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Madeira, Bianca Cecchele. "Avaliação de uma ferramenta online para indicar pacientes candidatos à cirurgia da epilepsia." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/139953.
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Introdução: A epilepsia é uma das condições mais comuns na prática neurológica. Sua prevalência na população em geral é expressiva (cerca de 2%). Dentre esses pacientes, existem aqueles que são fármaco-resistentes, ou seja aqueles que não atingem controle de suas crises com dois fármacos adequados de maneira otimizada, os quais correspondem a cerca de 20-40%. Esses pacientes apresentam um controle inadequado de sua condição crônica e o tratamento a longo prazo torna-se insatisfatório e de alto custo, sem levar em consideração a redução da qualidade de vida do paciente, o impacto psicossocial, as incapacidades e o risco aumentado de morte. Somando-se a isso, existe o fato de eles, muitas vezes, necessitarem de cuidadores, geralmente familiares, os quais, por consequência, também deixam de produzir. Sendo assim, é imperativo que tratamentos alternativos custo-efetivos sejam disponibilizados para esses pacientes. A cirurgia da epilepsia é uma opção muito adequada para pacientes selecionados, uma vez que ela pode melhorar substancialmente a qualidade de vida dos pacientes, em muitos casos fazendo até mesmo com que o paciente fique livre de crises, além da redução dos custos à longo prazo. O grande problema é anterior à cirurgia: reside no fato de existir uma certa dificuldade em identificar e encaminhar esses pacientes para uma avaliação adequada, seja por desconhecimento por parte dos médicos em geral, seja pela escassez de recomendações formais. Objetivos: Avaliar uma ferramenta online para indicar pacientes candidatos à cirurgia da epilepsia, colaborando, assim com uma maior facilidade para fins de tomada de decisão clínica com uma melhor identificação destes pacientes. Métodos: Realizamos um estudo transversal avaliando a indicação cirúrgica de pacientes com epilepsia focal, conforme testagem de uma ferramenta online disponível para este fim. Este trabalho foi realizado com pacientes consecutivos que frequentaram o Ambulatório de Epilepsia do Serviço de Neurologia do Hospital de Clínicas de Porto Alegre, no período de janeiro a abril de 2014. Todos os pacientes incluídos no estudo apresentavam o diagnóstico de epilepsia e suas informações foram retiradas da revisão de seus prontuários através de um questionário padronizado respondido pelos pesquisadores. As informações que porventura não constavam registradas em prontuário foram coletadas durante a consulta de rotina. No total, foram avaliados 211 pacientes. Resultados: No nosso estudo, primeiramente realizamos uma análise de prevalência, encontrando um resultado de 56,9% de pacientes com indicação à avaliação cirúrgica. Além disso, realizamos uma avaliação das variáveis que contribuem para a indicação ou não do tratamento cirúrgico. Nessa etapa, encontramos a frequência das crises, o número de fármacos testados e a presença de efeitos colaterais como as variáveis com maior significância estatística para indicação ao tratamento cirúrgico. Conclusão: Acreditamos que este trabalho possui grande relevância clínica por se tratar de uma ferramenta que pode ajudar na tomada de decisão para fins de tratamento, beneficiando, assim, pacientes e possivelmente reduzindo custos do sistema de saúde a médio e longo prazo.Background: Epilepsy is one of the most commons neurological conditions in practice. Its prevalence in the general population is significant (about 2%). Among these patients, there are those that are drug-resistant (those who do not achieve control of their seizures with two suitable drugs optimally), which correspond to about 20-40%. These patients have inadequate control of their chronic condition and long-term treatment becomes unsatisfactory and expensive, regardless of the reduced quality of life of patients, the psychosocial impact, disability and increased risk of death. In addition, the fact that they often need caregivers usually familiar, which, therefore, also fail to produce. It is therefore imperative that cost-effective alternative treatments are available for these patients. The epilepsy surgery is a suitable option for selected patients, since it can substantially improve the quality of life of patients, in many cases making even the patient seizure free, in addition to reducing costs in the long term. The big problem is before surgery: lies in the fact that there is some difficulty in identifying and referring these patients for proper evaluation, either by ignorance on the part of physicians in general, and the lack of formal recommendations. Objectives: Evaluate an online tool to nominate patients candidates for epilepsy surgery, thus contributing to a larger facility for the purposes of clinical decision-making with better identification of these patients. Methods: We conducted a cross-sectional study evaluating the surgical indication in patients with focal epilepsy, as testing of an online tool available for this purpose. This work was performed with consecutive outpatients attending at the Epilepsy Clinic of the Hospital de Clínicas de Porto Alegre, in the period of January-April 2014. All patients included in the study had a diagnosis of epilepsy and their information was taken from the review of their medical records using a standardized questionnaire answered by researchers. The informations who were not registered, were collected during a routine visit. In total, 211 patients were evaluated. Results: In our study, first we conducted a prevalence analysis, finding a result of 56.9% of patients referred for surgical evaluation. In addition, we conducted an evaluation of variables that contribute to the indication or not of surgical treatment. At this stage, we found the frequency of seizures, the number of tested drugs and the presence of side effects such as variables with greater statistical significance for indication for surgical treatment. Conclusion: We believe that this work has great clinical relevance because it is a tool that can help in decision making for treatment, thus benefiting patients and reducing health care costs in the medium and long term.
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Räty, Lena. "Living with epilepsy : young people with uncomplicated epilepsy and adults with newly debuted epilepsy /." Linköping : Univ, 2002. http://www.bibl.liu.se/liupubl/disp/disp2003/med764s.pdf.
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Oliveira, Elton Pallone de. "Estudo crítico dos modelos experimentais em epilepsia espontânea do tipo ausência." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-24052011-135103/.
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A epilepsia é uma das afecções neurológica mais comum na população mundial. Trata-se de uma condição crônica altamente incapacitante que acomete indivíduos de ambos os sexos e de todas as faixas etárias, com um discreto predomínio em homens e, maior freqüência em crianças abaixo de dois anos e idosos acima de 65 anos. As conseqüências de morbidade e mortalidade desta patologia repercutem negativamente na sociedade e, conseqüentemente na economia global. Estima-se que de 60 a 100 milhões de pessoas ao redor do mundo apresentaram alguma condição epiléptica durante suas vidas. Segundo alguns autores a incidência da epilepsia varia de 11 a 131/100 mil habitantes por ano e a prevalência de 1,5 a 30/1000 habitantes por ano, sendo que os maiores valores encontram-se nos países em desenvolvimento, particularmente na America Latina e na África. As epilepsias generalizadas idiopáticas (EGI) constituem-se cerca de um terço de todas as formas de epilepsias e são 15 a 20% mais freqüentes em relação aos demais tipos de epilepsia. As EGI do tipo ausência, as quais são estritamente relacionadas à faixa etária infantil e adolescente podem muitas vezes (2,8 5,7% dos casos) afetar pacientes com idade superior a 15 anos. A fisiopatologia, assim como, as causas reais da ocorrência e/ou recorrência das crises de ausência na idade adulta não estão completamente esclarecidos e se representam um importante desafio para os epileptologistas. As epilepsias generalizadas idiopáticas (EGIs), (etiologia genética) são classificadas em: a) crises de ausência típicas, b) crises de ausência atípicas, c) crises de ausência com fatores especiais, d) crises mioclônicas, e) crises mioclônicas atônicas, f) crises mioclônicas tônicas, g) crises clônicas, h) crises tônicas e, i) crises atônicas. O tratamento e comumente farmacológico e as crises são controladas na maioria dos casos, no entanto, cerca de um terço dos pacientes são refratários às drogas anticonvulsivantes. Tendo como principal finalidade a elucidação de mecanismos básicos e, auxílio no desenvolvimento de abordagens terapêuticas eficazes para esses pacientes, pesquisadores do mundo inteiro dedicam muitos esforços para o desenvolvimento de modelos experimentais capazes de mimetizar o fenômeno que se pretende reproduzir. Dentre os principais modelos experimentais em EGIs, pode-se citar: (1) o modelo de epilepsia generalizada induzida por penicilina em gatos; (2) modelos de investigação da bicuculina; (3) indução por estimulação elétrica; (4) ratos geneticamente epilépticos de Strasbourg (GAERS); (5) cepa WAG/Rij; (6) modelo do gama-hidroxibutirato (GHB) e (7) os camundongos mutantes. Tais modelos experimentais têm provido meios para que os pesquisadores possam avaliar e quantificar adequadamente as alterações neuronais que ocorrem durante os processos epileptógenos tanto in vitro ou in vivo, possibilitando importantes avanços no desenvolvimento de novas abordagens terapêuticas e, melhora na qualidade de vida de portadores de epilepsiaEpilepsy is a very commom neurological disorders in world population. It is a chronicle condition highly disabling that affects both genera male and female independent of your age with a soft predominance in men and is more frequent in child under 2 years old and adult above 65 years old. The morbidity and mortality consequences of this disorder have many negative repercussions at society and global economy consequently. It is estimated about 60 to 100 millions of people around the world present any epileptic condition during their lives. According some researchers the epilepsy incidence varies about 11 to 131/100 thousand habitants for year and the prevalence between 1.5 to 30/1000 habitants for year, about this statics the higher values are found in developing countries, Latin America and Africa particularly. The Idiopathic Generalized Epilepsy (IGE) are about a third of all others kinds of epilepsies and are 15 to 20% more frequent tha n others types of epilepsies. The absences IGEs are strictly related with childhood and adolescence age group and sometimes can affect patients (2.8 5.7 of cases) with age higher than 15 years old. The physiopathology as the real causes of to occur and to reoccur of absences crises in adult age are not completely enlightened and represent a important challenge to epileptlogists. The IGEs (genetic etiology) are classified in: a) typical absence seizures, b) atypical absence seizures, c) absence seizures with special factors, d) mioclonics seizures, f) tonic mioclonic seizures, g) clone seizures, h) tonic seizures and i) atonic seizures. The treatment commonly is pharmacologic and seizures are controlled in major parts of cases although about a third of patients are refratory to anticonvulsants drugs. Having as principal finality the elucidation of basic mechanisms and help of development of effectiv e therapeutical approaches to these patients, researchers around the world spend many efforts to develop experimental models able to reproduce the phenomena that want to reproduce. Among the principal experimental models of IGEs, it is possible to cite: (1) the general epilepsy model induced by penicillin in cats; (2) the models of investigation of bicuculin; (3) induction by electrical stimulation; (4) Genetic Absence Epilepsy Rats of Strasbourg (GAERS); (5) cepa WAG/Rij; (6) the model of gamma-hydroxybutyric (GHB) and (7) mutant rats. These experimental models have promoted ways to researchers can to evaluate and quantify adequately the neuronal alterations that occur during epileptigenes process both in vitro or in vivo, making possible important advances in development of new therapeutical approaches and improvement in quality of life of epilepsy carriers
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Hendriks, Marc P. H. "Memory deficits in epilepsy patients referred to tertiary epilepsy centres." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 2005. http://arno.unimaas.nl/show.cgi?fid=6293.
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Sprissler, Ryan Steven, and Ryan Steven Sprissler. "Genetics of Epilepsy." Diss., The University of Arizona, 2017. http://hdl.handle.net/10150/625894.
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Epilepsy, characterized primarily by seizures, is one of the most common forms of neurological dysfunction in humans. This dissertation will explore the genetic components and responses to seizures in both animal and human models. This will encompass different forms of seizure etiology including genetically derived channelopathies leading to generalized seizures as well as temporal lobe epilepsy with a wide rage of etiologies. Specific attention is paid to changes in the transcriptional profile of the hippocampus in these various forms of epilepsy before and after seizure activity.
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Courville, Aaron. "Chaosmakers for epilepsy." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0003/MQ45985.pdf.
