Avaliação dos efeitos das medicações anticrises na conectividade funcional cerebral de pacientes com epilepsia generalizada idiopática
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Data
2022-03-11
Autores
Alves, Karen Fernanda
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Universidade Estadual Paulista (Unesp)
Resumo
Nas epilepsias generalizadas idiopáticas (EGI) o controle das crises é conseguido com fármacos anticrise (FACs). Os efeitos das medicações na conectividade cerebral de pacientes com EGI ainda estão sob investigação. Nossa hipótese é de que a concentração sérica dos FACs pode influenciar na conectividade cerebral. 25 pacientes com EGI e 25 controles foram selecionados. Todos os sujeitos foram submetidos à RM de 3T. Sequências volumétricas em T1 foram usadas para análise anatômica, e sequências BOLD foram adquiridas para a análise da conectividade funcional. A taxa de FAC foi calculada baseada no número de medicações e nos níveis séricos. O processamento das imagens foi feito por meio da ferramenta Conn e mapas de correlação foram calculados. Análise estatística da conectividade baseada em sementes de toda a substância cinzenta e do tálamo foram realizadas usando modelo linear geral (GLM). Uma análise complementar foi conduzida explorando as correlações entre os mapas funcionais e as taxas de FACs. A análise de correlação entre a taxa de FACs e a conectividade dos pacientes mostrou para a análise da substância cinzenta apenas correlação positiva com a conectividade envolvendo o giro frontal superior porção medial. Para o tálamo direito foram observadas áreas de correlação positiva na região parietal esquerda e giro temporal médio esquerdo. A análise do tálamo esquerdo mostrou áreas de correlação positiva no giro angular esquerdo e no polo temporal esquerdo. 55 conexões entre 11 ROIs foram avaliadas sendo 4 da rede de modo padrão e 7 da rede saliência. A análise de correlação mostrou 2 agrupamentos principais intra-rede de correlações positivas entre a conectividade funcional e a taxa dos FACs relacionados a rede de modo padrão (F=66,4 e p < 0,001) e a rede saliência (F = 88,9 e p < 0,001). Um agrupamento de anticorrelação foi observado conectando estas duas redes (F = 18,6 e p < 0,001). Esses achados podem indicar um padrão de resposta às medicações. No futuro, esse padrão pode ser usado para auxiliar a titulação das FACs, e o alcance da dose ótima.
In idiopathic generalized epilepsies (IGE) seizure control is usually achieved with antiepileptic medications (AEDs). Effects of medications in the brain connectivity of patients with IGE is still under investigation. We hypothesized that AEDs concentration may directly influence brain connectivity. 25 patients (10 women, 33±10 years) with IGE and 25 controls were enrolled. All subjects underwent 3T MRI. T1 volumetric sequences were used for anatomical analysis. BOLD fMRI time-series during rest were acquired for functional connectivity. Blood samples were collected, and dosage of medications were performed. AEDs ratios were calculated based on the number of medications and the blood levels. Image processing was conducted using Conn toolbox. Functional time-series were realigned, co-registered with the anatomical images, smoothed and submitted to denoising. Correlations maps were calculated for each subject. Statistical analysis of seed-based connectivity of the whole gray matter and the thalamus was performed using general linear model (GLM). Differences between patients and controls were investigated. A complementary analysis was conducted exploring the correlations between functional maps and AEDs ratio. The correlation analysis between AEDs rate and patient connectivity showed for the gray matter analysis only positive correlation with connectivity involving the superior frontal gyrus medial portion. For the right thalamus, areas of positive correlation were observed in the left parietal region and left middle temporal gyrus. Analysis of the left thalamus showed areas of positive correlation in the left angular gyrus and left temporal pole. 55 connections between 11 ROIs were evaluated, 4 from the default mode network and 7 from the salience network. Correlation analysis showed 2 main intra-network clusters of positive correlations between functional connectivity and AEDs rates related to the default mode network (F=66.4 ep < 0.001) and the salience network (F = 88.9 ep < 0.001). An anticorrelation cluster was observed connecting these two networks (F = 18.6 and p < 0.001). These findings may indicate a pattern of response to medications. In the future, this standard can be used to help titrate FACs and reach the optimal dose.
In idiopathic generalized epilepsies (IGE) seizure control is usually achieved with antiepileptic medications (AEDs). Effects of medications in the brain connectivity of patients with IGE is still under investigation. We hypothesized that AEDs concentration may directly influence brain connectivity. 25 patients (10 women, 33±10 years) with IGE and 25 controls were enrolled. All subjects underwent 3T MRI. T1 volumetric sequences were used for anatomical analysis. BOLD fMRI time-series during rest were acquired for functional connectivity. Blood samples were collected, and dosage of medications were performed. AEDs ratios were calculated based on the number of medications and the blood levels. Image processing was conducted using Conn toolbox. Functional time-series were realigned, co-registered with the anatomical images, smoothed and submitted to denoising. Correlations maps were calculated for each subject. Statistical analysis of seed-based connectivity of the whole gray matter and the thalamus was performed using general linear model (GLM). Differences between patients and controls were investigated. A complementary analysis was conducted exploring the correlations between functional maps and AEDs ratio. The correlation analysis between AEDs rate and patient connectivity showed for the gray matter analysis only positive correlation with connectivity involving the superior frontal gyrus medial portion. For the right thalamus, areas of positive correlation were observed in the left parietal region and left middle temporal gyrus. Analysis of the left thalamus showed areas of positive correlation in the left angular gyrus and left temporal pole. 55 connections between 11 ROIs were evaluated, 4 from the default mode network and 7 from the salience network. Correlation analysis showed 2 main intra-network clusters of positive correlations between functional connectivity and AEDs rates related to the default mode network (F=66.4 ep < 0.001) and the salience network (F = 88.9 ep < 0.001). An anticorrelation cluster was observed connecting these two networks (F = 18.6 and p < 0.001). These findings may indicate a pattern of response to medications. In the future, this standard can be used to help titrate FACs and reach the optimal dose.
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Palavras-chave
Neuroimagem, Epilepsia, Neuroimagem funcional, Epilepsia generalizada idiopática, Eletroencefalografia