeutic options able to reduce the percentage of drug-resistant patients. AREAS COVERED: A number of hypotheses trying to explain the development of pharmacoresistance have been put forward. These include: target hypothesis (altered AED targets), transporter (overexpression of brain efflux transporters), pharmacokinetic (overexpression of peripheral efflux transporters in the intestine or kidneys), intrinsic severity (initial high seizure frequency), neural network (aberrant networks), and gene variant hypothesis (genetic polymorphisms). EXPERT OPINION: A continuous search for newer AEDs or among non-AEDs (blockers of efflux transporters, interleukin antagonists, cyclooxygenase inhibitors, mTOR inhibitors, angiotensin II receptor antagonists) may provide efficacious drugs for the management of drug-resistant epilepsy. Also, combinations of AEDs exerting synergy in preclinical and clinical studies (for instance, lamotrigine + valproate, levetiracetam + valproate, topiramate + carbamazepine) might be of importance in this respect. Preclinically antagonistic combinations must be avoided (lamotrigine + carbamazepine, lamotrigine + oxcarbazepine).


Assuntos
Anticonvulsivantes/farmacologia , Resistência a Medicamentos/fisiologia , Epilepsia/tratamento farmacológico , Animais , Anticonvulsivantes/administração & dosagem , Sinergismo Farmacológico , Quimioterapia Combinada , Epilepsia/fisiopatologia , Humanos , Qualidade de Vida
5.
Nutrients ; 13(7)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202047

RESUMO

Ketogenic diet therapies (KDTs) are widely used treatments for epilepsy, but the factors influencing their responsiveness remain unknown. This study aimed to explore the predictors or associated factors for KDTs effectiveness by evaluating the subtle changes in brain functional connectivity (FC) before and after KDTs. Segments of interictal sleep electroencephalography (EEG) were acquired before and after six months of KDTs. Analyses of FC were based on network-based statistics and graph theory, with a focus on different frequency bands. Seventeen responders and 14 non-responders were enrolled. After six months of KDTs, the responders exhibited a significant functional connectivity strength decrease compared with the non-responders; reductions in global efficiency, clustering coefficient, and nodal strength in the beta frequency band for a consecutive range of weighted proportional thresholds were observed in the responders. The alteration of betweenness centrality was significantly and positively correlated with seizure reduction rate in alpha, beta, and theta frequency bands in weighted adjacency matrices with densities of 90%. We conclude that KDTs tended to modify minor-to-moderate-intensity brain connections; the reduction of global connectivity and the increment of betweenness centrality after six months of KDTs were associated with better KD effectiveness.


Assuntos
Dieta Cetogênica/psicologia , Eletroencefalografia , Epilepsia/dietoterapia , Epilepsia/fisiopatologia , Modelos Teóricos , Adolescente , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Dieta Cetogênica/métodos , Feminino , Humanos , Lactente , Masculino , Redes Neurais de Computação , Adulto Jovem
6.
Nat Commun ; 12(1): 4444, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290240

RESUMO

Episodic recall depends upon the reinstatement of cortical activity present during the formation of a memory. Evidence from functional neuroimaging and invasive recordings in humans suggest that reinstatement organizes our memories by time or content, yet the neural systems involved in reinstating these unique types of information remain unclear. Here, combining computational modeling and intracranial recordings from 69 epilepsy patients, we show that two cortical systems uniquely reinstate the semantic content and temporal context of previously studied items during free recall. Examining either the posterior medial or anterior temporal networks, we find that forward encoding models trained on the brain's response to the temporal and semantic attributes of items can predict the serial position and semantic category of unseen items. During memory recall, these models uniquely link reinstatement of temporal context and semantic content to these posterior and anterior networks, respectively. These findings demonstrate how specialized cortical systems enable the human brain to target specific memories.


