Objective: Determine the role of genetic factors in selecting candidates for, and evaluating outcomes of, deep-brain stimulation (DBS) within the framework of the multi-national Genetic Epidemiology of Parkinson’s Disease (GEoPD) consortium.

Background: DBS is an established treatment modality in Parkinson’s disease (PD) with the subthalamic nucleus (STN) and globus pallidum internus (GPi) as preferred targets. There is heterogeneity in candidate selection, based on age at disease onset, complications of levodopa therapy, as well as in the timing of implantation, post-operative management and clinical outcomes. Genetic variability has an impact on DBS outcomes (Ligaard et al 2019). Monogenic PD patients with GBA mutations may experience a more rapid cognitive decline post-DBS (Lythe et al., 2017), those with LRRK2, parkin, and VPS35 mutations may have a good response (Over et al., 2021), whereas those with ATP1A3-associated rapid onset parkinsonism-dystonia DBS have no symptomatic benefit (Brucke et al., 2015). SNCA variants may also affect outcomes (Weiss et al, 2016). Given this variability, large numbers of cases from many centers are necessary to establish predictors of outcomes.

Method: The GEoPD Consortium, with its worldwide membership (60 sites in 30 countries on six continents) and 41,988 PD cases, is uniquely positioned to address these issues. In addition to genomic information, DBS target placement by CT/MRI, preoperative cognitive assessment, age at disease onset, disease duration, motor-subtype, family history, time of emergence and duration of levodopa complications, we collect standardized clinical information longitudinally: motor and cognitive assessment, autonomic dysfunction and comorbidities.

Results: Retrospective studies of DBS cases will obtain a detailed phenotypic and genotypic characterization from participating sites, and a prospective study will include longitudinal follow up of these established and new DBS cases. We will present results from the first phase of this effort, a global survey of DBS centers willing to participate in a common effort to improve DBS patient selection and inform prognosis and outcomes.

Conclusion: Given the complexity of the DBS clinical response, we hypothesize that an analysis of the genotype of DBS candidates will inform candidate selection and assist in prognosis of clinical outcomes.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-role-of-genetics-in-patient-selection-and-outcomes-of-deep-brain-stimulation-in-parkinsons-disease/