Fundamentação e Objetivo: A epilepsia é a doença neurológica mais comum em crianças. A avaliação da qualidade de vida destas crianças é importante para otimizar o tratamento delas. É importante para obter os pontos de vista das próprias crianças e seus pais. No entanto, existem poucos instrumentos que avaliem a qualidade de vida através da visão das crianças e dos seus pais. O objetivo deste estudo foi desenvolver e validar uma nova ferramenta para avaliação da qualidade de vida em crianças com epilepsia através de seus pais e dos pacientes. Material e Métodos: Baseada no trabalho anterior de Arunkumar e colaboradores, foi elaborada uma escala de múltipla escolha com 20 questões independentes para as crianças e seus pais: A Quality-of-Life in Pediatric Epilepsy Scale (QLPES). A análise fatorial com rotação VARIMAX foi usada para identificar possíveis áreas para as 20 questões propostas e alfa de Cronbach foi utilizado para testar a consistência das escalas. As respostas dadas pelos pacientes e seus pais ou cuidadores foram correlacionadas com frequência e gravidade das crises e com outras variáveis relacionadas com a epilepsia. Resultados: No total, 171 pacientes e seus pais participaram deste estudo. Setenta e quatro pacientes (43,3%) eram do sexo feminino, com médias de 13,3 (DP = 3,0) anos de idade e de 5,1 (DP = 3,1) anos de escolaridade. O alfa de Cronbach para cada domínio isolado sugerido pela analise fatorial foi abaixo de 0,7 para cada grupo. Entretanto, o alfa de Cronbach para todas as perguntas na escala dos pais foi de 0,83, e de 0,74 para as crianças. Para os pais ou cuidadores, as pontuações do QLPES foram menores para as mães/cuidadoras, para as crianças que usavam dois ou mais medicamentos antiepilépticos, para crianças com mais tempo de epilepsia, com maior duração de crises, ou aquelas com maior número de crises. Para as crianças, a pontuação QLPES foi menor para pacientes do sexo feminino, para as crianças que usavam dois ou mais medicamentos antiepilépticos, para aquelas com maior frequência de crises, e para crianças com EEG normal. Conclusão: A QLPES apresenta validade interna, consistência interna, confiabilidade teste-reteste e boa sensibilidade. A QLPES é um instrumento útil, preciso, rápido e fácil de usar, que reflete adequadamente a forma como a epilepsia afeta a qualidade de vida de crianças/adolescentes, assim como ele reflete como a epilepsia pediátrica afeta a qualidade de vida dos pacientes na perspectiva de seus pais ou cuidadores. / Background and Purpose: Epilepsy is the most common neurological condition in children. The evaluation of the quality of life of these children is important to optimize the treatment of them. It is important to obtain the views of the children themselves and of their parents. However, there are few scales assessing quality of life through both. The purpose of this study was to develop and validate a new parent- and patient- tool for evaluating health-related quality-of-life in pediatric epilepsy. Design and Methods: Based on previous work of Arunkumar and colleagues, we created a multiple choice scale with 20 independent questions for children and their parents. The Quality-of-Life in Pediatric Epilepsy Scale (QLPES). Factor analysis with VARIMAX rotation was used to identify possible areas for the 20 proposed questions, and Cronbach's alpha was used to test the scale’s consistency. The answers given by patients and their parents or caregivers were correlated with frequency and severity of the seizures and with other epilepsy-related variables. Results: A total of 171 patients and their parents participated in this study. Seventy four (43.3%) patients were female, with mean of 13.3 (SD=3.0) years of age and 5.1 (SD=3.1) years of schooling. The Cronbach's alpha of isolated domains suggested by the factor analysis were less than 0.7 for each group. However, alpha Cronbach for all the questions in the parents’ scale was 0.83 and 0.74 for children. For parents or caregivers, QLPES scores were lower for females responders, for children using two or more antiepileptic drugs, for children with longer time of epilepsy, longer seizure duration, or those with higher number of seizures. For children, QLPES scores were lower for female patients, for children using two or more antiepileptic drugs, for those with higher frequency of seizures, and for children with normal EEG. Conclusion: QLPES exhibits internal validity, internal consistency, test–retest reliability, and good sensitivity. QLPES is a useful, accurate, brief and easy to use instrument that adequately reflects the way epilepsy affects the quality of life of children/adolescents, as well as it reflects how pediatric epilepsy affects quality of life in the perspective of their parents or caregivers.

