RESUMEN
OBJECTIVE: Studies of absence seizures (AS) using EEG with fMRI (EEG-fMRI) show a consistent network with prominent thalamic activation and a variety of cortical changes. Despite evidence suggesting a role of frontal cortex in seizure generation, group studies have not detected consistent AS-related changes in this region. We hypothesized that only a subgroup may show frontal cortical activation. METHOD: We studied 13 subjects with AS during EEG-fMRI to classify the different individual patterns of frontal cortical activation associated with AS. RESULTS: Based upon visual inspection of surface-rendered activation maps we identified 2 subgroups that could be distinguished by the activation in the dorsolateral prefrontal cortex (DLPFC). One group of patients (n = 7) showed a primarily positive signal change (DLPFC-POS), whereas the other group (n = 6) showed a primarily negative signal change (DLFPC-NEG). When the DLPFC-POS group was compared to the DLPFC-NEG group, time-course analysis revealed a larger positive blood oxygenation level-dependent deflection following onset of the AS in cortical and subcortical areas beyond the DLPFC. This suggests a basic biological difference between these groups. CONCLUSION: These observations suggest that there may be at least 2 mechanisms underpinning AS in individuals with absence epilepsy. This may have phenotypic and genetic implications for understanding epilepsy syndromes.
Asunto(s)
Electroencefalografía , Epilepsia Tipo Ausencia/fisiopatología , Lóbulo Frontal/fisiopatología , Imagen por Resonancia Magnética , Adolescente , Niño , Preescolar , Epilepsia Tipo Ausencia/patología , Femenino , Lóbulo Frontal/patología , Humanos , Masculino , Corteza Prefrontal/fisiopatologíaRESUMEN
OBJECTIVES: We used EEG-fMRI to study epileptiform activity in a cohort of untreated children with typical absence seizures (AS). Our aim was to identify cortical and subcortical regions involved in spike and wave events and to explore the timing of activity in these regions. METHODS: Eleven children with AS confirmed on video-EEG underwent EEG-fMRI. An event-related analysis of epileptiform activity was performed. Regions of interest (ROIs), identified in the event-related analysis, were used to study the time course of the blood oxygen level-dependent (BOLD) signal prior to and immediately following events of interest in these ROIs. RESULTS: Group analysis confirmed positive BOLD in the thalamus and negative BOLD in the lateral and mesial parietal lobe, caudate nuclei, and additionally the brainstem reticular formation. The event-related time course differed between the thalamus, the parietal cortex, and the pons and caudate nuclei. In the subcortical structures, BOLD signal change occurred at, or immediately after, electrographic onset. Importantly, in the parietal cortex, but not in other cortical regions, there was a subtle BOLD signal increase for 10 seconds prior to the onset of epileptiform activity. CONCLUSIONS: In children with typical AS, we have confirmed a core network of structures involved in generalized epileptiform activity that includes the reticular structures of the brainstem. Furthermore, we have identified changes in parietal BOLD signal which precede the onset of epileptiform activity, suggesting the parietal cortex has a role in the initiation of epileptiform activity.
Asunto(s)
Corteza Cerebral/fisiopatología , Epilepsia Tipo Ausencia/fisiopatología , Red Nerviosa/fisiopatología , Tálamo/fisiopatología , Adolescente , Mapeo Encefálico , Niño , Preescolar , Electroencefalografía , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Selección de Paciente , Procesamiento de Señales Asistido por ComputadorRESUMEN
Genome-wide association studies are utilized for gene discovery in common diseases. Genotypes of large groups of unrelated patients are compared to controls. This has become feasible due to the recent technical advances in genomics and convincing positive results are now regularly being published. This review is an accessible introduction to the genetic and technical knowledge needed to interpret such studies. Genome-wide association studies are being applied to many neurologic diseases. Here we use idiopathic generalized epilepsy as an example to highlight the phenotyping, sample size, and statistical issues that must be addressed in such studies. These studies are likely to transform our understanding of complex neurologic diseases in the next few years.