The time course of the return of upper limb bradykinesia after cessation of subthalamic stimulation in Parkinson's disease

doi:10.1016/j.parkreldis.2006.12.003

Parkinsonism & Related Disorders

Volume 13, Issue 7, October 2007, Pages 438-442

https://doi.org/10.1016/j.parkreldis.2006.12.003 Get rights and content

Abstract

To investigate the time span within which bradykinesia re-occurs, we registered movement parameters immediately after the termination of deep brain stimulation of the subthalamic nucleus (STN) in nine Parkinson patients with chronically implanted bilateral STN electrodes. Two repetitive movements were investigated: finger-tapping and forearm pronation–supination. When stimulation was switched off, the amplitude and velocity of the investigated movements significantly declined, but the frequency did not. The time course of this decline was modeled by an exponential function that yielded time constants between 15 and 30 s. The effect of stimulation had completely disappeared within 1 min. These results suggest that it is necessary to wait at least for 1 min after the end of stimulation before performing further assessments.

Introduction

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for levodopa-responsive motor symptoms in advanced Parkinson's disease (PD) [1]. To position the electrode during surgery, and to optimize stimulation parameters post-operatively, stimulation is frequently switched on and off. After switching the stimulator off, Parkinsonian symptoms usually recur within minutes and gradually worsen over 30 min, whereas clinical improvement after activating the stimulator takes less time [2]. Thus, it would be of considerable clinical relevance to determine the “immediate” effect of the termination of DBS on bradykinesia. Our study had three aims. First, to investigate two simple sequential movements, routinely used in the clinical assessment and also included in the unified PD rating scale (UPDRS) [3]: thumb-index tapping (TIT; item 23) and alternate forearm pronation–supination (PS; item 25). Second, the impact of physical fatigue (during continuous stimulation) on the performance in both tasks was determined. Third, because distal and more proximal muscles were differently engaged in both movements, we also investigated whether STN–DBS has a different effect on distal than on more proximal muscle groups.

Section snippets

Subjects

Nine male patients with advanced-stage PD, a mean age of 61.3 years (range, 49–69), and mean duration of PD of 15.4 years (range, 10–20) took part. The subjects gave their written informed consent to participate in the study in agreement with the Declaration of Helsinki and the study was approved by the local ethics committee. Patients with tremor, which could possibly influence the results of the tests, were not included. All had had bilateral STN-stimulating electrodes chronically implanted

Results

The average UPDRS motor score increased from 28 to 52 (increase of 80%) after the DBS was switched off (Table 1; Wilcoxon test: p<0.008). The analysis of the experimental outcome parameters revealed the following results. The curves of tests with and without stimulation significantly differed on the basis of non-overlapping confidence intervals for AMP and VEL, but not for FRE (Fig. 1). MANOVA revealed a significant change over time of AMP and VEL for all stim-off tests but also for PS stim-on.

Discussion

Our findings demonstrate that the performance of repetitive upper limb movements deteriorates by 60–80% within a minute after switching the stimulator off. This decline can be modeled by an exponential decay function with time constants in the range of 15–30 s. Physical fatigue during stim-on trials resulted in a decay of about 30% and was significantly less than in the tests after the termination of stimulation.

Of the parameters used for evaluation, we found that amplitude and velocity of

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Cited by (12)

