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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Is Ignorance Bliss? Attributions for Seizures and Consequences of those Attributions among Participants with Psychogenic Non-epileptic Seizures

January 2012 (has links)
abstract: Psychogenic non-epileptic seizures (PNES), is a conversion disorder thought to be linked to unresolved emotional distress. While some studies suggest that PNES patients do not attribute their somatic symptoms to severe psychological experiences (Stone, Binzer, & Sharpe, 2004; LaFrance & Barry, 2005), it is unclear what PNES patients do think causes their seizures, and the psychological consequences of those attributions. The aim of the present study was to investigate PNES patients' attributions for their seizures, and to determine how these attributions relate to stress and emotion regulation. It was hypothesized that participants who attribute their seizures to something (i.e., have an explanation for their seizures) will have lower perceived stress and less difficulty with emotion regulation than those who are unsure of the cause of their seizures. Twenty-four PNES participants completed a questionnaire assessing seizure diagnosis, characteristics of seizure impact, perceived stress, psychological symptoms, emotion regulation, attributions for seizures, and coping resources. Contrary to the hypothesis, having an explanation for seizures, rather than being “unsure” of seizure cause, was related to greater perceived stress. While it would seem that attributing unpredictable seizure events to a cause would lower perceived stress and emotion regulation difficulty, this study indicates that an attribution to an unknown cause may be more beneficial for the individual. / Dissertation/Thesis / M.S. Psychology 2012
2

The role of serotonin in cortical excitability and network dynamics

Puzerey, Pavel A. 13 February 2015 (has links)
No description available.
3

Narrative accounts of family caregivers of adults diagnosed with non-epileptic attack disorder

Davies, Rebecca Lara January 2012 (has links)
The experiences of family caregivers of adults diagnosed with Non-Epileptic Attack Disorder (NEAD) are under-researched. To address this lack of research and the Department of Health’s (DOH) aim to focus on the experiences of caregivers to inform the development of appropriate services (DOH, 2010), this narrative inquiry focuses on the stories told by eight caregivers of adults diagnosed with NEAD. Each narrative, which was collected through loosely structured interviews, was analysed from both a content and performative perspective. Multiple readings of the narratives revealed that caregivers told two different story ‘types’ about their experiences: stories of ‘biographical continuity’ and stories of ‘biographical disruption’. These findings are discussed in relation to the relevant literature and clinical implications. Methodological limitations and directions for future research are also presented. The study provides a valuable insight for any professional working with caregivers of individuals with NEAD and it is hoped that this research will promote dialogue amongst professionals and readers.
4

Improving the Ability of the MMPI-2-RF to Discriminate between Psychogenic Non-epileptic Seizures and Epileptic Seizures

January 2013 (has links)
abstract: The use of bias indicators in psychological measurement has been contentious, with some researchers questioning whether they actually suppress or moderate the ability of substantive psychological indictors to discriminate (McGrath, Mitchell, Kim, & Hough, 2010). Bias indicators on the MMPI-2-RF (F-r, Fs, FBS-r, K-r, and L-r) were tested for suppression or moderation of the ability of the RC1 and NUC scales to discriminate between Epileptic Seizures (ES) and Non-epileptic Seizures (NES, a conversion disorder that is often misdiagnosed as ES). RC1 and NUC had previously been found to be the best scales on the MMPI-2-RF to differentiate between ES and NES, with optimal cut scores occurring at a cut score of 65 for RC1 (classification rate of 68%) and 85 for NUC (classification rate of 64%; Locke et al., 2010). The MMPI-2-RF was completed by 429 inpatients on the Epilepsy Monitoring Unit (EMU) at the Scottsdale Mayo Clinic Hospital, all of whom had confirmed diagnoses of ES or NES. Moderated logistic regression was used to test for moderation and logistic regression was used to test for suppression. Classification rates of RC1 and NUC were calculated at different bias level indicators to evaluate clinical utility for diagnosticians. No moderation was found. Suppression was found for F-r, Fs, K-r, and L-r with RC1, and for all variables with NUC. For F-r and Fs, the optimal RC1 and NUC cut scores increased at higher levels of bias, but tended to decrease at higher levels of K-r, L-r, and FBS-r. K-r provided the greatest suppression for RC1, as well as the greatest increases in classification rates at optimal cut scores, given different levels of bias. It was concluded that, consistent with expectations, taking account of bias indicator suppression on the MMPI-2-RF can improve discrimination of ES and NES. At higher levels of negative impression management, higher cut scores on substantive scales are needed to attain optimal discrimination, whereas at higher levels of positive impression management and FBS-r, lower cut scores are needed. Using these new cut scores resulted in modest improvements in accuracy in discrimination. These findings are consistent with prior research in showing the efficacy of bias indicators, and extend the findings to a psycho-medical context. / Dissertation/Thesis / Ph.D. Psychology 2013
5

