BACKGROUND: A number of epilepsy syndromes are characterized by sleep-activated epileptiform discharges, however drivers of this process are not well understood. Previous research has found that thalamic injury in early life may increase the odds of sleep-activated spikes. Benign childhood epilepsy with centrotemporal spikes (BECTS) is among the most common pediatric-onset epilepsy syndromes, characterized by sleep-potentiated spike activity, a focal sensorimotor seizure semiology, and deficits in language, attention, and behavioral functioning. Though ictal and interictal electro-clinical activity resolves during mid-adolescence, adverse psychosocial outcomes may persist. Previous findings from monozygotic twin and neuroimaging studies suggest a multifactorial pattern of disease and raise suspicion for structural changes in thalamocortical connectivity focal to the seizure onset zone, though this has not been explored. OBJECTIVE: This research aims to (1) assess white matter differences in focal thalamocortical connectivity between BECTS cases and healthy controls using validated probabilistic tractography methods, (2) assess the association between spike burden and white matter connectivity focal to the seizure onset zone, and (3) evaluate longitudinal changes in thalamocortical connectivity across four cases. METHODS: 42 subjects ages 6-15 years were recruited between November 2015 and February 2018, including 23 BECTS cases and 19 healthy controls. Subjects underwent 3 Tesla structural and diffusion-weighted magnetic resonance imaging (2mm x 2mm x 2mm) with 64 gradient directions (b-value=2000) and 72 electrode sleep-deprived electroencephalographic (EEG) recordings. Seed and target regions of interest (ROIs) were created within each hemisphere using the Desikan-Killiany atlas, with the thalamus set as a seed ROI, and SOZ cortex and non-SOZ (NSOZ) cortex as target ROIs. Probabilistic tractography was executed using PROBTRACKX2 with 500 streamlines per seed voxel, 0.5 millimeter steps, and a curvature threshold of 0.2. All streamlines reaching the target ROI were summed and normalized by seed voxel count. Results for BECTS and healthy controls were plotted by age. The slope of thalamocortical connectivity versus age was computed for each group and compared between groups using nonparametric bootstrap analysis. Additionally, the association between SOZ connectivity and spike burden was assessed in a subgroup analysis using a linear regression model, controlling for age. RESULTS: A significant difference in the developmental trajectory of thalamocortical connectivity to the SOZ in BECTS cases compared to healthy controls was found (p=0.014), where the increase in connectivity with age observed in healthy controls was not present in BECTS children. These results did not extend to NSOZ thalamocortical connections (p=0.192). Longitudinal results support these observations, where all BECTS cases who underwent repeat imaging (N=4) showed a decrease in thalamocortical connectivity to the SOZ over the follow-up period. No relationship was found between thalamocortical connectivity and spike burden (p=0.840). CONCLUSIONS: These findings suggest that children with BECTS show subtle alterations in thalamocortical white matter development focal to the seizure onset zone. Thalamocortical connectivity to the SOZ does not appear to directly mediate non-REM sleep spike potentiation in BECTS. Limitations of this study include the potential for selection bias and limited power to detect sample differences. Additional research is needed to further characterize thalamocortical network changes and electrographic and neuropsychological correlates.