Fundamentação e Objetivo: A epilepsia é a doença neurológica mais comum em crianças. A avaliação da qualidade de vida destas crianças é importante para otimizar o tratamento delas. É importante para obter os pontos de vista das próprias crianças e seus pais. No entanto, existem poucos instrumentos que avaliem a qualidade de vida através da visão das crianças e dos seus pais. O objetivo deste estudo foi desenvolver e validar uma nova ferramenta para avaliação da qualidade de vida em crianças com epilepsia através de seus pais e dos pacientes. Material e Métodos: Baseada no trabalho anterior de Arunkumar e colaboradores, foi elaborada uma escala de múltipla escolha com 20 questões independentes para as crianças e seus pais: A Quality-of-Life in Pediatric Epilepsy Scale (QLPES). A análise fatorial com rotação VARIMAX foi usada para identificar possíveis áreas para as 20 questões propostas e alfa de Cronbach foi utilizado para testar a consistência das escalas. As respostas dadas pelos pacientes e seus pais ou cuidadores foram correlacionadas com frequência e gravidade das crises e com outras variáveis relacionadas com a epilepsia. Resultados: No total, 171 pacientes e seus pais participaram deste estudo. Setenta e quatro pacientes (43,3%) eram do sexo feminino, com médias de 13,3 (DP = 3,0) anos de idade e de 5,1 (DP = 3,1) anos de escolaridade. O alfa de Cronbach para cada domínio isolado sugerido pela analise fatorial foi abaixo de 0,7 para cada grupo. Entretanto, o alfa de Cronbach para todas as perguntas na escala dos pais foi de 0,83, e de 0,74 para as crianças. Para os pais ou cuidadores, as pontuações do QLPES foram menores para as mães/cuidadoras, para as crianças que usavam dois ou mais medicamentos antiepilépticos, para crianças com mais tempo de epilepsia, com maior duração de crises, ou aquelas com maior número de crises. Para as crianças, a pontuação QLPES foi menor para pacientes do sexo feminino, para as crianças que usavam dois ou mais medicamentos antiepilépticos, para aquelas com maior frequência de crises, e para crianças com EEG normal. Conclusão: A QLPES apresenta validade interna, consistência interna, confiabilidade teste-reteste e boa sensibilidade. A QLPES é um instrumento útil, preciso, rápido e fácil de usar, que reflete adequadamente a forma como a epilepsia afeta a qualidade de vida de crianças/adolescentes, assim como ele reflete como a epilepsia pediátrica afeta a qualidade de vida dos pacientes na perspectiva de seus pais ou cuidadores. / Background and Purpose: Epilepsy is the most common neurological condition in children. The evaluation of the quality of life of these children is important to optimize the treatment of them. It is important to obtain the views of the children themselves and of their parents. However, there are few scales assessing quality of life through both. The purpose of this study was to develop and validate a new parent- and patient- tool for evaluating health-related quality-of-life in pediatric epilepsy. Design and Methods: Based on previous work of Arunkumar and colleagues, we created a multiple choice scale with 20 independent questions for children and their parents. The Quality-of-Life in Pediatric Epilepsy Scale (QLPES). Factor analysis with VARIMAX rotation was used to identify possible areas for the 20 proposed questions, and Cronbach's alpha was used to test the scale’s consistency. The answers given by patients and their parents or caregivers were correlated with frequency and severity of the seizures and with other epilepsy-related variables. Results: A total of 171 patients and their parents participated in this study. Seventy four (43.3%) patients were female, with mean of 13.3 (SD=3.0) years of age and 5.1 (SD=3.1) years of schooling. The Cronbach's alpha of isolated domains suggested by the factor analysis were less than 0.7 for each group. However, alpha Cronbach for all the questions in the parents’ scale was 0.83 and 0.74 for children. For parents or caregivers, QLPES scores were lower for females responders, for children using two or more antiepileptic drugs, for children with longer time of epilepsy, longer seizure duration, or those with higher number of seizures. For children, QLPES scores were lower for female patients, for children using two or more antiepileptic drugs, for those with higher frequency of seizures, and for children with normal EEG. Conclusion: QLPES exhibits internal validity, internal consistency, test–retest reliability, and good sensitivity. QLPES is a useful, accurate, brief and easy to use instrument that adequately reflects the way epilepsy affects the quality of life of children/adolescents, as well as it reflects how pediatric epilepsy affects quality of life in the perspective of their parents or caregivers.