Perspectives on psychogenic non-epileptic seizures

Fairclough, Gillian January 2012 (has links)
This thesis explores the perspectives of people on psychogenic non-epileptic seizures (PNES). It is presented in three separate papers: a systematic literature review; an empirical research paper and a critical reflection of the research process as a whole. The systematic literature review aimed to provide a detailed understanding of stakeholder perspectives on PNES. A systematic search identified relevant studies that were subsequently synthesised using thematic analysis and the broader principles of narrative synthesis. Three broad themes relating to stakeholder perspectives were identified: the nature of PNES as a condition; diagnosis; and management and treatment issues. It was found that both patients and professionals experienced uncertainties in relation to understanding and managing the condition. This highlighted the need for further information and awareness of PNES and the development of clear treatment guidelines. Important differences in opinion were also identified between patients and professionals and consideration was given to how these may disrupt the development of effective partnerships in care. The research into patients' and families' perspectives was found to be lacking and further research was identified as being needed in this area. The empirical paper reports an exploratory qualitative study that aimed to provide an in-depth understanding of the perceived treatment needs of patients with PNES. Semi-structured interviews were conducted and findings were analysed inductively using the principles of thematic analysis. Four key themes were identified: return to normality; post-diagnostic limbo; uncertainty and apprehension about therapy; and need for validation. Patients with PNES described clear goals for their recovery and clear ideas about their treatment needs. However, following their diagnosis, many felt caught in 'limbo' due to uncertainties about their diagnosis and as a result of a lack of post-diagnostic support. Being in 'limbo' also linked to patients' uncertainties about psychology meeting their needs and for some there was apprehension about the potential negative consequences of therapy. The clinical implications of the research are discussed and recommendations for future research are made. The third paper is a critical reflection of the research process as a whole. It provides an overview and evaluation of the first two papers and personal reflections of the lead researcher are offered throughout. Implications for further research and clinical practice are offered and a summary of the research as a whole is offered.
6

Analysis of signals related to the generation process of extreme events : towards a unified approach

Minadakis, George January 2013 (has links)
In the last decades, although the scientific community has attempted to explain a series of complex phenomena, ranging from natural hazards to physical conditions and economic crises, aspects of their generation process still escape our full understanding. The present thesis intends to promote our understanding of the spatiotemporal behavior and the generation mechanisms that govern large and strong earthquakes, employing a broad multidisciplinary perspective for the interpretation of catastrophic events. Two main questions are debated. The first question concentrates on “whether the generation process of an extreme event has more than one facets prior to its final appearance”. In the scientific study of earthquakes, attention is drawn to the predictive capability and monitoring of different precursory observations. Among them preseismic electromagnetic emissions have been also observed indicating that the science of earthquake prediction should be from the start multidisciplinary. Drawing on recently introduced models for earthquake dynamics, that address issues such as long-range correlations, self-affinity, complexity-organization and fractal structures, the present work endeavors to further penetrate on the analysis of preseismic electromagnetic emissions and elucidate their link with the generation process of large and strong earthquakes. A second question deals with “whether there is a unified approach for the study of catastrophic events”. This question implies the possibility for common statistical behavior of diverse extreme events and the potential for transferability of methods from the study of earthquake dynamics across other fields. On these grounds, the present work extends the focus of inquiry to the analysis of electroencephalogram recordings related to epileptic seizures, in the prospect to identify common mechanisms that may explain the nature and the generation process of both phenomena, and to open up different directions for future research. Finally, with a view to consider alternative ways of studying key theoretical principles associated with the generation process of catastrophic phenomena, a relevant framework based on proposed algorithms is presented, focusing on parameters such as: the energy of earthquakes, the mean and maximum magnitude of the sample, the probability that two samples may come from the same population. Such an attempt aims to contribute to the knowledge of natural phenomena, by extending the existing theory and models and providing a few more ways for their interpretation.
7