Orientadores: Marilisa Mantovani Guerreiro, Catarina Abrão Guimarães / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-19T22:11:29Z (GMT). No. of bitstreams: 1 Neri_MarinaLiberalesso_D.pdf: 1266603 bytes, checksum: 21ed75ba94dfafe79f7d15127e020891 (MD5) Previous issue date: 2012 / Resumo: A epilepsia benigna da infância com pontas centrotemporais (EBIPCT) ou rolândica (ER) é a forma mais freqüente de epilepsia na infância e é classificada como sendo focal, genética e de evolução benigna. Apesar de não haver déficit intelectual, essas crianças podem apresentar alterações cognitivas específicas. O presente estudo teve como objetivos: identificar e descrever alterações de funções executivas em crianças com ER e verificar a influência de variáveis clínicas da epilepsia nas funções executivas. Os participantes foram submetidos à aplicação de testes de funções executivas. Foram incluídas crianças com diagnóstico clínico e eletroencefalográfico de ER. A maioria dos pacientes estava controlada e muitos deles encontravam-se sem medicação. Os resultados obtidos foram comparados com os de um grupo de crianças de um grupo-controle (GC) constituído de indivíduos normais, com idade e nível sócio-educacional semelhantes ao das crianças com epilepsia. Os dados coletados nos dois grupos foram analisados e comparados através dos testes estatísticos: Mann-Whitney, teste Qui-quadrado e teste Exato de Fisher. Os resultados mostraram que quanto aos dados numéricos crianças com ER obtiveram pior desempenho em cinco das seis categorias consideradas do Wisconsin Card Sorting Test (WCST): nº de erros, nº de erros perseverativos, nº de respostas perseverativas, nº de categorias completadas e nº de fracassos em manter o set. Considerando-se resultados categóricos crianças com ER obtiveram pior desempenho no Trail Making Test (TMT) parte B, no Teste de fluência verbal FAS e em três categorias do WCST: nº de erros, nº de erros perseverativos e nº de respostas perseverativas. Em relação à variável idade de início da epilepsia, crianças com início mais precoce apresentaram pior desempenho em um dos instrumentos utilizados quando comparadas com crianças com início mais tardio da epilepsia; em relação às demais variáveis da epilepsia, não foi possível qualquer tipo de análise; quanto às variáveis das crises, não houve diferença nos resultados obtidos pelos pacientes divididos em grupos. Diante desses resultados concluímos que: as crianças com ER apresentaram déficit em funções executivas quando comparadas com o grupo-controle; a bateria utilizada mostrou-se adequada para detecção das disfunções apresentadas pelas crianças com ER; em relação à variável da epilepsia idade de início, crianças com início mais precoce apresentaram pior desempenho do que crianças com início mais tardio da epilepsia; em relação às demais variáveis da epilepsia e às variáveis das crises, não houve diferença entre os dois grupos. Assim, nosso estudo segue a linha de raciocínio de que o termo benigno deve ser usado com cautela uma vez que nossos pacientes apresentaram déficits neuropsicológicos em funções executivas, independentemente da fase ativa da epilepsia e do uso de medicações / Abstract: The benign childhood epilepsy with centrotemporal spikes (EBIPCT) or rolandic epilepsy (RE) is the most common type of childhood epilepsy and is considered to be a focal, genetic and benign epilepsy. Although there is no intellectual deficit, these children may have specific cognitive impairments. This study aimed: to identify and describe changes in executive functions in children with RE and to verify the influence of clinical variables of epilepsy in executive functions. Participants were evaluated with tests to assess executive functions. We included children with clinical and EEG features of RE. Most patients were controlled and several were without medication. The results were compared with those of a control group (CG) comprised of normal subjects with age and socioeconomic level similar to that of the RE group. The data collected from both groups were analyzed and compared using statistical tests: Mann-Whitney, Chi-square and Fisher exact tests. The results showed that concerning the numerical data, children with RE had the worst performance in five of the six categories of the WCST: number of errors, number of perseverative errors, number of perseverative answers, number of completed categories and number of failures to maintain the set. Considering categorical results, children with RE had worse performance in Trail Making Test part B, Verbal fluency test FAS and three categories of the WCST: number of errors, number of perseverative errors and number of perseverative answers. Concerning the