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1.
Adv Neurobiol ; 29: 219-253, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36255677

RESUMO

The chapter is devoted to neurological aspects of congenital disorders of glycosylation (CDG). At the beginning, the various types of CDG with neurological presentation of symptoms are summarized. Then, the occurrence of various neurological constellation of abnormalities (for example: epilepsy, brain anomalies on neuroimaging, ataxia, stroke-like episodes, autistic features) in different CDG types are discussed followed by data on possible biomarkers and limited treatment options.


Assuntos
Defeitos Congênitos da Glicosilação , Epilepsia , Humanos , Defeitos Congênitos da Glicosilação/diagnóstico , Glicosilação , Biomarcadores
2.
Neuropharmacology ; 222: 109303, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36309046

RESUMO

Epilepsy is one of the most common and disabling chronic neurological diseases affecting people of all ages. Major challenges of epilepsy management include the persistently high percentage of drug-refractoriness among patients, the absence of disease-modifying treatments, and its diagnosis and prognosis. To date, long-term video-electroencephalogram (EEG) recordings remain the gold standard for an epilepsy diagnosis. However, this is very costly, has low throughput, and in some instances has very limited availability. Therefore, much effort is put into the search for non-invasive diagnostic tests. Purinergic signalling, via extracellularly released adenosine triphosphate (ATP), is gaining increasing traction as a therapeutic strategy for epilepsy treatment which is supported by evidence from both experimental models and patients. This includes in particular the ionotropic P2X7 receptor. Besides that, other components from the ATPergic signalling cascade such as the metabotropic P2Y receptors (e.g., P2Y1 receptor) and ATP-release channels (e.g., pannexin-1), have also been shown to contribute to seizures and epilepsy. In addition to the therapeutic potential of purinergic signalling, emerging evidence has also shown its potential as a diagnostic tool. Following seizures and epilepsy, the concentration of purines in the blood and the expression of different compounds of the purinergic signalling cascade are significantly altered. Herein, this review will provide a detailed discussion of recent findings on the diagnostic potential of purinergic signalling for epilepsy management and the prospect of translating it for clinical application. This article is part of the Special Issue on 'Purinergic Signaling: 50 years'.


Assuntos
Epilepsia , Humanos , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Convulsões/metabolismo , Trifosfato de Adenosina/metabolismo , Transdução de Sinais , Eletroencefalografia , Receptores Purinérgicos/metabolismo , Receptores Purinérgicos P2X7/metabolismo
3.
Neuropharmacology ; 222: 109310, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36341806

RESUMO

Temporal lobe epilepsy is the most common form of acquired epilepsy and can arise due to multiple inciting events, including central nervous system (CNS) infection. CNS infection with the Theiler's murine encephalomyelitis virus (TMEV) in male C57Bl/6J mice leads to acute, drug-resistant handling-induced seizures. Cholesterol 24-hydroxylase (CH24H) is a brain-specific enzyme that converts cholesterol into 24S-hydroxycholesterol; the primary mechanism of cholesterol catabolism in the brain. The novel CH24H inhibitor, soticlestat (SOT; or TAK-935), demonstrates the potential to restore excitatory/inhibitory balance in multiple preclinical models of hyperexcitability. This study thus sought to characterize the anticonvulsant potential of SOT in the TMEV model. Treatment with SOT (30 mg/kg, p.o.; n = 30) 0-7 days post-infection (DPI) reduced overall seizure burden and severity. SOT administration significantly delayed onset of infection-induced Racine stage 5 seizures, from 8.6 ± 0.6 (VEH-treated) to 10.8 ± 0.8 (SOT-treated) observation sessions. Infected mice were then allowed 36 days treatment-free recovery before assessing impact of earlier drug administration on epilepsy-related cognitive and behavioral comorbidities, including a non-habituated open field (OF) task. Total OF distance traveled was significantly less in SOT-treated mice compared to VEH-treated mice, suggesting attenuated TMEV-induced spatial memory deficits, or reduced chronic hyperexcitability. Mice with history of SOT treatment also spent significantly more time and traveled farther in the OF center, indicative of reduced epilepsy-induced anxiety-like behavior. These studies suggest that SOT is a mechanistically novel agent for symptomatic seizure control. Moreover, acute SOT administration during an epileptogenic insult may attenuate the resulting long-term behavioral comorbidities of epilepsy.


