INTRODUÇÃO: A classificação recente das Crises Hipercinéticas (CH) proposta por Rheims et al. (2008) sugere dois padrões de CH, baseado na semiologia ictal (Tipos I e II): no Tipo I, a zona epileptogênica foi identificada na região ventral pré-frontal, enquanto que no Tipo II, na região mesial pré-motora. Estudos com SPECT ictal em pacientes com CH evidenciaram hiperperfusão nas regiões frontais e extrafrontais, incluindo ínsula e lobo temporal, além de áreas subcorticais, tais como cerebelo, tálamo, gânglios da base e tronco encefálico. OBJETIVO: Avaliar a rede neural ativada nas CH através do SPECT ictal, correlacionando-a aos dois subtipos de CH (Tipos I e II). MATERIAL E MÉTODOS: Uma amostra de 25 pacientes com idade entre 0 e 60 anos com CH que realizaram SPECT ictal foi submetida a análise do VEEG e das imagens do SPECT ictal a fim de determinar o tipo de CH e as áreas de hiperpefusão ativadas, bem como sua correlação. RESULTADOS: Nove pacientes (36%) tiveram CH do Tipo I, dez (40%), do Tipo II e seis (24%), do Tipo Misto. Não houve diferenças significativas entre os tipos de CH e a presença de semiologia ictal não hipercinética durante as crises, bem como o tempo de doença, frequência das crises, história familiar positiva e exame de neuroimagem anormal. A duração média do tempo de injeção do RF foi de 32,2 segundos. O SPECT demonstrou ativação difusa, com predomínio nas regiões subcorticais, temporal lateral, occipital mesial e frontal dorsolateral. Não houve correlação entre os diferentes tipos de CH e as áreas hiperperfundidas, exceto pela região occipital mesial, que foi significativamente maior no Tipo II. CONCLUSÃO: A classificação proposta por Rheims et al. (2008) é útil porém simplista, já que as CH abrangem uma fenomenologia complexa, não sendo possível classificar todos os pacientes em somente dois tipos (I e II). O SPECT ictal nesta amostra demonstrou a presença de hiperperfusão em diferentes áreas cerebrais, reforçando a hipótese de que uma rede neural ampla, que engloba as regiões frontais e possivelmente extrafrontais, incluindo áreas subcorticais, está envolvida na gênese destas crises. / BACKGROUND: The recent classification of hyperkinetic seizures (HS) proposed by Reims et al (2008) suggests two patterns of HS based on ictal symptomatology (Type I and II), whereas in Type I epileptogenic zone was identified in the ventromesial frontal córtex while in Type II, in the mesial premotor córtex. Ictal SPECT studies in patients with HS showed hyperperfusion in frontal and extrafrontal regions, including insula and temporal lobe, and subcortical areas, such as cerebellum, thalamus, basal ganglia and brain stem. OBJECTIVE: To evaluate the neural network activated in HS through the ictal SPECT and to correlate it to the two subtypes of HS (Type I and II). METHODS: We retrospective analyzed ictal signs and ictal SPECT data in 25 patients with HS aged between 0 and 60 years in order to determine the type of HS and the hyperperfused areas, as well as their correlation. RESULTS: Nine patients (36%) were classified as Type I, ten (40%) as Type II and 6 (24%) as a mixed type. There were no significant differences between the types of HS and the presence of non-hyperkinetic ictal semiology, as well as epilepsy duration, frequency of seizures, positive family history and abnormal neuroimage. The average injection duration time was 32.2 seconds. The ictal SPECT showed diffuse activation, predominantly in subcortical regions and the following areas: lateral temporal, mesial occipital and dorsolateral frontal cortex. There was no correlation between the different types of HS and the hyperperfused areas but the mesial occipital region that was significantly higher in Type II. CONCLUSION: The classification proposed by Rheims et al (2008) is useful but simplistic. Since the HS consists of a complex phenomenology, it is not possible to classify all patients in only two types (I and II). The ictal SPECT in this sample showed the presence of hyperperfusion in different brain areas, reinforcing the hypothesis that a broad neural network, which includes the frontal and possibly extrafrontal regions, including subcortical areas, are involved in the genesis of these seizures.

