<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.

A Epilepsia Benigna da Infância com Paroxismos Centrotemporais (EBICT) é uma epilepsia focal e de etiologia indeterminada. O termo benigno é, atualmente, questionado pelo reconhecimento de que, apesar da remissão completa das crises epilépticas em 80% dos casos e da farmacorresponsividade nessa síndrome, há comorbidades psiquiátricas que podem comprometer a qualidade de vida e o desempenho escolar. A comorbidade psiquiátrica mais frequente nessa epilepsia é o Transtorno do Déficit de Atenção e Hiperatividade (TDAH). Uma das mais importantes funções cognitivas, as Funções Executivas (FE), nos seus domínios frios (flexibilidade mental, rastreio mental de informações, capacidade de abstração e atenção) e quentes (tomada de decisão, cognição social e controle de impulsividade), podem estar alteradas, tanto na EBICT quanto no TDAH. Apesar da alta prevalência dessa síndrome, o TDAH e as FE, principalmente as quentes, são pouco investigadas e descritas nessa população. Além disso, com os poucos estudos previamente realizados, não é possível descrever se os déficits executivos encontrados estão relacionados às variáveis clínicas da epilepsia, à atividade epileptiforme em si, à comorbidade psiquiátrica ou à soma destes fatores. Dessa forma, o objetivo geral deste estudo foi analisar o perfil de desempenho executivo em crianças e adolescentes com EBICT. Este foi um estudo de coorte transversal, controlado (duplo pareamento) e não randomizado. O desempenho executivo das crianças e adolescentes, de ambos os sexos, com idades de 6 a 16 anos, foi avaliado através da análise comparativa de três grupos (total de 63 sujeitos): Grupo I (23 pacientes com EBICT); Grupo II (20 pacientes com TDAH e sem epilepsia) e Grupo III (20 crianças e adolescentes saudáveis sem epilepsia, sem TDAH e sem nenhum diagnóstico neurológico ou psiquiátrico). A avaliação neuropsicológica foi composta por uma bateria abrangente com 22 instrumentos, para investigação detalhada das funções executivas em seus múltiplos domínios (atenção, FE frias e quentes), potencial intelectual e desempenho acadêmico. Nossos resultados demonstraram que os pacientes com EBICT apresentam pior desempenho em domínios do funcionamento executivo frio e quente em comparação aos controles. A presença do TDAH esteve associada a um maior prejuízo no funcionamento executivo dos pacientes com EBICT. Além disso, o perfil executivo e atencional desses pacientes demonstrou-se distinto daquele apresentado pelas crianças com TDAH e sem epilepsia. Houve correlação entre as variáveis clínicas da epilepsia (especialmente tempo de controle de crises, número de fármacos antiepilépticos, presença e lateralidade da atividade epileptiforme) e um pior funcionamento executivo. Dessa forma, salienta-se a necessidade de maior atenção às funções executivas quentes e à presença da coexistência do TDAH na EBICT, ambas negligenciadas nos estudos com essa síndrome epiléptica da infância. Assim, pode-se propiciar um melhor delineamento das dificuldades cognitivas, do prognóstico e da intervenção adequados e eficazes para crianças e adolescentes com EBICT / Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS) is focal epilepsy with undetermined etiology. At the moment, the term benign has been questioned by the recognition that despite the complete remission of epileptic seizures in 80% of cases and pharmaco-responsivity, there are cognitive and psychiatric comorbidities that may compromise quality of life and school performance. The most frequent psychiatric comorbidity is Attention Deficit Hyperactivity Disorder (ADHD). One of the most important cognitive functions, the Executive Functions (EF), in its cool (mental flexibility, mental information tracking, abstraction capacity and attention) and hot domains (decision making, social cognition and impulse control), may be impaired in both disorders, BECTS and ADHD. Despite the high prevalence of this syndrome, ADHD and EF are poorly investigated and described in this population. Moreover, with the few studies previously done, it is not possible to describe if the executive deficits found are related to the clinical variables of epilepsy, the epileptiform activity itself, the psychiatric