Assuntos
Epilepsia , Theilovirus , Viroses , Masculino , Animais , Camundongos , Colesterol 24-Hidroxilase , Convulsões/tratamento farmacológico , Convulsões/etiologia , Epilepsia/tratamento farmacológico , Epilepsia/etiologia
4.
Physiol Rev ; 103(1): 433-513, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35951482

RESUMO

Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of disorders characterized by early-onset, often severe epileptic seizures and EEG abnormalities on a background of developmental impairment that tends to worsen as a consequence of epilepsy. DEEs may result from both nongenetic and genetic etiologies. Genetic DEEs have been associated with mutations in many genes involved in different functions including cell migration, proliferation, and organization, neuronal excitability, and synapse transmission and plasticity. Functional studies performed in different animal models and clinical trials on patients have contributed to elucidate pathophysiological mechanisms underlying many DEEs and have explored the efficacy of different treatments. Here, we provide an extensive review of the phenotypic spectrum included in the DEEs and of the genetic determinants and pathophysiological mechanisms underlying these conditions. We also provide a brief overview of the most effective treatment now available and of the emerging therapeutic approaches.


Assuntos
Epilepsia , Animais , Epilepsia/genética , Heterogeneidade Genética , Mutação
6.
Zhonghua Bing Li Xue Za Zhi ; 51(11): 1123-1128, 2022 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-36323541

RESUMO

Objective: To investigate the expression of cation chloride cotransporter (NKCC1/KCC2) in the neurons from cerebral lesions of children with focal cortical dysplasia (FCD) type Ⅱ, to provide a morphological basis for revealing the possible mechanism of epilepsy. Methods: Eight cases of FCD type Ⅱ diagnosed at Beijing Haidian Hospital, Beijing, China and 12 cases diagnosed at Xuanwu Hospital, Capital Medical University, Beijing, China from February 2017 to December 2019 were included. The expression of NKCC1 and KCC2 in FCD type Ⅱa and FCD type Ⅱb was detected using immunohistochemistry and double immunohistochemical stains. The average optical density of NKCC1 in dysmorphic neurons and normal neurons was also determined using immunohistochemical staining in FCD type Ⅱa (10 cases). Results: The patients were all younger than 14 years of age. Ten cases were classified as FCD type IIa, and 10 cases as FCD type Ⅱb. NKCC1 was expressed in the cytoplasm of normal cerebral cortex neurons and KCC2 expressed on cell membranes. In dysmorphic neurons of FCD type Ⅱa, expression of NKCC1 increased, which was statistically higher than that of normal neurons (P<0.01). Aberrant expression of KCC2 in dysmorphic neurons was also noted in the cytoplasm. In the FCD Ⅱb type, the expression pattern of NKCC1/KCC2 in dysmorphic neurons was the same as that of FCD type Ⅱa. The aberrant expression of NKCC1 in balloon cells was negative or weakly positive on the cell membrane, while the aberrant expression of KCC2 was absent. Conclusions: The expression pattern of NKCC1/KCC2 in dysmorphic neurons and balloon cells is completely different from that of normal neurons. The NKCC1/KCC2 protein-expression changes may affect the transmembrane chloride flow of neurons, modify the effect of inhibitory neurotransmitters γ-aminobutyric acid and increase neuronal excitability. These effects may be related to the occurrence of clinical epileptic symptoms.


Assuntos
Epilepsia , Malformações do Desenvolvimento Cortical do Grupo I , Simportadores , Criança , Humanos , Encéfalo/patologia , Cátions/metabolismo , Cloretos/metabolismo , Epilepsia/metabolismo , Malformações do Desenvolvimento Cortical do Grupo I/metabolismo , Membro 2 da Família 12 de Carreador de Soluto/metabolismo , Simportadores/metabolismo
7.
BMC Neurol ; 22(1): 401, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36324076

RESUMO

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease. Patients with NIID may present with heterogeneous clinical symptoms, including episodic encephalopathy, dementia, limb weakness, cerebellar ataxia, and autonomic dysfunction. Among the NIID cases reported in China, patients often have complicated and severe manifestations. Therefore, many clinicians do not consider the disease when the patient presents with relatively minor complaints. CASE PRESENTATION: We present the case of a 39-year-old man showing migraine-aura-like symptoms for the past 3 years. Brain magnetic resonance imaging (MRI) revealed hyperintense signals in the splenium of the corpus callosum and corticomedullary junction on diffusion-weighted imaging (DWI) over time. In addition, brain atrophy that was not concomitant with the patient's age was detected while retrospectively reviewing the patient's imaging results. Genetic analysis and skin biopsy confirmed a diagnosis of NIID. The patient was treated with sibelium, and the symptoms did not recur. DISCUSSION AND CONCLUSIONS: Migraine-aura-like symptoms may be the predominant clinical presentation in young patients with NIID. Persistent high-intensity signals on DWI in the brain and early-onset brain atrophy might be clues for the diagnosis of NIID.


