Focal epilepsy in childhood is associated with increased risk for developing behavioral, emotional, cognitive and social–adaptive impairments. The present thesis focused on mental health difficulties in paediatric refractory focal epilepsy. It undertook a detailed evaluation of the predictive power of several demographic (gender, age at assessment), clinical (age at onset and duration of epilepsy, seizure frequency), localization (lobe and lateralization of pathology) and cognitive variables (performance in intellectual, memory and academic attainment measures) for mood, conduct, inattention/hyperactivity and peer relationship difficulties, as assessed by parental report. Data from a population of 282 children and adolescents, previously collected for clinical purposes, were examined, using a series of univariate and multivariate analyses. Mental health difficulties were found to be highly prevalent, with peer relationships the most frequently reported area of difficulty, followed by inattention/hyperactivity and emotional difficulties. Different patterns of associations between the variables examined here and individual emotional/behavioural difficulties were revealed, partially confirming and extending previous findings in the literature. Longer duration of epilepsy was found to increase the risk for developing emotional difficulties; male gender and earlier age at onset the risk for conduct difficulties; male gender, earlier age at onset, longer duration and frontal lobe localization the risk for attention/hyperactivity difficulties; and finally longer duration, higher seizure frequency and right hemisphere lateralization the risk for peer difficulties. Lower cognitive functioning was found associated with overall increased mental health difficulties and a lower VIQ was predictive of all types of difficulties. Developing a firm understanding of the risk factors that contribute to mental health comorbidities in focal paediatric epilepsy can help identify and provide assessment and intervention to children who are at higher risk earlier, thus significantly improving quality of life.

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.

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.

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.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24881号 / 医博第5015号 / 新制||医||1068(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 古川 壽亮, 教授 髙橋 良輔, 教授 阪上 優 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Mon travail de thèse porte sur les épilepsies focales avec ou sans malformations cérébrales de type dysplasie corticale focale. Il s'articule autour de (1) une étude fonctionnelle et génétique sur tissu cérébral postopératoire humain et (2) la caractérisation d'un nouveau modèle génétique chez l'animal. Tout d'abord, des mutations germinales hétérozygotes perte de fonction ont été identifiées dans DEPDC5, NPRL2 et NPRL3 qui codent pour le complexe GATOR1, un inhibiteur du complexe 1 de mTOR (mTORC1). Par la suite, des mutations somatiques cérébrales gain de fonction ont été identifiées dans MTOR. Nous avons émis l'hypothèse que ces mutations entrainent une hyperactivité de mTORC1, responsable des malformations cérébrales et de l'épilepsie des patients. J'ai observé une hyperactivité de mTORC1 dans les cellules cytomégaliques obtenues à partir de tissu cérébral post-opératoire de patients porteurs de mutations dans les gènes de GATOR1 ou MTOR. En parallèle, la caractérisation du premier modèle KO de Depdc5 a montré que les rats Depdc5+/- présentent des anomalies corticales rappelant celles des patients : délamination des couches corticales et cellules cytomégaliques avec une hyperactivité de mTORC1. Ce phénotype est prévenu par l'injection de rapamycine, un inhibiteur spécifique de mTORC1. Une susceptibilité accrue aux crises épileptiques induites par le pentylènetétrazole ainsi qu'un défaut des propriétés neuronales passives et actives ont été rapportés chez les rats Depdc5+/-. En conclusion, mes travaux de thèse ont contribué à mettre en évidence l'implication de la voie GATOR1-mTORC1 dans les épilepsies et dysplasies corticales focales. / In my PhD thesis work, I investigated focal epilepsies with and without brain malformations such as focal cortical dysplasia. I focused on two complementary aspects: (1) genetics and functional studies on human tissue samples and (2) characterization of a novel genetic animal model. First, germline heterozygous loss-of-function mutations were identified in DEPDC5, NPRL2 and NPRL3 genes that encode proteins which together form the GATOR1 complex, a repressor of the mTOR complex 1 (mTORC1). Additionally, brain somatic gain-of- function mutations were identified in MTOR gene that encodes mTOR itself. Both types of mutations are thought to lead to mTORC1 hyperactivity, and cause brain malformation and epilepsy in patients. To test this hypothesis, mTORC1 activity was monitored on post-operative brain tissue from patients carrying GATOR1 or mTOR genes mutations. Cytomegalic cells with mTORC1 hyperactivity were observed. Besides, the characterization of the first Depdc5 KO model revealed that Depdc5+/- rats present cortical structural abnormalities reminiscent of patient histopathology hallmarks: cortical layer dyslamination and cytomegalic cells with increased mTORC1 activity. This phenotype was prevented by rapamycin injection, a specific mTORC1 inhibitor. An increased susceptibility to pentylenetetrazol-induced epileptic seizures, as well as impaired passive and active neuronal properties were observed in Depdc5+/- rats compared to Depdc5+/+ rats. In conclusion, my PhD work largely contributed to emphasize the prominent role of the GATOR1-mTORC1 pathway in focal cortical dysplasia and epilepsies.