This dissertation introduces a new approach for assessing the effects of pediatric epilepsy on the language connectome. Two novel data-driven network construction approaches are presented. These methods rely on connecting different brain regions using either extent or intensity of language related activations as identified by independent component analysis of fMRI data. An auditory description decision task (ADDT) paradigm was used to activate the language network for 29 patients and 30 controls recruited from three major pediatric hospitals. Empirical evaluations illustrated that pediatric epilepsy can cause, or is associated with, a network efficiency reduction. Patients showed a propensity to inefficiently employ the whole brain network to perform the ADDT language task; on the contrary, controls seemed to efficiently use smaller segregated network components to achieve the same task. To explain the causes of the decreased efficiency, graph theoretical analysis was carried out. The analysis revealed no substantial global network feature differences between the patient and control groups. It also showed that for both subject groups the language network exhibited small-world characteristics; however, the patient’s extent of activation network showed a tendency towards more random networks. It was also shown that the intensity of activation network displayed ipsilateral hub reorganization on the local level. The left hemispheric hubs displayed greater centrality values for patients, whereas the right hemispheric hubs displayed greater centrality values for controls. This hub hemispheric disparity was not correlated with a right atypical language laterality found in six patients. Finally it was shown that a multi-level unsupervised clustering scheme based on self-organizing maps, a type of artificial neural network, and k-means was able to fairly and blindly separate the subjects into their respective patient or control groups. The clustering was initiated using the local nodal centrality measurements only. Compared to the extent of activation network, the intensity of activation network clustering demonstrated better precision. This outcome supports the assertion that the local centrality differences presented by the intensity of activation network can be associated with focal epilepsy.

Objective: Project ECHO (Extension for Community Healthcare Outcomes), a telementoring program, utilizes lectures, case-based learning, and an “all teach–all learn” approach to increase primary care provider (PCP) knowledge/confidence in managing chronic health conditions. The American Academy of Pediatrics (AAP) Epilepsy and Comorbidities ECHO incorporated quality improvement (QI) methodology to create meaningful practice change, while increasing PCP knowledge/self-efficacy in epilepsy management using the ECHO model. Methods: Monthly ECHO sessions (May 2018 to December 2018) included lectures, case presentations/discussion, and QI review. Pediatric practices were recruited through the AAP. Practices engaged in ECHO sessions and improvement activities including monthly Plan-Do-Study-Act cycles, team huddles, chart reviews, and QI coaching calls to facilitate practice change. They were provided resource toolkits with documentation templates, safety handouts, and medication side effects sheets. QI measures were selected from the American Academy of Neurology Measurement Set for Epilepsy. The AAP Quality Improvement Data Aggregator was used for data entry, run chart development, and tracking outcomes. Participants completed retrospective surveys to assess changes in knowledge and self-efficacy. Results: Seven practices participated across five states. Average session attendance was 14 health professionals (range = 13-17). A total of 479 chart reviews demonstrated improvement in six of seven measures: health care transition (45.3%, P =.005), safety education (41.6%, P =.036), mental/behavioral health screening (32.2% P =.027), tertiary center referral (26.7%, not significant [n.s.]), antiseizure therapy side effects (23%, n.s.), and documenting seizure frequency (7.1%, n.s.); counseling for women of childbearing age decreased by 7.8%. Significance: This project demonstrated that integrating QI into an ECHO model results in practice change and increases PCP knowledge/confidence/self-efficacy in managing epilepsy.