variable age of onset of epilepsy, children with earlier onset of epilepsy had a worse performance in one of the tools when compared with children with later onset of epilepsy; the other variables of epilepsy did not allow any analysis; considering seizure variables, there was no difference between the two groups. We conclude that: children with RE showed deficits in executive functions when compared with the control group; the set of tests was adequate to detect the dysfunctions presented by children with RE; in relation to the variable age of onset of epilepsy, children with earlier onset had a worse performance than children with later onset of epilepsy; concerning other epilepsy and seizure variables, there was no difference between the two groups. Thus, our study is in keeping with the idea that the term benign should be cautiously used since our patients had neuropsychological deficits in executive functions regardless of the active phase of epilepsy and the use of medications / Doutorado / Ciencias Biomedicas / Doutor em Ciências Médicas

Biomarker discovery and statistical modeling reveals the brain activity that supports brain function and dysfunction. Detecting abnormal brain activity is critical for developing biomarkers of disease, elucidating disease mechanisms and evolution, and ultimately improving disease course. In my thesis, we develop statistical methodology to characterize neural activity in disease from noisy electrophysiological recordings. First, we develop a modification of a classic statistical modeling approach - multivariate Granger causality - to infer coordinated activity between brain regions. Assuming the signaling dependencies vary smoothly, we propose to write the history terms in autoregressive models of the signals using a lower dimensional spline basis. This procedure requires fewer parameters than the standard approach, thus increasing the statistical power. we show that this procedure accurately estimates brain dynamics in simulations and examples of physiological recordings from a patient with pharmacoresistant epilepsy. This work provides a statistical framework to understand alternations in coordinated brain activity in disease. Second, we demonstrate that sleep spindles, thalamically-driven neural rhythms (9-15 Hz) associated with sleep-dependent learning, are a reliable biomarker for Rolandic epilepsy. Rolandic epilepsy is the most common form of childhood epilepsy and characterized by nocturnal focal epileptic discharges as well as neurocognitive deficits. We show that sleep spindle rate is reduced regionally across cortex and correlated with poor cognitive performance in epilepsy. These results provide evidence for a regional disruption to the thalamocortical circuit in Rolandic epilepsy, and a potential mechanistic explanation for the cognitive deficits observed. Finally, we develop a procedure to utilize delta rhythms (2-4 Hz), a sensitive biomarker for Angelman syndrome, as a non-invasive measure of treatment efficacy in clinical trials. Angelman syndrome is a rare neurodevelopmental disorder caused by reduced expression of the UBE3A protein. Many disease-modifying treatments are being developed to reinstate UBE3A expression. To aid in clinical trials, we propose a procedure that detects therapeutic improvements in delta power outside of the natural variability over age by developing a longitudinal natural history model of delta power. These results demonstrate the utility of biomarker discovery and statistical modeling for elucidating disease course and mechanisms with the long-term goal of improving patient outcomes.

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 5 uppsatser.

Nors Rolando epilepsijai (RE) būdinga gerybinė eiga, dalis sergančiųjų turi miego bei elgesio problemų. Nuosekliai ištyrėme 75 RE sergančius bei 32 lyginamosios grupės nesergančius epilepsija pacientus. Grupės nesiskyrė pagal amžių ir lytį. Suskirstėme sergančiuosius RE į dvi grupes pagal priepuolių pasikartojimą per paskutinius 6 mėnesius. Elgesio sutrikimai buvo vertinami pasitelkiant CBCL (angl. Child Behavior Checklist) klausimyną, miego sutrikimai-pagal vaikų miego sutrikimų skalę (SDSC) (angl. Sleep Disturbance Scale for Children). Vertinome miego ir elgesio problemas bei jų sąsajas su klinikiniais, EEG duomenimis bei vizualinės-motorinės reakcijos laiko duomenimis. Bendradarbiaudami su Vilniaus universiteto Matematikos ir informatikos fakultetu rankiniu ir automatiniu būdu tyrėme pacientų EEG. Tik tiems RE pacientams, kuriems buvo priepuolių per paskutinius 6 mėn., nustatėme patikimai aukštesnius SDSC klausimyno įverčius (padidintą mieguistumą, kvėpavimo sutrikimus miego metu, miego- budrumo ritmo