Εξόρυξη χωροχρονικών δεδομένων από τον ανθρώπινο εγκέφαλο και εφαρμογές στην ανίχνευση των επιληπτικών κρίσεων

Πίππα, Ευαγγελία 12 October 2013 (has links)
Αντικείμενο αυτής της εργασίας είναι η μελέτη τεχνικών για την ανάλυση δεδομένων που προέρχονται από συστήματα απεικόνισης της λειτουργίας του ανθρώπινου εγκεφάλου όπως το ηλεκτροεγκεφαλογράφημα. Σκοπός των τεχνικών ανάλυσης είναι η ανίχνευση συγκεκριμένων μορφών αυτών των σημάτων όπως για παράδειγμα οι επιληπτικές κρίσεις. Μία κρίση είναι μια παρέκκλιση στην ηλεκτρική δραστηριότητα του εγκεφάλου που παράγει αποδιοργανωτικά συμπτώματα για το άτομο και εκδηλώνεται κλινικά από εναλλαγή στη συμπεριφορά, στην κίνηση, στις αισθήσεις και στη συνειδητότητα. Οι κλινικές συμπεριφορές προηγούνται και στη συνέχεια συνοδεύονται από ηλεκτροεγκεφαλογραφικές αλλαγές. Η αυτόματη ανίχνευση των επιληπτικών κρίσεων μπορεί να αντιμετωπιστεί ως ένα πρόβλημα κατηγοριοποίησης των σημάτων σε κρίσεις ή όχι. Η ανίχνευση μπορεί να πραγματοποιηθεί σε δύο βήματα. Αρχικά εξάγονται χαρακτηριστικά που συλλαμβάνουν την μορφή και στη συνέχεια το διάνυσμα των χαρακτηριστικών δίνεται σε έναν εκπαιδευμένο κατηγοριοποιητή. / The subject of this work is the research of analysis techniques on data coming from neuroimaging systems such as Electroencephalogram. The aim of the data analysis techniques is the detection of specific morphologies of these signals such as the epileptic seizures. A seizure is a sudden breakdown of the neuronal activity of the brain that is clinically manifested by an involuntary alteration in behavior, movement, sensation, or consciousness. These clinical behaviors are preceded and then accompanied by electroencephalographic alterations. The automatic detection of epileptic seizures can be faced as a classification problem of the signals into seizures or non seizures. The detection can be carried out in two steps. Firstly, features which capture the morphology of the epileptic seizures are extracted and then the feature vector is given to an appropriately trained classifier.
8

O uso da vigabatrina como droga de adição no controle de crises epilépticas neonatais / The use of vigabatrin as a drug antiepileptic drug in the control of neonatal epileptic seizures

