Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease
Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease
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DOI：
10.1093/brain/awp229
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发表时间：
2010-01-01
期刊：
影响因子：
14.5
通讯作者：
Pollak, P.
中科院分区：
文献类型：
--
作者：
Ferraye, M. U.;Debu, B.;Pollak, P.
步态障碍在晚期帕金森病中是常见的和致残的。这些症状对通常的药物和手术治疗反应不佳，但据报道，通过刺激脚桥核可以改善。我们研究了刺激脚桥核区的影响，在6例严重冻结的步态，无反应的左旋多巴和丘脑底核刺激。将电极植入双侧脚桥核区域。通过术后磁共振成像检查电极放置。主要结果测量是在基线和一年随访时的步行方案期间的复合步态评分、步态冻结问卷评分和冻结发作的持续时间。双盲交叉研究在术后4至6个月进行，有或没有脚桥核区刺激。在一年的随访中，停药状态下的冻结事件持续时间以及与冻结相关的福尔斯。其他主要结局指标没有显著变化，双盲评价期间的结果也没有显著变化。个体结果显示，1例患者的所有步态指标均显著改善，4例患者的某些测试中度改善，1例患者整体恶化。刺激频率范围在15和25 Hz之间。视振荡和肢体肌阵挛可阻碍电压升高。未发生严重不良事件。虽然在某些帕金森病患者中，通过对脚桥核区域进行低频电刺激可以改善步态冻结，但与先前开放标签研究提出的高水平期望相比，我们的总体结果令人失望。需要进一步的对照研究来确定患者选择、靶向和刺激参数设置的优化是否可以将结果改善到可以将这种实验方法转化为具有合理风险-受益比的治疗的程度。
Gait disturbances are frequent and disabling in advanced Parkinson's disease. These symptoms respond poorly to usual medical and surgical treatments but were reported to be improved by stimulation of the pedunculopontine nucleus. We studied the effects of stimulating the pedunculopontine nucleus area in six patients with severe freezing of gait, unresponsive to levodopa and subthalamic nucleus stimulation. Electrodes were implanted bilaterally in the pedunculopontine nucleus area. Electrode placement was checked by postoperative magnetic resonance imaging. The primary outcome measures were a composite gait score, freezing of gait questionnaire score and duration of freezing episodes occurring during a walking protocol at baseline and one-year follow-up. A double-blind cross-over study was carried out from months 4 to 6 after surgery with or without pedunculopontine nucleus area stimulation. At one-year follow-up, the duration of freezing episodes under off-drug condition improved, as well as falls related to freezing. The other primary outcome measures did not significantly change, nor did the results during the double-blind evaluation. Individual results showed major improvement of all gait measures in one patient, moderate improvement of some tests in four patients and global worsening in one patient. Stimulation frequency ranged between 15 and 25 Hz. Oscillopsia and limb myoclonus could hinder voltage increase. No serious adverse events occurred. Although freezing of gait can be improved by low-frequency electrical stimulation of the pedunculopontine nucleus area in some patients with Parkinson's disease our overall results are disappointing compared to the high levels of expectation raised by previous open label studies. Further controlled studies are needed to determine whether optimization of patient selection, targeting and setting of stimulation parameters might improve the outcome to a point that could transform this experimental approach to a treatment with a reasonable risk-benefit ratio.