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Association of Deep Brain Stimulation Washout Effects With Parkinson Disease Duration

Scott E. Cooper, MD, PhD; Cameron C. McIntyre, PhD; Hubert H. Fernandez, MD; Jerrold L. Vitek, MD, PhD
JAMA Neurol. 2013;70(1):95-99. doi:10.1001/jamaneurol.2013.581.
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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.

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Figures

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Figure 1. Bradykinesia as a function of time in 2 patients. A, Patient with a medial electrode location. B, Patient with a lateral electrode location. Each point measures finger-tapping power (in units of degrees squared per second squared). Lower values indicate more bradykinesia. The half-life measures the rate of washout after deep brain stimulation (DBS) ceased. In the final 1200 seconds, stimulation is turned back on again.

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Figure 2. Washout rate (reciprocal of the half-life) as a function of Parkinson disease duration (time from the onset of symptoms to the time of testing) in 19 patients. One of 20 patients was excluded because the disease duration was missing from the medical record.

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