Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Brain. 2012 May;135(Pt 5):1446-54. doi: 10.1093/brain/aws039. Epub 2012 Mar 6.
Gait freezing is an episodic arrest of locomotion due to an inability to take normal steps. Pedunculopontine nucleus stimulation is an emerging therapy proposed to improve gait freezing, even where refractory to medication. However, the efficacy and precise effects of pedunculopontine nucleus stimulation on Parkinsonian gait disturbance are not established. The clinical application of this new therapy is controversial and it is unknown if bilateral stimulation is more effective than unilateral. Here, in a double-blinded study using objective spatiotemporal gait analysis, we assessed the impact of unilateral and bilateral pedunculopontine nucleus stimulation on triggered episodes of gait freezing and on background deficits of unconstrained gait in Parkinson's disease. Under experimental conditions, while OFF medication, Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions; off stimulation, unilateral stimulation and bilateral stimulation. Results were compared to Parkinsonian patients without gait freezing matched for disease severity and healthy controls. Pedunculopontine nucleus stimulation improved objective measures of gait freezing, with bilateral stimulation more effective than unilateral. During unconstrained walking, Parkinsonian patients who experience gait freezing had reduced step length and increased step length variability compared to patients without gait freezing; however, these deficits were unchanged by pedunculopontine nucleus stimulation. Chronic pedunculopontine nucleus stimulation improved Freezing of Gait Questionnaire scores, reflecting a reduction of the freezing encountered in patients' usual environments and medication states. This study provides objective, double-blinded evidence that in a specific subgroup of Parkinsonian patients, stimulation of a caudal pedunculopontine nucleus region selectively improves gait freezing but not background deficits in step length. Bilateral stimulation was more effective than unilateral.
步态冻结是一种由于无法正常行走而导致的间歇性运动停止。苍白球下核刺激是一种新兴的治疗方法，被提议用于改善步态冻结，即使对药物治疗有抵抗。然而，苍白球下核刺激对帕金森病步态障碍的疗效和确切作用尚未确定。这种新疗法的临床应用存在争议，也不知道双侧刺激是否比单侧刺激更有效。在这里，我们通过使用客观时空步态分析的双盲研究，评估了单侧和双侧苍白球下核刺激对帕金森病患者触发步态冻结发作和不受约束步态背景缺陷的影响。在实验条件下，当患者停止服用药物时，在桥脑被盖核下植入苍白球下核刺激器的严重步态冻结的帕金森病患者在三种情况下进行评估：关闭刺激、单侧刺激和双侧刺激。结果与疾病严重程度相匹配的无步态冻结的帕金森病患者和健康对照进行了比较。苍白球下核刺激改善了步态冻结的客观测量，双侧刺激比单侧刺激更有效。在不受约束的行走过程中，与无步态冻结的患者相比，经历步态冻结的帕金森病患者的步长缩短，步长变异性增加；然而，苍白球下核刺激并没有改变这些缺陷。慢性苍白球下核刺激改善了冻结步态问卷评分，反映了患者在日常环境和药物状态下遇到的冻结减少。这项研究提供了客观的、双盲的证据，表明在特定的帕金森病患者亚组中，刺激脑桥被盖核下部区域选择性地改善步态冻结，但不改善步长的背景缺陷。双侧刺激比单侧刺激更有效。
