Division of Neurosurgery, Department of Surgery, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Department of Neurology, Brain Institute, Nicklaus Children's Hospital, Miami, FL, USA.
Neuroimage Clin. 2017 Sep 22;16:634-642. doi: 10.1016/j.nicl.2017.09.015. eCollection 2017.
Although chronic vagus nerve stimulation (VNS) is an established treatment for medically-intractable childhood epilepsy, there is considerable heterogeneity in seizure response and little data are available to pre-operatively identify patients who may benefit from treatment. Since the therapeutic effect of VNS may be mediated by afferent projections to the thalamus, we tested the hypothesis that intrinsic thalamocortical connectivity is associated with seizure response following chronic VNS in children with epilepsy. Twenty-one children (ages 5-21 years) with medically-intractable epilepsy underwent resting-state fMRI prior to implantation of VNS. Ten received sedation, while 11 did not. Whole brain connectivity to thalamic regions of interest was performed. Multivariate generalized linear models were used to correlate resting-state data with seizure outcomes, while adjusting for age and sedation status. A supervised support vector machine (SVM) algorithm was used to classify response to chronic VNS on the basis of intrinsic connectivity. Of the 21 subjects, 11 (52%) had 50% or greater improvement in seizure control after VNS. Enhanced connectivity of the thalami to the anterior cingulate cortex (ACC) and left insula was associated with greater VNS efficacy. Within our test cohort, SVM correctly classified response to chronic VNS with 86% accuracy. In an external cohort of 8 children, the predictive model correctly classified the seizure response with 88% accuracy. We find that enhanced intrinsic connectivity within thalamocortical circuitry is associated with seizure response following VNS. These results encourage the study of intrinsic connectivity to inform neural network-based, personalized treatment decisions for children with intractable epilepsy.
虽然慢性迷走神经刺激（VNS）是治疗药物难治性儿童癫痫的一种既定方法，但癫痫发作的反应存在相当大的异质性，并且很少有数据可用于术前识别可能受益于治疗的患者。由于 VNS 的治疗效果可能通过向丘脑的传入投射来介导，因此我们检验了假设，即内在丘脑皮质连接与接受 VNS 治疗的癫痫儿童的癫痫发作反应有关。21 名患有药物难治性癫痫的儿童（年龄 5-21 岁）在植入 VNS 之前进行了静息状态 fMRI 检查。其中 10 人接受了镇静治疗，而 11 人没有。对丘脑感兴趣的区域进行了全脑连接性分析。使用多变量广义线性模型，在调整年龄和镇静状态的情况下，将静息状态数据与癫痫发作结果相关联。使用监督支持向量机（SVM）算法根据内在连通性对慢性 VNS 的反应进行分类。在 21 名受试者中，有 11 名（52%）的癫痫发作控制在 VNS 后有 50%或更大的改善。丘脑与前扣带皮层（ACC）和左侧脑岛的连接增强与 VNS 疗效更高有关。在我们的测试队列中，SVM 以 86%的准确率正确分类慢性 VNS 的反应。在 8 名儿童的外部队列中，预测模型以 88%的准确率正确分类了癫痫发作反应。我们发现，VNS 后丘脑皮质回路内在连通性增强与癫痫发作反应有关。这些结果鼓励对内在连通性进行研究，以告知基于神经网络的、针对难治性癫痫儿童的个性化治疗决策。