Assuntos
Córtex Cerebral/fisiologia , Memória Episódica , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Epilepsia/diagnóstico por imagem , Epilepsia/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Rememoração Mental/fisiologia , Modelos Neurológicos , Rede Nervosa/diagnóstico por imagem , Semântica
7.
Neuron ; 109(16): 2556-2572.e6, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34197732

RESUMO

Neurological and psychiatric disorders are associated with pathological neural dynamics. The fundamental connectivity patterns of cell-cell communication networks that enable pathological dynamics to emerge remain unknown. Here, we studied epileptic circuits using a newly developed computational pipeline that leveraged single-cell calcium imaging of larval zebrafish and chronically epileptic mice, biologically constrained effective connectivity modeling, and higher-order motif-focused network analysis. We uncovered a novel functional cell type that preferentially emerged in the preseizure state, the superhub, that was unusually richly connected to the rest of the network through feedforward motifs, critically enhancing downstream excitation. Perturbation simulations indicated that disconnecting superhubs was significantly more effective in stabilizing epileptic circuits than disconnecting hub cells that were defined traditionally by connection count. In the dentate gyrus of chronically epileptic mice, superhubs were predominately modeled adult-born granule cells. Collectively, these results predict a new maximally selective and minimally invasive cellular target for seizure control.


Assuntos
Comunicação Celular/fisiologia , Epilepsia/fisiopatologia , Neurônios/fisiologia , Convulsões/fisiopatologia , Animais , Giro Denteado/patologia , Giro Denteado/fisiopatologia , Rede Nervosa/fisiopatologia , Peixe-Zebra
8.
Curr Neurovasc Res ; 18(1): 162-168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34082680

RESUMO

BACKGROUND: Robust evidence has described that Parkinson´s disease (PD) is associated with an increased risk for developing epileptic seizures. In fact, an interplay between PD and epilepsy has been of interest for many years. An emerging hypothesis is that inflammation could link both diseases. OBJECTIVE: Bearing in mind the experience of our group in the field of Ca2+/cAMP signalling pathways, this article discussed, beyond inflammation, the role of these signalling pathways in this link between PD and epilepsy. METHODS: Publications involving Ca2+/cAMP signalling pathways, PD, and epilepsy (alone or combined) were collected by searching PubMed and EMBASE. RESULTS: The comprehension of the interplay between PD and epilepsy could improve the drug therapy. In addition, a Ca2+ signalling dyshomeostasis due to Coronavirus disease 2019 (COVID-19), an emerging and rapidly evolving situation, has been reported. CONCLUSION: Thus, this article also debated recent findings about therapeutics involving Ca2+ channel blockers for preventing Ca2+ signalling dyshomeostasis due to COVID-19, including the correlation among COVID-19, epilepsy, and PD.


Assuntos
Sinalização do Cálcio , AMP Cíclico , Epilepsia/complicações , Inflamação/complicações , Doença de Parkinson/complicações , Transdução de Sinais , COVID-19/complicações , Bloqueadores dos Canais de Cálcio/uso terapêutico , Epilepsia/fisiopatologia , Humanos , Inflamação/fisiopatologia , Doença de Parkinson/fisiopatologia
9.
Int J Mol Sci ; 22(11)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070389

RESUMO

Epilepsy as a chronic neurological disorder is characterized by recurrent, unprovoked epileptic seizures. In about half of the people who suffer from epilepsy, the root cause of the disorder is unknown. In the other cases, different factors can cause the onset of epilepsy. In recent years, the role of gut microbiota has been recognized in many neurological disorders, including epilepsy. These data are based on studies of the gut microbiota-brain axis, a relationship starting by a dysbiosis followed by an alteration of brain functions. Interestingly, epileptic patients may show signs of dysbiosis, therefore the normalization of the gut microbiota may lead to improvement of epilepsy and to greater efficacy of anticonvulsant drugs. In this descriptive review, we analyze the evidences for the role of gut microbiota in epilepsy and hypothesize a mechanism of action of these microorganisms in the pathogenesis and treatment of the disease. Human studies revealed an increased prevalence of Firmicutes in patients with refractory epilepsy. Exposure to various compounds can change microbiota composition, decreasing or exacerbating epileptic seizures. These include antibiotics, epileptic drugs, probiotics and ketogenic diet. Finally, we hypothesize that physical activity may play a role in epilepsy through the modulation of the gut microbiota.