Damasceno, Patrícia Gomes 26 June 2017 (has links)
Introdução: A vigabatrina (VGB - Gama-Vinil-GABA) é um fármaco que eleva os níveis de GABA no organismo, por inibição irreversível da GABA transaminase, cuja eficácia foi bem demonstrada no controle dos espasmos epilépticos em lactentes, especialmente na síndrome de West secundária à esclerose tuberosa. Há escassez de estudos clínicos evidenciando um possível papel deste fármaco no controle de crises epilépticas neonatais e pouco se sabe sobre o potencial impacto do seu uso nessa faixa etária, seus possíveis efeitos adversos, ou se sua introdução teria associações positivas com controle mais adequado das crises na evolução e melhor desenvolvimento neuropsicomotor da criança. A VGB foi introduzida em nosso serviço como terapia de adição para o controle de crises neonatais refratárias, há vários anos, instigando nossa impressão sobre a eficácia deste medicamento no período neonatal. Objetivos: Avaliar a efetividade do uso da VGB como adjuvante no controle das crises eletrográficas e eletroclínicas do período neonatal e seus efeitos sobre o padrão do eletroencefalograma (EEG); Avaliar a evolução clínica e eletrográfica das crianças durante seguimento ambulatorial; Pesquisar associação entre \"controle de crises neonatais com introdução de VGB\" e diversas características demográficas, clínicas e evolutivas destes recém nascidos; Quantificar e caracterizar a ocorrência de efeitos adversos precoces e durante o seguimento. Pacientes e métodos: Estudo transversal retrospectivo, envolvendo o levantamento dos prontuários de uma amostra de recém-nascidos que receberam VGB como tratamento para crises neonatais refratárias aos fármacos convencionais e status epilepticus, no período de janeiro de 2007 a março de 2014, no Serviço de Neonatologia e Terapia Intensiva Neonatal do HCFMRP-USP, mantendo seguimento ambulatorial por pelo menos 1 ano. Foram avaliados os dados demográficos, etiologia e semiologia clínico-eletroencefalográfica das crises, esquema terapêutico prescrito, indicação da introdução da VGB, tempo de internação e tempo para atingir o controle das crises, evolução clínica e eletrencefalográfica durante a internação e no seguimento ambulatorial, época da suspensão da VGB, além de seus efeitos adversos. Resultados: De 48 recém-nascidos avaliados, 34 (79,2 %) obtiveram controle de crises eletrográficas e/ou clínicas durante o período neonatal, havendo melhora no padrão eletrográfico após a introdução da VGB em 79%. Quanto aos critérios para sua indicação, 33,3% (16 indivíduos) iniciaram VGB devido a falha terapêutica no controle das crises com fenobarbital e/ou fenitoína; 27,1% (13 recém nascidos), pela presença de estado de mal epilético e, em 12 crianças (25%), por falha terapêutica do midazolam. Ao final do primeiro ano de vida, a atividade de base do EEG mostrou-se desorganizada em 58,1% (18 de 29 pacientes que o realizaram aos 12 meses de vida). No seguimento ambulatorial de 38 pacientes, algum grau de atraso do desenvolvimento neuropsicomotor foi detectado em 20 crianças (52,6%); 19 lactentes (39,5%) mantiveram o uso da VGB em politerapia, tendo 22 crianças (57,9%) evoluído com persistência das crises epilépticas. Já 37,8% (14 pacientes) enquadraram-se em um padrão de encefalopatia epiléptica, que correspondeu à síndrome de West em 13,9% (5 de 36 crianças). Quanto ao EEG realizado em 34 crianças nessa fase, 17,6% (6 casos) demonstraram a presença de hipsarritmia, enquanto anormalidades focais ou multifocais foram detectadas em 50% (17 lactentes). A taxa de óbito ao final do primeiro ano foi de 23,3% (10 de 43 crianças analisadas quanto a este dado). Não foi possível comprovar déficit visual relacionado diretamente ao uso da VGB. A variável \"controle de crises no período neonatal com o uso da VGB\" foi associada aos seguintes desfechos clínicos favoráveis: melhora no padrão eletrográfico (92,1%), proporção menor de crianças evoluindo para síndrome de West e outras encefalopatias epilépticas (71,9% não tiveram tal desfecho); menor frequência de hipsarritmia no EEG (92,9% sem hipsarritmia), maior alcance de desenvolvimento neuropsicomotor normal (56,2% com bom desenvolvimento neurológico), menor índice de óbito neonatal (97,4% vivos nesta fase) e durante os primeiros doze meses de vida (87,9%). Conclusão: Acreditamos que a VGB seja uma opção terapêutica efetiva e com adequada relação custo-benefício, a ser implementada no controle de crises epilépticas neonatais refratárias como fármaco adjuvante aos convencionais. Entretanto, estudos randomizados e controlados são