Tremor habituation to deep brain stimulation: Underlying mechanisms and solutions

Abstract

DBS of the ventral intermediate nucleus is an extremely effective treatment for essential tremor, although a waning benefit is observed after a variable time in a variable proportion of patients (ranging from 0% to 73%), a concept historically defined as “tolerance.” Tolerance is currently an established concept in the medical community, although there is debate on its real existence. In fact, very few publications have actually addressed the problem, thus making tolerance a typical example of science based on “eminence rather than evidence.” The underpinnings of the phenomena associated with the progressive loss of DBS benefit are not fully elucidated, although the interplay of different—not mutually exclusive—factors has been advocated. In this viewpoint, we gathered the evidence explaining the progressive loss of benefit observed after DBS. We grouped these factors in three categories: disease‐related factors (tremor etiology and progression); surgery‐related factors (electrode location, microlesional effect and placebo); and stimulation‐related factors (not optimized stimulation, stimulation‐induced side effects, habituation, and tremor rebound). We also propose possible pathophysiological explanations for the phenomenon and define a nomenclature of the associated features: early versus late DBS failure; tremor rebound versus habituation (to be preferred over tolerance). Finally, we provide a practical approach for preventing and treating this loss of DBS benefit, and we draft a possible roadmap for the research to come. © 2019 International Parkinson and Movement Disorder Society

Simultaneous combined unilateral ventralis intermedius (VIM) thalamotomy and contralateral VIM deep brain stimulation for head tremor: A case report

“…Recent studies have revealed that long‐term VIM‐DBS may induce waning benefits (tremor habituation to DBS) and delayed onset of gait ataxia in ET 9,10 . Shih et al 11 reported 73% experienced waning benefit in patients with ET who underwent VIM‐DBS.…”

Brain Atrophy Following Deep Brain Stimulation: Management of a Moving Target

“…While VIM-DBS is a safe and effective therapy for patients with severe refractory ET, up to 40-70% of patients will experience worsening of tremor over time [10,11]. Potential causative factors include disease progression, dis-ruption of oscillatory neuronal pathways, side effects from long-term stimulation, changes in impedance, tolerance, or a combination thereof [2, [12][13][14]. Stimulation of structures closer to the midline such as the thalamus and STN, can manifest ipsilateral benefits and side effects.…”

“…One strategy has been the reduction of current density by reducing PW or the amplitude of stimulation. After discovering the threshold for stimulation-induced cerebellar tremor or ataxia, the frequency and amplitudes can be slowly incremented until the tremor is controlled or intolerable adverse effects manifest [14]. The advent of directional DBS may possibly address these stimulationinduced side effects, which may potentially be avoided by delivering stimulation in an axially asymmetric fashion, away from unintended tracts.…”

“…Other suggested strategies include turning off the DBS at night [21], using DBS holidays, or activating the DBS only when needed (e.g. eating) [14]. Lead revision or rescue may sometimes be necessary when optimized programming fails to resolve the issue.…”

Optimal Parameters of Deep Brain Stimulation in Essential Tremor: A Meta-Analysis and Novel Programming Strategy

“…The long-term safety and efficacy of DBS are well-established [3], although it is not certain whether its initially reported superior tremor suppression is also achieved in successive cohorts [4]. Additionally, evidence shows that 33 out of 45 patients in one study (73.3%) reported waning tremor control at a mean time of 18.8 ± 15.1 months postoperatively [5].…”