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Neri, Marina Liberalesso 1980. "Avaliação neuropsicológica de crianças com epilepsia rolândica = funções executivas." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309169.
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Orientadores: Marilisa Mantovani Guerreiro, Catarina Abrão GuimarãesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A epilepsia benigna da infância com pontas centrotemporais (EBIPCT) ou rolândica (ER) é a forma mais freqüente de epilepsia na infância e é classificada como sendo focal, genética e de evolução benigna. Apesar de não haver déficit intelectual, essas crianças podem apresentar alterações cognitivas específicas. O presente estudo teve como objetivos: identificar e descrever alterações de funções executivas em crianças com ER e verificar a influência de variáveis clínicas da epilepsia nas funções executivas. Os participantes foram submetidos à aplicação de testes de funções executivas. Foram incluídas crianças com diagnóstico clínico e eletroencefalográfico de ER. A maioria dos pacientes estava controlada e muitos deles encontravam-se sem medicação. Os resultados obtidos foram comparados com os de um grupo de crianças de um grupo-controle (GC) constituído de indivíduos normais, com idade e nível sócio-educacional semelhantes ao das crianças com epilepsia. Os dados coletados nos dois grupos foram analisados e comparados através dos testes estatísticos: Mann-Whitney, teste Qui-quadrado e teste Exato de Fisher. Os resultados mostraram que quanto aos dados numéricos crianças com ER obtiveram pior desempenho em cinco das seis categorias consideradas do Wisconsin Card Sorting Test (WCST): nº de erros, nº de erros perseverativos, nº de respostas perseverativas, nº de categorias completadas e nº de fracassos em manter o set. Considerando-se resultados categóricos crianças com ER obtiveram pior desempenho no Trail Making Test (TMT) parte B, no Teste de fluência verbal FAS e em três categorias do WCST: nº de erros, nº de erros perseverativos e nº de respostas perseverativas. Em relação à variável idade de início da epilepsia, crianças com início mais precoce apresentaram pior desempenho em um dos instrumentos utilizados quando comparadas com crianças com início mais tardio da epilepsia; em relação às demais variáveis da epilepsia, não foi possível qualquer tipo de análise; quanto às variáveis das crises, não houve diferença nos resultados obtidos pelos pacientes divididos em grupos. Diante desses resultados concluímos que: as crianças com ER apresentaram déficit em funções executivas quando comparadas com o grupo-controle; a bateria utilizada mostrou-se adequada para detecção das disfunções apresentadas pelas crianças com ER; em relação à variável da epilepsia idade de início, crianças com início mais precoce apresentaram pior desempenho do que crianças com início mais tardio da epilepsia; em relação às demais variáveis da epilepsia e às variáveis das crises, não houve diferença entre os dois grupos. Assim, nosso estudo segue a linha de raciocínio de que o termo benigno deve ser usado com cautela uma vez que nossos pacientes apresentaram déficits neuropsicológicos em funções executivas, independentemente da fase ativa da epilepsia e do uso de medicações
Abstract: The benign childhood epilepsy with centrotemporal spikes (EBIPCT) or rolandic epilepsy (RE) is the most common type of childhood epilepsy and is considered to be a focal, genetic and benign epilepsy. Although there is no intellectual deficit, these children may have specific cognitive impairments. This study aimed: to identify and describe changes in executive functions in children with RE and to verify the influence of clinical variables of epilepsy in executive functions. Participants were evaluated with tests to assess executive functions. We included children with clinical and EEG features of RE. Most patients were controlled and several were without medication. The results were compared with those of a control group (CG) comprised of normal subjects with age and socioeconomic level similar to that of the RE group. The data collected from both groups were analyzed and compared using statistical tests: Mann-Whitney, Chi-square and Fisher exact tests. The results showed that concerning the numerical data, children with RE had the worst performance in five of the six categories of the WCST: number of errors, number of perseverative errors, number of perseverative answers, number of completed categories and number of failures to maintain the set. Considering categorical results, children with RE had worse performance in Trail Making Test part B, Verbal fluency test FAS and three categories of the WCST: number of errors, number of perseverative errors and number of perseverative answers. Concerning the variable age of onset of epilepsy, children with earlier onset of epilepsy had a worse performance in one of the tools when compared with children with later onset of epilepsy; the other variables of epilepsy did not allow any analysis; considering seizure variables, there was no difference between the two groups. We conclude that: children with RE showed deficits in executive functions when compared with the control group; the set of tests was adequate to detect the dysfunctions presented by children with RE; in relation to the variable age of onset of epilepsy, children with earlier onset had a worse performance than children with later onset of epilepsy; concerning other epilepsy and seizure variables, there was no difference between the two groups. Thus, our study is in keeping with the idea that the term benign should be cautiously used since our patients had neuropsychological deficits in executive functions regardless of the active phase of epilepsy and the use of medications
Doutorado
Ciencias Biomedicas
Doutor em Ciências Médicas
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Rocha, Renata Pina. "Epilepsia reflexa evacuatória: revisão de literatura e descrição de caso clínico com registro de crise ao vídeo-eletroencefalograma." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/17/17160/tde-25042018-161435/.
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Introdução: a epilepsia reflexa é uma condição na qual todas as crises são desencadeadas por um estímulo específico e, na grande maioria dos casos, apresenta-se com crises refratárias ao tratamento. São vários os fatores desencadeantes, entre os quais se destaca pela raridade a evacuação. Objetivos: realizar revisão de literatura sobre epilepsia reflexa, identificar a evacuação como possível fator desencadeador de crise epiléptica e relatar o caso de um paciente com crise reflexa evacuatória documentada à monitorização por vídeo-eletroencefalograma Métodos: revisão de literatura acerca de epilepsias reflexas e revisão de prontuário de um paciente com suspeita clínica de epilepsia reflexa evacuatória. Resultados: o paciente deste estudo, um menino de 10 anos de idade, com dominância manual esquerda, iniciou, aos 4 anos, crises associadas à evacuação. Na monitorização por vídeo-eletroencefalograma, durante episódio de evacuação, apresentou parada comportamental, desvio cefálico para a direita, automatismos em membro superior esquerdo e arresponsividade, coçando o nariz tardiamente com a mão esquerda. O EEG ictal demonstrou atividade rítmica teta em região temporal esquerda com posterior envolvimento frontal esquerdo e de áreas homólogas contralaterais. As ressonâncias magnéticas de encéfalo não evidenciaram alterações e o SPECT interictal identificou hipoperfusão discreta na porção anterior do lobo temporal esquerdo. Com uso de ácido valpróico e carbamazepina o paciente segue livre de crises. Avaliações neuropsicológicas e de qualidade de vida sugerem comprometimento global, tanto antes como após o controle da epilepsia. Conclusão: este é apenas o terceiro caso de epilepsia reflexa evacuatória descrito na literatura, e o segundo com crises dessa ordem documentadas por vídeo-eletroencefalograma. Ambos sugeriram lateralização e localização em região temporal esquerda, elegendo esta região como potencial zona epileptogênica. O tratamento com ácido valpróico e carbamazepina mostrou-se eficaz para controle de crises neste paciente, podendo ser uma opção de tratamento em outros pacientes com este tipo de epilepsia.Background: Reflex epilepsy is a condition in which all seizures are triggered by a specific stimulus. There are many known stimulus, including defecation which has rarely been reported. In the majority of cases, it presents with refractory seizures. Objective: review the literature on reflex epilepsy, as well as identify defecation as a possible trigger and report a case of a patient with reflex seizures triggered by defecation documented by video-electroencephalogram monitoring. Methods: literature review on reflex epilepsies and review of medical records of a patient with reflex epilepsy triggered by defecation. Results: we present a 10-year-old-boy patient, left-handed, whose epilepsy onset was at the age of four. Its seizures were characterized by episodes of loss of consciousness and atonia during defecation. Video-electroencephalogram monitoring had shown a seizure triggered by defecation, characterized by right head deviation, left upper limb automatisms, associated with consciousness impairment and afterwards nose wiping with the left hand. The ictal EEG demonstrated theta rhythmic activity in the left temporal lobe. The brain magnetic resonance was normal. The interictal SPECT identified left anterior temporal lobe mild hypoperfusion. The patient became seizure free after the treatment with valproic acid and carbamazepine. Neuropsychological and quality of life assessments suggested global impairment, before and after seizure control. Conclusion: this is the third case of epilepsy induced by defecation, and the second with seizures documented by videoelectroencephalogram. Similar to this case, both had suggested lateralization and localization over the left temporal region, suggesting this region as a potential epileptogenic zone in patients with this type of reflex epilepsy. In our patient, the treatment with valproic acid and carbamazepine was effective for the seizure control and may be an option to other patients with this condition.
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Kemper, Birgit. "Neuropsychologische Untersuchung bei Frontallappenepilepsien ein Vergleich kognitiver Leistungen zwischen Patienten mit Frontal- und Temporallappenepilepsie im Rahmen der prächirurgischen Diagnostik /." Münster : Universität Münster, 1995. http://catalog.hathitrust.org/api/volumes/oclc/64528329.html.
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Santos, Renato Oliveira dos. "Investigando o papel de genes candidatos na epilepsia do lobo temporal mesi = genes PTPRM e IL1B = Investigating candidates genes in mesial temporal lobe epilepsy : PTPRM and IL1B genes." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312709.