necessários para confirmar sua eficácia quando comparada a outros medicamentos disponíveis para uso nesta população, bem como para avaliar seus possíveis efeitos adversos a longo prazo. / Introduction: Vigabatrin (VGB - Gama-Vinil-GABA) is an antiepileptic drug which increases systemic GABA levels by irreversibly inhibiting GABA transaminase, with well demonstrated efficacy in the control of infantile epileptic spasms, specially related to West syndrome due to tuberous sclerosis. Clinical studies demonstrating a possible role of VGB in the control of neonatal seizures are still very scarce and very little is known on the impact of its use at this early age, as well as on its possible side effects or eventual positive associations from its use with more adequate seizure control or better neuropsychomotor development in the outcome. VGB has been used in our service as an add-on therapy for refractory neonatal seizures arising the impression that this could be an effective antiepileptic medication in the neonatal period. Objectives: To evaluate the use of VGB as an add-on medication regarding its effectiveness for the control of neonatal electrographic and electroclinical seizures, as well as its effects over the EEG pattern; To evaluate clinical and electrographic evolution of the children in follow-up; To estimate VGB efficacy on the control of neonatal seizures in relation to the demographical and clinical characteristics of those newborns; To quantify and characterize the occurrence of early and late side effects of this medication along follow-up. Patients and methods: This is a transverse retrospective study carried out through charts analysis from a sample of newborns who received VGB as add-on medication for seizures and/or status epilepticus refractory to conventional drugs, from January 2007 through March 2014, at the Neonatal Intensive Care Service of HCFMRP-USP, keeping follow-up in our institution for at least 1 year. Demographical and etiological data were analyzed, as well as clinical-electrographical semiology, VGB prescription indication, therapeutic schedule, time to reach seizure control, clinical and electrographical evolution while in hospital and at the follow-up, age at VGB withdrawal, besides adverse effects. Results: Among 48 newborns evaluated, 34 (79.2%) reached control of electrographic and/or clinical seizures during neonatal period, with improvement of the EEG pattern after VGB introduction in 79%. As for drug introduction criteria, 33.3% (16 children) were started on VGB due to therapeutic failure of phenobarbital and/or phenytoin; 27.1% (13 newborns), due to status epilepticus and, in 12 babies (25%), due to therapeutic failure of midazolam. By the end of the first year of life, EEG background activity was disorganized in 58.1% (18 out of 29 children who had EEG registered at 12 month of life). Along the one year follow-up of 38 patients, 20 infants (52.6%) showed some degree of neurodevelopmental delay; 19 children (39.5%) remained on VGB in polytherapy, with seizure persistence in 22 (57.9%). Evolution to an epileptic encephalopathy was found in 14 kids (37.8%), with West Syndrome being characterized in 13.9% (5 out of 36 kids). As for the EEG carried out in 34 children at the follow-up, 17.6% (6 cases) showed hypsarrhythmia while focal or multifocal abnormalities were seen in 50% (17 infants). Up to 12 month of life, the death rate was 23.3% (10 out of 43 children evaluated for such endpoint). Visual deficit directly related to VGB use could not be determined. The variable \"seizure control during the neonatal period after VGB use\" was associated to the following endpoints: improvement of the EEG pattern (92,1% of children with seizure control after VGB), lower proportion of children evolving into West syndrome and other epileptic encephalopathies (71.9% did not show such endpoint), lower frequency of hypsarrhythmia in the EEG (92.9% without hypsarrhythmia), better milestones reached regarding neuropsychomotor development (56.2% with good neurological outcome), lower rate of neonatal death (97.4% alive by the end of neonatal period) and along the first year of life (87.9%). Conclusion: VGB is an effective therapeutic option with adequate cost-benefit relationship which should be implemented for the control of refractory neonatal seizures as add-on therapy to conventional drugs. However, controlled randomized studies are necessary to confirm such efficacy as compared to other drugs available for use in the neonatal period, as well as to evaluate its possible long term side effects.
9

