Genetic background and outcome of Deep Brain Stimulation in Parkinson's disease

Abstract

Deep Brain Stimulation (DBS) is a well-established therapeutic option for patients with Parkinson's disease (PD). The high variability observed in the outcome demands better prediction criteria to select candidate patients that may obtain the best results from DBS. Recent advances in genetics have provided important tools to investigate variability in clinical features of PD patients, creating the possibility to correlate the patient's individual genotypes with clinical outcome of therapeutic responsiveness. The purpose of this review is to examine current evidence supporting the role of genetic background on the DBS efficacy. Three databases were searched to identify relevant articles reporting the outcomes of DBS in patients with PD and related genetic mutations. Twelve studies that compared the DBS response in different genetic forms of PD and non-mutated cases were found; mutations in PRKN, LRRK2 and GBA were the most common PD-related mutations. All the studies confirmed the effectiveness of DBS to control motor symptoms independently from the genetic status of patients, although some differences in the response to DBS were found. Due to the several limitations of the available data, all the existing evidence is preliminary. Future well-designed studies are needed to draw more consistent conclusions about genotype-related differences on DBS outcome.

Keywords: Deep brain stimulation; GBA; Genetics; LRKK2; Parkin; Parkinson's disease.