<p>Rolandic epilepsy (RE) is the most common focal epilepsy syndrome in the pediatric age group with an onset between 3 and 13 years. The syndrome is defined by electro-clinically typical features and has been considered benign according to seizure remission before the age of 16 years.</p><p>The aim of this thesis was to investigate children with typical RE with different methods and to discuss the delineation of the syndrome. Thirty-eight children, aged 6–14 years, participated in one up to four studies.</p><p>Eighteen children were investigated with MRI. Hippocampal abnormalities were found in six (33%), volume asymmetry in five (28%) and high signal intensities on T2-weighted images in three (17%). Additionally, high signal intensities in T2-weighted images were revealed subcortically in temporal and frontal lobes bilaterally in five children (28%).</p><p>The hippocampal region was evaluated metabolically using proton magnetic resonance spectroscopy (¹H-MRS) in 13 children with RE and 15 matched controls. A metabolic asymmetry of the hippocampal regions was found in the patients compared to controls indicating an abnormal neuronal function.</p><p>Seventeen children with RE and 17 matched controls were investigated with a neuropsychological test battery. The RE children showed lower performance in auditory-verbal tests and in executive functions compared to controls.</p><p>Twenty RE children and 24 controls were assessed concerning their oromotor function. The RE children had greater problems concerning tongue movements including articulation. A dichotic listening test was also performed in a subgroup showing poorer results in the RE group. </p><p>A simple classification is proposed with RE ‘pure’ as the main group and the frame for this study.</p><p>In conclusion, these investigations disclosed various abnormalities in children with RE, challenging the benign concept during the active phase. It is assumed that maturational factors comprise causal mechanism to the deviant findings, which probably successively will normalize.</p>

Rolandic epilepsy (RE) is the most common focal epilepsy syndrome in the pediatric age group with an onset between 3 and 13 years. The syndrome is defined by electro-clinically typical features and has been considered benign according to seizure remission before the age of 16 years. The aim of this thesis was to investigate children with typical RE with different methods and to discuss the delineation of the syndrome. Thirty-eight children, aged 6–14 years, participated in one up to four studies. Eighteen children were investigated with MRI. Hippocampal abnormalities were found in six (33%), volume asymmetry in five (28%) and high signal intensities on T2-weighted images in three (17%). Additionally, high signal intensities in T2-weighted images were revealed subcortically in temporal and frontal lobes bilaterally in five children (28%). The hippocampal region was evaluated metabolically using proton magnetic resonance spectroscopy (1H-MRS) in 13 children with RE and 15 matched controls. A metabolic asymmetry of the hippocampal regions was found in the patients compared to controls indicating an abnormal neuronal function. Seventeen children with RE and 17 matched controls were investigated with a neuropsychological test battery. The RE children showed lower performance in auditory-verbal tests and in executive functions compared to controls. Twenty RE children and 24 controls were assessed concerning their oromotor function. The RE children had greater problems concerning tongue movements including articulation. A dichotic listening test was also performed in a subgroup showing poorer results in the RE group. A simple classification is proposed with RE ‘pure’ as the main group and the frame for this study. In conclusion, these investigations disclosed various abnormalities in children with RE, challenging the benign concept during the active phase. It is assumed that maturational factors comprise causal mechanism to the deviant findings, which probably successively will normalize.

Abstract The purpose of the present study was to gain more insight into the blood oxygen level-dependent (BOLD)-contrast functional MRI (fMRI) in the brain and its connection to EEG, both in global and local scales of their temporal and spatial relations. BOLD signal changes were studied during hyperventilation (HV) induced EEG reactivity of intermittent rhythmic delta activity (IRDA). The BOLD signal in gray matter decreased 30% more in subjects with IRDA (N = 4) than in controls (N = 4), during the first two minutes of HV. This difference disappeared during IRDA in EEG. BOLD signal changes may provide additional information about dynamic hemodynamic changes relative to HV induced EEG reactivity. BOLD signal changes were investigated during sudden deepening of thiopental anesthesia into EEG burst-suppression level in pigs (N = 5). Positive (6–8%) or negative (-3– -8%) group average BOLD signal changes correlated to the thiopental bolus injection were seen. Positive and negative responses covered 1.6% and 2.3% of the brain voxels, respectively. BOLD signal changes in brain are associated with sudden deepening of thiopental anesthesia into EEG burst-suppression level, but they are spatially inconsistent and scarce. Somatosensory BOLD response was studied in brain before and after globally induced methotrexate (MTX) exposition in pigs (N = 4). After the MTX exposure, reduced (from 2–4% to 0–1%) or negative (-2% to -3%) BOLD responses were detected. Somatosensory BOLD-contrast response shows a slight difference in brain before and after globally induced MTX exposition. An experimental epilepsy model for development of simultaneous EEG and BOLD-contrast fMRI in the localization of epilepsy was developed and tested. Dynamic penicillin induced local epilepsy was applied in deep isoflurane anesthesia in pigs (N = 6). Relatively high (10–20%) and localized BOLD signal increase was found. The dynamic penicillin induced focal epilepsy model in deep isoflurane anesthesia with simultaneous EEG and BOLD-contrast fMRI is feasible for the development of these methods for localization of epileptic focus or foci. In conclusion, with careful experimental design and analysis, BOLD-contrast fMRI with EEG provides a potential tool for monitoring and localising functional changes in the brain.

No description available.