Assuntos
Epilepsia , Transtornos de Enxaqueca , Doenças Neurodegenerativas , Masculino , Humanos , Adulto , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/diagnóstico por imagem , Estudos Retrospectivos , Atrofia/complicações , Cefaleia/complicações , Transtornos de Enxaqueca/complicações , Epilepsia/complicações
8.
Sleep Med Clin ; 17(4): 639-645, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36333082

RESUMO

Both epilepsy and obstructive sleep apnea are common conditions and hence frequently coexist in a given patient. A complex bidirectional relationship exists between the 2 conditions where the presence of one affects the other. Treatment of obstructive sleep apnea with continuous positive airway pressure may improve seizure control in medically refractory epilepsy patients, leading to improved quality of life. Understanding of this complex relationship between epilepsy, sleep, and sleep disorders such as obstructive sleep apnea continues to evolve.


Assuntos
Epilepsia , Apneia Obstrutiva do Sono , Humanos , Qualidade de Vida , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Pressão Positiva Contínua nas Vias Aéreas , Epilepsia/complicações , Epilepsia/terapia , Resultado do Tratamento
9.
Oxid Med Cell Longev ; 2022: 7692215, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338344

RESUMO

Stroke is the most common cause of epilepsy and ultimately leads to a decrease in the quality of life of those affected. Ischemic and hemorrhagic strokes can both lead to poststroke epilepsy (PSE). Significant risk factors for PSE include age < 65age less than 65 years, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), cortical involvement, and genetic factors such as TRPM6 polymorphism. The diagnosis of PSE is made by using imaging modalities, blood biomarkers, and prognostic criteria. Electroencephalography (EEG) is currently the gold standard to diagnose PSE, while new combinations of modalities are being tested to increase diagnostic specificity. This literature review uncovers a newly found mechanism for the pathology of poststroke epilepsy. The pathogenesis of early-onset and late-onset is characterized by sequelae of neuronal cellular hypoxia and disruption of the blood-brain barrier, respectively. Interleukin-6 is responsible for increasing the activity of glial cells, causing gliosis and hyperexcitability of neurons. Epinephrine, high-mobility group protein B1, downregulation of CD32, and upregulation of HLA-DR impact the pathology of poststroke epilepsy by inhibiting the normal neuronal immune response. Decreased levels of neuropeptide Y, a neurotransmitter, act through multiple unique mechanisms, such as inhibiting intracellular Ca2+ accumulation and acting as an anti-inflammatory, also implemented in the worsening progression of poststroke epilepsy. Additionally, CA1 hippocampal resonant neurons that increase theta oscillation are associated with poststroke epilepsy. Hypertensive small vessel disease may also have an implication in the temporal lobe epilepsy by causing occult microinfarctions. Furthermore, this review highlights the potential use of statins as primary prophylaxis against PSE, with multiple studies demonstrating a reduction in incidence using statins alone, statins in combination with antiepileptic drugs (AEDs), and statins with aspirin. The evidence strongly suggests that the second generation AEDs are a superior treatment method for PSE. Data from numerous studies demonstrate their relative lack of significant drug interactions, increased tolerability, and potential superiority in maintaining seizure-free status.