Assuntos
Encéfalo/fisiopatologia , Disbiose , Epilepsia , Firmicutes , Microbioma Gastrointestinal , Epilepsia/metabolismo , Epilepsia/microbiologia , Epilepsia/fisiopatologia , Firmicutes/classificação , Firmicutes/metabolismo , Humanos
10.
Commun Biol ; 4(1): 680, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083748

RESUMO

Genetic engineering techniques have contributed to the now widespread use of zebrafish to investigate gene function, but zebrafish-based human disease studies, and particularly for neurological disorders, are limited. Here we used CRISPR-Cas9 to generate 40 single-gene mutant zebrafish lines representing catastrophic childhood epilepsies. We evaluated larval phenotypes using electrophysiological, behavioral, neuro-anatomical, survival and pharmacological assays. Local field potential recordings (LFP) were used to screen ∼3300 larvae. Phenotypes with unprovoked electrographic seizure activity (i.e., epilepsy) were identified in zebrafish lines for 8 genes; ARX, EEF1A, GABRB3, GRIN1, PNPO, SCN1A, STRADA and STXBP1. We also created an open-source database containing sequencing information, survival curves, behavioral profiles and representative electrophysiology data. We offer all zebrafish lines as a resource to the neuroscience community and envision them as a starting point for further functional analysis and/or identification of new therapies.


Assuntos
Modelos Animais de Doenças , Embrião não Mamífero/metabolismo , Epilepsia/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Animais Geneticamente Modificados , Criança , Embrião não Mamífero/citologia , Embrião não Mamífero/embriologia , Epilepsia/patologia , Epilepsia/fisiopatologia , Expressão Gênica , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Larva/genética , Mutação , Fenótipo , Análise de Sobrevida , Sequenciamento Completo do Exoma/métodos , Peixe-Zebra/embriologia
11.
Medicine (Baltimore) ; 100(26): e26478, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190172

RESUMO

ABSTRACT: This study aims to evaluate the effect of dose titration for different oral antiepileptic medications among children with epilepsy in Riyadh, Saudi Arabia.A single-center prospective pilot, cohort study was undertaken at a tertiary hospital in Riyadh, Saudi Arabia. All medical records of pediatric patients below the age of 14 years of age who has been newly diagnosed with epilepsy by attending a medical specialist or on a new epileptic treatment plans were enrolled in the study.A total of 76 epileptic patients were screened for 3 months' period and 48 patients were included in this study. Out of the 48 patients, 31 patients followed the regular practice in the titration processes and 17 patients were in the British national formulary (BNF) guideline. Fifteen children who were on monotherapy of levetiracetam were in regular practice guideline experienced poor seizure control with a recorded number of seizure incidence (n = 10). The patient in regular practice guidelines using a combination therapy of phenytoin and levetiracetam were experiencing some behavioral disturbance and sedation effect. Seventeen patients followed in the BNF guideline who were on levetiracetam were experienced less adverse effect (n = 2) with no behavioral changes.The group who followed the regular practice found having a greater incidence of documented adverse effects compared to the patients following the BNF guideline. The titrating antiepileptic medication has a detrimental effect on the pediatric population as observed in this study.


Assuntos
Anticonvulsivantes , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Epilepsia , Conduta do Tratamento Medicamentoso , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/classificação , Criança , Saúde da Criança , Estudos de Coortes , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Epilepsia/fisiopatologia , Feminino , Humanos , Masculino , Conduta do Tratamento Medicamentoso/organização & administração , Conduta do Tratamento Medicamentoso/normas , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Estudos Prospectivos , Arábia Saudita/epidemiologia
12.
Clin Neurophysiol ; 132(7): 1433-1443, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34023625

RESUMO

The electroencephalogram (EEG) is a fundamental tool in the diagnosis and classification of epilepsy. In particular, Interictal Epileptiform Discharges (IEDs) reflect an increased likelihood of seizures and are routinely assessed by visual analysis of the EEG. Visual assessment is, however, time consuming and prone to subjectivity, leading to a high misdiagnosis rate and motivating the development of automated approaches. Research towards automating IED detection started 45 years ago. Approaches range from mimetic methods to deep learning techniques. We review different approaches to IED detection, discussing their performance and limitations. Traditional machine learning and deep learning methods have yielded the best results so far and their application in the field is still growing. Standardization of datasets and outcome measures is necessary to compare models more objectively and decide which should be implemented in a clinical setting.