sutrikimus, ilgesnę miego latenciją) bei patikimai aukštesnius CBCL klausimyno rodiklius (socialinių sunkumų, mąstymo sunkumų, dėmesio sunkumų, agresyvaus elgesio bei bendrų sunkumų skalių įverčius). Elgesio problemos buvo susiję su ilgesne epilepsijos trukme, sunkesniais ir dažnesniais priepuoliais, miego problemomis bei miego EEG pakitimais (>35/min pikų kiekiu bei pikų lokalizacija ir kitose nei centrotemporalinės srityse). Budrumo EEG nustatytas >17/min pikų kiekis buvo... [toliau žr. visą tekstą] / Although patients with benign Rolandic epilepsy (RE) exhibit a benign course of the disease, some of them display sleep and behavioural problems. Seventy five patients with RE, aged 6–11 years, were included in this study. The patients were divided into two subgroups according to the presence of seizures over the preceding 6 months. The comparison group comprised 32 patients without epilepsy and with similar characteristics in terms of age and sex. All patients underwent evaluation of sleep (Sleep Disturbance Scale for Children) and behaviour (Lithuanian version of Child Behaviour Checklist). We examined the sleep and behavioural problems in correlation with the clinical data, EEG data, and simple visual-motor reaction time data. We automatically and manually analysed EEG in the collaboration with Vilnius University Faculty of Mathematics and Informatics. Only patients who had had seizures over the preceding 6 months displayed significantly higher scores for sleep problems (disorders of excessive daytime sleepiness, disorders of sleep breathing, and disorders of sleep-wake transition, longer sleep onset latency), and behavioural problems (social problems, thought problems, attention problems, and aggressive behavior) than the patients of the comparison group. Behavioural problems were associated with the longer epilepsy duration, more frequent and more severe seizures, sleep problems and sleep EEG data (spike frequency >35/min and spike focus, spreading to the other than... [to full text]

Nors Rolando epilepsijai (RE) būdinga gerybinė eiga, dalis sergančiųjų turi miego bei elgesio problemų. Nuosekliai ištyrėme 75 RE sergančius bei 32 lyginamosios grupės nesergančius epilepsija pacientus. Grupės nesiskyrė pagal amžių ir lytį. Suskirstėme sergančiuosius RE į dvi grupes pagal priepuolių pasikartojimą per paskutinius 6 mėnesius. Elgesio sutrikimai buvo vertinami pasitelkiant CBCL (angl. Child Behavior Checklist) klausimyną, miego sutrikimai-pagal vaikų miego sutrikimų skalę (SDSC) (angl. Sleep Disturbance Scale for Children). Vertinome miego ir elgesio problemas bei jų sąsajas su klinikiniais, EEG duomenimis bei vizualinės-motorinės reakcijos laiko duomenimis. Bendradarbiaudami su Vilniaus universiteto Matematikos ir informatikos fakultetu rankiniu ir automatiniu būdu tyrėme pacientų EEG. Tik tiems RE pacientams, kuriems buvo priepuolių per paskutinius 6 mėn., nustatėme patikimai aukštesnius SDSC klausimyno įverčius (padidintą mieguistumą, kvėpavimo sutrikimus miego metu, miego- budrumo ritmo sutrikimus, ilgesnę miego latenciją) bei patikimai aukštesnius CBCL klausimyno rodiklius (socialinių sunkumų, mąstymo sunkumų, dėmesio sunkumų, agresyvaus elgesio bei bendrų sunkumų skalių įverčius). Elgesio problemos buvo susiję su ilgesne epilepsijos trukme, sunkesniais ir dažnesniais priepuoliais, miego problemomis bei miego EEG pakitimais (>35/min pikų kiekiu bei pikų lokalizacija ir kitose nei centrotemporalinės srityse). Budrumo EEG nustatytas >17/min pikų kiekis buvo... [toliau žr. visą tekstą] / Although patients with benign Rolandic epilepsy (RE) exhibit a benign course of the disease, some of them display sleep and behavioural problems. Seventy five patients with RE, aged 6–11 years, were included in this study. The patients were divided into two subgroups according to the presence of seizures over the preceding 6 months. The comparison group comprised 32 patients without epilepsy and with similar characteristics in terms of age and sex. All patients underwent evaluation of sleep (Sleep Disturbance Scale for Children) and behaviour (Lithuanian version of Child Behaviour Checklist). We examined the sleep and behavioural problems in correlation with the clinical data, EEG data, and simple visual-motor reaction time data. We automatically and manually analysed EEG in the collaboration with Vilnius University Faculty of Mathematics and Informatics. Only patients who had had seizures over the preceding 6 months displayed significantly higher scores for sleep problems (disorders of excessive daytime sleepiness, disorders of sleep breathing, and disorders of sleep-wake transition, longer sleep onset latency), and behavioural problems (social problems, thought problems, attention problems, and aggressive behavior) than the patients of the comparison group. Behavioural problems were associated with the longer epilepsy duration, more frequent and more severe seizures, sleep problems and sleep EEG data (spike frequency >35/min and spike focus, spreading to the other than... [to full text]

