Objective: This study aims to improve clinical applicability, patient comfort and safety of stimulation withdrawal to differentiate stimulation-induced side effects from disease progression.

Background: Gait disturbances are both frequent side effects of chronic thalamic deep brain stimulation (DBS) as well as a feature of disease progress of essential tremor (ET) and therefore difficult to differentiate. Recent studies have used stimulation withdrawal periods of several days[1,2] that leave patients incapacitated due to the inevitable reoccurrence of severe tremor, requiring hospitalization for this period without offering any therapeutic benefit.

Method: 10 patients with gait disturbances following VIM-DBS (ET_GAIT) underwent unilateral overnight stimulation withdrawal (stim off) [8-16 hours] corresponding to the non-dominant hemisphere. 10 patients with ET without gait disturbances (ET_NORM) were recruited as a control group. Body-worn sensors (Mobility Lab, APDM) were used to assess gait performance in one session in ET_NORM and at 3 time-points in ET_GAIT: i) ON DBS, ii) immediately after unilateral stim off, and iii) after overnight unilateral stim off period. Spatiotemporal gait parameters and their coefficient of variation (CoV) were extracted from raw data using the Mobility lab software. Severity of tremor and ataxia were assessed using Fahn-Tolosa-Marin Tremor Rating Score(TRS) and Scale or Assessment and Rating of Ataxia(SARA).

Results: Variability of spatial and temporal gait parameters stride length, stride velocity, stride time, cadence and range of motion (RoM) of shanks and knees was significantly higher in ET_GAIT during ON DBS compared to ET_NORM (Mann-Whitney U-test, p<0.05). Overnight withdrawal led to a significant reduction of CoV of stride length and RoM of shanks. Assessment immediately after stim off did not show this effect. SARA score items 1-3 failed to depict changes of gait performance. Lateralized TRS scores showed significant increases only contralateral to the stim off hemisphere (p<0.01), not affecting tremor control for the dominant hand.

Conclusion: A short term unilateral withdrawal of deep brain stimulation may suffice to differentiate adverse effects from disease progression if sensor based technology allowing quantitative assessment is used. As the dominant hand remains functional in these patients this protocol is widely applicable, e.g. in ambulant settings or for anxious patients.

References: 1. Reich MM, Brumberg J, Pozzi NG, et al. Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy? Brain : a journal of neurology 2016. 2. Kroneberg D, Ewert S, Meyer AC, Kuhn AA. Shorter pulse width reduces gait disturbances following deep brain stimulation for essential tremor. Journal of neurology, neurosurgery, and psychiatry 2019.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/overnight-unilateral-withdrawal-of-vim-dbs-to-identify-reversibility-of-gait-disturbances/