Assuntos
Encéfalo/fisiopatologia , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Aprendizado de Máquina , Redes Neurais de Computação , Epilepsia/diagnóstico , Humanos , Processamento de Sinais Assistido por Computador
13.
Clin Neurophysiol ; 132(7): 1543-1549, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34030055

RESUMO

OBJECTIVE: The operational definition of interictal epileptiform discharges (IEDs) of the International Federation of Clinical Neurophysiology (IFCN) described six morphological criteria. Our objective was to assess the impact of pattern-repetition in the EEG-recording, on the diagnostic accuracy of using the IFCN criteria. For clinical implementation, specificity over 95% was set as target. METHODS: Interictal EEG-recordings of 20-minutes, containing sharp-transients, from 60 patients (30 with epilepsy and 30 with non-epileptic paroxysmal events) were evaluated by three experts, who first marked IEDs solely based on expert opinion, and then, independently from the first session evaluated the presence of the IFCN criteria for each sharp-transient. The gold standard was derived from long-term video-EEG recordings of the patients habitual paroxysmal episodes. RESULTS: Presence of at least one discharge fulfilling five criteria provided a specificity of 100% (sensitivity: 70%). For discharges fulfilling fewer criteria, a higher number of discharges was needed to keep the specificity over 95% (5 discharges, when only 3 criteria were fulfilled). A sequential combination of these sets of criteria and thresholds provided a specificity of 97% and sensitivity of 80%. CONCLUSIONS: Pattern-repetition and IED morphology influence diagnostic accuracy. SIGNIFICANCE: Systematic application of these criteria will improve quality of clinical EEG interpretation.


Assuntos
Potenciais de Ação/fisiologia , Encéfalo/fisiopatologia , Eletroencefalografia/normas , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Gravação em Vídeo/normas , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Eletroencefalografia/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Gravação em Vídeo/classificação , Adulto Jovem
14.
Clin Neurophysiol ; 132(7): 1584-1592, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34030056

RESUMO

OBJECTIVE: To quantify effects of sleep and seizures on the rate of interictal epileptiform discharges (IED) and to classify patients with epilepsy based on IED activation patterns. METHODS: We analyzed long-term EEGs from 76 patients with at least one recorded epileptic seizure during monitoring. IEDs were detected with an AI-based algorithm and validated by visual inspection. We then used unsupervised clustering to characterize patient sub-cohorts with similar IED activation patterns regarding circadian rhythms, deep sleep activation, and seizure occurrence. RESULTS: Five sub-cohorts with similar IED activation patterns were found: "Sporadic" (14%, n = 10) without or few IEDs, "Continuous" (32%, n = 23) with weak circadian/deep sleep or seizure modulation, "Nighttime & seizure activation" (23%, n = 17) with high IED rates during normal sleep times and after seizures but without deep sleep modulation, "Deep sleep" (19%, n = 14) with strong IED modulation during deep sleep, and "Seizure deactivation" (12%, n = 9) with deactivation of IEDs after seizures. Patients showing "Deep sleep" IED pattern were diagnosed with temporal lobe epilepsy in 86%, while 80% of the "Sporadic" cluster were extratemporal. CONCLUSIONS: Patients with epilepsy can be characterized by using temporal relationships between rates of IEDs, circadian rhythms, deep sleep and seizures. SIGNIFICANCE: This work presents the first approach to data-driven classification of epilepsy patients based on their fully validated temporal pattern of IEDs.