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Orientadores: IÍscia Teresinha Lopes Cendes, Cláudia Vianna Maurer-MorelliTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: As epilepsias formam um grupo de doenças neurológicas crônicas caracterizadas por crises epilépticas, as quais podem ser definidas como um distúrbio intermitente do sistema nervoso causado por descarga elétrica anormal, súbita e sincronizada dos neurônios cerebrais. A epilepsia de lobo temporal (ELT) é a mais frequente, representando aproximadamente 50% dos casos em adultos e tem como manifestação típica, a crise parcial complexa. Além disso, é frequentemente refratária ao tratamento medicamentoso. Os principais sintomas gerados pela ELT são predominantemente pelo acometimento das estruturas mediais do lobo temporal, sendo a ELT mesial (ELTM), a forma mais comum de ELT. Atualmente é ainda controversa a participação de fatores genéticos contribuindo na etiologia das epilepsias, principalmente da ELTM, que não teve até hoje nenhum gene inequivocamente associado a sua predisposição. O objetivo deste trabalho foi investigar o papel de dois genes candidatos: o PTPRM e o IL1B na predisposição à ELTM. Para tanto utilizamos as seguintes modalidades de estudo em pacientes com ELTM (i) estudo de associação genética através da genotipagem de polimorfismos de nucleotídeo único (SNPs) localizados nos referidos genes candidatos (esta etapa do estudo foi realizada durante o mestrado); (ii) quantificação dos transcritos de ambos os genes, por PCR em tempo real em tecido das estruturas mediais do lobo temporal (principalmente hipocampo) que foi obtido através da realização de cirurgia para tratamento das crises refratárias. (iii) Para o PTPRM, foi também realizada a localização do transcrito pela técnica de hibridação "in situ" em tecido hipocampal de pacientes e de controle. Além disso, como existem evidências do envolvimento do PTPRM em etapas importantes do desenvolvimento cerebral, e pouco se conhece da função específica desse gene no cérebro realizamos (iv) a quantificação do transcrito de PTPRM durante o desenvolvimento em cérebro de camundongos. (v) Finalmente, com o objetivo específico de avaliar se o aumento de expressão de IL1B no tecido hipocampal se refletia também na circulação realizamos a quantificação do transcrito e proteica do IL1B no plasma de pacientes com ELTM. Nossos resultados revelaram associação genética entre SNPs localizados em ambos os genes investigados e o fenótipo estudado. No entanto, em nenhum dos estudos uma variante funcional pode ser identificada. A quantificação dos transcritos em tecido hipocampal dos pacientes com ELTM indicou que ambos os genes PTPRM e IL1B estão hiper-regulados em pacientes quando comparados ao tecido controle. Não identificamos variação significativa na expressão do transcrito de PTPRM no cérebro de camundongos nas diferentes etapas de desenvolvimento. Não identificamos variação significativa na quantificação do transcrito e proteica de IL1B no plasma dos pacientes com ELTM quando comparados aos controles. Em conclusão, nossos resultados dos estudos de associação indicam um papel de PTPRM e de IL1B na predisposição à ELTM, porém não fomos capazes de encontrar uma variante funcional associada ao fenótipo. Corroborando o papel de ambos os genes nosso estudo de expressão gênica no tecido acometido indicou um aumento de expressão de ambos os genes. No entanto, o aumento de expressão de IL-1beta no tecido hipocampal não se traduziu pelo aumento no plasma dos pacientes. Finalmente, nosso estudo do perfil de expressão de PTPRM durante o desenvolvimento cerebral não aponta para um papel desse gene em etapas específicas do desenvolvimento
Abstract: The epilepsies are a group of chronic neurological disorders characterized by seizures, which can be defined as an intermittent disorder caused by an abnormal and sudden electrical discharge of neurons in the brain. Temporal lobe epilepsy (TLE) is the most frequent form, representing approximately 50% of cases in adults, and it is often refractory to drug treatment. The main symptoms in TLE are generated by the involvement of the medial temporal lobe structures, characterizing mesial TLE (MTLE). The contribution of genetic factor to MTLE it is still controversial and to date, no gene has been unequivocally associated with the predisposition to MTLE. Therefore, the aim of this study was to investigate the role of two candidate genes: PTPRM and IL1B in the predisposition to MTLE. To achieve this we use the following type study modalities in patients with MTLE (i) genetic association study by genotyping of single nucleotide polymorphisms (SNPs) located in these two candidate genes; (ii) quantification of the transcripts of both genes by real-time PCR in hippocampal tissue obtained from epilepsy surgery for the treatment of refractory seizures. (iii) For PTPRM we also performed in situ hybridization experiments in order to localize the transcript in hippocampal tissue from patients and controls. Furthermore, since there is evidence that PTPRM could be involved in key stages of brain development and little is known about the specific role of this gene in the brain, we performed (iv) quantification of its transcript during development in mouse brain. (v) Finally, with the specific objective of assessing whether the increase of IL1B expression in hippocampal tissue was also seen outside the central nervous system we quantified IL1B transcript and protein in plasma of patients with MTLE. Our results revealed genetic association between SNPs located in both genes and the phenotype. The quantification of transcripts in hippocampal tissue of patients with MTLE indicated that both genes are hyper-regulated when compared to control tissue. We did not find any significant variation in transcript expression of PTPRM in mouse brain during developed. In addition, no difference in transcript expression and protein levels of IL1B was observed in plasma of patients with MTLE. In conclusion, our results indicate an involvement of PTPRM and IL1B in the predisposition to MTLE; however, we are unable to find a functional variant associated with the phenotype. Corroborating the role of both genes in MTLE gene expression in affected tissue (hippocampus) indicated an up-regulation of both genes. However, the increase in IL1B expression in hippocampal tissue was not reflected by an increase of transcript or protein in plasma of patients with MTLE. Finally, our expression profile of PTPRM during brain development does not point to a role for this gene in specific stages of development
Doutorado
Fisiopatologia Médica
Doutora em Ciências
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Hendges, Laurize Palma. "Epilepsia e cefaleia : diferenças entre faixas etárias de início da epilepsia e aspectos neuropediátricos." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2013. http://hdl.handle.net/10183/72130.
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Epilepsia e cefaleia são doenças neurológicas comuns. A epilepsia atinge cerca de 1% da população mundial, enquanto a cefaleia têm prevalência muito mais elevada, ocorrendo em 38-50% das pessoas. As duas condições dividem mecanismos fisiopatogênicos comuns. Relatos de cefaleia em pacientes neuropediátricos com epilepsia correm, mas são pouco estudados devido ao pequeno número de pacientes e dificuldade de diagnóstico de cefaleia nessa população. Nesse estudo avaliamos a prevalência e as características de cefaleia em pacientes com epilepsia focal de início na infância, na idade adulta e após os 50 nos de idade. Foram analisados 167 pacientes com epilepsia focal. Cento e vinte e cinco destes pacientes (74.8%) apresentaram cefaleia. No primeiro grupo, a idade de início da epilepsia variou de 0-17 anos, no segundo de 18-50 anos e no terceiro acima de 50 anos. Para cada paciente entrevistado, foi utilizado um questionário padronizado, verificando a existência de epilepsia e cefaleia, idade de início, frequência, intensidade, classificação e resposta ao tratamento. No nosso estudo, quanto mais precoce o início da epilepsia, maior a chance de do paciente ser refratário e de apresentar cefaleia. Todos os tipos de cefaleia foram mais comuns em pacientes que iniciaram ainda jovens com epilepsia. A cefaleia foi mais comum em mulheres que iniciaram com epilepsia até 50 anos. Após essa idade, a cefaleia em epilepsia foi mais frequentemente observada em pacientes masculinos. Quando a epilepsia iniciou na infância, a cefaleia ocorreu mais frequentemente associada às crises, sendo predominantemente observada no período pós-ictal e ocorrendo mais comumente na região occipital. Esses achados podem sugerir que ocorre maior sobreposição fisiopatológica entre epilepsia e cefaleia quando a epilepsia inicia na infância. No conjunto, nosso estudo demonstrou que a cefaleia observada em epilepsia tem características dependentes da idade de início das crises. Parece ocorrer uma sobreposição de mecanismos de doença entre cefaleia e epilepsia quando a epilepsia inicia na infância. Essa associação é menos observada quando a epilepsia ocorre após os 50 anos de idade, sugerindo diferentes mecanismos fisiopatogênicos para ocorrência da cefaleia em epilepsia, de acordo com a época de início da epilepsia.Epilepsy and headache are common neurological diseases. Epilepsy affects around 1% of the world population, while headache prevalence is much higher, occurring in 38-50% of people. Both conditions share mutual physiopathogenic mechanisms. Reports of headache in neuropediatric patients with epilepsy occur, but they are poorly studied due to the small number of patients and difficulty of headache diagnosis on this population. This study evaluated the prevalence and characteristics of headache in patients with focal epilepsy of childhood onset, adulthood and after 50 years old. We analyzed 167 patients with focal epilepsy. One hundred twenty five of those patients (74.8%) had headache. In the first group, the age at onset of epilepsy varied between 0-17 years; in the second group, from 18-50 years; and in the third group above 50 years. For each patient interviewed, a standardized survey was used to verify the occurrence of epilepsy and headache, the age at onset, frequency, intensity, classification and response to treatment. In this study, the earlier the onset of headache, the greater the chances of the patient is refractory and to present headache. All kinds of headache were more common in patients who started at a young age with epilepsy. Headache was more common in women who started until 50 years old with epilepsy. After this age, headache in epilepsy was more often observed in male patients. When epilepsy started at childhood, headache occurred more often related to the crises, being predominantly observed during post-ictal period and most commonly occurring in the occipital region. These findings may suggest that physiopathologic superposition between epilepsy and headache occurs more often at childhood. As a whole, the study demonstrated that the headache observed in epilepsy has characteristics dependent on the onset age of crises. There seems to be a superposition of disease mechanisms between headache and epilepsy when epilepsy starts during childhood. This association is less observed when epilepsy occurs after 50 years old, suggesting different physiopathogenic mechanisms for headache occurrence in epilepsy, according to the time of onset of epilepsy.
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Nuttycombe, Rachael Eileen. "Parenting children with epilepsy." Thesis, University of Hull, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.440230.
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Wallace, Robyn. "Molecular genetics of epilepsy /." Title page, contents and summary only, 1997. http://web4.library.adelaide.edu.au/theses/09PH/09phw193.pdf.
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Thesis (Ph. D.)--University of Adelaide, Dept. of Paediatrics, 1997.Errata pasted onto back end-paper. Copies of author's previously published articles inserted. Includes bibliographical references (leaves 157-176).
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Adjei, P. "Autonomic function in epilepsy." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1121227/.
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Autonomic function may help to localize and manage the epilepsies. It is likely that the mechanisms of Sudden Unexpected death in Epilepsy (SUDEP) involve autonomic disturbance and a better understanding of these might lead to measures that would help reduce the mortality in patients afflicted with epilepsy. In this thesis, I first provide a comprehensive literature review of the association between epilepsy and the autonomic nervous system. I then evaluate heart rate variability and other cardiac and endocrine parameters as indices of cardiac autonomic function to test three hypothesis; 1) Changes in heart rate variability (HRV), can occur in the peri-ictal period during both (a) subclinical electrographic seizures and (b) clinically overt partial seizures, and can help to localise and lateralise the ictal discharge. 2) Intractable epilepsy can disrupt the heart rate variability and its circadian rhythm. 3) Epileptic seizures affect the serum concentration of the catecholamines and the electrolytes and that these changes could impact on the corrected QT interval. Subjects (n=207) with intractable epilepsy who were being evaluated with video-EEG telemetry for epilepsy surgery were recruited for this study. I found that subclinical seizures have no effect on the HRV. However, in overt partial seizures, HRV decreases, corrected QT is prolonged and plasma catecholamines increases. The reduction in HRV during seizures is not affected by the hemispheric or lobar location of the epileptic focus. However, in the interictal period, reduced HRV differs in left vs. right hemisphere, and in temporal vs. extratemporal areas. The diurnal pattern of HRV is not altered in epilepsy and the mean day HRV were significantly different from mean night HRV. The reduction in HRV is also associated with the following clinical factors: prolonged medical history of epilepsy, the cortical pathology itself, the nature of the seizures, higher seizure frequency and the antiepileptic drug treatment. The plasma electrolytes: Na, K+, Ca2+ and cardiac troponin are not affected after a seizure. However, plasma Mg2+ was seen to increase after a seizure. These abnormalities in autonomic control, particularly the reduction in HRV might be one contributory mechanism of Sudden Unexpected Death in Epilepsy (SUDEP).
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Mccagh, Jane Teresa. "Social cognition in epilepsy." Thesis, Liverpool John Moores University, 2009. http://researchonline.ljmu.ac.uk/5954/.
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Some of the psychological problems associated with epilepsy have their origins in the ability of people with epilepsy (PWE) to engage in meaningful and appropriate social interactions. PWE often report difficulties in social settings, yet there is a paucity of research investigating the socio-cognitive skills of this group. This thesis aimed to investigate these skills and relate them to the patient's perceived impact of epilepsy on their social competence. An additional objective was to see whether studying social cognition in focal epilepsy might provide some insight into the organic basis of social cognitive abilities in the normal population. The thesis consists of four separate studies which aimed to investigate social cognition and social functioning in patients with focal epilepsy. With this in mind, a test battery assessing a range of skills linked to social cognition was administered to a cross section of experimental groups (N=95). These included patients with seizure foci in the right frontal lobe (RF), left frontal lobe (LF), right temporal lobe (RT), left temporal lobe (LT) and a group with idiopathic generalised epilepsy (IGE). A normal control group (NC) and a frontal head injured (FHI) group with no epilepsy were also recruited for the study. In Studies 1 and 2 theory of mind (ToM) deficits were apparent in people with RF and LT epilepsy. These groups demonstrated impairment in the appreciation of false belief and deception at first and second order levels of intentionality. They also exhibited deficits in the appreciation of pragmatic language when attempting to infer the meaning underlying hints given by story characters. These impairments were in part attributable to deficits in narrative memory in the LT group. In Study 3 embedding problems within a social context significantly facilitated conditional reasoning in the NC, LT and RF groups but not in the other experimental groups. This finding was unexpected and suggests a double dissociation between ToM and social conditional reasoning. Study 4 investigated the extent to which socio-cognitive impairment was associated with the perceived impact of epilepsy on everyday social functioning. No statistically significant relationship between these variables was found, although a significant negative correlation between education level and impact of epilepsy was observed. Taken together the findings suggest that impairment in ToM may be a particular feature of right frontal lobe pathology and that social conditional reasoning and ToM may be functionally dissociated. PWE do not appear to have insight into their social functioning difficulties, which may well reflect underlying pathology. In light of this, future research should obtain objective measures of social competence from `significant others'. This is the only series of studies to date to assess social cognition in people with frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE) within the same design. It is also the first time that social conditional reasoning in epilepsy has been systematically assessed and represents one of the largest lesion studies within the field of social cognition. It is hoped that some of the test material used in the thesis, may prove to be a useful and inexpensive clinical resource to help identify PWE who are at risk of reduced social competence, and in localising the site of seizure foci in patients during clinical audit, particularly where anterior foci are suspected.