Epilepsy, as the most common chronic neurological disease, affects a significant part of population (0.5-1%). Drug resistant epilepsy has a significant negative effect on the quality of life, psychiatric comorbidities, neurocognitive performance and the risk of SUDEP in children. Therefore, resective epilepsy surgery, the only curative treatment of this condition, can fundamentally reverse this unfavorable prognosis. An inevitable prerequisite for a good postoperative result is complete removal of the epileptogenic zone (EC) and preservation of eloquent areas (EC). At present, even with improving and new preoperative non-invasive methods, we don't have an exclusive diagnostic method for theirs delineation. The aim of this PhD study is to assess benefit of individual intraoperative electrophysiological (iEF) methods in pediatric patients with focal intractable epilepsy. The first study evaluates the importance of intraoperative electrocorticography (iECoG) in the localization of EZ. The study proved that iECoG serves as a reliable tool to guide surgical resection and may predict results of epilepsy surgery. iECoG-based modification of surgical plan is not associated with increased risk of significant complications. The second presented study analyzed the contribution of intraoperative electrical...

Thèse de doctorat présentée en vue de l'obtention du doctorat en psychologie (Ph.D). / L'enfance et l'adolescence sont des périodes uniques de la vie où les changements neuronaux favorisent l'établissement de réseaux cérébraux matures et le développement des capacités intellectuelles. Le langage est un domaine cognitif qui est, non seulement essentiel pour la communication interhumaine, mais qui contribue également au développement de nombreuse capacités et prédit de manière significative la réussite académique. Les régions cérébrales frontotemporales sont des régions clés du réseau langagier du cerveau. Il a été démontré que les neuropathologies telles que l'épilepsie des lobes frontal et temporal (ELF et ELT) interfèrent avec le développement des réseaux cérébraux du langage et provoquent des circuits cérébraux aberrants. Les patrons exacts de réorganisation des réseaux cérébraux fonctionnels ne sont toutefois, pas entièrement compris et l'association avec le profil neuropsychologique reste spéculative. Par conséquent, l'objectif principal de cette thèse est d'accroître la compréhension des altérations du réseau langagier et d'améliorer les connaissances de l'association de l'architecture du réseau et des capacités cognitives chez les enfants et les adolescents avec ELF ou ELT. La présente thèse est composée de trois articles scientifiques, les deux premiers présentant des travaux méthodologiques qui ont permis d'optimiser les méthodes appliquées dans le troisième article, l'étude empirique principale menée auprès d'enfants avec ELF et ELT. Le premier article présente le bilan neuropsychologique pédiatrique comme un outil important pour estimer les capacités cognitives et dresser un profil cognitif avec ses forces et ses faiblesses. Dans le deuxième article, l'analyse factorielle parallèle (PARAFAC) est présentée et validée comme une nouvelle technique employée pour corriger les artefacts de mouvement qui contaminent le signal hémodynamique évalué par la spectroscopie fonctionnelle proche infrarouge (fNIRS). Une meilleure qualité du signal permet une interprétation fiable de la réponse cérébrale en plis de déduire des métriques d'organisation du réseau cérébral. Le troisième article consiste en une étude empirique, où le traitement cérébral du langage, est comparé entre des enfants avec ELF et ELT, et des pairs neuroptypiques. Les schémas de connectivité fonctionnelle indiquent que le groupe de patients présente moins de connexions intra-hémisphériques dans l'hémisphère gauche et entre les hémisphères, et des connexions accrues dans l'hémisphère droit par rapport au groupe témoin. Les mesures de l'architecture du réseau révèlent en outre une efficacité de traitement local plus élevée dans l'hémisphère droit chez les enfants atteints de ELF et ELT par rapport aux enfants en bonne santé. L'architecture du réseau local de l'hémisphère gauche et la capacité intellectuelle globale dans le groupe de patients sont négativement liées, tandis que dans le groupe contrôle, aucune association de ce type n'est identifiable. Ces résultats suggèrent que la réorganisation du réseau de langage chez les enfants avec ELF ou ELT semble dans certains cas soutenir un meilleur résultat cognitif, soit lorsque l'efficacité du traitement local dans l'hémisphère gauche est diminuée. Au contraire, une plus grande efficacité de traitement local semble être une caractéristique d'un réseau de langage cérébral associé à de moins bonnes capacités cognitives. Les travaux de recherche de cette thèse de doctorat fournissent des lignes directrices pour l'utilisation de l'évaluation neuropsychologique pédiatrique, à la fois dans un contexte clinique et scientifique. L'introduction de PARAFAC pour corriger les artefacts de mouvement dans le signal fNIRS est un ajout important au pipeline de prétraitement qui permet d'augmenter la qualité du signal pour une analyse ultérieure. De futurs projets pourront s'appuyer sur cette validation initiale et étendre l'utilisation