Assuntos
Inteligência Artificial , Análise de Dados , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Convulsões/fisiopatologia , Sono/fisiologia , Ritmo Circadiano/fisiologia , Epilepsia/diagnóstico , Humanos , Estudos Retrospectivos , Convulsões/diagnóstico
15.
Clin Neurophysiol ; 132(7): 1622-1635, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34034087

RESUMO

OBJECTIVE: To assess whether ictal electric source imaging (ESI) on low-density scalp EEG can approximate the seizure onset zone (SOZ) location and predict surgical outcome in children with refractory epilepsy undergoing surgery. METHODS: We examined 35 children with refractory epilepsy. We dichotomized surgical outcome into seizure- and non-seizure-free. We identified ictal onsets recorded with scalp and intracranial EEG and localized them using equivalent current dipoles and standardized low-resolution magnetic tomography (sLORETA). We estimated the localization accuracy of scalp EEG as distance of scalp dipoles from intracranial dipoles. We also calculated the distances of scalp dipoles from resection, as well as their resection percentage and compared between seizure-free and non-seizure-free patients. We built receiver operating characteristic curves to test whether resection percentage predicted outcome. RESULTS: Resection distance was lower in seizure-free patients for both dipoles (p = 0.006) and sLORETA (p = 0.04). Resection percentage predicted outcome with a sensitivity of 57.1% (95% CI, 34-78.2%), a specificity of 85.7% (95% CI, 57.2-98.2%) and an accuracy of 68.6% (95% CI, 50.7-83.5%) (p = 0.01). CONCLUSION: Ictal ESI performed on low-density scalp EEG can delineate the SOZ and predict outcome. SIGNIFICANCE: Such an application may increase the number of children who are referred for epilepsy surgery and improve their outcome.


Assuntos
Eletroencefalografia/tendências , Epilepsia/diagnóstico por imagem , Epilepsia/fisiopatologia , Convulsões/diagnóstico por imagem , Convulsões/fisiopatologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Epilepsia/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética/tendências , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Convulsões/cirurgia , Tomografia Computadorizada de Emissão de Fóton Único/tendências , Resultado do Tratamento , Adulto Jovem
16.
Sleep Med Clin ; 16(2): 389-408, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33985663

RESUMO

Electroencephalogram (EEG) recording is essential in the evaluation of complex movement and behaviors during sleep, but in particular for differentiating epileptic versus nonepileptic events. In general, epileptiform discharges occur with greater density in the first few nonerapid eye movement cycles, and approximately 12% to 20% of seizures occur exclusively at night. This review examines the epilepsy types and syndromes whose presentation is strongly influenced by the sleep state, with an appraisal about the role that sleep plays in facilitating seizures, while deleaneatign EEG findings and clinical manifestation. The review will summarize the typical semiology of sleep-related hypermotor seizures and contrasted with those occurring during none/rapid eye movement parasomnias and sleep-related movement disorders.


Assuntos
Epilepsia/fisiopatologia , Convulsões/etiologia , Sono/fisiologia , Eletroencefalografia , Humanos , Parassonias/fisiopatologia
17.
Neurology ; 97(2): e178-e190, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-33947776

RESUMO

OBJECTIVE: To determine whether 1-stage, limited corticectomy controls seizures in patients with MRI-positive, bottom-of-sulcus dysplasia (BOSD). METHODS: We reviewed clinical, neuroimaging, electrocorticography (ECoG), operative, and histopathology findings in consecutively operated patients with drug-resistant focal epilepsy and MRI-positive BOSD, all of whom underwent corticectomy guided by MRI and ECoG. RESULTS: Thirty-eight patients with a median age at surgery of 10.2 (interquartile range [IQR] 6.0-14.1) years were included. BOSDs involved eloquent cortex in 15 patients. Eighty-seven percent of patients had rhythmic spiking on preresection ECoG. Rhythmic spiking was present in 22 of 24 patients studied with combined depth and surface electrodes, being limited to the dysplastic sulcus in 7 and involving the dysplastic sulcus and gyral crown in 15. Sixty-eight percent of resections were limited to the dysplastic sulcus, leaving the gyral crown. Histopathology was focal cortical dysplasia (FCD) type IIb in 29 patients and FCDIIa in 9. Dysmorphic neurons were present in the bottom of the sulcus but not the top or the gyral crown in 17 of 22 patients. Six (16%) patients required reoperation for postoperative seizures and residual dysplasia; reoperation was not correlated with ECoG, neuroimaging, or histologic abnormalities in the gyral crown. At a median 6.3 (IQR 4.8-9.9) years of follow-up, 33 (87%) patients are seizure-free, 31 off antiseizure medication. CONCLUSION: BOSD can be safely and effectively resected with MRI and ECoG guidance, corticectomy potentially being limited to the dysplastic sulcus, without need for intracranial EEG monitoring and functional mapping. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that 1-stage, limited corticectomy for BOSD is safe and effective for control of seizures.