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Bonnett, Laura. "Prognostic factors for epilepsy." Thesis, University of Liverpool, 2012. http://livrepository.liverpool.ac.uk/8933/.
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Introduction and Aims: Epilepsy is a neurological disorder and is a heterogeneous condition both in terms of cause and prognosis. Prognostic factors identify patients at varying degrees of risk for specific outcomes which facilitates treatment choice and aids patient counselling. Few prognostic models based on prospective cohorts or randomised controlled trial data have been published in epilepsy. Patients with epilepsy can be loosely categorised as having had a first seizure, being newly diagnosed with epilepsy, having established epilepsy or frequent unremitting seizures despite optimum treatment. This thesis concerns modelling prognostic factors for these patient groups, for outcomes including seizure recurrence, seizure remission and treatment failure. Methods: Methods for modelling prognostic factors are discussed and applied to several examples including eligibility to drive following a first seizure and following withdrawal of treatment after a period of remission from seizures. Internal and external model validation techniques are reviewed. The latter is investigated further in a simulation study, the results of which are demonstrated in a motivating example. Mixture modelling is introduced and assessed to better predict whether a patient would achieve remission from seizures immediately, at a later time point, or whether they may never achieve remission. Results: Multivariable models identified a number of significant factors. Future risk of a seizure was therefore obtained for various patient subgroups. The models identified that the chance of a second seizure was below the risk threshold for driving, set by the DVLA, after six months, and the risk of a seizure following treatment withdrawal after a period of remission from seizures was below the risk threshold after three months. Selected models were found to be internally valid and the simulation study indicated that concordance and a variety of imputation methods for handling covariates missing from the validation dataset were useful approaches for external validation of prognostic models. Assessing these methods for a selected model indicated that the model was valid in independent datasets. Mixture modelling techniques begin to show an improved prognostic model for the frequently reported outcome time to 12-month remission. Conclusions: The models described within this thesis can be used to predict outcome for patients with first seizures or epilepsy aiding individual patient risk stratification and the design and analysis of future epilepsy trials. Prognostic models are not commonly externally validated. A method of external validation in the presence of a missing covariate has been proposed and may facilitate validation of prognostic models making the evidence base more transparent and reliable and instil confidence in any significant findings.
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Suleiman, Jehan. "Autoimmune Epilepsy in Childhood." Thesis, The University of Sydney, 2013. http://hdl.handle.net/2123/9790.
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The role of immune mediated mechanisms is increasingly recognised in patients with seizures and epilepsies. Recently the term "autoimmune epilepsy" has been used to imply involvement of the adaptive immune system (particularly humoral) in the pathogenesis of epilepsy. Specific neuronal antibodies against cell surface proteins as well as some intracellular antigens are now recognised in a proportion of adult patients with seizures. The seizures are often severe and not isolated, but rather accompanied by encephalopathy or other neurologic symptoms. Evidence of brain inflammation might be found in cerebrospinal fluid or imaging. The best recognised disorders are limbic encephalitis (associated with antibodies against many neuronal antigens such as VGKC-complex proteins and GAD), and NMDAR encephalitis. However neuronal antibodies are also found in some adult patients with seizures and epilepsies in the absence of encephalopathy or other features. My PhD project aimed to study and investigate neuronal antibodies in children with seizures. This study hoped to help identify children who may have ‘autoimmune seizures and epilepsies’. The studies conducted as part of this thesis found VGKC-complex antibodies in 4 of 10 patients with unexplained encephalitis. Furthermore neuronal antibodies were found in 11 of 114 children with new onset seizures mainly those with epilepsy of unknown cause (predominantly focal). Neuronal antibodies were also found in 7 of 13 patients who had suspected autoimmune epilepsy. The findings in these studies are novel and have shed some light into the importance of neuronal antibodies in paediatric seizures. While the pathogenic role of these antibodies remains a hot topic for debates and future studies, we think that the presence of these antibodies define a group of patients where immune mechanisms are important, and where immunotherapy might improve the clinical outcome.
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Wood, David L. "Comorbidities of Pediatric Epilepsy." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/5188.
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Wood, David L. "Comorbidities of Childhood Epilepsy." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/5186.
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Davis, Lauren Elizabeth. "Extraction : one woman's epilepsy." Thesis, University of Iowa, 2012. https://ir.uiowa.edu/etd/3281.
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Oliveira, Ana Valeria Duarte. "Avaliação do impacto da cirurgia de epilepsia no desenvolvimento de crianças com epilepsia refratária." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/17/17140/tde-22082017-170746/.
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A epilepsia é uma desordem cerebral definida por pelo menos duas crises não provocadas ocorrendo em um intervalo maior que 24 horas, uma crise não provocada e uma probabilidade de futuras crises similar ao risco de recorrência geral depois de duas crises não provocadas (pelo menos 60%) nos próximos 10 anos; ou o diagnóstico de uma síndrome epiléptica. Após o diagnóstico do tipo de epilepsia, existem situações em que o paciente não responde ao tratamento medicamentoso, apresentando pelo menos uma crise epiléptica por mês por um período mínimo de 2 anos. Se durante esse período, dois ou três diferentes fármacos antiepilépticos foram utilizados em monoterapia ou politerapia, e o paciente não obtém controle das crises, configura-se o quadro de epilepsia farmacorresistente. A intervenção cirúrgica é uma opção para essas crianças, atuando no controle das crises e, potencialmente no desenvolvimento neuropsicomotor. Neste estudo, avaliamos as variáveis clínicas como a idade de início da epilepsia, duração da epilepsia, frequência de crises, etiologia e a Escala de Comportamento Adaptativo de Vineland (ECAV) para caracterizar aspectos referentes aos domínios da comunicação, socialização, habilidades diárias e habilidades motoras, no período pré e pós-operatório de cirurgia de epilepsia. A nossa intenção foi determinar o impacto da cirurgia de epilepsia no desempenho dos pacientes nessas esferas avaliadas pela ECAV. Como resultados, encontramos que o grupo de participantes livre de crises após a cirurgia de epilepsia apresentou melhor desempenho cognitivo na segunda avaliação pós-operatória, quando comparado ao grupo que não teve controle de crises. A variável clínica duração da epilepsia influenciou a equivalência etária e as pontuações padrão da ECAV no período pré-operatório, sendo considerada determinante para o atraso neuropsicomotor dos pacientes submetidos à cirurgia de epilepsia. Quanto aos fatores preditivos de melhora das crises pós-operatórias, observou-se que Engel e cirurgia foram as variáveis consideradas significativas. A maioria dos pacientes (63,9%) na segunda avaliação pós-operatória ainda apresentou convulsões ou não obteve melhora. Nos achados da investigação sobre o impacto das crises em relação ao desenvolvimento neuropsicomotor na primeira avaliação 21,3 meses após a cirurgia, foi observado um ganho abaixo do esperado de apenas 4,4 meses na equivalência etária, não evidenciando melhora em curto prazo após a cirurgia, independente do controle de crises. Após 41,3 meses do procedimento cirúrgico os pacientes que apresentaram controle de crises tiveram ganhos adaptativos significativos de 15 meses na equivalência etária quando comparados com os que não apresentavam controle das crises. Nesses últimos pacientes, a equivalência etária permaneceu praticamente estável com um incremento de apenas 3 meses quando analisada as fases pré e pós - operatóriaEpilepsy is a disease of the brain defined by at least two unprovoked seizures occurring 24 h apart, one unprovoked seizure and a probability of further seizures like the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years or diagnosis of an epilepsy syndrome. After epilepsy diagnosis, there are situations where patients do not respond to drug treatment, developing one seizure per month for a minimum of 2 years. If during this period two or three antiepileptic drugs different used as monotherapy or in combination, a condition known as drug-resistant epilepsy. Epilepsy surgery is an option for children with drug-resistant epilepsy acting on the seizure control seizures and, potentially on neuropsychomotor development. In this study, we evaluated clinical variables such as epilepsy age of onset, epilepsy duration, seizure frequency, etiology and adaptive behavior scale of Vineland to characterize aspects related to age equivalence through the domains of communication, socialization, daily skills and motor skills pre- and post-surgical period. Our intention was to determine the impact of epilepsy surgery on the performance of patients in these areas evaluated by Vineland. Thus, we found that the seizure free group participants showed better cognitive performance in the second evaluation, compared to the group that not seizure controlled. The clinical variable duration of epilepsy influenced the age equivalence and standard Vineland scores in the preoperative period, being considered determinant for the neuropsychomotor delay of patients submitted to epilepsy surgery. Regarding the predictive factors of improvement of postoperative crises, it was observed that Engel and surgery were the variables considered significant. The majority of the patients (63.9%) in the second postoperative evaluation still had seizures or did not improve. The findings of the research on the impact of crises on neuropsychomotor were that in the first evaluation 21.3 months after surgery there was a below-expected gain of only 4.4 months of age equivalence, not showing improvement in the short term after surgery, independent of control crisis. After 41.3 months of the surgical procedure, the patients presenting with seizure control had significant adaptive gains of 15 months when compared to those without seizure control. In the latter patients, the age equivalence remained practically stable with an increase of o preoperative only 3 months, analyzing the phases pre and postoperative evaluation
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Pniewski, Krystne. "The assessment and treatment of concerns and anxiety in patients undergoing pre-surgical monitoring for epilepsy /." Connect to thesis, 2006. http://eprints.unimelb.edu.au/archive/00002908.
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Petty, Karen Hammack. "Pediatric temporal lobe epilepsy versus frontal lobe epilepsy : how does cognitive performance differ ? /." Full text available from ProQuest UM Digital Dissertations, 2007. http://0-proquest.umi.com.umiss.lib.olemiss.edu/pqdweb?index=0&did=1414130851&SrchMode=1&sid=2&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1221160824&clientId=22256.
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Galer, Sophie. "Impact de l'activité épileptique interictale sur le traitement cognitif: approche neurophysiologique et comportementale." Doctoral thesis, Universite Libre de Bruxelles, 2013. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/241299.
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Barbosa, Patricia Horn 1980. "Associação entre alterações eletroencefalográficas interictais, ressonância magnética e resultado cirúrgico de pacientes com epilepsia de lobo temporal." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312639.