Assuntos
Epilepsia , Inibidores de Hidroximetilglutaril-CoA Redutases , Acidente Vascular Cerebral , Humanos , Idoso , Incidência , Qualidade de Vida , Epilepsia/tratamento farmacológico , Convulsões/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Fatores de Risco
10.
BMC Psychiatry ; 22(1): 674, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319991

RESUMO

BACKGROUND: Common mental disorders are severe and frequent co-morbid psychiatric illnesses with epilepsy. Different study findings across the world showed that patients with epilepsy have a higher burden of mental disorders than the general population. However, these issues in patients with epilepsy have been consistently undiagnosed. OBJECTIVES: The study aimed to screen common mental disorders and the determinants among patients with epilepsy attending at Fenote Selam hospital. METHODS: An institutional-based cross-sectional study was conducted among patients with Epilepsy from March 10 to May 15, 2019. Patients were assessed for the risk of common mental disorders using a pretested, structured, self-reporting questionnaire (SRQ-20). The collected data were entered into Epi-data version 3.1 software and analyzed using R version 4.0 software. Descriptive statistics were computed using frequency, percent, mean, and standard deviations. A simple logistic regression model was fit to identify the association and strength of exploratory variables and common mental disorders at a 95% confidence interval and p-value < 0.05. RESULTS: The study included 202 patients diagnosed with epilepsy and yielded a response of 91.4%. About 53% of the patients were males. The magnitude of common mental disorders among patients with epilepsy was 57.9% (95% CI: 44.56, 71.24). Being more than one substance user (AOR = 5.7; 95%CI: 1.6, 20.7) and Not having social support (AOR = 4.3; 95%CI: 1.5, 11.9) were the identified determinants of common mental disorders. CONCLUSION: The magnitude of common mental disorders among patients with epilepsy were high. Not having social support and khat chewing were the identified risk factors significantly associated with common mental disorders. Early screening and treatments are the key interventions to prevent complications and deaths from common mental disorders.


Assuntos
Epilepsia , Transtornos Mentais , Masculino , Humanos , Feminino , Estudos Transversais , Etiópia/epidemiologia , Prevalência , Transtornos Mentais/epidemiologia , Epilepsia/complicações
11.
Sensors (Basel) ; 22(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36366141

RESUMO

Epilepsy is a severe neurological disorder that is usually diagnosed by using an electroencephalogram (EEG). However, EEG signals are complex, nonlinear, and dynamic, thus generating large amounts of data polluted by many artefacts, lowering the signal-to-noise ratio, and hampering expert interpretation. The traditional seizure-detection method of professional review of long-term EEG signals is an expensive, time-consuming, and challenging task. To reduce the complexity and cost of the task, researchers have developed several seizure-detection approaches, primarily focusing on classification systems and spectral feature extraction. While these methods can achieve high/optimal performances, the system may require retraining and following up with the feature extraction for each new patient, thus making it impractical for real-world applications. Herein, we present a straightforward manual/automated detection system based on the simple seizure feature amplification analysis to minimize these practical difficulties. Our algorithm (a simplified version is available as additional material), borrowing from the telecommunication discipline, treats the seizure as the carrier of information and tunes filters to this specific bandwidth, yielding a viable, computationally inexpensive solution. Manual tests gave 93% sensitivity and 96% specificity at a false detection rate of 0.04/h. Automated analyses showed 88% and 97% sensitivity and specificity, respectively. Moreover, our proposed method can accurately detect seizure locations within the brain. In summary, the proposed method has excellent potential, does not require training on new patient data, and can aid in the localization of seizure focus/origin.


Assuntos
Epilepsia , Processamento de Sinais Assistido por Computador , Humanos , Convulsões/diagnóstico , Eletroencefalografia/métodos , Epilepsia/diagnóstico , Algoritmos
12.
Sci Rep ; 12(1): 19430, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371527

RESUMO

Biomedical ontologies are widely used to harmonize heterogeneous data and integrate large volumes of clinical data from multiple sources. This study analyzed the utility of ontologies beyond their traditional roles, that is, in addressing a challenging and currently underserved field of feature engineering in machine learning workflows. Machine learning workflows are being increasingly used to analyze medical records with heterogeneous phenotypic, genotypic, and related medical terms to improve patient care. We performed a retrospective study using neuropathology reports from the German Neuropathology Reference Center for Epilepsy Surgery at Erlangen, Germany. This cohort included 312 patients who underwent epilepsy surgery and were labeled with one or more diagnoses, including dual pathology, hippocampal sclerosis, malformation of cortical dysplasia, tumor, encephalitis, and gliosis. We modeled the diagnosis terms together with their microscopy, immunohistochemistry, anatomy, etiologies, and imaging findings using the description logic-based Web Ontology Language (OWL) in the Epilepsy and Seizure Ontology (EpSO). Three tree-based machine learning models were used to classify the neuropathology reports into one or more diagnosis classes with and without ontology-based feature engineering. We used five-fold cross validation to avoid overfitting with a fixed number of repetitions while leaving out one subset of data for testing, and we used recall, balanced accuracy, and hamming loss as performance metrics for the multi-label classification task. The epilepsy ontology-based feature engineering approach improved the performance of all the three learning models with an improvement of 35.7%, 54.5%, and 33.3% in logistics regression, random forest, and gradient tree boosting models respectively. The run time performance of all three models improved significantly with ontology-based feature engineering with gradient tree boosting model showing a 93.8% reduction in the time required for training and testing of the model. Although, all three models showed an overall improved performance across the three-performance metrics using ontology-based feature engineering, the rate of improvement was not consistent across all input features. To analyze this variation in performance, we computed feature importance scores and found that microscopy had the highest importance score across the three models, followed by imaging, immunohistochemistry, and anatomy in a decreasing order of importance scores. This study showed that ontologies have an important role in feature engineering to make heterogeneous clinical data accessible to machine learning models and also improve the performance of machine learning models in multilabel multiclass classification tasks.