Assuntos
Córtex Cerebral/cirurgia , Epilepsia/cirurgia , Malformações do Desenvolvimento Cortical do Grupo I/cirurgia , Adolescente , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Criança , Epilepsia/diagnóstico por imagem , Epilepsia/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical do Grupo I/diagnóstico por imagem , Malformações do Desenvolvimento Cortical do Grupo I/fisiopatologia , Monitorização Fisiológica , Procedimentos Neurocirúrgicos/métodos , Cuidados Pré-Operatórios , Resultado do Tratamento
18.
PLoS Biol ; 19(5): e3001279, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34038402

RESUMO

Hyperactivation of the mammalian target of rapamycin (mTOR) pathway can cause malformation of cortical development (MCD) with associated epilepsy and intellectual disability (ID) through a yet unknown mechanism. Here, we made use of the recently identified dominant-active mutation in Ras Homolog Enriched in Brain 1 (RHEB), RHEBp.P37L, to gain insight in the mechanism underlying the epilepsy caused by hyperactivation of the mTOR pathway. Focal expression of RHEBp.P37L in mouse somatosensory cortex (SScx) results in an MCD-like phenotype, with increased mTOR signaling, ectopic localization of neurons, and reliable generalized seizures. We show that in this model, the mTOR-dependent seizures are caused by enhanced axonal connectivity, causing hyperexcitability of distally connected neurons. Indeed, blocking axonal vesicle release from the RHEBp.P37L neurons alone completely stopped the seizures and normalized the hyperexcitability of the distally connected neurons. These results provide new evidence of the extent of anatomical and physiological abnormalities caused by mTOR hyperactivity, beyond local malformations, which can lead to generalized epilepsy.


Assuntos
Proteína Enriquecida em Homólogo de Ras do Encéfalo/metabolismo , Convulsões/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Axônios/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças , Epilepsia/metabolismo , Epilepsia/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Convulsões/fisiopatologia , Transdução de Sinais , Córtex Somatossensorial/metabolismo
20.
Clin Neurophysiol ; 132(6): 1234-1240, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33867258

RESUMO

OBJECTIVE: Automating detection of Interictal Epileptiform Discharges (IEDs) in electroencephalogram (EEG) recordings can reduce the time spent on visual analysis for the diagnosis of epilepsy. Deep learning has shown potential for this purpose, but the scarceness of expert annotated data creates a bottleneck in the process. METHODS: We used EEGs from 50 patients with focal epilepsy, 49 patients with generalized epilepsy (IEDs were visually labeled by experts) and 67 controls. The data was filtered, downsampled and cut into two second epochs. We increased the number of input samples containing IEDs through temporal shifting and using different montages. A VGG C convolutional neural network was trained to detect IEDs. RESULTS: Using the dataset with more samples, we reduced the false positive rate from 2.11 to 0.73 detections per minute at the intersection of sensitivity and specificity. Sensitivity increased from 63% to 96% at 99% specificity. The model became less sensitive to the position of the IED in the epoch and montage. CONCLUSIONS: Temporal shifting and use of different EEG montages improves performance of deep neural networks in IED detection. SIGNIFICANCE: Dataset augmentation can reduce the need for expert annotation, facilitating the training of neural networks, potentially leading to a fundamental shift in EEG analysis.


Assuntos
Aprendizado Profundo , Epilepsia/fisiopatologia , Redes Neurais de Computação , Eletroencefalografia , Humanos
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