INTRODUÇÃO: A classificação recente das Crises Hipercinéticas (CH) proposta por Rheims et al. (2008) sugere dois padrões de CH, baseado na semiologia ictal (Tipos I e II): no Tipo I, a zona epileptogênica foi identificada na região ventral pré-frontal, enquanto que no Tipo II, na região mesial pré-motora. Estudos com SPECT ictal em pacientes com CH evidenciaram hiperperfusão nas regiões frontais e extrafrontais, incluindo ínsula e lobo temporal, além de áreas subcorticais, tais como cerebelo, tálamo, gânglios da base e tronco encefálico. OBJETIVO: Avaliar a rede neural ativada nas CH através do SPECT ictal, correlacionando-a aos dois subtipos de CH (Tipos I e II). MATERIAL E MÉTODOS: Uma amostra de 25 pacientes com idade entre 0 e 60 anos com CH que realizaram SPECT ictal foi submetida a análise do VEEG e das imagens do SPECT ictal a fim de determinar o tipo de CH e as áreas de hiperpefusão ativadas, bem como sua correlação. RESULTADOS: Nove pacientes (36%) tiveram CH do Tipo I, dez (40%), do Tipo II e seis (24%), do Tipo Misto. Não houve diferenças significativas entre os tipos de CH e a presença de semiologia ictal não hipercinética durante as crises, bem como o tempo de doença, frequência das crises, história familiar positiva e exame de neuroimagem anormal. A duração média do tempo de injeção do RF foi de 32,2 segundos. O SPECT demonstrou ativação difusa, com predomínio nas regiões subcorticais, temporal lateral, occipital mesial e frontal dorsolateral. Não houve correlação entre os diferentes tipos de CH e as áreas hiperperfundidas, exceto pela região occipital mesial, que foi significativamente maior no Tipo II. CONCLUSÃO: A classificação proposta por Rheims et al. (2008) é útil porém simplista, já que as CH abrangem uma fenomenologia complexa, não sendo possível classificar todos os pacientes em somente dois tipos (I e II). O SPECT ictal nesta amostra demonstrou a presença de hiperperfusão em diferentes áreas cerebrais, reforçando a hipótese de que uma rede neural ampla, que engloba as regiões frontais e possivelmente extrafrontais, incluindo áreas subcorticais, está envolvida na gênese destas crises. / BACKGROUND: The recent classification of hyperkinetic seizures (HS) proposed by Reims et al (2008) suggests two patterns of HS based on ictal symptomatology (Type I and II), whereas in Type I epileptogenic zone was identified in the ventromesial frontal córtex while in Type II, in the mesial premotor córtex. Ictal SPECT studies in patients with HS showed hyperperfusion in frontal and extrafrontal regions, including insula and temporal lobe, and subcortical areas, such as cerebellum, thalamus, basal ganglia and brain stem. OBJECTIVE: To evaluate the neural network activated in HS through the ictal SPECT and to correlate it to the two subtypes of HS (Type I and II). METHODS: We retrospective analyzed ictal signs and ictal SPECT data in 25 patients with HS aged between 0 and 60 years in order to determine the type of HS and the hyperperfused areas, as well as their correlation. RESULTS: Nine patients (36%) were classified as Type I, ten (40%) as Type II and 6 (24%) as a mixed type. There were no significant differences between the types of HS and the presence of non-hyperkinetic ictal semiology, as well as epilepsy duration, frequency of seizures, positive family history and abnormal neuroimage. The average injection duration time was 32.2 seconds. The ictal SPECT showed diffuse activation, predominantly in subcortical regions and the following areas: lateral temporal, mesial occipital and dorsolateral frontal cortex. There was no correlation between the different types of HS and the hyperperfused areas but the mesial occipital region that was significantly higher in Type II. CONCLUSION: The classification proposed by Rheims et al (2008) is useful but simplistic. Since the HS consists of a complex phenomenology, it is not possible to classify all patients in only two types (I and II). The ictal SPECT in this sample showed the presence of hyperperfusion in different brain areas, reinforcing the hypothesis that a broad neural network, which includes the frontal and possibly extrafrontal regions, including subcortical areas, are involved in the genesis of these seizures.