Objective: To evaluate the clinical effects of using interleaving stimulation to simultaneously treat Parkinson’s disease (PD) symptoms and dyskinesia by the generation of two symptom-specific volume of tissue activation (VTA) areas in patients with subthalamic (STN) deep brain stimulation (DBS).

Background: A direct and acute effect on dyskinesia has been reported with stimulation adjustment in PD patients with STN DBS despite medication reduction[1]. Interleaving stimulation (ILS) is a programming option to optimize stimulation involving multiple areas of interest and alleviating stimulation side effects[2-4].

Method: Retrospective analysis of patients implanted with STN DBS receiving ILS for dyskinesia treatment. The main outcomes of the study were improvement of motor symptoms by the UPDRS III and improvement of dyskinesia by the CAPSIT dyskinesia scale. Individual VTA models and heat maps were used to identify stimulation sites with anti-dyskinesia effect.

Results: Baseline clinical characteristics: Mean UPDRS III (33.9 ±11.0) off medication and (16.0 ±5.9) on medication; CAPSIT dyskinesia score ((12.9±7.1); UPDRS IV (8.5 ±3.8), LEDD (1268 ±498) mg/day. With non-ILS the mean UPDRS III improvement was: 56 ±22% off med/on stim from off med at baseline (p<0.001), and 70.2 ±19.2% on med/on stim relative to the off med at baseline (p <0.001). The CAPSIT dyskinesia score improved by 70 ±20,6% compared to baseline (p <0.003). After the transition to ILS, the CAPSIT dyskinesia improved 82.0 ±27.3% relative to baseline (p<0.001) and 61.6 ±39.3% relative to non-ILS (p=0.006). There was no significant change in the UPDRS III score in the on med/on stim condition, however, there was slight deterioration (5.0 ±11 points; p=0.16)in the UPDRS III off med/on stim relative to non-ILS. There was no correlation between the LEDD reduction and CAPSIT dyskinesia improvement with ILS (p=0.75). The heat map analysis showed a concentration of the VTA’s within or bordering the STN during non-ILS. The ILS with the anti-dyskinesia effect generated a concentration of VTA’s above and laterally to the STN, likely involving the pallidofugal fibers.

Conclusion: DBS of the STN using ILS was more effective in suppressing dyskinesia directly, regardless of medication adjustment.Our results encourage the approach of delivering stimulation through dorsal DBS contacts using ILS to engage pallidofugal fibers and obtain a direct anti-dyskinesia effect.

References: 1. Herzog J, Pinsker M, Wasner M, et al. Stimulation of subthalamic fibre tracts reduces dyskinesias in STN-DBS. Mov. Disord. 2007;22(5):679–684. 2. Kern DS, Picillo M, Thompson JA, et al. Interleaving Stimulation in Parkinson’s Disease, Tremor, and Dystonia. Stereotact Funct Neurosurg 2018;96(6):379–391. 3. Miocinovic S, Khemani P, Whiddon R, et al. Outcomes, management, and potential mechanisms of interleaving deep brain stimulation settings. Parkinsonism and Related Disorders 2014;20(12):1434–1437. 4. Ramirez-Zamora A, Kahn M, Campbell J, et al. Interleaved programming of subthalamic deep brain stimulation to avoid adverse effects and preserve motor benefit in Parkinson’s disease. J Neurol 2015;262(3):578–584.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/interleaved-deep-brain-stimulation-for-dyskinesia-management-in-parkinsons-disease/