Evolução pós-Síndrome de West: aspectos clínicos e eletrográficos / Post-West Syndrome evolutions: clinical and electrographic aspects

Maia, Maria Goretti Lima [UNIFESP] 25 March 2009 (has links) (PDF)
Made available in DSpace on 2015-07-22T20:50:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-03-25 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Objetivos: avaliar a evolução clínica e eletrencefalográfica em 28 pacientes que tiveram diagnóstico de Síndrome de West (SW). Métodos: estudo retrospectivo no qual foram incluídos pacientes que tiveram diagnóstico clínico e eletrográfico de SW e admitidos para seguimento no Hospital São Paulo da Universidade Federal de São Paulo / Escola Paulista de Medicina, entre março de 2006 e dezembro de 2007. Todos foram submetidos a avaliações periódicas durante o tratamento da SW, incluindo VEEG e, no mínimo, um exame de VEEG, com duração de 6 a 12 horas, após o controle da SW por pelo menos um ano. Foram analisados dados demográficos, freqüência e semiologia das crises. Os EEGs e os VEEGs foram revisados para a quantificação e classificação das alterações eletrencefalográficas e das crises epilépticas. Resultados: a amostra foi composta por 28 pacientes com tempo médio de seguimento de 46,5 ± 13 meses, sendo 19 do sexo masculino (68%) e 9 (32%) do sexo feminino. A média de idade na admissão foi 10,5 ± 6,3 meses. Todos os pacientes apresentaram algum grau de atraso no DNPM. Os pacientes foram subdivididos em 2 grupos, criptogênicos (5 casos) e sintomáticos (23 casos). Dos 28 pacientes 16 (57%) evoluíram com crises epilépticas ao final do estudo e 12 (43%) evoluíram sem crises. Do total, 13 (46%) tiveram recidiva da SW. Dentre os 5 criptogênicos 4 (80%) evoluíram com controle de crises e dentre os 23 sintomáticos, apenas 8 (34,7%) evoluíram com controle das crises. Apenas 10,7% dos pacientes evoluíram para SLG (todos do grupo sintomático), permanecendo com crises de difícil controle até o final do seguimento. Dos que permaneceram com crises, 35,7% evoluíram para epilepsia focal, 14,2% com epilepsia generalizada e 7,1% tiveram ambos tipos de crises, focal e generalizada, sendo classificados como epilepsia indeterminada. Conclusões: A maioria dos casos de SW evoluiu para epilepsia focal, portanto, a SLG não foi a síndrome mais freqüente em nosso estudo. O grupo de pacientes sintomáticos apresentou pior evolução quanto ao controle das crises quando comparado com o grupo criptogênico. O tempo de duração da SW também influenciou na evolução. Recidiva da SW tem alta correlação com pior prognóstico. / Objectives: The goal of this study was to evaluate the clinical and electroencephalographic evolution of 28 patients that had WS. Patients and Methods: Retrospective study in which we included patients who had clinical diagnosis and electrographic of WS and admitted in the Hospital São Paulo, Federal University of São Paulo / Escola Paulista de Medicina, between March 2006 and December 2007, who had been submitted to periodic evaluations during treatment of SW, including video-EEG (VEEG) and, after controlling the same, at least, an examination of VEEG, lasting from 6 to 12 hours after the SW under control for at least 1 year. They were revised the handbooks of these patients for analysis of demographic data, frequency and semiology of seizures. The EEGs along the follow-up and the VEEGs were also reviewed for the quantification and classification of electroencephalographic changes and of epileptic seizures. Results: The sample consisted of 28 patients with mean follow-up of 46,5 ± 13 months, with 19 males (68%) and 9 (32%) female. The mean age at admission was 10,5 ± 6,3 months. All patients had some degree of delay in DNPM. The patients were divided into 2 groups, cryptogenics (5 cases) and symptomatics (23 cases). Of the 28 patients 16 (57%) evolved with seizures the end of the study and 12 (43%) evolved without crises. Of the total of patients, 13 (46%) had recurrence of the SW. Of the 5 cryptogenics 4 (80%) evolved with control of seizures and of the 23 symptomatic patients, only 8 (34,7%) evolved with control of the seizures. Only 10,7% of patients evolved to SLG (all of the symptomatic group) and remained with these crises difficult to control until the end of follow up. Of those who remain with crises, 35,7% evolved to focal epilepsy, 14,2% with generalized epilepsy and 7,1% had both types of crises, focal and generalized, being classified as undetermined epilepsy. Conclusions: The SLG wasn’t the evolution most frequent of the SW in our study. The most of these cases evolved with focal epilepsy. The group of symptomatic patients presented worse evolution in the control of seizures when compared with the group criptogenic. The time in which the patient remained in SW seems also influence the evolution. Recurrence of the SW has high correlation with poor prognosis. / TEDE / BV UNIFESP: Teses e dissertações
10

O uso da vigabatrina como droga de adição no controle de crises epilépticas neonatais / The use of vigabatrin as a drug antiepileptic drug in the control of neonatal epileptic seizures