comorbidity or the sum of these factors. Thus, the general objective of this study was to analyze the profile of executive performance in children and adolescents with BECTS. This was a cross-sectional, controlled (double-matched) and non-randomized cohort study. The executive profile of children and adolescents of both genders, aged 6 to 16 years, was evaluated through a comparative analysis of three groups (total of 63 subjects): Group I (23 patients with BECTS); Group II (20 patients with ADHD and without epilepsy) and Group III (20 healthy children and adolescents without epilepsy, without ADHD and without any neurological or psychiatric diagnosis). The neuropsychological evaluation consisted of a comprehensive battery with 22 instruments for detailed executive functions evaluation in its multiple domains (attention, cool and hot EF), intellectual potential and academic performance. Our results showed that patients with BECTS presented worse performance in the areas of cold and hot executive functioning compared to controls. The presence of ADHD was associated with greater impairment in the executive functioning of patients with BECTS. In addition, the executive and attentional profile of these patients was different from that presented by children with ADHD and without epilepsy. There was a correlation between the clinical variables of epilepsy (especially time of seizure control, number of antiepileptic medication, presence and laterality of epileptiform discharges) and worse executive functioning. Thus, the need for greater attention to the hot executive functions and to the presence of the coexistence of ADHD in the BECTS, both neglected in the studies with this epileptic syndrome of the childhood, is emphasized. Thus, a better delineation of adequate and effective cognitive difficulties, prognosis and intervention for children and adolescents with BECTS can be provided

Diese Dissertation zeigt, dass Hintergrundrhythmen mit Hilfe der gleichzeitigen Messung von EEG und fMRI Signalen untersucht werden können. Die Methodik dieses Ansatzes wurde durch den Einsatz einer speziellen fMRI Sequenz weiterentwickelt, und die Signalqualität durch visuell evozierte Potentiale überprüft. Der prominente okzipitale Alpha-Rhythmus und die vergleichsweise schwächeren rolandischen Rhythmen konnten in der elektromagnetisch störenden Umgebung des Magnetresonanztomografen, auch und gerade während der funktionellen Messsequenzen identifiziert werden. Durch den Einsatz der in dieser Arbeit vorgestellten Nachverarbeitungsmethoden kann die simultane Aufnahme von EEG und fMRI Signalen wertvolle Informationen über die neuronale Grundlage von Hirnrhythmen und ihrer hemodynamischer Korrelate liefern. Die hier vorgestellten Daten bekräftigen die Hypothese, dass die Amplitude der Hintergrundrhythmen mit spezifischen Deaktivierungen in sensorischen Hirnarealen einhergehen. Eine erhöhte Amplitude aller untersuchter Rhythmen war mit einem negativen BOLD Signal in sensorischen kortikalen Arealen verknüpft, was auf einen erniedrigten Energieverbrauch in Arealen mit höherer Synchronizität schliessen lässt. Der posteriore Alpha Rhythmus, ist invers mit dem hemodynamischen Signal in primären visuellen Arealen gekoppelt, während hämodynamische Korrelate der rolandischen Alpha und Beta Rhythmen in somatomotorischen Arealen lokalisiert wurden. Für den rolandischen Alpha und Beta Rhythmus wurden unterschiedliche regionale Netzwerke gefunden. Der rolandische Beta Rhythmus ist mit dem Motornetzwerk, während der rolandische Alpha Rhythmus mit einen somatosensorischen bzw. Assoziationsnetzwerk assoziert ist, was eine fundamentale Eigenschaft des Somatomotorischen Systems zu sein scheint. Die rolandischen Rhythmen könnten dadurch somatomotorische Areale während der Erhaltung oder Planung von Bewegungsabläufen funktional koppeln [Brovelli, et al., 2004]. Desweiteren wurde gezeigt, dass thalamische und cinguläre Strukturen mögliche Generatoren oder Modulatoren der hier untersuchten Hintergrundrhythmen sind. Die experimentellen Daten der hier vorgestellten Studien legen nahe, dass eine inverse Beziehung der Stärke eines Hintergrundrhythmus mit regional kortikalem Metabolismus und gleichzeitig eine „antagonistische“, positive Beziehung