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Orientador: Fernando CendesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Epilepsia de lobo temporal resulta com freqüência em refratariedade ao tratamento medicamentoso. Alguns fatores prognósticos da epilepsia focal e seu tratamento já foram descritos, mas outros ainda estão por ser melhor conhecidos. Nosso objetivo foi investigar associação entre alterações no EEG pré e pós-operatório e na ressonância de crânio pré-operatória com o resultado cirúrgico de pacientes com epilepsia de lobo temporal. Pacientes com epilepsia focal refratária submetidos a cirurgia após investigação não invasiva foram reavaliados. Calculamos o período livre de crises até a recorrência. Realizamos análise visual da RM crânio pré-operatória buscando sinais de atrofia hipocampal e alterações sutis no hipocampo contralateral. Revisamos exames de EEG pré e pós-operatórios buscando inicialmente a presença ou ausência de descargas epileptiformes. Posteriormente, quantificamos atividade epileptiforme interictal e buscamos associação com recorrência de crises. Utilizamos os testes estatísticos qui-quadrado e Fisher, quando adequados, e construímos curvas de sobrevivência de Kaplan-Meier, considerando recorrência de crises como desfecho, com comparação pelo método de Mantel. Na primeira parte do estudo foram incluídos 86 pacientes com atrofia hipocampal. EEG pré-operatório unilateral não se associou a resultado cirúrgico favorável; EEG pós-operatório com presença de atividade epileptiforme interictal não se associou a resultado cirúrgico desfavorável; RM cranio com hipocampo contralateral alterado se associou tanto a resultado cirúrgico desfavorável, quanto com bilateralidade nos EEGs pré-operatórios. Na segunda parte do estudo, com 129 pacientes incluídos, não encontramos associação significativa entre presença de atividade epileptiforme interictal no EEG pós-operatório e resultado cirúrgico. As curvas de sobrevivência dos grupos com descargas epileptiformes presentes versus ausentes não foram estatisticamente diferentes (p=0,09), porem observamos uma tendência, o que motivou a terceira parte. Desta forma, demonstramos, através da quantificação da atividade epileptiforme, associação entre descargas pouco frequentes no EEG pós-operatório com resultado cirúrgico favorável. Finalmente, na tentativa de estabelecer o EEG pós-operatório como preditor de recorrência de crises, não encontramos, com a amostra disponível, associação entre EEG pós-operatório com atividade epileptiforme pouco frequente e resultado cirúrgico favorável. Estes resultados demonstram que é importante valorizar alterações sutis no volume, conformação, eixo e sinal do hipocampo menos afetado na indicação de cirurgia de pacientes com epilepsia de lobo temporal e atrofia hipocampal. O resultado cirúrgico dos pacientes com hipocampo contralateral normal é mais favorável. Alteração eletrográfica bitemporal no EEG pré-operatório, em geral, está associada a alteração estrutural sutil no hipocampo contralateral, que muitas vezes não é valorizada. Tal achado corrobora evidências previamente descritas de que pacientes com EEG pré-operatório bitemporal tem prognóstico cirúrgico menos favorável. Os dados relacionados à análise quantitativa de descargas epileptiformes no EEG pós-operatório mostraram associação entre atividade epileptiforme e resultado cirúrgico. Tal achado sugere que o EEG pode ser uma ferramenta útil no seguimento clínico pós-operatório. Em conclusão, nossos resultados indicaram dois fatores importantes no prognóstico de controle de crises após cirurgia em ELT: presença de alteração hipocampal contralateral mesmo que sutil, e espículas em uma frequência maior que 4 por um período de 15 minutos
Abstract: Temporal lobe epilepsy is frequently linked to medical refractoriness. Many clinical prognostic data on focal epilepsy have repeatedly been described, while surgical outcome factors are yet to be fully known. We presently look into an association between interictal epileptiform discharges in pre and postoperative EEG, as well as preoperative brain magnetic resonance imaging, and surgical outcome of temporal lobe epilepsy. Patients with medically refractory focal epilepsy submitted to surgery following non invasive investigation were reassessed. We calculated time until seizure recurrence. We visually analysed preoperative MRI searching for signs of hipoccampal atrophy, as well as subtle contralateral hipoccampal changes. We reviewed pre and postoperative EEGs concerning presence or absence of interictal epileptiform discharges. Later on, we quantified interictal discharges and tested association with seizure freedom. We used chi square or Fisher¿s exact test, when most adequate. We also built Kaplan-Meier¿s survival curves setting seizure recurrence as endpoint, and compared curves by Mantel method. We initially included 86 patients with hipoccampal atrophy. Preoperative unilateral EEG was not associated with favorable surgical outcome; presence of IED in postoperative EEG was not associated with unfavorable outcome; contralateral hipoccampal changes on preoperative MRI was strongly associated with unfavorable surgical outcome, as well as with bilateral preoperative EEGs. We then studied postoperative EEGs of 129 individuals. There was not a significant association between postoperative EEG and surgical outcome. Survival curves of group of patients with interictal discharges present and absent were not statistically different (p=0.09), but we observed a tendency in that direction. Therefore, we were able to demonstrate through manual quantification of epileptiform discharges that postoperative EEG direct association with surgical outcome. Our ultimate goal was to establish postoperative EEG as predictor of seizure recurrence. Unfortunately we were not able to demonstrate it with data available on our sample. These results highlight importance of assessing subtle changes in volume, form, axis and signal intensity on contralateral hipoccampus prior to indication of surgery in patients with temporal lobe epilepsy with hipoccampal atrophy. Surgical outcome is more favorable when contralateral hipoccampus is normal. Bilateral discharges over temporal electrodes in pre-operative EEG are associated with subtle structural changes on contralateral hipoccampus, which may be underestimated. Such findings is in agreement with previously described evidence of bitemporal preoperative EEG associated with less favorable surgical outcome. Quantification data on postoperative EEG sets forth direct association with epileptiform discharges and surgical outcome. Such finding suggests EEG may be a useful tool in postoperative followup. In conclusion, our results indicate two important prognostic factors for seizure control in surgically treated temporal lobe epilepsy patients: presence of contralateral signs of hipoccampal sclerosis, even if subtle, and interictal epileptiform discharges occuring in a frequency higher than 4 at 15 minutes period
Doutorado
Neurociencias
Fisiopatologia Médica
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Monnerat, Bruno Zanotelli. "Uso do padrão ictal na epilepsia da região mesial do lobo temporal associada à esclerose hipocampal como marcador prognóstico pós-cirúrgico: uma coorte retrospectiva." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/17/17140/tde-31032012-090652/.
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Pacientes com epilepsia do lobo temporal farmacorresistente, frequentemente, possuem esclerose hipocampal como lesão epileptogênica. Muitas vezes, estes pacientes se beneficiam de lobectomia temporal para redução da ocorrência de crises epilépticas. Para que possam se submeter a este procedimento, é necessário o uso da videoeletroencefalografia prolongada para delimitação apurada da zona epileptogênica. Apesar dos avanços dos métodos diagnósticos nesta área, a busca por um instrumento que permita uma avaliação clara da chance de uma vida livre de crises após cirurgia permanece. No presente trabalho, a apresentação do padrão eletroencefalográfico ictal foi estudado, de forma a se pesquisar se existe relação entre a sua ocorrência e permanência em apenas um hemisfério cerebral com um melhor prognóstico pós-cirúrgico. Foram revisados os dados eletroencefalográficos ictais e os prontuários médicos de 284 pacientes. Procedeu-se à classificação de seus padrões eletroencefalográficos ictais em unilaterais ou bilaterais, e seu prognóstico após um, dois e cinco anos após cirurgia em livre de crise ou não livre de crise epiléptica. Apresentavam padrão unilateral 132 pacientes, e 152 apresentavam padrão bilateral. Estavam livres de crises 236 pacientes, e 48 ainda persistiam com crises epilépticas após cirurgia. Não houve associação entre padrões ictais unilaterais e uma vida livre de crises epilépticas após a cirurgia (diferença de 7,5%; p=0,092; chi-quadrado). Dessa forma, não se pode aplicar o padrão ictal eletroencefalográfico como ferramenta para predição de uma vida livre de crises após lobectomia temporal em pacientes com epilepsia da região mesial do lobo temporal associada à esclerose hipocampal.Patients with drug-resistant temporal lobe epilepsy usually have hippocampal sclerosis as an epileptogenic lesion. Most of the times, these patients are benefited from temporal lobectomy for seizure relief. For this procedure to occur, a long-term videoelectroencephalogram is necessary for the accurate delineation of the epileptogenic zone. Despite the developments in the diagnostic methods on this area, the quest continues for an instrument that allows a clear evaluation of the chance to obtain a seizure-free life after epilepsy surgery. In the present study, the electroencephalographic ictal patterns were evaluated, and the relationship between its occurrence and permanence in one cerebral hemisphere and the possibility of a seizure-free outcome after surgery were compared. The ictal electroencephalografic and medical records of 284 patients were analyzed. A classification of ictal patterns, whether unilateral or bilateral, was issued, and the seizure outcome after one, two, and five years after surgery annotated. Unilateral ictal patterns occurred in 132 patients, and bilateral ictal patterns in 152. Seizure-free status was obtained in 236 patients, and 48 still persisted with seizures. There was no association between a unilateral ictal status and a seizure-free outcome after surgery (difference of 7.5%, p=0.092; chi-square). So, the electroencephalographic ictal pattern is not a valuable tool for predictions regarding seizure outcome in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis that are submitted to temporal lobectomy.
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Jimenez, Jimenez Diego Mauricio. "Pathophysiology of seizure onset in human focal epilepsy and its relevance to epilepsy surgery." Thesis, King's College London (University of London), 2016. https://kclpure.kcl.ac.uk/portal/en/theses/pathophysiology-of-seizure-onset-in-human-focal-epilepsy-and-its-relevance-to-epilepsy-surgery(d062586c-22be-4351-84f2-0acc594c9460).html.
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Epilepsy is a major source of disability amongst all age groups. Most epilepsies are well controlled on antiepileptic drugs. However, significant proportions of patients are not controlled on medical treatment and may be successfully treated with resective surgery. Unfortunately, as many as 30% of patients remain with disabling seizures after resective surgery. In the present thesis I aim at identifying seizure onset patterns on intracranial EEG that are predictors of surgical outcome. Methods: I have studied all patients operated after intracranial recordings implantation between 1999 and 2010 with a follow up period longer than 1 year. I identified the first, the second ictal patterns and the presence of preceding epileptiform discharges, and correlated their presence with surgical outcome. As the initial pattern was bilateral in 33% of patients, I used single pulse electrical stimulation (SPES) to identify bilateral connections that could be responsible for bilateral changes at seizure onset. Results: Focal fast activity as first ictal pattern was associated with favourable outcome. Diffuse electrodecremental event as first ictal pattern was associated with poor outcome. A preceding focal, widespread or bilateral epileptiform discharge was not associated with neither favourable nor poor outcome. As second ictal pattern, fast activity was associated with poor outcome whereas diffuse electrodecremental event with good outcome. Delayed second ictal patterns (≥10sec) appear to be associated with good outcome in temporal lobe epilepsy. Hippocampus and amygdala have a low incidence of contralateral connections (5.0%). Fusiform gyrus showed the highest incidence of contralateral functional connections (≤7.1%). Bi-temporal connectivity is related neither to bilateral seizure onset nor postsurgical outcome. Conclusion: The prognostic value of ictal patterns depends where they occur during seizure evolution. Early bilateral changes at seizure onset cannot solely be explained by functional bilateral connections.
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Johnson, Adrienne L. "The Role of Cigarette Smoking in Epilepsy-Related Quality of Life and Epilepsy Severity." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1530266095820498.
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McLaughlin, Deirdre P. "Ageing and epilepsy : psychosocial impact /." [St. Lucia, Qld.], 2005. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe19068.pdf.
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Ribenis, Aksels. "Epilepsy surgery around language cortex." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-98318.
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Cormack, Karl Frederick Magnus. "Children's cognitive representations of epilepsy." Thesis, University of Southampton, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396777.
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McGinnity, Colm Joseph. "Quantitative imaging in epilepsy (PET)." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/40095.