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23420号 / 医博第4765号 / 新制||医||1053(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙橋 良輔, 教授 林 康紀, 教授 福田 和彦 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Orientador: Andriana Susana Lopes de Oliveira Campanharo / Resumo: A epilepsia é uma patologia cerebral caracterizada pela presença de crises epilépticas que afeta em torno de 1% de toda a população mundial. As crises epilépticas podem ocasionar perda de consciência gerando grande impacto na vida das pessoas que sofrem da doença. Atualmente, a técnica de EletroEncefaloGrafia (EEG) é um dos testes diagnósticos mais importantes para a identificação das crises epilépticas e de eventos entre crises, chamados de Descargas Epileptiformes Interictais (DEIs). A zona epileptogênica é a região neuronal responsável pela geração das crises em pacientes com epilepsia focal, e em alguns casos, seu tratamento consiste em uma cirurgia para a remoção desta região. Estudos que relacionam séries temporais com a teoria de redes complexas ganharam grande destaque e importância, mostrando que é possível mapear uma série temporal em uma rede complexa sem grande perdas de informações. Neste sentido, o objetivo deste trabalho consiste na utilização do mapeamento proposto por Campanharo et al., utilizando o conceito de bins, em uma aplicação inovadora: na detecção automática das crises epilépticas, das DEIs por meio da análise de sinais de EEG de pacientes com epilepsia e na localização da zona epileptogênica a partir de uma técnica não-invasiva. A metodologia proposta apresentou performance satisfatória na identificação das crises epilépticas e das DEIs, caracterizadas por uma grande variação de amplitude e frequência. Valores médios de sensibilidade de 83,3% e de 9... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Epilepsy is a cerebral pathology characterized by the presence of epileptic seizures that affects around 1% of the entire world population. Epileptic seizures can cause loss of consciousness generating great impact on the lives of people who suffer from the disease. Currently, the ElectroEncefaloGraphy(EEG) technique is one of the most important diagnostic tests for the identification of epileptic seizures and events between seizures, called Intertictal Epileptiform Discharges (DEIs). The epileptogenic zone is the neuronal region responsible for generating seizures in patients with focal epilepsy, and in some cases, treatment consists of surgery to remove this region. Studies that relate time series to the theory of complex networks have gained great prominence and importance, showing that it is possible to map a time series in a complex network without great loss of information. In this sense, the objective of this work is to use the mapping proposed by Campanharo et al., using the concept of bins, in a novel application: in the automatic detection of epileptic seizures, of DEIs through the analysis of EEG signals of patients with epilepsy and the location of the epileptogenic zone using a non-invasive technique. The proposed methodology presented satisfactory performance in the identification of epileptic seizures and EIDs, characterized by a high variation in amplitude and frequency. Average sensitivity values 83,3% and 93,2% were reached in the detection of epileptic seiz... (Complete abstract click electronic access below) / Mestre

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-12-11T14:10:12Z No. of bitstreams: 1 KARINA NIQUE FRANZ SILBERMANN.pdf: 24305952 bytes, checksum: 2707c9d644d7f53ccbd72659a1adda31 (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-12-13T18:40:06Z (GMT) No. of bitstreams: 1 KARINA NIQUE FRANZ SILBERMANN.pdf: 24305952 bytes, checksum: 2707c9d644d7f53ccbd72659a1adda31 (MD5) / Made available in DSpace on 2018-12-13T19:18:32Z (GMT). No. of bitstreams: 1 KARINA NIQUE FRANZ SILBERMANN.pdf: 24305952 bytes, checksum: 2707c9d644d7f53ccbd72659a1adda31 (MD5) Previous issue date: 2018-08-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / The equipment and processes used in nuclear medicine must be included in a quality control program that includes a series of tests and calibrations following the frequency established by current standards, which are based on international institutions protocols. The capability of anthropomorphic