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1.
Epilepsia ; 61(9): 1906-1918, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32761902

RESUMO

OBJECTIVE: Seizure detection is a major facet of electroencephalography (EEG) analysis in neurocritical care, epilepsy diagnosis and management, and the instantiation of novel therapies such as closed-loop stimulation or optogenetic control of seizures. It is also of increased importance in high-throughput, robust, and reproducible pre-clinical research. However, seizure detectors are not widely relied upon in either clinical or research settings due to limited validation. In this study, we create a high-performance seizure-detection approach, validated in multiple data sets, with the intention that such a system could be available to users for multiple purposes. METHODS: We introduce a generalized linear model trained on 141 EEG signal features for classification of seizures in continuous EEG for two data sets. In the first (Focal Epilepsy) data set consisting of 16 rats with focal epilepsy, we collected 1012 spontaneous seizures over 3 months of 24/7 recording. We trained a generalized linear model on the 141 features representing 20 feature classes, including univariate and multivariate, linear and nonlinear, time, and frequency domains. We tested performance on multiple hold-out test data sets. We then used the trained model in a second (Multifocal Epilepsy) data set consisting of 96 rats with 2883 spontaneous multifocal seizures. RESULTS: From the Focal Epilepsy data set, we built a pooled classifier with an Area Under the Receiver Operating Characteristic (AUROC) of 0.995 and leave-one-out classifiers with an AUROC of 0.962. We validated our method within the independently constructed Multifocal Epilepsy data set, resulting in a pooled AUROC of 0.963. We separately validated a model trained exclusively on the Focal Epilepsy data set and tested on the held-out Multifocal Epilepsy data set with an AUROC of 0.890. Latency to detection was under 5 seconds for over 80% of seizures and under 12 seconds for over 99% of seizures. SIGNIFICANCE: This method achieves the highest performance published for seizure detection on multiple independent data sets. This method of seizure detection can be applied to automated EEG analysis pipelines as well as closed loop interventional approaches, and can be especially useful in the setting of research using animals in which there is an increased need for standardization and high-throughput analysis of large number of seizures.


Assuntos
Eletrocorticografia/métodos , Epilepsias Parciais/diagnóstico , Aprendizado de Máquina , Convulsões/diagnóstico , Processamento de Sinais Assistido por Computador , Animais , Área Sob a Curva , Modelos Animais de Doenças , Eletroencefalografia , Epilepsias Parciais/fisiopatologia , Agonistas de Aminoácidos Excitatórios/toxicidade , Ácido Caínico/toxicidade , Modelos Lineares , Curva ROC , Ratos , Reprodutibilidade dos Testes , Convulsões/induzido quimicamente , Convulsões/fisiopatologia
2.
Epilepsia ; 60(3): 475-484, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30669183

RESUMO

OBJECTIVE: Medication nonadherence directly contributes to poor seizure control. A lack of emphasis on correcting poor adherence and failures in patient adherence can result in unwarranted alterations to a patient's drug regimen. We have modeled nonadherent patients in an animal model of epilepsy to study how alterations to pharmacotherapy, made without consideration of a patient's adherence, result in changes to seizure control. METHODS: Newly diagnosed rats with epilepsy were treated with carbamazepine (CBZ) during a 4-week baseline period to establish their baseline seizure rate in the presence of 50% adherence. Next, animals were randomized to one of three treatment interventions and monitored for 6 weeks. Groups included: (1) no change in therapy-rats continued the 50% adherent paradigm; (2) dose escalation-the dose of CBZ was doubled, and the 50% adherent paradigm continued; and (3) nonadherence corrected-rats continued the initial dose of CBZ, but the adherence rate was adjusted to 100% (ie, fully adherent). RESULTS: The rats in the no change in therapy arm displayed a 61% increase in seizure burden over the 6-week intervention phase. Similarly, rats in the dose escalation arm had a 66% worsening of their daily seizure burden. In contrast, rats in the nonadherence corrected arm displayed a 33% reduction in their daily seizure burden; a significant improvement when compared to the normalized seizure burden scores of rats in the other two treatment arms (P < 0.01). SIGNIFICANCE: We found that failure to correct medication nonadherence resulted in an increase in daily seizure burden in rats, even following dose escalation. In the presence of nonadherence, dose escalation worsened seizure control. In contrast, correcting nonadherence alone resulted in improved seizure control. These findings suggest that improving adherence should be prioritized over dose escalation in the clinical management of uncontrolled epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Epilepsia/tratamento farmacológico , Adesão à Medicação , Convulsões/prevenção & controle , Animais , Anticonvulsivantes/administração & dosagem , Carbamazepina/administração & dosagem , Modelos Animais de Doenças , Eletroencefalografia , Epilepsia/psicologia , Masculino , Ratos , Ratos Sprague-Dawley
3.
Exp Neurol ; 279: 116-126, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26896834

RESUMO

More efficient or translationally relevant approaches are needed to model acquired temporal lobe epilepsy (TLE) in genetically tractable mice. The high costs associated with breeding and maintaining transgenic, knock-in, or knock-out lines place a high value on the efficiency of induction and animal survivability. Herein, we describe our approaches to model acquired epilepsy in C57BL/6J mice using repeated, low-dose kainate (KA) administration paradigms. Four paradigms (i.p.) were tested for their ability to induce status epilepticus (SE), temporal lobe pathology, and the development of epilepsy. All four paradigms reliably induce behavioral and/or electrographic SE without mortality over a 7d period. Two of the four paradigms investigated produce features indicative of TLE pathology, including hippocampal cell death, widespread astrogliosis, and astrocyte expression of mGluR5, a feature commonly reported in TLE models. Three of the investigated paradigms were able to produce aberrant electrographic features, such as interictal spiking in cortex. However, only one paradigm, previously published by others, produces spontaneous recurrent seizures over an eight week period. Presentation of spontaneous seizures is rare (N=2/14), with epilepsy preferentially developing in animals having a high number of seizures during SE. Overall, repeated, low-dose KA administration improves the efficiency and pathological relevance of a systemic KA insult, but does not produce a robust epilepsy phenotype under the experimental paradigms described herein.


Assuntos
Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/patologia , Agonistas de Aminoácidos Excitatórios/toxicidade , Ácido Caínico/toxicidade , Animais , Astrócitos/patologia , Morte Celular/efeitos dos fármacos , Modelos Animais de Doenças , Eletroencefalografia , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/induzido quimicamente , Gliose/patologia , Hipocampo/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptor de Glutamato Metabotrópico 5/biossíntese , Convulsões/induzido quimicamente , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/patologia
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