Introdução: Uma importante aplicação da técnica de Ressonância Magnética funcional é em pesquisa clínica, acerca das funções cognitivas de pacientes, como por exemplo atenção, memória, linguagem, dentre outras. Pacientes com Epilepsia Idiopática da Infância podem apresentar déficits cognitivos e não possuem alterações estruturais detectáveis o que facilita a aplicação de técnicas computacionais de registro e normalização em estudos de neuroimagem o que possibilita a geração de imagens de um grupo de indivíduos e suas diversas possibilidades de inferências estatísticas. Este estudo teve como objetivo descrever as funções cognitivas em pacientes com Epilespia Rolândica (ER) e Epilepsia de Ausência (EA) através da RMf. Métodos: 57 indíviduos, 23 pacientes com ER ((média= 10,7 anos), 20 pacientes com EA (média= 9,9 anos) e 14 controles saudáveis (média=10 anos) foram submetidos ao vídeo-EEg, testes neuropsicológicos para avaliação das funções cognitivas (QI, funções executivas, dentre outras) e um paradigma de atenção Stoptask Gonogo e um paradigma Resting State (RS). Os dados foram analisados e foram gerados mapas limirializados de ativação da função BOLD. Resultados: As principais áreas ativas em pacientes e controles no paradigma Stoptask foram: hemisférios cerebelares bilateral, córtex orbito frontal bilateral, giros fusiformes, ínsula bilateral, córtex dorso latero pré-frontal, giro do Cíngulo anterior direito e esquerdo, bordas dos sulcos intraparietais, giros frontais superiores, eye-field.(p < 0,01). No paradigma RS as áreas encontradas foram: Córtex medial prefrontal, giro angular, giro supramarginal, giro do cíngulo posterior, giro frontal superior, sulco intraparietal, área motora suplementar, córtex prefrontal lateral (p < 0,05). OS mapas comparativos de grupos mostraram diferenças em ativaçao entre pacientes e controles. Discussão: Nossos mapas de ativação da resposta BOLD são semelhantes aos encontrados por outros autores na literatura tanto no paradigma Stoptask quanto no RS. As diferenças entre os grupos são devido aos deficits cognitivos que os pacientes apresentam. Conclusões: Crinaças com ER e EA apresentam deficits cognitivos e hipofrontalidade, mais estudos são necessários para melhoir entendimento da extensão dos deficits cognitivos em Epilepsia Idiopática da Infância / Introduction: An important application of functional MRI is in clinical research about the cognitive functions of patients, such as attention, memory, language, among others. Patients with Idiopathic Epilepsy of Childhood may show cognitive deficits and have no detectable structural changes which facilitates the application of computational techniques and standardization of registration in neuroimaging studies, which enables to obtain a group map of individuals and their various possibilities for statistical inferences. This study aimed to describe the cognitive functions in patients with Rolandic Epilepsy (RE) and absence epilepsy (AE) by fMRI. Methods: 57 individuals, 23 patients with RE (mean = 10.7 years), 20 patients with AE (mean = 9.9 years) and 14 healthy controls (mean = 10 years) underwent video-EEG, neuropsychological tests for assessment of cognitive function (IQ, executive functions, amongothers) theu also perform an attention paradigm Stoptask Gonogo and the Resting State (RS). Data were analyzed and maps were generated for BOLD activation function. Results: The main areas active in patients and controls in the paradigm Stoptask were bilateral cerebellar hemispheres, bilateral frontal orbital cortex, fusiform gyrus, bilateral insula, dorsal lateral prefrontal cortex, anterior cingulate gyrus right and left edges of the intraparietal sulcus, superior frontal gyrus, eye -field. (p < 0.01). In the RS paradigm areas observed were: medial prefrontal cortex, angular gyrus, supramarginal gyrus, posterior cingulate gyrus, superior frontal gyrus, intraparietal sulcus, supplementary motor area, lateral prefrontal cortex (p < 0.05). there were no statistically significant differences between group means (p < 0,01)Discussion: Our activation maps of BOLD response are similar to those found by other authors in the literature both in Stoptask paradigm as in the RS. The diferences between groups may be due cognitive deficts in patients group. Conclusions: Patients with RE and AE presente cognitive impairment and hypofrontality, more studies are necessary for better understanding of the extension of the cognitive deficits in Idiophatic Childhood Epilepsy patients

