Fisher Robert S
Department of Neurology and Neurological Sciences and Neurosurgery by Courtesy, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 213 Quarry Road, Room 4865, Palo Alto, CA 94304, USA.
Neurobiol Dis. 2023 Apr;179:106045. doi: 10.1016/j.nbd.2023.106045. Epub 2023 Feb 20.
Neuromodulation (neurostimulation) is a relatively new and rapidly growing treatment for refractory epilepsy. Three varieties are approved in the US: vagus nerve stimulation (VNS), deep brain stimulation (DBS) and responsive neurostimulation (RNS). This article reviews thalamic DBS for epilepsy. Among many thalamic sub-nuclei, DBS for epilepsy has been targeted to the anterior nucleus (ANT), centromedian nucleus (CM), dorsomedial nucleus (DM) and pulvinar (PULV). Only ANT is FDA-approved, based upon a controlled clinical trial. Bilateral stimulation of ANT reduced seizures by 40.5% at three months in the controlled phase (p = .038) and 75% by 5 years in the uncontrolled phase. Side effects related to paresthesias, acute hemorrhage, infection, occasional increased seizures, and usually transient effects on mood and memory. Efficacy was best documented for focal onset seizures in temporal or frontal lobe. CM stimulation may be useful for generalized or multifocal seizures and PULV for posterior limbic seizures. Mechanisms of DBS for epilepsy are largely unknown, but animal work points to changes in receptors, channels, neurotransmitters, synapses, network connectivity and neurogenesis. Personalization of therapies, in terms of connectivity of the seizure onset zone to the thalamic sub- nucleus and individual characteristics of the seizures, might lead to improved efficacy. Many questions remain about DBS, including the best candidates for different types of neuromodulation, the best targets, the best stimulation parameters, how to minimize side effects and how to deliver current noninvasively. Despite the questions, neuromodulation provides useful new opportunities to treat people with refractory seizures not responding to medicines and not amenable to resective surgery.
神经调节（神经刺激）是一种相对较新且发展迅速的难治性癫痫治疗方法。在美国，有三种类型已获批准：迷走神经刺激（VNS）、深部脑刺激（DBS）和反应性神经刺激（RNS）。本文综述了用于癫痫治疗的丘脑DBS。在众多丘脑亚核中，用于癫痫治疗的DBS靶点包括前核（ANT）、中央中核（CM）、背内侧核（DM）和丘脑枕（PULV）。仅ANT获得了美国食品药品监督管理局（FDA）的批准，这是基于一项对照临床试验。在对照阶段，三个月时双侧刺激ANT可使癫痫发作减少40.5%（p = 0.038），在非对照阶段，五年时减少75%。副作用包括感觉异常、急性出血、感染、偶尔癫痫发作增加，以及通常对情绪和记忆的短暂影响。颞叶或额叶局灶性发作的疗效记录最为充分。CM刺激可能对全身性或多灶性发作有用，而PULV刺激对后边缘叶发作有用。DBS治疗癫痫的机制在很大程度上尚不清楚，但动物研究表明其与受体、通道、神经递质、突触、网络连接性和神经发生的变化有关。根据癫痫发作起始区与丘脑亚核的连接性以及癫痫发作的个体特征进行治疗个体化，可能会提高疗效。关于DBS仍有许多问题，包括不同类型神经调节的最佳候选者、最佳靶点、最佳刺激参数、如何将副作用降至最低以及如何非侵入性地施加电流。尽管存在这些问题，但神经调节为治疗对药物无反应且不适合切除性手术的难治性癫痫患者提供了有用的新机会。
