Deep Brain Stimulation in Patients With Mutations in Parkinson's Disease–Related Genes: A Systematic Review

Abstract

Background Background: Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), and careful selection of candidates is a key component of successful therapy. Although it is recognized that factors such as age, disease duration, and levodopa responsiveness can influence outcomes, it is unclear whether genetic background should also serve as a parameter. Objectives Objectives: The aim of this systematic review is to explore studies that have evaluated DBS in patients with mutations in PD-related genes. Methods Methods: We performed a selective literature search for articles regarding the effects of DBS in autosomal dominant or recessive forms of PD or in PD patients with genetic risk factors. Data regarding changes in motor and nonmotor scores and the presence of adverse events after the stimulation were collected. ResultsResults: A total of 25 studies were included in the systematic review, comprising 135 patients. In the shorter term, most patients showed marked or satisfactory response to subthalamic DBS, although leucine rich repeat kinase 2 carriers of R114G mutations had higher rates of unsatisfactory outcome. Longer term follow-up data were scarce but suggested that motor benefit is sustained. Patients with the glucosidase beta acid (GBA) mutation showed higher rates of cognitive decline after surgery. Motor outcome was scarce for pallidal DBS. Few adverse events were reported. Conclusions Conclusions: Subthalamic DBS results in positive outcomes in the short term in patients with Parkin, GBA, and leucine-rich repeat kinase 2 (non-R144G) mutations, although the small sample size limits the interpretation of our findings. Longer and larger cohorts of follow-up, with broader nonmotor symptom evaluations will be necessary to better customize DBS therapy in this population.

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

“…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). For instance, several studies have shown that glucocerebrosidase (GBA) mutation carriers fare worse with STN-DBS compared with non-mutation carriers from a cognitive standpoint, though they still maintain motor benefit (9)(10)(11)(12)(13).…”

“…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). For instance, several studies have shown that glucocerebrosidase (GBA) mutation carriers fare worse with STN-DBS compared with non-mutation carriers from a cognitive standpoint, though they still maintain motor benefit (9)(10)(11)(12)(13). In contrast, LRRK2 G2019S mutation carriers fare the same as non-mutation carriers from a cognitive standpoint and have at least the same or even better motor outcome compared with sporadic PD patients (9)(10)(11)(12)(13).…”

The Successful Three‐Year Outcome of Deep Brain Stimulation in Gaucher Disease Type 1 Associated Parkinson's Disease: A Case Report

“…Although early response appears to be favorable, the progressive nature of the disease and the relatively young age of the patient raise the question of long‐term efficacy. Research has showed long‐term efficacy after seven and a half years in a DBS cohort of GBA‐related PD patients; however, there were patients who did not exhibit cognitive decline and had sustained improvement 2,8 . Even though the longer‐term efficacy is still unclear, the benefits of early DBS in these aggressive forms of the disease can have a significant impact on everyday functioning of the patients.…”

Machine Learning’s Application in Deep Brain Stimulation for Parkinson’s Disease: A Review

“…This allows experts to translate ML decision-making criteria, and could potentially provide insights into the fundamental nature of DBS. Additional insights may be found in the growing body of literature that proposes using PD-related genetic mutations and genetic profiles to identify DBS therapy effectiveness [110,111]. Furthermore, ML methods generally benefit from large data sets.…”