The Potential of Asymmetric Stimulation Frequency in Subthalamic Stimulation for Parkinson’s Disease - European Medical Journal
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The Potential of Asymmetric Stimulation Frequency in Subthalamic Stimulation for Parkinson’s Disease

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2 Mins
Authors:
*Guillaume Baille,1 Alexandre Kreisler,2 Gustavo Touzet,3 Luc Defebvre,2 David Devos,4 Caroline Moreau2
Disclosure:

Prof Defebvre has served on the advisory board, served as a consultant, and given lectures for AbbVie, Orkyn’, and Aguettant. Dr Kreisler declared that there are no conflicts of interest relevant to this work and reports personal fees from Allergan France SAS, Merz Pharma France, and grants and personal fees from Ipsen outside the submitted work. Prof Devos has received PHRC grants from the French Ministry of Health and research funding from the ARSLA charity, the France Parkinson charity, and European Commission (H2020). He has served on the advisory board, served as a consultant, and given lectures for ApoPharma, Orkyn’, Air Liquide, Aguettant, Ever Pharma, and Boston Scientific. Dr Moreau has received grants from the France Parkinson charity and honoraria from Orkyn’, ApoPharma, and Boston Scientific for consultancy and lectures on Parkinson’s disease at symposia. The remaining authors have declared no conflicts of interest.

Citation
EMJ Neurol. ;8[1]:50-52. Abstract Review No: AR8.

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

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BACKGROUND AND AIMS

Subthalamic deep brain stimulation (STN-DBS) is an effective treatment for motor fluctuations in Parkinson’s disease (PD). Several parameters can be controlled to improve the clinical outcomes. Among them, frequency has variable clinical effects,1 perhaps owing to the differential impact on downstream networks. High-frequency stimulation (HFS) (i.e., above 100 Hz) is classically the best choice to control the segmental PD symptoms2 and may also improve akinesia and tremor. Higher frequencies (i.e., 130–180 Hz) can further improve the tremor;1 however, they may also worsen axial symptoms in late-stage PD patients as exemplified in gait.3 Thus, there is a potential benefit to fine-tune stimulation frequency independently in both hemispheres to account for asymmetric symptom expression. Beyond directional leads4 the Cartesia-Boston® system for STN-DBS (Vercise Cartesia™, Boston Scientific, Santa Clarita, California, USA) allows configuring different frequencies of stimulation between left and right hemispheres (called differentiated frequency).5 The authors sought to explore if differentiated frequency can improve the asymmetrical tremor in patients with STN-DBS.

METHODS

Seventeen PD patients with STN-DBS (implanted with the Cartesia-Boston® system) were assessed under four conditions (stimulation on/medication off, stimulation off/medication off, stimulation off/medication on, stimulation on/medication on) 1 year after implantation. All patients participated in the PREDI-STIM study,6 a multicentre study of the predictive factors of the therapeutic response to subthalamic stimulation on the long-term quality of life in 700 people with PD. Four of these patients (Table 1) were not satisfied with their DBS outcomes because of persistent asymmetrical tremor. All patients were initially programmed with a stimulation frequency of 130 Hz bilaterally. The persistent tremor was not resolved with medication changes, increased stimulation amplitude, or stimulation on different contacts (including directional stimulation). Pulse width was reduced in two patients.

Table 1: Clinical features of the four patients and DBS parameters proposed to relieve their tremor.

Best on condition: stimulation on/medication on; F: female; LEDD change: levodopa equivalent daily dose change between pre- and post-DBS implementation; M: male; MDS-UPDRS: Movement Disorder Society-unified Parkinson’s disease rating scale; worst off condition: stimulation off/medication off.

Increasing the frequency of stimulation reduced the  asymmetrical tremor, but all four patients reported worsening of the akinesia and hypertonia on the opposite side. Therefore, differentiated frequency was proposed with the higher frequency programmed contralateral to the side with the persistent tremor. To assess the efficacy of tremor reduction on the most affected side, the authors calculated a tremor subscore corresponding to the sum of the following items of the Movement Disorder Society-unified Parkinson’s disease rating scale (MDS-UPDRS) Part III: 3.15 (postural tremor of the hands), 3.16 (kinetic tremor4.0of, the hands), 3.17 (rest tremor amplitude for upper and lower limb), and 3.18 (constancy of rest tremor).

RESULTS

With differentiated HFS, (185 Hz versus 140 Hz for three patients, 174 Hz versus 130 Hz for the last one) tremor subscore decreased for three patients (Table 1). Patient clinical global impression improved one point for three patients in comparison with symmetrical HFS (130 Hz on both sides). One patient did not report any change and no worsening of the total MDS-UPDRS III
was observed.

CONCLUSION

Expanded programming flexibility with the opportunity to programme different frequencies for each side could be optimal for certain patients to reduce tremor and maintain a good control of the other symptoms. Despite this proof of concept, further clinical trials remain necessary because of interpatient variability.

References
Su D et al. Frequency-dependent effects of subthalamic deep brain stimulation on motor symptoms in Parkinson's disease: a meta-analysis of controlled trials. Sci Rep. 2018;8(1):14456. Moro E et al. The impact on Parkinson's disease of electrical parameter settings in STN stimulation. Neurology. 2002;59(5):706-13. Annic A et al. Predictive factors for improvement of gait by low-frequency stimulation in Parkinson's disease. J Parkinsons Dis. 2014;4(3):413-20. Eleopra R et al. Brain impedance variation of directional leads implanted in subthalamic nuclei of Parkinsonian patients. Clin Neurophysiol. 2019;130(9):1562-9. Cheung T et al. Longitudinal impedance variability in patients with chronically implanted DBS devices. Brain Stimul. 2013;6(5):746-51. University Hospital, Lille. Predictive Factors and Subthalamic Stimulation in Parkinson's Disease (PREDI-STIM). NCT02360683. https://clinicaltrials.gov/ct2/show/NCT02360683.