Assuntos
Epilepsia , Aprendizado de Máquina , Humanos , Fluxo de Trabalho , Estudos Retrospectivos , Epilepsia/diagnóstico , Convulsões , Registros Médicos
13.
Clin Neuropharmacol ; 45(6): 175-176, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36383916

RESUMO

OBJECTIVES: The purpose of the current study was to investigate whether taking valproic acid (VPA) was protective against coronavirus disease 2019 (COVID-19) infection or severity in patients with epilepsy. METHODS: This was a questionnaire study of 150 people who were taking VPA in monotherapy or polytherapy (since the start of the pandemic or longer) and also 150 people who were not taking VPA (since the start of the pandemic), registered in our epilepsy database. The data compared rates of the seropositivity and severity of infection of COVID-19 between the 2 groups. The latter was assessed, by proxy, vis-à-vis rates of hospital admission and intensive care unit admission. RESULTS: Two hundred forty-one patients were studied, including 130 (53.9%) male and 111 (46.1%) female patients. The mean age of the patients was 30.7 ± 11.4 years. The infection rate and severity of COVID-19 did not significantly differ among patients who were taking VPA and those who were not taking VPA (P = 0.587) and (P = 0.648), respectively. CONCLUSIONS: In this pilot study, no support was found for the hypothesis of a protective effect of VPA against the infectivity rate of COVID-19. Neither was there any indication of a disease-modulating effect of VPA in people with active COVID-19 infection. Larger, randomized controlled trials would be warranted to substantiate our conclusion.


Assuntos
COVID-19 , Epilepsia , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Ácido Valproico/uso terapêutico , Anticonvulsivantes/uso terapêutico , Projetos Piloto , Epilepsia/tratamento farmacológico
14.
Trials ; 23(1): 943, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397081

RESUMO

BACKGROUND: A Core Outcome Set (COS) is a standardised list of outcomes that should be reported as a minimum in all clinical trials. In epilepsy, the choice of outcomes varies widely among existing studies, particularly in clinical trials. This diminishes opportunities for informed decision-making, contributes to research waste and is a barrier to integrating findings in systematic reviews and meta-analyses. Furthermore, the outcomes currently being measured may not reflect what is important to people with epilepsy. Therefore, we aim to develop a COS specific to clinical effectiveness research for adults with epilepsy using Delphi consensus methodology. METHODS: The EPSET Study will comprise of three phases and follow the core methodological principles as outlined by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. Phase 1 will include two focused literature reviews to identify candidate outcomes from the qualitative literature and current outcome measurement practice in phase III and phase IV clinical trials. Phase 2 aims to achieve international consensus to define which outcomes should be measured as a minimum in future trials, using a Delphi process including an online consensus meeting involving key stakeholders. Phase 3 will involve dissemination of the ratified COS to facilitate uptake in future trials and the planning of further research to identify the most appropriate measurement instruments to use to capture the COS in research practice. DISCUSSION: Harmonising outcome measurement across future clinical trials should ensure that the outcomes measured are relevant to patients and health services, and allow for more meaningful results to be obtained. CORE OUTCOME SET REGISTRATION: COMET Initiative as study 118 .