de PARAFAC pour les analyses du signal fNIRS. Sur cette base méthodologique solide, le travail empirique confirme l'incidence accrue de circuits cérébraux aberrants liés au traitement du langage chez les enfants atteints de ELF et de ELT, et soutient en outre l'efficacité du réseau local en tant que déterminant clé de l'impact de la plasticité cérébrale précoce sur les capacités cognitives. Afin de mieux comprendre les altérations du réseau en réponse aux neuropathologies et leur impact, des études avec des échantillons plus grands et de différents groupes d'âge, devraient étudier plus spécifiquement le rôle des facteurs cliniques (e.g., le type d'épilepsie, la latéralisation de l'épilepsie, le contrôle des crises, etc.) et aborder leurs influences sur le développement. À long terme, cela augmentera le pronostic des phénotypes cliniques chez les patients pédiatriques atteints de ELF et de ELT, et offrira des opportunités d'interventions précoces pour soutenir un développement typique. / Childhood and adolescence are unique periods in life where neuronal changes support the establishment of mature brain networks and the development of intellectual capacities. Language is one cognitive domain that is not only an essential part of inter-human communication but also contributes to the development of other capacities and significantly influences academic achievement. Frontotemporal brain areas are key regions of the brain's language network. Neuropathologies such as frontal and temporal lobe epilepsies (FLE and TLE) have been shown to interfere with developing brain language networks and cause aberrant cerebral circuits. The exact patterns of functional brain network reorganization are not fully understood and the association with the neuropsychological profile remains speculative. Therefore, the main objective of this thesis was to increase comprehension of language network alterations and enhance the knowledge on the association of network topology and cognitive capacities in children and adolescents with FLE or TLE. This thesis consists of three scientific articles, with the first two presenting methodological work that allowed for the optimization of the methods applied in the third article, which is the main empirical study conducted on children with FLE and TLE. The first article presents the pediatric neuropsychological assessment as a valuable tool to estimate cognitive capacities and draw a cognitive profile with strengths and weaknesses. In the second article, parallel factor analysis (PARAFAC) is presented and validated as a novel technique to correct motion artifacts that contaminate the hemodynamic signal assessed with functional near-infrared spectroscopy (fNIRS). A better signal quality is the basis for a reliable interpretation of the cerebral response and derive metrics of brain network organization. The third article consists of an empirical study where cerebral language processing is compared between children with FLE and TLE, and neuroptypical peers. Patterns of functional connectivity indicate that the patient group demonstrates fewer intra-hemispheric connections in the left hemisphere and between hemispheres, and increased connections within the right hemisphere as compared to the control group. Metrics of network architecture further reveal a higher local processing efficiency within the right hemisphere in children with FLE and TLE compared to healthy peers. Local network architecture of the left hemisphere and the overall intellectual capacity in the patient group is negatively related, while in the control group no such association is identifiable. These findings suggest that language network reorganization in children with FLE or TLE in some cases seems to support a better cognitive outcome, namely when local processing efficiency in the left hemisphere is decreased. On the contrary, a higher local processing efficiency seems to be a characteristic of a brain language network that goes along with worse cognitive capacities. The research work of this doctoral thesis provides guidelines for the use of pediatric neuropsychological assessment both in a clinical and scientific context. The introduction of PARAFAC to correct motion artifact in the fNIRS signal is an important add-on to the preprocessing pipeline that allows to increase signal quality for subsequent analysis. Future projects will be able to build on this initial validation and extend PARAFAC's use for fNIRS analysis. On this solid methodological foundation, the empirical work confirms the increased incidence of aberrant brain circuits related to language processing in children with FLE and TLE, and further supports local network efficiency as a key determinant of the impact of early brain plasticity on cognitive capacities. In order to further understand network alterations in response to neuropathologies and their impact, studies with larger samples sizes and different age groups should further investigate the specific role of clinical factors (e.g., epilepsy type, epilepsy lateralization, seizure control, etc.) and address developmental influences. Ultimately, this will increase prognosis of clinical phenotypes in pediatric patients with FLE and TLE, and offer opportunities for early interventions to support a healthy development.