Frequency-dependent, transient effects of subthalamic nucleus deep brain stimulation on methamphetamine-induced circling and neuronal activity in the hemiparkinsonian rat
2017, Behavioural Brain Research
Citation Excerpt :
Therefore, we quantified this transient behavioral effect of DBS as a function of stimulation frequency, and analyzed single unit neuronal activity from the basal ganglia to determine the neuronal basis for transient contralateral circling. Such time-dependent changes in behavior and neural activity may shed light on the differential time-dependent effects of STN DBS on symptoms in persons with PD [27,10,8,2]. We conducted stereotactic surgery in Long Evans rats (250 g–300 g, n = 11) under 2% isoflurane anesthesia using coordinates from the rat brain atlas [30].
Methamphetamine-induced circling is used to quantify the behavioral effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in hemiparkinsonian rats. We observed a frequency-dependent transient effect of DBS on circling, and quantified this effect to determine its neuronal basis. High frequency STN DBS (75–260 Hz) resulted in transient circling contralateral to the lesion at the onset of stimulation, which was not sustained after the first several seconds of stimulation. Following the transient behavioral change, DBS resulted in a frequency-dependent steady-state reduction in pathological ipsilateral circling, but no change in overall movement. Recordings from single neurons in globus pallidus externa (GPe) and substantia nigra pars reticulata (SNr) revealed that high frequency, but not low frequency, STN DBS elicited transient changes in both firing rate and neuronal oscillatory power at the stimulation frequency in a subpopulation of GPe and SNr neurons. These transient changes were not sustained, and most neurons exhibited a different response during the steady-state phase of DBS. During the steady-state, DBS produced elevated neuronal oscillatory power at the stimulus frequency in a majority of GPe and SNr neurons, and the increase was more pronounced during high frequency DBS than during low frequency DBS. Changes in oscillatory power during both transient and steady-state DBS were highly correlated with changes in firing rates. These results suggest that distinct neural mechanisms were responsible for transient and sustained behavioral responses to STN DBS. The transient contralateral turning behavior following the onset of high frequency DBS was paralleled by transient changes in firing rate and oscillatory power in the GPe and SNr, while steady-state suppression of ipsilateral turning was paralleled by sustained increased synchronization of basal ganglia neurons to the stimulus pulses. Our analysis of distinct frequency-dependent transient and steady-state responses to DBS lays the foundation for future mechanistic studies of the immediate and persistent effects of DBS.
Return of bradykinesia after subthalamic stimulation ceases: Relationship to electrode location
2011, Experimental Neurology
Citation Excerpt :
That is, DBS effects “lingered” for a while after stimulation ceased. Lopiano et al. (2003) and Waldau et al. (2011) obtained similar results but Keresztenyi et al. (2007) measured time constants between 15 and 30 s (half lives about 10–20 s). We propose that their subject populations, like ours, exhibited both fast and slow processes, but that differences in experimental design led to their differing results: Keresztenyi et al. (2007) (measurement over 5 min after DBS turned off) could not exclude an additional slower decay over tens of minutes.
In 20 subjects we quantified the rate at which subthalamic nucleus deep brain stimulation effects on Parkinson's bradykinesia “washed-out” after stimulation ceased. We found that wash-out was a two-step process, consisting of an initial fast decrease in stimulation's therapeutic effect, followed by a further, slow decline. Moreover, the relative contribution of the fast and slow components differed between patients. Finally, we found that lateral stimulation caused more of the fast-decaying component, while medial stimulation caused more of the slow-decaying component. This implies the existence of at least two separate mechanisms by which subthalamic nucleus deep brain stimulation improves bradykinesia, associated with activation of spatially separate zones in the vicinity of the subthalamic nucleus.
Opening velocity, a novel parameter, for finger tapping test in patients with Parkinson's disease
2009, Parkinsonism and Related Disorders
Citation Excerpt :
Accuracy and reproducibility in the quantitative analysis of FT performance are indispensable for evaluating the severity of PD. The FT test has been analyzed by various methods including the use of a computer keyboard [6–8], a metal plate [9–11], a telegraph key [12] or a tri-axial accelerometer [13] for frequency and/or rhythm of FT, a musical instrument digital interface [14,15] for frequency and velocity of FT, and a goniometer [16], a three-dimensional (3D) motion and position measurement system [17–20] or image-based motion analyzer [21] for amplitude and/or velocity of FT. However, these systems were not employed at the bedside or clinically. For daily clinical use, a measuring system should be low in cost, small in size, provide a large amount of information, and easy to use.