Assuntos
Epilepsia , Projetos de Pesquisa , Adulto , Humanos , Técnica Delfos , Revisões Sistemáticas como Assunto , Avaliação de Resultados em Cuidados de Saúde , Epilepsia/diagnóstico , Epilepsia/terapia
15.
Proc Natl Acad Sci U S A ; 119(46): e2206828119, 2022 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-36343238

RESUMO

Focused ultrasound (FUS) is a powerful tool for noninvasive modulation of deep brain activity with promising therapeutic potential for refractory epilepsy; however, tools for examining FUS effects on specific cell types within the deep brain do not yet exist. Consequently, how cell types within heterogeneous networks can be modulated and whether parameters can be identified to bias these networks in the context of complex behaviors remains unknown. To address this, we developed a fiber Photometry Coupled focused Ultrasound System (PhoCUS) for simultaneously monitoring FUS effects on neural activity of subcortical genetically targeted cell types in freely behaving animals. We identified a parameter set that selectively increases activity of parvalbumin interneurons while suppressing excitatory neurons in the hippocampus. A net inhibitory effect localized to the hippocampus was further confirmed through whole brain metabolic imaging. Finally, these inhibitory selective parameters achieved significant spike suppression in the kainate model of chronic temporal lobe epilepsy, opening the door for future noninvasive therapies.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Animais , Epilepsia/terapia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Ultrassonografia , Hipocampo/diagnóstico por imagem
16.
J Stroke Cerebrovasc Dis ; 31(12): 106858, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36343476

RESUMO

OBJECTIVES: Ischemic stroke is one of the most common causes of epilepsy in adults. The incidence of post-stroke epilepsy (PSE) is approximately 7%. Risk factors are higher stroke severity, cortical localization, higher National Institute of Health Stroke Scale (NIHSS) upon admission and acute symptomatic seizures. We analyzed the predictive factors of PSE development in our population. MATERIALS AND METHODS: Retrospective observational cohort of adult patients (age ≥ 18 years) with ischemic stroke assessed between January 2012 and June 2020. Patients with personal history of epilepsy and potentially epileptogenic structural injury other than acute or chronic stroke were excluded. Demographic, clinical and imaging variables were evaluated in a multivariate analysis for independent risk factors associated with PSE. RESULTS: Medical records of 1586 stroke patients were reviewed, 691 met the inclusion criteria and had at least one year of follow-up. Of them, 428 (61.9%) were males. During follow-up, 6.2% had diagnosis of PSE (42/691) with a higher frequency of: previous ischemic stroke, higher NIHSS upon admission, treatment with rt-PA, higher Fazekas scale grade, cortical involvement, hemorrhagic transformation, acute symptomatic seizures, longer hospitalization and higher modified Rankin Scale (mRS) at discharge compared to the group without PSE. In a multivariate analysis, acute symptomatic seizures (OR=3.22, p: 0.033), cortical involvement (OR=0.274, p < 0.05), Fazekas scale score (OR=0.519, p < 0.05) and mRS at discharge (OR=1.33, p: 0.043) were independent risk factors. CONCLUSIONS: The variables related to higher risk of PSE were similar to those reported in the literature, highlighting the importance of neuroimaging findings, acute symptomatic seizures during hospitalization and neurological deficit at discharge. The data obtained will serve as the basis for construction of predictive models, allowing to individualize PSE probability in our population.


Assuntos
Epilepsia , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Adolescente , Feminino , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/diagnóstico por imagem , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Epilepsia/etiologia , Convulsões/diagnóstico , Convulsões/epidemiologia , Convulsões/etiologia , Fatores de Risco
17.
Exp Brain Res ; 240(12): 3339-3349, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36344756

RESUMO

Temporal lobe epilepsy (TLE) is the most common type of epilepsy in humans. Cognitive impairment and memory consolidation problems are common among TLE patients. To understand the changes in the cellular process of memory in TLE, we studied the long-term depression (LTD) in Schaffer-collateral (Sc) CA1 synapses in an epilepsy model. Long-term potentiation (LTP) was investigated in patient samples and animal models by several groups, but LTD was not studied with the same interest in epilepsy research. Here we induced epileptiform activity in rat hippocampal slices using magnesium-free high-potassium (7.5 mM K +) artificial cerebrospinal fluid (HK-ACSF) and characterized the LTD in Sc-CA1 synapses. We found that epileptiform activity abolished/impaired LTD and depotentiation in the Sc-CA1 synapses. In control slices, application of NMDA (30 µM for 3 min) induced chemical LTD (c-LTD) in Sc-CA1 synapses, whereas epileptiform activity induced slices showed slow onset potentiation. Induction of LTD using 1 Hz, 900 pulses yielded a similar outcome as c-LTD. Both forms of LTD were NMDA receptor dependent. In addition, we found that the polarity changes in the synaptic plasticity in epileptiform-induced slices were blocked by GluN2B antagonists ifenprodil and Ro 25-6981. Our data suggest that epileptiform-induced metaplasticity inhibits LTD in Sc-CA1 synapses. We provide new insight into the cellular mechanism of memory formation during epilepsy.