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Introduction Epilepsy is a heterogeneous collection of neurological diseases characterised clinically by recurrent seizures. Pre-clinical models implicate derangements in ligand-gated receptor-mediated neurotransmission in seizure generation and termination. In this thesis, the author quantified activated N-methyl D-aspartate- and opioid peptide receptor availability in adults with focal epilepsy. Methods This thesis consists of three positron emission tomography (PET) studies of adults with focal epilepsy, using [18F]GE-179 (activated NMDA receptors) and [11C]diprenorphine (DPN; opioid receptors) radioligands. A novel resolution-recovery technique, Structural Functional Synergistic-Resolution Recovery (SFS-RR), was applied to pre-existing paired [11C]DPN PET datasets acquired from adults with temporal lobe epilepsy (TLE). Activated NMDA receptor availability was quantified in adults with frequent interictal epileptiform discharges (IEDs), by regional compartmental modelling and model-free voxelwise analyses. Statistical parametric mapping was used to identify significant differences in volumes-of-distribution (VT) between populations. Results [18F]GE-179 had good brain extraction with a relatively homogeneous distribution and moderately-paced kinetics in grey matter. The two brain compartments, four rate-constants model best described the radioligand's kinetics in grey matter. Global increases in [18F]GE-179 VT were seen for seven of 11 participants with frequent IEDs. Focal increases in [18F]GE-179 VT of up to nearly 24% were also identified for three of the 11 participants. A post-ictal increase in [11C]DPN VT was identified in the ipsilateral parahippocampal gyrus. Discussion This first-in-man evaluation of [18F]GE-179 evidenced several properties that are desirable in PET radioligands, but the specificity of binding requires further characterisation. The results suggest focal increases in activated NMDA receptor availability in participants with refractory focal epilepsy, and also post-ictal increases in opioid peptide availability in the parahippocampal gyrus in TLE. Both findings may have pathophysiological relevance, and illustrate the potential of quantitative ligand PET with advanced post-processing to investigate changes in inhibitory and excitatory receptor systems in the epilepsies in vivo.
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Jolin, Paula. "Epilepsy in medieval Islamic history." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0025/MQ50527.pdf.
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Loukas, Andrew. "Sodium channel mutations causing epilepsy." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=80321.
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Ion channels mediate the electrical properties of neurons and other excitable cells. Mutations in ion channel genes have been linked to several neurological disorders. For example, a rare familial form of epilepsy, generalized epilepsy with febrile seizures plus (GEFS+), is associated with mutations in voltage gated sodium channels. We examined how two such mutations (C121W, D188V) alter the functional properties of the channel through voltage-clamp studies in Xenopus oocytes and HEK cells respectively. D188V is located in the alpha subunit and C121W in the auxiliary beta1 subunit of the sodium channel.The C121W mutation causes a 100 fold reduction in efficacy of current modulation as well as a reduction of current amplitude. This may cause increased sodium currents via a negative shift of the steady-state inactivation curve. alpha-D188V channels recover faster from the inactivated state which causes a resistance to frequency-dependent cumulative inactivation of current amplitude. This may contribute to cellular hyperexcitability resulting in ictal events in the epileptic patient.
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Farrow, Tom F. D. "Hippocampus, cognitive function and epilepsy." Thesis, University of Sheffield, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322874.
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Hammers, Alexander. "PET investigations in focal epilepsy." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396330.
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Novy, J. "Somatic co-morbidities in epilepsy." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1458552/.
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People with epilepsy seem to have more concomitant medical conditions than the general population. The burden of somatic co‐morbidities plays an important role in the premature mortality in epilepsy. I sought to explore the relation between somatic co‐morbidities and epilepsy, attempting to avoid biases in previous studies. In a first study, I collected clinical, demographic and somatic co‐morbidity data in 2016 consecutive people with epilepsy referred for assessment at a tertiary centre and in 1297 people with epilepsy in the community. In a second study, I analysed the lifelong course of epilepsy of an historical cohort of 235 people who were in residential care at the Chalfont Centre for Epilepsy: 122 had comprehensive post‐mortem examination. Confounders (causes or consequences of epilepsy/ its treatment) were distinguished from co‐morbidities. In the first study, somatic co‐morbidities were significantly more frequent in the referral centre than in the community (49% vs 37%). Consistent risk factors were found in both cohorts. When adjusting for age, epilepsy duration, and absence of underlying brain lesion were independently associated with an increased burden of somatic conditions. In the second study, age at death showed an early peak of mortality between 45‐50 years old. High seizure frequency was an independent predictor of early death due to co‐morbidities. Those who survived increasingly went into spontaneous remission lasting until death; older age and presence of neuropathologically‐confirmed degenerative changes were independent predictors of terminal remission. Somatic co‐morbidities do not occur randomly in relation with epilepsy. Greater epilepsy severity seems to be a risk factor; several other consistent predictors were identified. Epilepsy may cause premature death indirectly through co‐morbid conditions. Ageing and degenerative changes could improve epilepsy drug responsiveness.
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Elwes, R. D. C. "The early prognosis of epilepsy." Thesis, University of Edinburgh, 1988. http://hdl.handle.net/1842/18865.
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Correll, Cynthia Marie. "Seizure awareness among epilepsy patients." [New Haven, Conn. : s.n.], 2008. http://ymtdl.med.yale.edu/theses/available/etd-12022008-101323/.
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Scott, Amelia Jane. "Anxiety in People with Epilepsy." Thesis, The University of Sydney, 2019. https://hdl.handle.net/2123/21333.
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Anxiety in people with epilepsy (PWE) is a common but poorly understood comorbidity. This thesis aimed to better understand the prevalence and nature of anxiety in epilepsy, and address the current barriers to improved detection and management for PWE and anxiety. This thesis includes two meta-analyses (studies 1 and 2) which confirm that anxiety disorders in PWE are common (22% in adults and 19% in children) and higher than in people without epilepsy. Evidence also emerged that anxiety disorders are being under-detected in some clinical and research settings. In study 3, we replicated our above findings in two samples of people with epilepsy, one sample recruited from a hospital outpatient department and a community sample. We found high rates of anxiety disorders and further evidence of under-detection and under-treatment. We also conducted a qualitative study (study 4) which aimed to build a theoretical model of how anxiety may develop in the context of epilepsy. PWE took part in semi-structured interviews, and the resulting model theorises the processes involved in the development of anxiety in epilepsy. Study 5 utilised a mixed-methods approach in order to develop and evaluate two questionnaires that might accurately assess anxiety in PWE; the Epilepsy Anxiety Survey Instrument (EASI) and its brief version (brEASI). These questionnaires demonstrated excellent performance on indices of validity and reliability, and good accuracy to detect anxiety disorders. Overall, this body of research has made a significant and much-needed contribution regarding anxiety in epilepsy. We have identified high rates of anxiety disorders in PWE, and provided a hypothesised theoretical model of anxiety in PWE to guide further research. Also, the EASI and brEASI provide the means to better assess anxiety in PWE. Altogether, this thesis asserts that anxiety disorders in PWE deserve closer attention, improved understanding and most importantly attempts to design efficacious treatment.
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CATTANEO, STEFANO. "Combinatorial gene therapy for epilepsy." Doctoral thesis, Università Vita-Salute San Raffaele, 2022. http://hdl.handle.net/20.500.11768/128275.
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Epilepsy is a neurological disease characterized by a persistent predisposition to generate seizures, that affects about 1% of the world population. About 30% of epileptic patients are drug-resistant, thus refractory to currently available anti-epileptic drugs (AEDs). Less than 10% of these drug-resistant patients are eligible for resective brain surgery, often due to generalized or multiple epileptic foci, or due to proximity of the epileptic focus to eloquent brain areas. Therefore, gene therapy may represent a doable approach for the unmet medical need of these patients.
Neuropeptide Y (NPY) can act as an endogenous anticonvulsant. NPY expression is increased both in rodent and human hippocampal sections from temporal lobe epilepsy surgical samples, despite the strong loss of hilar GABAergic interneurons. Therefore, NPY-based gene therapy may represent a novel approach for the treatment of focal epilepsies. Ideally, however, such vectors should contain multiple elements (at least NPY and Y2Rs driven by appropriate promoters).
In the past, great advancements in the field of viral vectors based on HSV-1 have been made by our laboratory. We therefore aimed at combining the potential of HSV vectors to accommodate large payloads with the complexity of the NPY system to create an “ideal” combinatorial therapeutic cassette. However, residual concerns on the safety and translatability of our new generation HSV-1 based vectors (named J∆NI8) let us first characterize their electrophysiological properties in primary neuronal culture, to assess both safety and efficacy profiles. Surprisingly and disappointingly, we show that mutations in the envelope glycoprotein B (gB), which is responsible for viral entry and cell fusion, might arise during viral vector production. In turn, mutated gB can increase firing frequency while reducing both input resistance and resting membrane potential of transduced neurons. Altogether, these data suggest that careful evaluation of envelope glycoproteins is needed to develop safe HSV-1 replication-defective vectors for the treatment of CNS disorders. We, therefore, decided to move to LV vectors, a more robustly characterized platform despite a more limited packaging capacity compared with HSV vectors.
To potentiate the protective effect of NPY, we developed a combinatorial gene therapy approach based on the expression of NPY together with its receptor (Y2). Since Y2 receptors act mainly pre-synaptically to reduce glutamate release by lowering Ca2+
influx, transgenes expression was driven by the minimal CamKII promoter, thereby biasing their expression in excitatory neurons. We characterized the ability of our lentiviral vectors to express NPY and its functional Y2 receptor in hippocampal neurons and mouse brains. Telemetry video-EEG monitoring was then used to assess the effect of the therapeutic genes on the epileptic phenotype of a genetic mouse model of epilepsy.
We found that the combined expression of NPY and Y2 is sufficient to reduce both the frequency and duration of seizures in the Synapsin triple-KO epilepsy model. These data further strengthen the hypothesis that strategies aimed at the delivery of NPY and Y2 may be successful for the treatment of epilepsy, particularly for pharmaco-resistant and genetic forms of the disease.L'epilessia è una malattia neurologica caratterizzata da una persistente predisposizione a generare crisi, che colpisce circa l'1% della popolazione mondiale. Circa il 30% dei pazienti epilettici sono resistenti ai farmaci, quindi refrattari ai farmaci antiepilettici attualmente disponibili (AED). Meno del 10% di questi pazienti resistenti ai farmaci sono eleggibili per la chirurgia, spesso a causa di foci epilettici generalizzati o multipli, o a causa della vicinanza del focus epilettico alle aree cerebrali eloquenti. Pertanto, la terapia genica può rappresentare un approccio fattibile. Il neuropeptide Y (NPY) può agire come un anticonvulsivo endogeno. L'espressione di NPY è aumentata sia nelle sezioni ippocampali di roditori che in quelle di campioni chirurgici umani di epilessia del lobo temporale, nonostante la forte perdita di interneuroni GABAergici a livello dell’ilo. Pertanto, la terapia genica basata su NPY può rappresentare un nuovo approccio per il trattamento delle epilessie focali. Idealmente, tuttavia, tali vettori dovrebbero contenere più elementi (almeno NPY e Y2R guidati da promotori appropriati). In passato, il nostro laboratorio ha fatto grandi progressi nel campo dei vettori virali basati su HSV-1. Abbiamo quindi mirato a combinare il potenziale dei vettori HSV di ospitare DNA di grandi dimensioni, e la complessità del sistema NPY, per creare una cassetta terapeutica combinatoria "ideale". Tuttavia, le preoccupazioni residue in merito alla sicurezza della nostra nuova generazione di vettori basati su HSV-1 (chiamati J∆NI8) ci hanno spinto a valutare i profili di sicurezza ed efficacia in vitro per valutare l’effetto dell’infezione sulle proprietà elettrofisiologiche in neuroni primari. Sorprendentemente e in maniera deludente, abbiamo dimostrato che mutazioni nella glicoproteina B dell'involucro (gB), che è responsabile dell'entrata virale e della fusione cellulare, potrebbero sorgere durante la produzione del vettore virale. A livello elettrofisiologico, abbiamo inoltre visto che la gB mutata può aumentare la frequenza di potenziali d’azione e contemporaneamente ridurre sia la resistenza di ingresso che il potenziale di riposo neuroni trasdotti. Complessivamente, questi dati suggeriscono che un'attenta valutazione delle glicoproteine dell'involucro è necessaria per sviluppare vettori sicuri non replicativi basati su HSV-1 per il trattamento dei disturbi del SNC. Abbiamo quindi deciso di passare ai vettori Lentivirali (LV), una piattaforma più robusta e caratterizzata nonostante una capacità di carico più limitata rispetto ai vettori HSV. Per potenziare l'effetto protettivo di NPY, abbiamo sviluppato un approccio combinatorio di terapia genica basato sull'espressione di NPY insieme al suo recettore (Y2). Poiché i recettori Y2 agiscono principalmente a livello pre-sinaptico per diminuire il rilascio di glutammato riducendo l’ingresso di Ca2+, l'espressione dei transgeni è stata guidata dal promotore minimal CamKII, orientando così la loro espressione selettivamente nei neuroni eccitatori. Abbiamo successivamente caratterizzato la capacità dei nostri vettori LV di esprimere NPY e il suo recettore funzionale Y2 nei neuroni ippocampali e nel cervello dei topi. In seguito, abbiamo utilizzato un sistema di monitoraggio video-EEG mediante telemetria per valutare l'effetto dei geni terapeutici sul fenotipo epilettico in un modello genetico di epilessia. Abbiamo scoperto che l'espressione combinata di NPY e Y2 è sufficiente a ridurre sia la frequenza che la durata delle crisi nel modello di epilessia Synapsin triple-KO. Questi dati rafforzano ulteriormente l'ipotesi che le strategie mirate all’utilizzo di NPY e Y2 possono avere successo per il trattamento dell'epilessia, in particolare per le forme resistenti ai farmaci ma anche per forme genetiche della malattia.