Patrícia Gomes Damasceno 26 June 2017 (has links)
Introdução: A vigabatrina (VGB - Gama-Vinil-GABA) é um fármaco que eleva os níveis de GABA no organismo, por inibição irreversível da GABA transaminase, cuja eficácia foi bem demonstrada no controle dos espasmos epilépticos em lactentes, especialmente na síndrome de West secundária à esclerose tuberosa. Há escassez de estudos clínicos evidenciando um possível papel deste fármaco no controle de crises epilépticas neonatais e pouco se sabe sobre o potencial impacto do seu uso nessa faixa etária, seus possíveis efeitos adversos, ou se sua introdução teria associações positivas com controle mais adequado das crises na evolução e melhor desenvolvimento neuropsicomotor da criança. A VGB foi introduzida em nosso serviço como terapia de adição para o controle de crises neonatais refratárias, há vários anos, instigando nossa impressão sobre a eficácia deste medicamento no período neonatal. Objetivos: Avaliar a efetividade do uso da VGB como adjuvante no controle das crises eletrográficas e eletroclínicas do período neonatal e seus efeitos sobre o padrão do eletroencefalograma (EEG); Avaliar a evolução clínica e eletrográfica das crianças durante seguimento ambulatorial; Pesquisar associação entre \"controle de crises neonatais com introdução de VGB\" e diversas características demográficas, clínicas e evolutivas destes recém nascidos; Quantificar e caracterizar a ocorrência de efeitos adversos precoces e durante o seguimento. Pacientes e métodos: Estudo transversal retrospectivo, envolvendo o levantamento dos prontuários de uma amostra de recém-nascidos que receberam VGB como tratamento para crises neonatais refratárias aos fármacos convencionais e status epilepticus, no período de janeiro de 2007 a março de 2014, no Serviço de Neonatologia e Terapia Intensiva Neonatal do HCFMRP-USP, mantendo seguimento ambulatorial por pelo menos 1 ano. Foram avaliados os dados demográficos, etiologia e semiologia clínico-eletroencefalográfica das crises, esquema terapêutico prescrito, indicação da introdução da VGB, tempo de internação e tempo para atingir o controle das crises, evolução clínica e eletrencefalográfica durante a internação e no seguimento ambulatorial, época da suspensão da VGB, além de seus efeitos adversos. Resultados: De 48 recém-nascidos avaliados, 34 (79,2 %) obtiveram controle de crises eletrográficas e/ou clínicas durante o período neonatal, havendo melhora no padrão eletrográfico após a introdução da VGB em 79%. Quanto aos critérios para sua indicação, 33,3% (16 indivíduos) iniciaram VGB devido a falha terapêutica no controle das crises com fenobarbital e/ou fenitoína; 27,1% (13 recém nascidos), pela presença de estado de mal epilético e, em 12 crianças (25%), por falha terapêutica do midazolam. Ao final do primeiro ano de vida, a atividade de base do EEG mostrou-se desorganizada em 58,1% (18 de 29 pacientes que o realizaram aos 12 meses de vida). No seguimento ambulatorial de 38 pacientes, algum grau de atraso do desenvolvimento neuropsicomotor foi detectado em 20 crianças (52,6%); 19 lactentes (39,5%) mantiveram o uso da VGB em politerapia, tendo 22 crianças (57,9%) evoluído com persistência das crises epilépticas. Já 37,8% (14 pacientes) enquadraram-se em um padrão de encefalopatia epiléptica, que correspondeu à síndrome de West em 13,9% (5 de 36 crianças). Quanto ao EEG realizado em 34 crianças nessa fase, 17,6% (6 casos) demonstraram a presença de hipsarritmia, enquanto anormalidades focais ou multifocais foram detectadas em 50% (17 lactentes). A taxa de óbito ao final do primeiro ano foi de 23,3% (10 de 43 crianças analisadas quanto a este dado). Não foi possível comprovar déficit visual relacionado diretamente ao uso da VGB. A variável \"controle de crises no período neonatal com o uso da VGB\" foi associada aos seguintes desfechos clínicos favoráveis: melhora no padrão eletrográfico (92,1%), proporção menor de crianças evoluindo para síndrome de West e outras encefalopatias epilépticas (71,9% não tiveram tal desfecho); menor frequência de hipsarritmia no EEG (92,9% sem hipsarritmia), maior alcance de desenvolvimento neuropsicomotor normal (56,2% com bom desenvolvimento neurológico), menor índice de óbito neonatal (97,4% vivos nesta fase) e durante os primeiros doze meses de vida (87,9%). Conclusão: Acreditamos que a VGB seja uma opção terapêutica efetiva e com adequada relação custo-benefício, a ser implementada no controle de crises epilépticas neonatais refratárias como fármaco adjuvante aos convencionais. Entretanto, estudos randomizados e controlados são necessários para confirmar