Assuntos
Epilepsia , Receptores de N-Metil-D-Aspartato , Humanos , Ratos , Animais , Sinapses , Potenciação de Longa Duração , Hipocampo/metabolismo , Plasticidade Neuronal
18.
Science ; 378(6619): 471-472, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36378973

RESUMO

On-demand inhibition of neuronal activity reduced spontaneous seizures in mice.


Assuntos
Epilepsia , Terapia Genética , Neurônios , Animais , Camundongos , Modelos Animais de Doenças , Epilepsia/genética , Epilepsia/terapia , Neurônios/fisiologia , Convulsões/genética , Convulsões/terapia
19.
Science ; 378(6619): 523-532, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36378958

RESUMO

Several neurodevelopmental and neuropsychiatric disorders are characterized by intermittent episodes of pathological activity. Although genetic therapies offer the ability to modulate neuronal excitability, a limiting factor is that they do not discriminate between neurons involved in circuit pathologies and "healthy" surrounding or intermingled neurons. We describe a gene therapy strategy that down-regulates the excitability of overactive neurons in closed loop, which we tested in models of epilepsy. We used an immediate early gene promoter to drive the expression of Kv1.1 potassium channels specifically in hyperactive neurons, and only for as long as they exhibit abnormal activity. Neuronal excitability was reduced by seizure-related activity, leading to a persistent antiepileptic effect without interfering with normal behaviors. Activity-dependent gene therapy is a promising on-demand cell-autonomous treatment for brain circuit disorders.


Assuntos
Epilepsia , Terapia Genética , Canal de Potássio Kv1.1 , Humanos , Encéfalo/metabolismo , Epilepsia/genética , Epilepsia/terapia , Canal de Potássio Kv1.1/genética , Convulsões/genética , Convulsões/terapia , Convulsões/metabolismo , Animais , Camundongos , Neurônios/fisiologia
20.
ASN Neuro ; 14: 17590914221136662, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36383501

RESUMO

Depression is a common psychiatric comorbidity in patients with epilepsy, especially those with temporal lobe epilepsy (TLE). The aim of this study was to assess changes in high mobility group box protein 1 (HMGB1) expression in epileptic patients with and without comorbid depression. Sixty patients with drug-resistant TLE who underwent anterior temporal lobectomy were enrolled. Anterior hippocampal samples were collected after surgery and analyzed by immunofluorescence (n = 7/group). We also evaluated the expression of HMGB1 in TLE patients with hippocampal sclerosis and measured the level of plasma HMGB1 by enzyme-linked immunosorbent assay. The results showed that 28.3% of the patients (17/60) had comorbid depression. HMGB1 was ubiquitously expressed in all subregions of the anterior hippocampus. The ratio of HMGB1-immunoreactive neurons and astrocytes was significantly increased in both TLE patients with hippocampal sclerosis and TLE patients with comorbid depression compared to patients with TLE only. The ratio of cytoplasmic to nuclear HMGB1-positive neurons in the hippocampus was higher in depressed patients with TLE than in nondepressed patients, which suggested that more HMGB1 translocated from the nucleus to the cytoplasm in the depressed group. There was no significant difference in the plasma level of HMGB1 among patients with TLE alone, TLE with hippocampal sclerosis, and TLE with comorbid depression. The results of the study revealed that the translocation of HMGB1 from the nucleus to the cytoplasm in hippocampal neurons may play a previously unrecognized role in the initiation and amplification of epilepsy and comorbid depression. The direct targeting of neural HMGB1 is a promising approach for anti-inflammatory therapy.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Proteína HMGB1 , Humanos , Esclerose/metabolismo , Esclerose/patologia , Proteína HMGB1/metabolismo , Epilepsia do Lobo Temporal/cirurgia , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Epilepsia/cirurgia , Epilepsia/metabolismo , Gliose/patologia , Citoplasma/metabolismo
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