How do parkinsonian signs return after discontinuation of subthalamic DBS?

Temperli, Philippe; Ghika, Joseph; Villemure, Jean‐Guy; Burkhard, Pierre; Bogousslavsky, J; Vingerhoets, François

doi:10.1212/wnl.60.1.78

Cited by 364 publications

(254 citation statements)

References 21 publications

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“…Response to DBS may change with chronic stimulation as has been noted in the case of Parkinson disease subthalamic nucleus DBS (Temperli et al 2003). Also, because this was our first investigation of intention tremor and was being conducted for research purposes outside of subjects' routine clinical visits, we had to restore all subjects to their original setting of 185 Hz at the completion of the study.…”

Section: Discussionmentioning

confidence: 99%

Effects of thalamic stimulation frequency on intention and postural tremor

Earhart

Hong

Tabbal

et al. 2007

Experimental Neurology

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Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus improves essential tremor. Suppression of the amplitude of the postural tremor component with VIM DBS depends on stimulation frequency. The purpose of this study is to determine the effect of DBS frequency on the intention tremor component, i.e. tremor that is enhanced by target-directed movement, and to compare it to the effect of DBS frequency on postural tremor in people with essential tremor. We measured tremor frequency and amplitude during trials of postural holding and voluntary reaching between two targets at 10 different stimulation frequency settings between 0 and 185 Hz. Tremor frequency did not change with changes in stimulation frequency. Amplitude suppression of both intention and postural tremor depended on stimulation frequency. Maximal tremor reduction occurred at approximately 130 Hz for both forms of tremor. However, at optimal frequencies the percent reduction in tremor amplitude relative to the DBS OFF condition was greater for postural than for intention tremor. These results suggest that VIM DBS stimulation frequencies near 130Hz may provide maximal control of intention and postural tremor. Identification of optimal stimulation settings should consider assessment of intention tremor not just postural tremor, as intention tremor may not be as well controlled as postural tremor but may be a better gauge for functional benefit.

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Section: Discussionmentioning

confidence: 99%

Effects of thalamic stimulation frequency on intention and postural tremor

Earhart

Hong

Tabbal

et al. 2007

Experimental Neurology

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“…It is also noteworthy that delayed temporal responses are the norm for both pallidotomy and DBS for dystonia, strongly suggesting that the mechanism of action may, in both cases, involves long-term plastic remodeling of cortical and brainstem mechanisms. The return of symptoms once DBS is turned off generally mirrors the time course of the onset times [267,268].…”

Section: Time Course Of Responsesmentioning

confidence: 92%

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

2016

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Deep brain stimulation (DBS) is highly effective for both hypo-and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal gangliathalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

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“…This is exemplified by the period of time necessary to achieve full reduction of symptoms once stimulation is initiated and the prolonged therapeutic effect once stimulation is stopped 108 (FIG. 3).…”

Section: Therapeutic Latencies During Dbs Onset and With Cessationmentioning

confidence: 99%

“…Recording experiments show that neural activity at the site of stimulation or in the site receiving projections from the stimulated site returns to baseline within milliseconds or seconds after stimulation ends, but it may take minutes, hours, or even days in some cases for symptoms to worsen. 108,109 When stimulation is initiated in PD patients, improvement in gait may take hours to occur, whereas tremor may disappear almost instantly. 110,111 A similar temporal disparity occurs with dystonia patients.…”

Section: Therapeutic Latencies During Dbs Onset and With Cessationmentioning

confidence: 99%

Mechanisms and Targets of Deep Brain Stimulation in Movement Disorders

et al. 2008

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Summary:Chronic electrical stimulation of the brain, known as deep brain stimulation (DBS), has become a preferred surgical treatment for medication-refractory movement disorders. Despite its remarkable clinical success, the therapeutic mechanisms of DBS are still not completely understood, limiting opportunities to improve treatment efficacy and simplify selection of stimulation parameters. This review addresses three questions essential to understanding the mechanisms of DBS. 1) How does DBS affect neuronal tissue in the vicinity of the active electrode or electrodes? 2) How do these changes translate into therapeutic benefit on motor symptoms? 3) How do these effects depend on the particular site of stimulation? Early hypotheses proposed that stimulation inhibited neuronal activity at the site of stimulation, mimicking the outcome of ablative surgeries. Recent studies have challenged that view, suggesting that although somatic activity near the DBS electrode may exhibit substantial inhibition or complex modulation patterns, the output from the stimulated nucleus follows the DBS pulse train by direct axonal excitation. The intrinsic activity is thus replaced by high-frequency activity that is time-locked to the stimulus and more regular in pattern. These changes in firing pattern are thought to prevent transmission of pathologic bursting and oscillatory activity, resulting in the reduction of disease symptoms through compensatory processing of sensorimotor information. Although promising, this theory does not entirely explain why DBS improves motor symptoms at different latencies. Understanding these processes on a physiological level will be critically important if we are to reach the full potential of this powerful tool.

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How do parkinsonian signs return after discontinuation of subthalamic DBS?

Abstract: STN DBS may act by different mechanisms on the four major parkinsonian signs. At least 3 hours off STN DBS is needed to estimate the clinical effect of stimulation.

Cited by 364 publications

References 21 publications

Effects of thalamic stimulation frequency on intention and postural tremor

Effects of thalamic stimulation frequency on intention and postural tremor

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

Mechanisms and Targets of Deep Brain Stimulation in Movement Disorders

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