sua eficácia quando comparada a outros medicamentos disponíveis para uso nesta população, bem como para avaliar seus possíveis efeitos adversos a longo prazo. / Introduction: Vigabatrin (VGB - Gama-Vinil-GABA) is an antiepileptic drug which increases systemic GABA levels by irreversibly inhibiting GABA transaminase, with well demonstrated efficacy in the control of infantile epileptic spasms, specially related to West syndrome due to tuberous sclerosis. Clinical studies demonstrating a possible role of VGB in the control of neonatal seizures are still very scarce and very little is known on the impact of its use at this early age, as well as on its possible side effects or eventual positive associations from its use with more adequate seizure control or better neuropsychomotor development in the outcome. VGB has been used in our service as an add-on therapy for refractory neonatal seizures arising the impression that this could be an effective antiepileptic medication in the neonatal period. Objectives: To evaluate the use of VGB as an add-on medication regarding its effectiveness for the control of neonatal electrographic and electroclinical seizures, as well as its effects over the EEG pattern; To evaluate clinical and electrographic evolution of the children in follow-up; To estimate VGB efficacy on the control of neonatal seizures in relation to the demographical and clinical characteristics of those newborns; To quantify and characterize the occurrence of early and late side effects of this medication along follow-up. Patients and methods: This is a transverse retrospective study carried out through charts analysis from a sample of newborns who received VGB as add-on medication for seizures and/or status epilepticus refractory to conventional drugs, from January 2007 through March 2014, at the Neonatal Intensive Care Service of HCFMRP-USP, keeping follow-up in our institution for at least 1 year. Demographical and etiological data were analyzed, as well as clinical-electrographical semiology, VGB prescription indication, therapeutic schedule, time to reach seizure control, clinical and electrographical evolution while in hospital and at the follow-up, age at VGB withdrawal, besides adverse effects. Results: Among 48 newborns evaluated, 34 (79.2%) reached control of electrographic and/or clinical seizures during neonatal period, with improvement of the EEG pattern after VGB introduction in 79%. As for drug introduction criteria, 33.3% (16 children) were started on VGB due to therapeutic failure of phenobarbital and/or phenytoin; 27.1% (13 newborns), due to status epilepticus and, in 12 babies (25%), due to therapeutic failure of midazolam. By the end of the first year of life, EEG background activity was disorganized in 58.1% (18 out of 29 children who had EEG registered at 12 month of life). Along the one year follow-up of 38 patients, 20 infants (52.6%) showed some degree of neurodevelopmental delay; 19 children (39.5%) remained on VGB in polytherapy, with seizure persistence in 22 (57.9%). Evolution to an epileptic encephalopathy was found in 14 kids (37.8%), with West Syndrome being characterized in 13.9% (5 out of 36 kids). As for the EEG carried out in 34 children at the follow-up, 17.6% (6 cases) showed hypsarrhythmia while focal or multifocal abnormalities were seen in 50% (17 infants). Up to 12 month of life, the death rate was 23.3% (10 out of 43 children evaluated for such endpoint). Visual deficit directly related to VGB use could not be determined. The variable \"seizure control during the neonatal period after VGB use\" was associated to the following endpoints: improvement of the EEG pattern (92,1% of children with seizure control after VGB), lower proportion of children evolving into West syndrome and other epileptic encephalopathies (71.9% did not show such endpoint), lower frequency of hypsarrhythmia in the EEG (92.9% without hypsarrhythmia), better milestones reached regarding neuropsychomotor development (56.2% with good neurological outcome), lower rate of neonatal death (97.4% alive by the end of neonatal period) and along the first year of life (87.9%). Conclusion: VGB is an effective therapeutic option with adequate cost-benefit relationship which should be implemented for the control of refractory neonatal seizures as add-on therapy to conventional drugs. However, controlled randomized studies are necessary to confirm such efficacy as compared to other drugs available for use in the neonatal period, as well as to evaluate its possible long term side effects.

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