Subthalamic Peak Beta Ratio Is Asymmetric in Glucocerebrosidase Mutation Carriers With Parkinson's Disease: A Pilot Study.

Fabian J David,William C Nichols,Philip T Hale,Miranda J Munoz,Sepehr Sani,Daniel M Corcos,Michael W Pauciulo,Leo Verhagen Metman,Gian D Pal,Jay L Shils,Mitra Afshari

doi:10.3389/fneur.2021.723476

Abstract

Introduction: Up to 27% of individuals undergoing subthalamic nucleus deep brain stimulation (STN-DBS) have a genetic form of Parkinson's disease (PD). Glucocerebrosidase (GBA) mutation carriers, compared to sporadic PD, present with a more aggressive disease, less asymmetry, and fare worse on cognitive outcomes with STN-DBS. Evaluating STN intra-operative local field potentials provide the opportunity to assess and compare symmetry between GBA and non-GBA mutation carriers with PD; thus, providing insight into genotype and STN physiology, and eligibility for and programming of STN-DBS. The purpose of this pilot study was to test differences in left and right STN resting state beta power in non-GBA and GBA mutation carriers with PD.Materials and Methods: STN (left and right) resting state local field potentials were recorded intraoperatively from 4 GBA and 5 non-GBA patients with PD while off medication. Peak beta power expressed as a ratio to total beta power (peak beta ratio) was compared between STN hemispheres and groups while co-varying for age, age of disease onset, and disease severity.Results: Peak beta ratio was significantly different between the left and the right STN for the GBA group (p < 0.01) but not the non-GBA group (p = 0.56) after co-varying for age, age of disease onset, and disease severity.Discussion: Peak beta ratio in GBA mutation carriers was more asymmetric compared with non-mutation carriers and this corresponded with the degree of clinical asymmetry as measured by rating scales. This finding suggests that GBA mutation carriers have a physiologic signature that is distinct from that found in sporadic PD.

Highlights

Up to 27% of individuals undergoing subthalamic nucleus deep brain stimulation (STN-DBS) have a genetic form of Parkinson’s disease (PD)
In this local field potentials (LFPs) pilot study, the peak beta ratio in GBA mutation carriers with PD was more asymmetric compared with nonmutation carriers and this corresponded to the degree of clinical asymmetry as measured by the bradykinesia-rigidity asymmetry score
This finding demonstrates that GBA mutation carriers may have a physiologic signature that is distinct from that found in sporadic PD

Summary

Introduction

Up to 27% of individuals undergoing subthalamic nucleus deep brain stimulation (STN-DBS) have a genetic form of Parkinson’s disease (PD). Evaluating STN intra-operative local field potentials provide the opportunity to assess and compare symmetry between GBA and non-GBA mutation carriers with PD; providing insight into genotype and STN physiology, and eligibility for and programming of STN-DBS The purpose of this pilot study was to test differences in left and right STN resting state beta power in non-GBA and GBA mutation carriers with PD. Though alterations in the rate and pattern of basal ganglia neurons may partly explain the phenotypic variation [8], the contribution of individual genotype to differences in beta power has not yet been explored This is important because an increasing number of studies have demonstrated that genotype is an important predictor of DBS outcome [9,10,11,12,13]. As LFP signals are being used clinically in adaptive DBS systems, these signals, when combined with genotypic data, may provide important insights into genotype-phenotype relationships and the variability in DBS outcomes

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Results

Conclusion