Bilateral Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson Disease Dementia A Randomized Clinical Trial
Bilateral Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson Disease Dementia A Randomized Clinical Trial
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DOI：
10.1001/jamaneurol.2017.3762
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发表时间：
2018-02-01
期刊：
影响因子：
29
通讯作者：
Foltynie, Thomas
中科院分区：
文献类型：
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作者：
Gratwicke, James;Zrinzo, Ludvic;Foltynie, Thomas
重要性 Meynert 基底核深部脑刺激 (NBM DBS) 已被提议作为帕金森病痴呆的一种治疗选择。 目的 评估 NBM DBS 对帕金森病痴呆患者的安全性和潜在症状影响。 设计、设置和参与者 一项随机、双盲、交叉临床试验评估了 6 名接受 NBM DBS 治疗的帕金森病痴呆患者的结果2012 年 10 月 26 日至 2015 年 7 月 31 日在英国神经外科转诊中心进行。符合条件的患者符合帕金森病痴呆症的诊断标准，有运动波动，除了同时患有痴呆症外，是合适的手术候选者，年龄在 35 至 80 岁之间，能够给予知情同意，简易精神状态检查得分为 21 至 26，有轻微萎缩。干预措施 手术后，患者被分配接受主动刺激（双侧低频 [20 Hz] NBM DBS）或假刺激 6 周，然后接受相反条件 6 周。 主要结果和测量 主要结果是简略认知电池（加州语言学习测试-II，韦克斯勒成人智力量表-III 数字跨度、语言流畅性、波斯纳隐性注意力测试以及简单反应和选择反应时间）在两种条件之间。次要结局是探索性的，包括认知、精神和运动症状标准化测量以及静息态功能磁共振成像的评分差异。 结果 所有 6 名患者（均为男性；平均 [SD] 年龄，65.2 [10.7] 岁）对手术和刺激的耐受性良好，试验期间没有出现严重不良事件。在主要认知结果或静息态功能磁共振成像结果中没有观察到一致的改善。与假刺激（12 分[范围，8-38 分]；中位差，5 分；95% CI，2.5-8.5 分；P = 0.03）和术前基线（13 分[范围，5-25 分]；中位差，2 分；P = 0.03）相比，NBM DBS 的神经精神量表评分有所改善（8.5 分[范围，4-26 分]）。 95% CI，-8 至 5.5 分；P = .69）。结论和相关性 低频 NBM DBS 在帕金森病痴呆患者中安全进行；然而，主要认知结果没有观察到改善。可能需要进一步的研究来探索其改善麻烦的神经精神症状的潜力。
IMPORTANCE Deep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a treatment option for Parkinson disease dementia.OBJECTIVE 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.INTERVENTIONS 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.MAIN OUTCOMES AND MEASURES 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.RESULTS 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).CONCLUSIONS AND RELEVANCE 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.