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深部脑刺激洗脱效应与帕金森病病程的关系。

Association of deep brain stimulation washout effects with Parkinson disease duration.

机构信息

Center for Neurological Restoration, Department of Neurology, Cleveland Clinic, Cleveland, Ohio 44195, USA.

出版信息

JAMA Neurol. 2013 Jan;70(1):95-9. doi: 10.1001/jamaneurol.2013.581.

Abstract

BACKGROUND

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves symptoms of Parkinson disease (PD), including bradykinesia. When stimulation ceases abruptly, bradykinesia returns gradually. The duration of the gradual, slow washout varies across patients, and although the origin of this variability is unclear, it is hypothesized to be related to 1 or more clinical characteristics of patients.

OBJECTIVE

To determine if a correlation exists between clinical characteristics of patients with Parkinson disease (age, age at disease onset, disease severity, disease duration, medication dose, or time since surgery) and the washout rate for bradykinesia when STN DBS is discontinued.

DESIGN

Serial quantitative assessments of bradykinesia were performed during a defined period following cessation of STN DBS.

SETTING

Academic research.

PATIENTS

Twenty-four patients with Parkinson disease who underwent STN DBS were enrolled in the study. Patients were assessed while off medication (medication had been discontinued 10½ to 16½ hours before testing), and stimulator settings were unchanged for a mean (median) of 20 (14) months.

MAIN OUTCOME MEASURES

We measured bradykinesia in the dominant hand by assessing finger tapping (item 23 on the Unified Parkinson Disease Rating Scale), which was quantified using an angular velocity transducer strapped on the index finger. Finger tapping was assessed every 2 minutes for 20 seconds at a time. This was performed during a 20-minute period with DBS on (baseline period), during a 50-minute period following discontinuation of STN DBS for the dominant hand, and again during a 20-minute period after turning on the device.

RESULTS

When STN DBS was turned off, an initial fast but partial loss of benefit was observed, which was followed by a further slow washout of the residual therapeutic effect. The half-life of the slow washout phase varied significantly across patients, and this variation was strongly related to disease duration: patients with shorter disease duration experienced slower washout, while patients with longer disease duration experienced faster washout.

CONCLUSIONS

Washout of STN DBS effects varies with Parkinson disease duration. Estimates of proper washout time based on one patient population may not apply to populations with different disease durations. In DBS clinical trials, washout intervals should be chosen conservatively or adjusted for individual variation in the rate at which washout occurs.

摘要

背景

丘脑底核(STN)的深部脑刺激(DBS)可改善帕金森病(PD)的症状,包括运动迟缓。当刺激突然停止时,运动迟缓会逐渐恢复。这种逐渐缓慢消退的持续时间因患者而异,尽管这种变异性的起源尚不清楚,但据推测与患者的 1 种或多种临床特征有关。

目的

确定帕金森病患者的临床特征(年龄、发病年龄、疾病严重程度、疾病持续时间、药物剂量或手术时间)与 STN-DBS 停止后运动迟缓消退率之间是否存在相关性。

设计

在停止 STN-DBS 后的特定时间段内,对运动迟缓进行一系列定量评估。

地点

学术研究。

患者

24 名接受 STN-DBS 的帕金森病患者参加了这项研究。在停药期间对患者进行评估(停药前 10 个半小时至 16 个半小时),刺激器设置在平均(中位数)20(14)个月内保持不变。

主要观察指标

我们通过评估食指上的角速度传感器测量优势手的运动迟缓(统一帕金森病评定量表第 23 项)来量化运动迟缓,这一指标通过评估食指的每分钟敲击次数来实现。每次评估持续 20 秒,间隔 2 分钟。在 STN-DBS 开启的 20 分钟内(基线期)、停止对优势手进行 STN-DBS 的 50 分钟内(停止刺激期)和再次开启设备后的 20 分钟内(恢复期)进行评估。

结果

当 STN-DBS 关闭时,观察到初始快速但部分丧失疗效,随后残留治疗效果进一步缓慢消退。缓慢消退阶段的半衰期在患者之间差异显著,这种变化与疾病持续时间密切相关:疾病持续时间较短的患者,消退速度较慢,而疾病持续时间较长的患者,消退速度较快。

结论

STN-DBS 效果的消退随帕金森病的持续时间而变化。基于一个患者群体的适当消退时间估计可能不适用于具有不同疾病持续时间的患者群体。在 DBS 临床试验中,应谨慎选择洗脱间隔时间或根据洗脱发生速度的个体差异进行调整。

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