Motor and Non-motor Outcomes of Deep Brain Stimulation across the Genetic Panorama of Parkinson's Disease: A Multi-Scale Meta-Analysis.

ABSTRACT

BACKGROUND: In the era of modern medicine, where high-throughput sequencing techniques are readily available, it is desirable to elucidate the role of genetic background in patients with Parkinson's Disease (PD) undergoing Deep Brain Stimulation (DBS). Genetic stratification of PD patients undergoing DBS may assist in patient selection and prediction of clinical outcomes and complement existing selection procedures such as levodopa challenge testing. OBJECTIVE: To capture a broad spectrum of motor and non-motor DBS outcomes in genetic PD patients with data from the recently updated literature. METHODS: A multi-scale meta-analysis with 380 genetic PD cases was conducted using the Cochrane Review Manager, JASP software and R. RESULTS: This meta-analysis revealed that overall, patients with genetic PD are good candidates for DBS but the outcomes might differ depending on the presence of specific mutations. PRKN carriers benefited the most regarding motor function, daily dose medication and motor complications. However, GBA carriers appeared to be more prone to cognitive decline after subthalamic nucleus DBS accompanied by a low quality of life with variable severity depending on genetic variants and concomitant alterations in other genes. Apart from GBA, cognitive worsening was also observed in SNCA carriers. Pre-operative levodopa responsiveness and a younger age of onset are associated with a favorable motor outcome. CONCLUSION: A personalized approach with a variant-based risk stratification within the emerging field of surgicogenomics is needed. Integration of polygenic risk scores in clinical-decision making should be encouraged.