Introdução: Uma importante aplicação da técnica de Ressonância Magnética funcional é em pesquisa clínica, acerca das funções cognitivas de pacientes, como por exemplo atenção, memória, linguagem, dentre outras. Pacientes com Epilepsia Idiopática da Infância podem apresentar déficits cognitivos e não possuem alterações estruturais detectáveis o que facilita a aplicação de técnicas computacionais de registro e normalização em estudos de neuroimagem o que possibilita a geração de imagens de um grupo de indivíduos e suas diversas possibilidades de inferências estatísticas. Este estudo teve como objetivo descrever as funções cognitivas em pacientes com Epilespia Rolândica (ER) e Epilepsia de Ausência (EA) através da RMf. Métodos: 57 indíviduos, 23 pacientes com ER ((média= 10,7 anos), 20 pacientes com EA (média= 9,9 anos) e 14 controles saudáveis (média=10 anos) foram submetidos ao vídeo-EEg, testes neuropsicológicos para avaliação das funções cognitivas (QI, funções executivas, dentre outras) e um paradigma de atenção Stoptask Gonogo e um paradigma Resting State (RS). Os dados foram analisados e foram gerados mapas limirializados de ativação da função BOLD. Resultados: As principais áreas ativas em pacientes e controles no paradigma Stoptask foram: hemisférios cerebelares bilateral, córtex orbito frontal bilateral, giros fusiformes, ínsula bilateral, córtex dorso latero pré-frontal, giro do Cíngulo anterior direito e esquerdo, bordas dos sulcos intraparietais, giros frontais superiores, eye-field.(p < 0,01). No paradigma RS as áreas encontradas foram: Córtex medial prefrontal, giro angular, giro supramarginal, giro do cíngulo posterior, giro frontal superior, sulco intraparietal, área motora suplementar, córtex prefrontal lateral (p < 0,05). OS mapas comparativos de grupos mostraram diferenças em ativaçao entre pacientes e controles. Discussão: Nossos mapas de ativação da resposta BOLD são semelhantes aos encontrados por outros autores na literatura tanto no paradigma Stoptask quanto no RS. As diferenças entre os grupos são devido aos deficits cognitivos que os pacientes apresentam. Conclusões: Crinaças com ER e EA apresentam deficits cognitivos e hipofrontalidade, mais estudos são necessários para melhoir entendimento da extensão dos deficits cognitivos em Epilepsia Idiopática da Infância / Introduction: An important application of functional MRI is in clinical research about the cognitive functions of patients, such as attention, memory, language, among others. Patients with Idiopathic Epilepsy of Childhood may show cognitive deficits and have no detectable structural changes which facilitates the application of computational techniques and standardization of registration in neuroimaging studies, which enables to obtain a group map of individuals and their various possibilities for statistical inferences. This study aimed to describe the cognitive functions in patients with Rolandic Epilepsy (RE) and absence epilepsy (AE) by fMRI. Methods: 57 individuals, 23 patients with RE (mean = 10.7 years), 20 patients with AE (mean = 9.9 years) and 14 healthy controls (mean = 10 years) underwent video-EEG, neuropsychological tests for assessment of cognitive function (IQ, executive functions, amongothers) theu also perform an attention paradigm Stoptask Gonogo and the Resting State (RS). Data were analyzed and maps were generated for BOLD activation function. Results: The main areas active in patients and controls in the paradigm Stoptask were bilateral cerebellar hemispheres, bilateral frontal orbital cortex, fusiform gyrus, bilateral insula, dorsal lateral prefrontal cortex, anterior cingulate gyrus right and left edges of the intraparietal sulcus, superior frontal gyrus, eye -field. (p < 0.01). In the RS paradigm areas observed were: medial prefrontal cortex, angular gyrus, supramarginal gyrus, posterior cingulate gyrus, superior frontal gyrus, intraparietal sulcus, supplementary motor area, lateral prefrontal cortex (p < 0.05). there were no statistically significant differences between group means (p < 0,01)Discussion: Our activation maps of BOLD response are similar to those found by other authors in the literature both in Stoptask paradigm as in the RS. The diferences between groups may be due cognitive deficts in patients group. Conclusions: Patients with RE and AE presente cognitive impairment and hypofrontality, more studies are necessary for better understanding of the extension of the cognitive deficits in Idiophatic Childhood Epilepsy patients

<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.