Carron Romain, Roncon Paolo, Lagarde Stanislas, Dibué Maxine, Zanello Marc, Bartolomei Fabrice
Department of Functional and Stereotactic Neurosurgery, Timone University Hospital, Aix-Marseille University, Marseille, France; APHM, INSERM, INS, Inst Neurosci Syst, Aix-Marseille University, Marseille, France.
Medical Affairs Neuromodulation International, LivaNova PLC, London, UK.
Neuromodulation. 2023 Apr;26(3):498-506. doi: 10.1016/j.neurom.2022.08.447. Epub 2022 Sep 2.
Vagus nerve stimulation (VNS) is approved as an adjunctive treatment for drug-resistant epilepsy. Although there is a substantial amount of literature aiming at unraveling the mechanisms of action of VNS in epilepsy, it is still unclear how the cascade of events triggered by VNS leads to its antiepileptic effect.
In this review, we integrated available peer-reviewed data on the effects of VNS in clinical and experimental research to identify those that are putatively responsible for its therapeutic effect. The topic of transcutaneous VNS will not be covered owing to the current lack of data supporting the differences and commonalities of its mechanisms of action in relation to invasive VNS.
There is compelling evidence that the effect is obtained through the stimulation of large-diameter afferent myelinated fibers that project to the solitary tract nucleus, then to the parabrachial nucleus, which in turn alters the activity of the limbic system, thalamus, and cortex. VNS-induced catecholamine release from the locus coeruleus in the brainstem plays a pivotal role. Functional imaging studies tend to point toward a common vagal network that comes into play, made up of the amygdalo-hippocampal regions, left thalamus, and insular cortex.
Even though some crucial pieces are missing, neurochemical, molecular, cellular, and electrophysiological changes occur within the vagal afferent network at three main levels (the brainstem, the limbic system [amygdala and hippocampus], and the cortex). At this final level, VNS notably alters functional connectivity, which is known to be abnormally high within the epileptic zone and was shown to be significantly decreased by VNS in responders. The effect of crucial VNS parameters such as frequency or current amplitude on functional connectivity metrics is of utmost importance and requires further investigation.
迷走神经刺激术（VNS）被批准作为耐药性癫痫的辅助治疗方法。尽管有大量文献旨在阐明VNS在癫痫中的作用机制，但VNS引发的一系列事件如何导致其抗癫痫作用仍不清楚。
在本综述中，我们整合了临床和实验研究中关于VNS作用的同行评审可用数据，以确定那些可能对其治疗效果负责的因素。由于目前缺乏支持经皮VNS与侵入性VNS作用机制异同的数据，因此不涉及经皮VNS的主题。
有令人信服的证据表明，这种作用是通过刺激投射到孤束核、然后到臂旁核的大直径有髓传入纤维获得的，臂旁核进而改变边缘系统、丘脑和皮质的活动。VNS诱导的脑干蓝斑去甲肾上腺素释放起关键作用。功能成像研究倾向于指向一个共同发挥作用的迷走神经网络，该网络由杏仁核 - 海马区域、左丘脑和岛叶皮质组成。
尽管仍缺少一些关键环节，但在迷走神经传入网络的三个主要层面（脑干、边缘系统[杏仁核和海马体]以及皮质）发生了神经化学、分子、细胞和电生理变化。在最后这个层面，VNS显著改变功能连接性，已知癫痫区域内的功能连接性异常高，而在有反应者中VNS使其显著降低。关键的VNS参数如频率或电流幅度对功能连接性指标的影响至关重要，需要进一步研究。