A new system consisting of an accelerometer and touch sensor was developed to find objective parameters for the finger tapping (FT) test in patients with Parkinson's disease (PD).
We recruited sixteen patients with PD and thirty-two age-matched healthy volunteers (HVs). By using this new system, various parameters related to velocity, amplitude, rhythm and number in the FT test were measured in patients with PD and examined in comparison with those of HVs on the basis of the Unified Parkinson's Disease Rating Scale (UPDRS) FT score.
The new system allowed us to measure fourteen parameters of FT movement very easily, and a radar chart showed obvious differences in most of these parameters between HVs and patients with PD. Principal component analysis showed that fourteen parameters were classified into three components: (1) both mean and standard deviation (SD) of both amplitude and velocity, (2) number of FT for 60 s and mean FT interval, and (3) SD of FT interval. The first (velocity- and amplitude-related parameters) and third (rhythm-related parameters) components contributed to discrimination of PD from HVs. Maximum opening velocity (MoV) was the best of these parameters because of its sensitivity and association with the UPDRS FT score.
A novel system for the FT test, which is compact, simple and efficient, has been developed. Velocity- and amplitude-related parameters were indicated to be valuable for evaluation of the FT test in patients with PD. In particular, we first propose that MoV is a novel marker for the FT test.
Acute effects of adaptive Deep Brain Stimulation in Parkinson's disease
2020, Brain Stimulation
Beta-based adaptive Deep Brain Stimulation (aDBS) is effective in Parkinson’s disease (PD), when assessed in the immediate post-implantation phase. However, the potential benefits of aDBS in patients with electrodes chronically implanted, in whom changes due to the microlesion effect have disappeared, are yet to be assessed.
To determine the acute effectiveness and side-effect profile of aDBS in PD compared to conventional continuous DBS (cDBS) and no stimulation (NoStim), years after DBS implantation, 13 PD patients undergoing battery replacement were pseudo-randomised in a crossover fashion, into three conditions (NoStim, aDBS or cDBS), with a 2-min interval between them. Patient videos were blindly evaluated using a short version of the Unified Parkinson’s Disease Rating Scale (subUPDRS), and the Speech Intelligibility Test (SIT).
Mean disease duration was 16 years, and the mean time since DBS-implantation was 6.9 years. subUPDRS scores (11 patients tested) were significantly lower both in aDBS (p=<.001), and cDBS (p = .001), when compared to NoStim. Bradykinesia subscores were significantly lower in aDBS (p = .002), and did not achieve significance during cDBS (p = .08), when compared to NoStim. Two patients demonstrated re-emerging tremor during aDBS. SIT scores of patients who presented stimulation-induced dysarthria significantly worsened in cDBS (p = .009), but not in aDBS (p = .407), when compared to NoStim. Overall, stimulation was applied 48.8% of the time during aDBS.
Beta-based aDBS is effective in PD patients with bradykinetic phenotypes, delivers less stimulation than cDBS, and potentially has a more favourable speech side-effect profile. Patients with prominent tremor may require a modified adaptive strategy.
Effect of low versus high frequency subthalamic deep brain stimulation on speech intelligibility and verbal fluency in Parkinson's disease: A double-blind study
2019, Journal of Parkinson's Disease
Bilateral adaptive deep brain stimulation is effective in Parkinson's disease
2016, Journal of Neurology, Neurosurgery and Psychiatry

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¹: Both authors contributed equally to this paper.

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Short communicationThe time course of the return of upper limb bradykinesia after cessation of subthalamic stimulation in Parkinson's disease

Abstract

Introduction

Section snippets

Subjects

Results

Discussion

J Electromyogr Kinesiol

Parkinsonism Relat Disord

Neurosci Lett

Neuropsychologia

A randomized trial of deep-brain stimulation for Parkinson's disease

N Engl J Med

Temporal changes in movement time during the switch of the stimulators in Parkinson's disease patients treated by subthalamic nucleus stimulation

Eur Neurol

Short communication
The time course of the return of upper limb bradykinesia after cessation of subthalamic stimulation in Parkinson's disease