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Matos, Alexandre Hilário Berenguer de 1986. "Expressão gênica em larga escala em modelos genéticos de epilepsia." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309736.
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Orientadores: Iscia Teresinha Lopes Cendes, Vinicius D'Ávila Bitencourt PascoalDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Wistar audiogenic rat (WAR) é um modelo genético de epilepsia de crises audiogênicas desencadeadas após alta intensidade de estimulação sonora. Outro modelo genético recentemente identificado é o da epilepsia generalizada com crises de ausência (GEAS). O objetivo do presente estudo foi caracterizar o perfil de expressão gênica destas duas cepas através de uma análise em larga escala. Para os estudos de expressão foi utilizada inicialmente a tecnologia de microarranjos seguida da validação dos resultados por técnica quantitativa de PCR em tempo real. Os resultados foram analisados em ambiente R, utilizando os pacotes AFFY e RankProd do bioconductor, utilizando o algoritmo MAS 5 os array foram normalizados e calculou-se a intensidade do sinal e a detecção (presença ou ausência de expressão). Após a detecção, os transcritos que estavam ausentes foram removidos. Para a análise estatística foi utilizado o teste RankProd, que é biologicamente projetado para testar e detectar genes diferencialmente expressos em experimentos de microarranjos. Foi utilizado um valor de p ? 0,01 e pfp ? 0,05, a fim de considerar os transcritos diferencialmente expressos. No geral, nossos resultados mostram uma assinatura molecular similar nos dois modelos de ratos genéticos analisados. Houve uma sobreposição na lista de genes diferencialmente expressos encontrados em ambos os modelos, quando comparado com controles. Além disso, descobrimos que duas importantes vias moleculares para epileptogênese: neurotransmissão GABAérgica e potencialização de longo prazo pós-sináptica NMDA-dependente, foram encontrados em ambos os modelos, quando combinamos os dados dos animais WAR e GEAS. No entanto, algumas diferenças nas vias de sinalização expressas nos dois modelos também foram identificadas. Portando os resultados mostram claramente a natureza heterogênea e complexa dos mecanismos moleculares envolvidos na epileptogênese
Abstract: Wistar audiogenic rat (WAR) is a genetic epilepsy model susceptible to audiogenic seizures, after high-intensity sound stimulation. Another genetic model we have recently identified is the generalized epilepsy with absence seizures (GEAS) rat. The aim of the present study was to characterize and compare the genetic profile of these two strains using gene expression analysis. Experiments were performed initially using microarray technology followed by quantitative real-time PCR. Results were analyzed in R environment using the Affy and RankProd packages from Bioconductor, using the algorithm MAS 5 we normalized the arrays and calculated the signal intensity and the detection (presence or absence of expression), after the detection, transcripts which were absent in all samples were removed. For statistical analysis we used the Rank Product test, which is biologically motivated and designed to test and detect differentially expressed genes in replicated microarray experiments. This is a simple non-parametric statistical method based on ranks of fold changes. We used a p-value ? 0.01 and a pfp ? 0.05 in order to consider a given transcript to be differentially expressed Overall, the results show a different molecular signature in the two genetic rat models analyzed, since different enriched gene ontology categories were found. However, there was some overlap in the list of genes differentially expressed found in both models when comparing to controls. In addition, we found that two important molecular pathways for epileptogenesis: GABAergic neurotransmission and: Neurophysiological process NMDA-dependent postsynaptic long-term potentiation in CA1 hippocampal neurons, were found to be present in both models when combining data from WAR and GEAS animals. In conclusion, our results clearly show the heterogeneous and intricate nature of the molecular mechanisms involved in epileptogenesis as well as the importance of studies looking at different regulatory pathways at once, in order to better appreciate this complexity
Mestrado
Neurociencias
Mestre em Ciências
43
Svensson, Emma, and Sofie Månsson. "Copingstrategier hos vuxna personer med diagnosen epilepsi : En litteraturstudie." Thesis, Högskolan i Halmstad, Akademin för hälsa och välfärd, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-30910.
Full textAbstract:
Antalet personer som får diagnosen epilepsi ökar för varje år. Med sjukdomen uppkommer problem som varje person ställs inför. För att vuxna personer med diagnosen epilepsi ska kunna hantera sina problem kan de ta hjälp av copingstrategier. Syftet med studien var att undersöka copingstrategier hos vuxna personer med diagnosen epilepsi. Studien genomfördes som en litteraturstudie där artikelsökning, granskning och urval genomfördes på ett strukturerat och systematiskt tillvägagångsätt. Resultatet grundades på åtta vetenskapliga artiklar. Efter analys av artiklarna framkom tre huvudkategorier: Inre copingstrategier, Yttre copingstrategier och Fördelning och användning av copingstrategier. Inre copingstrategier utmynnade i ytterligare två underkategorier: Kontroll över situationen och Kontroll över känslorna. Resultatet visar att de vanligaste copingstrategierna är anpassning, förnekelse och religion. Resultatet visar även på att liknande copingstrategier används i många olika länder och att skillnader går att finna kring olika användning av copingstrategier hos kvinnor respektive män. Ytterligare forskning kring copingstrategier behövs för att förståelsen kring olika copingstrategier i sin tur ska kunna utmynna i bättre omvårdnad för vuxna personer med diagnosen epilepsi. Detta genom att sjuksköterskan lättare ska kunna vägleda och förstå vuxna personer med diagnosen epilepsi.The number of people who are diagnosed with epilepsy increases each year and what is more each person stricken by the disease also experiences different issues all related to the illness. To be able handle the problems generated from epilepsy they can use different coping strategies. The aim of this study was to examine coping strategies among adults diagnosed with epilepsy and it was made as a literary study where article search, examination and selection was done according to a structural and methodical approach. The result was based upon eight scholarly articles. After an analysis of the articles three main categories emerged: Internalized coping strategy, external coping strategy and allocation and use of coping strategies. Internalized coping strategy gave rise to two additional lower categories: situation-focused coping and emotion-focused coping. The result shows that the most common coping strategies are adaption, denial and religion. Furthermore it is also shown that similar strategies are used among many countries, whereas there is a difference between men and women. Additional research is needed within this field to increase the knowledge about coping strategies among people with epilepsy. The effect of this knowledge is that it will be easier for nurses to guide and understand people diagnosed with epilepsy.
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Stroink, Hans. "Diagnosis and prognosis of seizures and epilepsy in childhood (Dutch study of epilepsy in childhood)." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2008. http://hdl.handle.net/1765/13133.
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Beresford, Bryony. "Coping with epilepsy in childhood : an examination into factors mediating adjustment in children with epilepsy." Thesis, University of Exeter, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316379.
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Rushe, Helen. "Living with a sibling with refractory epilepsy children's experience of having a sibling with epilepsy." Thesis, University of Essex, 2011. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.549276.
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Veronez, Djanira Aparecida da Luz. "Estudo morfologico e morfometrico do corpo amigdaloide para definição topografica nas amigdalo-hipocampectomias." [s.n.], 2006. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308848.
Full textAbstract:
Orientador: Donizeti Cesar HonoratoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: A epilepsia do lobo temporal (ELT) apresenta-se em um percentual elevado de pacientes que são refTatários ao tratamento clínico. Fato este que faz da ELT a epilepsia que melhor responde ao tratamento cirúrgico baseado na lobectomia do lobo temporal e na amígdalo-hipocampectomia. Esta última técnica cirúrgica consiste na ressecção parcial do corpo amigdalóide, do hipocampo e do giro para-hipocampal; estruturas consideradas epileptogênicas. Destas estruturas, o corpo amigdalóide é o único ainda com volume morfológico e morfométrico indeterminado. Com base nestes fatos, este trabalho apresenta como objetivos, determinar em cérebros de cadáveres humanos, parâmetros quantitativos e tridimensionais do corpo amigdalóide a partir da análise de cortes bidimensionais; definir os limites topográficos macroscópicos do corpo amigdalóide; estabelecer as distâncias entre o como temporal do ventrículo lateral e as superficies utilizadas nos acessos cirúrgicos; expressar os resultados em escalas métricas, da análise morfométrica e estereológica e sugerir o uso destas nas amígdalo-hipocampectomias. Para isto realizamos análise de cortes seriados, coronais e parassagitais do corpo amigdalóide, que foram avaliados através de um sistema de processamento e análise de imagem. O método de Cavalieri foi utilizado para estabelecer o volume absoluto do corpo amigdalóide. Por último, foram feitas análises estatísticas e apresentação gráfica dos resultados. Os hemisférios cerebrais, direitos e esquerdos foram analisados separadamente, para verificar a morfometria do corpo amigdalóide. Foram observadas diferenças inter-hemisféricas na volumetria do corpo amigdalóide. Nos cortes coronais a média do volume absoluto do corpo amigdalóide direito foi de 1.870mm3 e do corpo amigdalóide esquerdo foi de 1.807mm3, com índice de assimetria de 3,4%. Nos cortes parassagitais a média do volume absoluto do corpo amigdalóide direito foi de 1.927mm3 e do corpo amigdalóide esquerdo foi de 1.878mm3, com índice de assimetria de 2,6%. Não foi identificada variabilidade anatômica significativa na topografia dos ventrículos laterais e do corpo amigdalóide. Nossos resultados demonstram que a análise morfométrica e estereológica aplicada ao corpo amigdalóide e as medidas obtidas na topografia do lobo temporal constitui instrumento confiável, que pode auxiliar nas cirurgias de amígdalo-hipocampectomias
Abstract: The temporallobe epilepsy (TLE) has a high percentage of patients who are reffactory to a clinical treatment. This fact makes TLE the epilepsy that best responds to a surgi cal treatment. It is based on lobectomy of temporallobe and on amygdalohippocampectomy. This surgi cal technique consists of a partial resection of the amygdaloid complex, hippocampus, and gyrus parahippocampal. These structures are considered as epileptogenics. Among these structures, the amygdaloid complex is the only with undetermined morphological and morphometric volume. Based on these facts, this study will have the following objectives: to determine in brains of human corpses the quantitative and three-dimensional parameters of the amygdaloid complex obtained ITom analyses of two-dimensional slices; to define the topographic macroscopic limits of the amygdaloid complex; to establish the distances between the temporal hom of the lateral ventricles and the surfaces used for the surgi cal approaches; to express the results in metrical scales of morphometric and estereological analysis of the amygdaloid complex, and to suggest the use of them in an amygdalohippocampectomy. In order to do this, we have accomplished analysis of serial, coronary and parasagital slices of the amygdaloid complex, which were evaluated through a processing system and an image analysis. The Cavalieri Method was used to establish the absolute volume of the amygdaloid complexo Finally, estatistics analyses and a graphical presentation of the results were done. Right and left brain hemispheres were analyzed separately in order to verify the morphometry of the amygdaloid complexo The inter-hemispherical differences in the volumetry of the amygdaloid complex were observed. In the coronal slices the absolute medium volume of the right amygdaloid complex was 1.894mm3, and the left was 1.837mm3 with an index of asymmetry of 3,4%. In the parassagital si ices the absolute medium volume of the right amygdaloid complex was of 1.927mm3 and the left amygdaloid complex was 1.878mm3 with an index of asymmetry of 2,6%. We have verified that there was no significant anatomical variation in the topography of lateral ventricles and the amygdaloid complexo Our results demonstrate that a morphometric and estereological analysis applied to the amygdaloid complex and measurements obtained in the topography of the temporallobe is a reliable instrument, which can help in surgeries ofthe amygdalohippocampectomy
Doutorado
Ciencias Biomedicas
Doutor em Ciências Médicas
48
Amorim, Barbara Juarez. "Analise estatistica baseada em voxel do SPECT cerebral em pacientes com epilepsia de lobo temporal." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313716.
Full textAbstract:
Orientadores: Fernando Cendes, Elba Cristina Sa de Camargo EtchebehereTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: O statistical parametric mapping (SPM) é uma ferramenta de quantificação que tem sido usada no SPECT de perfusão cerebral (SPECT), mas apenas poucos trabalhos na literatura comparam a sua sensibilidade com a da análise visual em pacientes com epilepsia de lobo temporal (ELT) OBJETIVO: Avaliar a capacidade da análise com SPM no SPECT em detectar o foco epileptogênico e alterações perfusionais em regiões extra-temporais em pacientes com epilepsia de lobo temporal mesial (ELTM), comparando os seus achados com os da análise visual MÉTODOS: Foram realizados SPECTs ictal e interictal em 22 pacientes com ELTM refratários ao tratamento clínico. O lado do foco epileptogênico foi definido com base na história clínica, ressonância magnética, eletroencefaiogramas seriados e telemetria. Os SPECTs foram submetidos à análise visual sendo que os SPECTs interictal e ictal foram analisados em conjunto pelos observadores (SPECT-visual-inter e SPECT-visual-ictal). Foi aplicado o SPM2 que comparou os pacientes com um grupo controle de 50 indivíduos normais. No SPM foram realizadas as seguintes comparações: grupo de SPECT interictal com o grupo controle (SPM-grupo-inter); SPECT interictal de cada paciente com o grupo controle (SPM-indiv-inter); grupo de SPECT ictal com o grupo controle (SPM-grupo-ictal); SPECT ictal de cada paciente com o grupo controle (SPM-indiv-ictal). Foram também comparadas as intensidades das alterações perfusionais nos lobos temporais procurando-se por um aumento da perfusão no SPECT ictal em relação ao interictal (SPM-indiv-ictal/inter). RESULTADOS: Não foi observada nenhuma alteração perfusional significativa no SPM-grupo-inter Já no SPM-grupo-ictal o foco epileptogênico foi a região de hiperperfusão mais significativa No SPM-indiv-inter a sensibilidade na localização do foco foi de 45% e no SPM-indiv-ictal a sensibilidade foi de 64%. O SPM-indiv-ictal/inter apresentou a maior sensibilidade para detectar o foco dentre as análises realizadas no SPM (77%) A sensibilidade do SPECT-visual-inter foi de 68% e para o SPECT-visuai-ictal foi de 100%. Por outro lado, diversas áreas de hiperperfusão e hipoperfusão à distância no SPECT ictal foram detectadas principalmente com o SPM CONCLUSÃO: O SPM é uma ferramenta que não depende do operador e é capaz de demonstrar mais áreas de alteração perfusional à distância do foco epileptogênico do que a análise visual. Ele pode ajudar a entender melhor a patofisiologia das crises epilépticas em pacientes com ELTM estudando a relação das diferentes regiões corticais e subcorticais na gênese e na propagação das crises parciais. Entretanto, essa ferramenta não acrescentou um aumento na sensibilidade na localização do foco epileptogênico em relação á análise visual, tanto do SPECT interictal quanto do SPECT ictal
Abstract: Statistical parametric mapping (SPM) is a quantitative tool which has been used in the brain perfusion SPECT (SPECT) However, few works in literature compare its sensitivity with the visual analysis in patients with temporal lobe epilepsy (TLE). PURPOSE: To investigate the capability of SPM analysis in SPECT to detect the epileptogenic focus and distant perfusion abnormalities in patients with mesial temporal lobe epilepsy (MTLE) and to compare these findings to the visual analysis. METHODS: Interictal and ictal SPECTs of 22 patients with refractory MTLE were performed. Epileptic foci were determined based on clinical history, magnetic resonance, electroencephalograms (EEG) and ictal video-EEG. SPECTs were submitted to visual analysis. Ictal and interictal SPECTs were analyzed together by the nuclear physicians (SPECT-visual-inter and SPECT-visual-ictal). It was also performed the SPM2 analysis which used a control group composed of 50 volunteers. The following comparisons were performed in SPM: interictal SPECT group with control group (SPM-group-inter); interictal SPECT from each patient with control group (SPM-indiv-inter); ictal SPECT group with control group (SPM-group-ictal), ictal SPECT from each patient with control group (SPM-indiv-ictal). It was also compared the perfusion intensity in temporal lobes looking for an increase in perfusion on ictal SPECT in relation to interictal SPECT (SPM-indiv-ictal/inter). RESULTS: No significant perfusion alterations were observed on SPM-group-inter. On the other hand, the epileptogenic temporal lobe was the region with most significant hypoperfusion on SPM-group-ictal. The sensitivity to localize the focus on SPM-indiv-inter was 45% and on SPM-indiv-ictal was 64%. The SPM-indiv ictal/inter revealed the highest sensitivity among the SPM analysis to detect the focus (77%). The sensitivity of SPECT-visual-inter was 68% and to SPECT-visual-ictal was 100%. On the other hand, several areas of distant hypoperfusion and hypoperfusion were detected mainly with SPM. CONCLUSION: SPM is a tool which does not depend on the operator and can detect more distant perfusion abnormalities than the visual analysis. It can improve the understanding of pathophysiology in seizures of patients with MTLE by studying the relation among different cortical and subcortical areas in the genesis and propagation of partial seizures. However, this tool did not increase the visual analysis sensitivity to localize the epileptogenic focus in interictal SPECT as well as in ictal SPECT
Doutorado
Neurologia
Doutor em Ciências Médicas
49
Mory, Susana Barretto. "Alteração morfofuncional talamica em epilepsia mioclonica juvenil." [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310347.
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Orientadores: Li Li Min, Fernando CendesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A epilepsia mioclônica juvenil é o subtipo mais frequente entre as epilepsias generalizadas idiopáticas. Apresenta bom prognóstico e fácil controle em relação às crises epilépticas. O nosso objetivo foi a análise do tálamo combinada com métodos funcional e estruturais de neuroimagem. Estudamos vinte e um pacientes (treze do sexo feminino com média de idade 30 ± 9 anos) com epilepsia mioclônica juvenil do ambulatório de epilepsia dos Hospital das Clínicas da UNICAMP em Campinas. O grupo controle foi constitúído de dezoito voluntários hígidos (onze do sexo feminino) com média de idade 35 ± 16 anos. Todos foram submetidos ao protocolo de pesquisa incluindo ressonância magnética. Além da ressonância diagnóstica, foi realizada uma sequência em 3D para investigação estrutural e a colocação de um voxel único de (2x2x2cm3) em tálamo direito para a ressonância por espectroscopia de prótons. A morfometria baseada em voxel e análise da forma demonstraram as anormalidades talâmicas restritas em porção anterior e inferior. A espectroscopia evidenciou uma redução da relação de N-acetil aspartato e creatina. Existe alteração morfofuncional do tálamo e este padrão de comprometimento estrutural e funcional do tálamo é sugestivo da participação desta estrutura em uma rede neural na epilepsia mioclônica juvenil
Abstract: Juvenile myoclonic epilepsy is a common disease found among the group of all idiopathic generalized epilepsies. It shows a good prognosis, and seizures can be controlled easily. The objective of the present study was to make a comparison between thalamic analysis and functional and structural neuroimaging. We selected twenty-one patients (thirteen females) with mean age 30 ± 9 years old from our clinic in Hospital das Clinicas da UNICAMP, in (Campinas). Eighteen healthy volunteers (eleven females) with mean age 35 ± 6 years old were selected for the control group,. All subjects were submitted to a structured protocol of research including magnetic resonance. A 3D sequence with a single voxel (2x2x2cm3) on right thalamus was also performed for spectroscopy. Voxel based morphometry and shape analysis demonstrated thalamic abnormalities in anterior and inferior portions. Brain spectroscopy showed a decrease in NAA/Cr ratio. There is a dysfunction of the thalamus, and this pattern of structural abnormality suggests that the thalamus is involved in the neural network associated with myoclonic epilepsy
Doutorado
Neurociencias
Doutor em Fisiopatologia Medica
50
Chaddad, Neto Feres Eduardo Aparecido. "Estudo do posicionamento nas craniotomias pterionais, pre-temporais e orbitozigomaticas e suas variações nas cirurgias vasculares e de epilepsia." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309215.
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Orientador: Evandro Pinto da Luz de OliveiraTese (doutorado) - Universidade Estadual de Campinas. Faculdade de Ciencias Medicas
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Resumo: A craniotomia pterional é o acesso cirúrgico mais utilizado na prática neurocirúrgica atual. É utilizada para abordar a maior parte dos aneurismas da circulação anterior e lesões tumorais envolvendo a região supra-selar e parte das estruturas da fossa anterior e média. No entanto, se caracteriza como sendo um acesso limitado para as lesões que envolvem a maior parte do lobo temporal, o assoalho da fossa média do crânio e o complexo da artéria basilar. Para tanto, foram desenvolvidas as craniotomias pré-temporal e orbitozigomática. No entanto a literatura é ainda relativamente carente quanto ao estudo do posicionamento exato da cabeça para a melhor abordagem de cada patologia, em particular. Esse trabalho tem por objetivo estudar o melhor posicionamento da cabeça para a realização das craniotomias mencionadas, visando a melhor exposição de cada lesão em particular
Abstract: The pterional approach is the most applied neurosurgical access in the customized practice nowadays. It is used for approaching most of the anterior circulation aneurysms and tumors involving the anterior and the middle cranial space. However, it is considered a limited approach to some pathologies involving the temporal lobe, the middle cranial space floor and the basilar artery complex region. As a result, the orbitozygomatic and the pretemporal craniotomies developed since it was necessary to enlarge such access to the temporal area. However, there is not a systematic evaluation of head positioning study about the best approach to each specific pathology. This study aims to demonstrate the best way to position the head according to each specific pathology, in order to offer a better surgical visualization by using the most appropriated craniotomy
Doutorado
Neurologia
Doutor em Ciências Médicas