mit thalamischen oder cingulären Struktuen ein gernerelles orgnaisatorisches Prinzip des Gehirns zu sein scheint. Der Begriff der Grundaktivität des Gehirns [Gusnard, et al., 2001] müsste daher in verschiedene Netzwerke der Grundaktivität unterteilt werden, die elektrophysiologisch durch Hintergrundrhythmen definiert wären. / The data provided by this thesis show that imaging of brain rhythms can be achieved by simultaneous EEG-fMRI recordings. This methodology was developed further by implementing an adapted MR sequence and the EEG-fMRI signal quality was confirmed by means of visual evoked potentials. Together with the post processing methods applied in this work, simultaneous EEG-fMRI recordings can thus provide valuable information about the neuronal basis of brain rhythms and their regional hemodynamic correlates. The data further substantiate the hypothesis that ‘idling’ rhythms indicate distinct deactivated sensory cortical areas. Increased power of all examined rhythms was associated with negative BOLD signal in sensory cortical areas, indicating less energy consumption in those areas with higher synchronicity. The posterior alpha or so-called Berger rhythm is coupled inversely to the hemodynamics in primary visual areas, whereas rolandic alpha and beta rhythm could be localized to somatomotor areas. Different networks were found for rolandic alpha and beta rhythms. The rolandic beta rhythm is more associated with a motor-network whereas the rolandic alpha rhythm is more associated with a sensory and association network which represents a fundamental characteristic of the sensorimotor system. The rolandic oscillations may bind sensorimotor areas into a functional loop during pre-movement motor maintenance behaviour [Brovelli, et al., 2004]. Furthermore thalamic and cingulate structures were shown to be possible generative or modulatory structures for the brain rhythms examined in this study. The experimental data obtained in this work suggest that the inverse correlation of an ‘idling’ rhythm’s strength with the metabolism in ‘its cortical areas’, and the positive correlation with cingulate or thalamic areas are both general organizational principles. The notion of a default mode of the brain [Gusnard, et al., 2001] may perhaps be further subdivided into different networks with a “default mode”, each of them electro-physiologically defined by its “idle rhythm”.

A Epilepsia Benigna da Infância com Paroxismos Centrotemporais (EBICT) é uma epilepsia focal e de etiologia indeterminada. O termo benigno é, atualmente, questionado pelo reconhecimento de que, apesar da remissão completa das crises epilépticas em 80% dos casos e da farmacorresponsividade nessa síndrome, há comorbidades psiquiátricas que podem comprometer a qualidade de vida e o desempenho escolar. A comorbidade psiquiátrica mais frequente nessa epilepsia é o Transtorno do Déficit de Atenção e Hiperatividade (TDAH). Uma das mais importantes funções cognitivas, as Funções Executivas (FE), nos seus domínios frios (flexibilidade mental, rastreio mental de informações, capacidade de abstração e atenção) e quentes (tomada de decisão, cognição social e controle de impulsividade), podem estar alteradas, tanto na EBICT quanto no TDAH. Apesar da alta prevalência dessa síndrome, o TDAH e as FE, principalmente as quentes, são pouco investigadas e descritas nessa população. Além disso, com os poucos estudos previamente realizados, não é possível descrever se os déficits executivos encontrados estão relacionados às variáveis clínicas da epilepsia, à atividade epileptiforme em si, à comorbidade psiquiátrica ou à soma destes fatores. Dessa forma, o objetivo geral deste estudo foi analisar o perfil de desempenho executivo em crianças e adolescentes com EBICT. Este foi um estudo de coorte transversal, controlado (duplo pareamento) e não randomizado. O desempenho executivo das crianças e adolescentes, de ambos os sexos, com idades de 6 a 16 anos, foi avaliado através da análise comparativa de três grupos (total de 63 sujeitos): Grupo I (23 pacientes com EBICT); Grupo II (20 pacientes com TDAH e sem epilepsia) e Grupo III (20 crianças e adolescentes saudáveis sem epilepsia, sem TDAH e sem nenhum diagnóstico neurológico ou psiquiátrico). A avaliação