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使用大麻二酚作为辅助抗癫痫治疗的药物难治性癫痫性脑病中基于脑电图的功能连接性研究

Functional Connectivity Derived From Electroencephalogram in Pharmacoresistant Epileptic Encephalopathy Using Cannabidiol as Adjunctive Antiepileptic Therapy.

作者信息

Morales Chacón Lilia Maria, Galan García Lidice, Berrillo Batista Sheyla, González González Judith, Sánchez Coroneaux Abel

机构信息

Department of Clinical Neurophysiology/Video EEG Unit, International Center for Neurological Restoration, Havana, Cuba.

Department of Neuroinformatics, Cuban Neuroscience Center, La Habana, Cuba.

出版信息

Front Behav Neurosci. 2021 Feb 23;15:604207. doi: 10.3389/fnbeh.2021.604207. eCollection 2021.

Abstract

To explore brain function using functional connectivity and network topology derived from electroencephalogram (EEG) in patients with pharmacoresistant epileptic encephalopathy with cannabidiol as adjunctive antiepileptic treatment. Sixteen epileptic patients participated in the study, six of whom had epileptic encephalopathy with a stable dose of cannabidiol Epidiolex (CBD) as adjunctive therapy. Functional connectivity derived from EEG was analyzed based on the synchronization likelihood (SL). The analysis also included reconstructing graph-theoretic measures from the synchronization matrix. Comparison of functional connectivity data between each pathological group with the control group was carried out using a nonparametric permutation test applied to SL values between pairs of electrodes for each frequency band. To compare the association patterns between graph-theoretical properties of each pathological group with the control group, Crawford was calculated as a measure of distance. There were differences between pairs of electrodes in all frequency bands evaluated in encephalopathy epileptic patients with CBD adjunctive therapy compared with the control ( < 0.05, permutation test). In the epileptic encephalopathy group without CBD therapy, the SL values were higher than in the control group for the beta, theta, and delta EEG frequency bands, and lower for the alpha frequency band. Interestingly, patients who had CBD as adjunctive therapy demonstrated greater synchronization for all frequency bands, showing less spatial distribution for alpha frequency compared with the control. When comparing both epileptic groups, those patients who had adjunctive CBD treatment also showed increased synchronization for all frequency bands. In epileptic encephalopathy with adjunctive CBD therapy, the pattern of differences for graph-theoretical measures according to Crawford indicated less segregation and greater integration suggesting a trend towards the random organization of the network principally for alpha and beta EEG bands. This exploratory study revealed a tendency to an overconnectivity with a random network topology mainly for fast EEG bands in epileptic encephalopathy patients using CBD adjunctive therapy. It can therefore be assumed that the CBD treatment could be related to inhibition of the transition of the interictal to ictal state and/or to the improvement of EEG organization and brain function.

摘要

使用源自脑电图(EEG)的功能连接性和网络拓扑结构,探索以大麻二酚作为辅助抗癫痫治疗的药物难治性癫痫性脑病患者的脑功能。16名癫痫患者参与了该研究,其中6名患有癫痫性脑病,以稳定剂量的大麻二酚 Epidiolex(CBD)作为辅助治疗。基于同步似然性(SL)分析源自EEG的功能连接性。该分析还包括从同步矩阵重建图论指标。使用应用于每个频段电极对之间SL值的非参数置换检验,对每个病理组与对照组之间的功能连接性数据进行比较。为了比较每个病理组与对照组的图论特性之间的关联模式,计算克劳福德距离作为距离度量。与对照组相比,接受CBD辅助治疗的癫痫性脑病患者在所有评估频段的电极对之间均存在差异(置换检验,P<0.05)。在未接受CBD治疗的癫痫性脑病组中,β、θ和δ EEG频段的SL值高于对照组,而α频段的SL值低于对照组。有趣的是,接受CBD辅助治疗的患者在所有频段表现出更大的同步性,与对照组相比,α频段的空间分布更少。当比较两个癫痫组时,接受CBD辅助治疗的患者在所有频段也表现出同步性增加。在接受CBD辅助治疗的癫痫性脑病中,根据克劳福德距离的图论指标差异模式表明,隔离减少且整合增加,这表明主要针对α和β EEG频段的网络有向随机组织发展的趋势。这项探索性研究揭示,在使用CBD辅助治疗的癫痫性脑病患者中,主要针对快速EEG频段存在过度连接和随机网络拓扑结构的趋势。因此,可以假设CBD治疗可能与抑制发作间期向发作期的转变和/或与改善EEG组织及脑功能有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/562b/7940673/77710cf34dc4/fnbeh-15-604207-g0001.jpg

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