Should we offer deep brain stimulation to Parkinson’s disease patients with GBA mutations?

Abstract

Parkinson’s disease (PD) patients who are carriers of glucosylceramidase β1 (GBA1) gene mutations typically have an earlier age at onset and a more aggressive disease course, with a higher burden of neuropsychological issues. The use of deep brain stimulation (DBS) in PD patients with disabling motor fluctuations and absence of dementia is a widespread therapeutic option, often with good results in terms of improvement in activities of daily living and quality of life. Although all PD patients, when fulfilling the common selection criteria for DBS, can benefit from this intervention, some studies have raised attention toward the fact that PD patients who are carriers of GBA1 variants may have a worse DBS outcome possibly due to an accelerated progression of cognitive decline. From this viewpoint, we summarize the current literature, highlighting the knowledge gaps and proposing suggestions for further research as well as for clinical practice in this timeframe of uncertainty related to using DBS in PD patients who are carriers of GBA1 variants.

Deep brain stimulation of globus pallidus internus and subthalamic nucleus in Parkinson’s disease: a multicenter, retrospective study of efficacy and safety

“…Our data are also insufficient to perform an adequate stratification of patients’ outcomes in relation to their genetic status. Genetic characterization of patients enrolled for DBS will become very important in the future, especially in the light of recent evidence on prognostic implications for patients with genetically determined PD undergoing STN-DBS, like GBA-mutated patients [ 23 ].…”

Surgical treatment of movement disorders in neurometabolic conditions

“…Additionally, Parkinson's disease patients who carry a single GBA variant present with earlier onset of symptoms and a more aggressive disease course. Certain variants of the GBA gene carry a higher risk in this context (101). While STN-DBS has been associated with good motor outcomes in this population, it has been suggested that it may have negative effects on cognitive outcomes.…”

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

“…Our study demonstrated that GBA carriers undergoing STN‐DBS had good motor and pharmacological outcomes, but they experienced the worst cognitive outcome and the worst quality of life. To date, the most rational approach would be to detect the presence of GBA variants through sequencing techniques in candidates for DBS and to discuss thoroughly with the patient and the caregiver the potential risks 81 . A personalized approach aided by genetic information and variant‐based risk stratification should be implemented, whenever possible.…”