neuropsicológica foi composta por uma bateria abrangente com 22 instrumentos, para investigação detalhada das funções executivas em seus múltiplos domínios (atenção, FE frias e quentes), potencial intelectual e desempenho acadêmico. Nossos resultados demonstraram que os pacientes com EBICT apresentam pior desempenho em domínios do funcionamento executivo frio e quente em comparação aos controles. A presença do TDAH esteve associada a um maior prejuízo no funcionamento executivo dos pacientes com EBICT. Além disso, o perfil executivo e atencional desses pacientes demonstrou-se distinto daquele apresentado pelas crianças com TDAH e sem epilepsia. Houve correlação entre as variáveis clínicas da epilepsia (especialmente tempo de controle de crises, número de fármacos antiepilépticos, presença e lateralidade da atividade epileptiforme) e um pior funcionamento executivo. Dessa forma, salienta-se a necessidade de maior atenção às funções executivas quentes e à presença da coexistência do TDAH na EBICT, ambas negligenciadas nos estudos com essa síndrome epiléptica da infância. Assim, pode-se propiciar um melhor delineamento das dificuldades cognitivas, do prognóstico e da intervenção adequados e eficazes para crianças e adolescentes com EBICT / Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS) is focal epilepsy with undetermined etiology. At the moment, the term benign has been questioned by the recognition that despite the complete remission of epileptic seizures in 80% of cases and pharmaco-responsivity, there are cognitive and psychiatric comorbidities that may compromise quality of life and school performance. The most frequent psychiatric comorbidity is Attention Deficit Hyperactivity Disorder (ADHD). One of the most important cognitive functions, the Executive Functions (EF), in its cool (mental flexibility, mental information tracking, abstraction capacity and attention) and hot domains (decision making, social cognition and impulse control), may be impaired in both disorders, BECTS and ADHD. Despite the high prevalence of this syndrome, ADHD and EF are poorly investigated and described in this population. Moreover, with the few studies previously done, it is not possible to describe if the executive deficits found are related to the clinical variables of epilepsy, the epileptiform activity itself, the psychiatric comorbidity or the sum of these factors. Thus, the general objective of this study was to analyze the profile of executive performance in children and adolescents with BECTS. This was a cross-sectional, controlled (double-matched) and non-randomized cohort study. The executive profile of children and adolescents of both genders, aged 6 to 16 years, was evaluated through a comparative analysis of three groups (total of 63 subjects): Group I (23 patients with BECTS); Group II (20 patients with ADHD and without epilepsy) and Group III (20 healthy children and adolescents without epilepsy, without ADHD and without any neurological or psychiatric diagnosis). The neuropsychological evaluation consisted of a comprehensive battery with 22 instruments for detailed executive functions evaluation in its multiple domains (attention, cool and hot EF), intellectual potential and academic performance. Our results showed that patients with BECTS presented worse performance in the areas of cold and hot executive functioning compared to controls. The presence of ADHD was associated with greater impairment in the executive functioning of patients with BECTS. In addition, the executive and attentional profile of these patients was different from that presented by children with ADHD and without epilepsy. There was a correlation between the clinical variables of epilepsy (especially time of seizure control, number of antiepileptic medication, presence and laterality of epileptiform discharges) and worse executive functioning. Thus, the need for greater attention to the hot executive functions and to the presence of the coexistence of ADHD in the BECTS, both neglected in the studies with this epileptic syndrome of the childhood, is emphasized. Thus, a better delineation of adequate and effective cognitive difficulties, prognosis and intervention for children and adolescents with BECTS can be provided