Department of Clinical & Movement Neurosciences, UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
Department of Clinical & Movement Neurosciences, UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
Brain Stimul. 2020 Jul-Aug;13(4):1031-1039. doi: 10.1016/j.brs.2020.04.010. Epub 2020 Apr 22.
Dementia with Lewy bodies (DLB) is the second most common form of dementia. Current symptomatic treatment with medications remains inadequate. Deep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a potential new treatment option in dementias.
To assess the safety and tolerability of low frequency (20 Hz) NBM DBS in DLB patients and explore its potential effects on both clinical symptoms and functional connectivity in underlying cognitive networks.
We conducted an exploratory randomised, double-blind, crossover trial of NBM DBS in six DLB patients recruited from two UK neuroscience centres. Patients were aged between 50 and 80 years, had mild-moderate dementia symptoms and were living with a carer-informant. Patients underwent image guided stereotactic implantation of bilateral DBS electrodes with the deepest contacts positioned in the Ch4i subsector of NBM. Patients were subsequently assigned to receive either active or sham stimulation for six weeks, followed by a two week washout period, then the opposite condition for six weeks. Safety and tolerability of both the surgery and stimulation were systematically evaluated throughout. Exploratory outcomes included the difference in scores on standardised measurements of cognitive, psychiatric and motor symptoms between the active and sham stimulation conditions, as well as differences in functional connectivity in discrete cognitive networks on resting state fMRI.
Surgery and stimulation were well tolerated by all six patients (five male, mean age 71.33 years). One serious adverse event occurred: one patient developed antibiotic-associated colitis, prolonging his hospital stay by two weeks. No consistent improvements were observed in exploratory clinical outcome measures, but the severity of neuropsychiatric symptoms reduced with NBM DBS in 3/5 patients. Active stimulation was associated with functional connectivity changes in both the default mode network and the frontoparietal network.
Low frequency NBM DBS can be safely conducted in DLB patients. This should encourage further exploration of the possible effects of stimulation on neuropsychiatric symptoms and corresponding changes in functional connectivity in cognitive networks.
NCT02263937.
路易体痴呆（DLB）是第二大常见痴呆类型。目前针对症状的药物治疗仍然不够充分。基底核内苍白球（NBM）深部脑刺激（DBS）已被提议作为痴呆症的一种新的潜在治疗选择。
评估低频（20Hz）NBM DBS 在 DLB 患者中的安全性和耐受性，并探索其对潜在认知网络中临床症状和功能连接的潜在影响。
我们在英国的两个神经科学中心招募了 6 名 DLB 患者进行了一项探索性、随机、双盲、交叉的 NBM DBS 试验。患者年龄在 50 至 80 岁之间，有轻度至中度痴呆症状，且有照料者提供信息。患者接受了双侧 DBS 电极的图像引导立体定向植入术，最深的接触点位于 NBM 的 Ch4i 扇区。随后，患者被分配接受六周的主动或假刺激，然后是两周的洗脱期，然后是六周的相反条件。在整个过程中系统地评估了手术和刺激的安全性和耐受性。探索性结果包括在主动和假刺激条件下，标准化认知、精神病和运动症状测量评分的差异，以及静息状态 fMRI 中离散认知网络的功能连接的差异。
所有 6 名患者（5 名男性，平均年龄 71.33 岁）均能很好地耐受手术和刺激。发生了一起严重不良事件：一名患者出现抗生素相关性结肠炎，住院时间延长了两周。在探索性临床结局测量中没有观察到一致的改善，但在 5 名患者中的 3 名中，NBM DBS 降低了神经精神症状的严重程度。主动刺激与默认模式网络和额顶叶网络的功能连接变化有关。
低频 NBM DBS 可安全地应用于 DLB 患者。这应鼓励进一步探索刺激对神经精神症状和认知网络中功能连接的可能影响。
NCT02263937。
