Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, London, England.
Unit of Functional Neurosurgery, The National Hospital for Neurology and Neurosurgery, London, England.
JAMA Neurol. 2018 Feb 1;75(2):169-178. doi: 10.1001/jamaneurol.2017.3762.
Deep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a treatment option for Parkinson disease dementia.
To evaluate the safety and potential symptomatic effects of NBM DBS in patients with Parkinson disease dementia.
DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, crossover clinical trial evaluated the results of 6 patients with Parkinson disease dementia who were treated with NBM DBS at a neurosurgical referral center in the United Kingdom from October 26, 2012, to July 31, 2015. Eligible patients met the diagnostic criteria for Parkinson disease dementia, had motor fluctuations, were appropriate surgical candidates aside from the coexistence of dementia, were age 35 to 80 years, were able to give informed consent, had a Mini-Mental State Examination score of 21 to 26, had minimal atrophy seen on results of brain magnetic resonance imaging, and lived at home with a caregiver-informant.
After surgery, patients were assigned to receive either active stimulation (bilateral, low-frequency [20 Hz] NBM DBS) or sham stimulation for 6 weeks, followed by the opposite condition for 6 weeks.
The primary outcome was the difference in scores on each item of an abbreviated cognitive battery (California Verbal Learning Test-II, Wechsler Adult Intelligence Scale-III digit span, verbal fluency, Posner covert attention test, and simple and choice reaction times) between the 2 conditions. Secondary outcomes were exploratory and included differences in scores on standardized measurements of cognitive, psychiatric, and motor symptoms and resting state functional magnetic resonance imaging.
Surgery and stimulation were well tolerated by all 6 patients (all men; mean [SD] age, 65.2 [10.7] years), with no serious adverse events during the trial. No consistent improvements were observed in the primary cognitive outcomes or in results of resting state functional magnetic resonance imaging. An improvement in scores on the Neuropsychiatric Inventory was observed with NBM DBS (8.5 points [range, 4-26 points]) compared with sham stimulation (12 points [range, 8-38 points]; median difference, 5 points; 95% CI, 2.5-8.5 points; P = .03) and the preoperative baseline (13 points [range, 5-25 points]; median difference, 2 points; 95% CI, -8 to 5.5 points; P = .69).
Low-frequency NBM DBS was safely conducted in patients with Parkinson disease dementia; however, no improvements were observed in the primary cognitive outcomes. Further studies may be warranted to explore its potential to improve troublesome neuropsychiatric symptoms.
clinicaltrials.gov Identifier: NCT01701544.
基底核内 Meynert 核（NBM）的深部脑刺激已被提议作为帕金森病痴呆的治疗选择。
评估 NBM DBS 对帕金森病痴呆患者的安全性和潜在的症状影响。
设计、地点和参与者：一项随机、双盲、交叉临床试验评估了 2012 年 10 月 26 日至 2015 年 7 月 31 日在英国神经外科转诊中心接受 NBM DBS 治疗的 6 例帕金森病痴呆患者的结果。符合帕金森病痴呆诊断标准、有运动波动、除痴呆共存外适合手术、年龄 35 至 80 岁、能够知情同意、迷你精神状态检查评分 21 至 26、脑磁共振成像结果显示最小萎缩且在家中与护理员-告知者同住的患者有资格入组。
手术后，患者被分配接受为期 6 周的主动刺激（双侧、低频[20 Hz]NBM DBS）或假刺激，然后进行相反的条件 6 周。
主要结局是两种情况下简短认知测试（加州语言学习测试-II、韦氏成人智力量表-III 数字跨度、言语流畅性、波斯纳隐匿注意力测试和简单和选择反应时间）每个项目得分的差异。次要结局是探索性的，包括认知、精神和运动症状的标准化测量以及静息状态功能磁共振成像的差异。
所有 6 名患者（均为男性；平均[标准差]年龄，65.2[10.7]岁）均能很好地耐受手术和刺激，试验期间无严重不良事件。主要认知结局或静息状态功能磁共振成像结果未观察到一致的改善。与假刺激（12 分[范围，8-38 分]）相比，NBM DBS 可改善神经精神病学评定量表（Neuropsychiatric Inventory）评分（8.5 分[范围，4-26 分]）（中位数差异，5 分；95%CI，2.5-8.5 分；P=0.03）和术前基线（13 分[范围，5-25 分]）（中位数差异，2 分；95%CI，-8 至 5.5 分；P=0.69）。
低频 NBM DBS 在帕金森病痴呆患者中安全进行；然而，主要认知结局未观察到改善。可能需要进一步研究以探索其改善恼人神经精神症状的潜力。
clinicaltrials.gov 标识符：NCT01701544。