simulators mimic realistic situations are widely appointed to gauge essential data that guarantee the quality in medical generating processes. The purpose of this study was developing a cerebral anthropomorphic phantom for image simulation of ictal activity in nuclear medicine with 18F, PET-CT. It was made in an industrial printer with SLS (Selective Laser Sintering) technology, 4mm thick, using nylon 12. The model was segmented from a magnetic resonance study of a 40-year-old female adult. Two 40 nm thickness metal (Ag) electrodes were inserted in the right frontal lobe region to simulate ictal activity. For the images acquisition, the phantom was filled with distillated water and the 18F radioisotope. The images were acquired in PET-CT equipment with specific protocol for tomographic and dynamic cerebral studies. Images from the simulator without the insertion of the electrodes were acquired as pattern (basal), also were acquired images from the simulator with the electrodes and without electric field application, and the simulator with electric field application. The images were compared through SUV maximum values and uptake index. The non-parametric Wilcoxon-Mann-Whitney test was used as statistic approach, considering the three image conditions as independent groups. There was significant difference amongst the groups, being p < 0,001 when compared the average SUV maximum values by slices in the situations: basal x with electric field, and basal x without electric field, p = 0,129 when compared situations with electric field x without electric field, suggesting that this difference is not significant. All the groups presented significant differences for the uptake indexes obtained, being p < 0,001 in the situations basal x with electric field and basal x without electric field. The TAC (time-activity-curve) curves were obtained in A PET-CT dynamic protocol to demonstrate the 18F uptake in time, in the conditions with electric field and without electric field. The images were subtracted through SISCOM, using the basal condition as reference. The values found for p (SUV and uptake index) are compatible. The SISCOM histograms demonstrate differences for the three image comparisons. Although there are gradual raise of 18F uptake in time obtained in TAC evaluation for both with and without electric field conditions, the highest uptake visualized was when the electric field is applied. The anthropomorphic phantom developed is capable of simulating compatible zones with ictal activity, however the material used as resin in the electrodes must be modified so that the product may be commercialized in the future. / Os equipamentos e processos utilizados em medicina nuclear devem estar inclu?dos em um programa de controle de qualidade, o que inclui uma s?rie de testes e calibra??es com periodicidade estabelecida pelas normas vigentes, baseadas nos protocolos de institui??es internacionais. Os simuladores antropom?rficos, pela sua capacidade de mimetizar situa??es real?sticas, s?o amplamente empregados para aferir dados essenciais que garantam a qualidade nos processos geradores de imagens m?dicas. O objetivo deste trabalho foi desenvolver um phantom antropom?rfico cerebral para simula??o de imagens de atividade ictal em medicina nuclear, utilizando metodologia PET com Fl?or-18 (18F). O phantom foi confeccionado em impressora industrial com tecnologia SLS (Selective Laser Sintering), de espessura de 4 mm, utilizando como mat?ria prima nylon 12. O modelo foi segmentado a partir de um estudo de resson?ncia magn?tica de um adulto normal, do sexo feminino, com 40 anos. Para a simula??o de atividade ictal foram inseridos, na regi?o correspondente ao lobo frontal direito, dois eletrodos met?licos constitu?dos de filme fino de 40 nm de prata (Ag). Para a aquisi??o das imagens, o modelo foi preenchido com ?gua destilada e com o radiois?topo 18F. As imagens foram adquiridas em equipamento de PET-CT com protocolo espec?fico para estudos cerebrais tomogr?fico e din?mico. Foram adquiridas imagens: (1) simulador sem a inser??o dos eletrodos (padr?o/basal), (2) simulador com eletrodos sem aplica??o de campo el?trico e (3) simulador com os eletrodos e aplica??o de campo el?trico. As imagens foram comparadas entre si atrav?s dos valores de SUV m?ximo e do ?ndice de capta??o. A abordagem estat?stica utilizada considerou as tr?s condi??es de imagens como grupos independentes e o teste n?o param?trico de Wilcoxon-Mann-Whitney foi aplicado. Houve diferen?a significativa entre os grupos, sendo o valor de p < 0,001 quando comparados os valores de m?dia de SUV m?ximo por corte nas situa??es basal x sem campo el?trico e basal x com campo el?trico. Na compara??o sem campo el?trico x com campo el?trico, o valor de p = 0,129 indica que a diferen?a entre os grupos n?o ? significativa. Quando avaliado o ?ndice de capta??o entre os grupos, todas as condi??es apresentaram diferen?a significativa, sendo p < 0,001 para os grupos basal x sem campo el?trico e basal x com campo el?trico, e p = 0,0123 na compara??o sem campo el?trico x com campo el?trico. As curvas TAC (time-activity-curve) foram adquiridas para demonstrar a capta??o de 18F no tempo, nas condi??es com campo el?trico e sem campo el?trico, em estudo din?mico de PET-CT. As imagens foram subtra?das atrav?s da metodologia SISCOM, utilizando a condi??o basal como refer?ncia. Os valores encontrados para p, tanto para SUV como para ?ndice de capta??o, s?o compat?veis com os achados visualizados nas imagens obtidas. Os histogramas gerados com a metodologia SISCOM demonstram que h? diferen?as entre as tr?s condi??es de imagem. As curvas TAC tra?adas correspondem ao aumento gradativo da concentra??o 18F no tempo, embora exista este aumento nas condi??es sem campo e com campo, obtivemos a maior concentra??o quando o sistema est? sob efeito do campo el?trico. O phantom antropom?rfico desenvolvido ? capaz de simular zonas an?logas ?s de imagens de atividade ictal, por?m o material utilizado como resina nos eletrodos deve ser modificado para que o produto possa ser comercializado futuramente.

Assessing complex brain activity as a function of the type of epilepsy and in the context of the 3D source of seizure onset remains a critical and challenging endeavor. In this dissertation, we tried to extract the attributes of the epileptic brain by looking at the modular interactions from scalp electroencephalography (EEG). A classification algorithm is proposed for the connectivity-based separation of interictal epileptic EEG from normal. Connectivity patterns of interictal epileptic discharges were investigated in different types of epilepsy, and the relation between patterns and the epileptogenic zone are also explored in focal epilepsy. A nonlinear recurrence-based method is applied to scalp EEG recordings to obtain connectivity maps using phase synchronization attributes. The pairwise connectivity measure is obtained from time domain data without any conversion to the frequency domain. The phase coupling value, which indicates the broadband interdependence of input data, is utilized for the graph theory interpretation of local and global assessment of connectivity activities. The method is applied to the population of pediatric individuals to delineate the epileptic cases from normal controls. A probabilistic approach proved a significant difference between the two groups by successfully separating the individuals with an accuracy of 92.8%. The investigation of connectivity patterns of the interictal epileptic discharges (IED), which were originated from focal and generalized seizures, was resulted in a significant difference ( ) in connectivity matrices. It was observed that the functional connectivity maps of focal IED showed local activities while generalized cases showed global activated areas. The investigation of connectivity maps that resulted from temporal lobe epilepsy individuals has shown the temporal and frontal areas as the most affected regions. In general, functional connectivity measures are considered higher order attributes that helped the delineation of epileptic individuals in the classification process. The functional connectivity patterns of interictal activities can hence serve as indicators of the seizure type and also specify the irritated regions in focal epilepsy. These findings can indeed enhance the diagnosis process in context to the type of epilepsy and effects of relative location of the 3D source of seizure onset on other brain areas.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal