Clinical Utility of GBA Genotyping Prior to Deep Brain Stimulation: A Narrative Review

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• GBA gene variants are the most common genetic risk factor for Parkinson's disease (PD), often linked to a more aggressive disease course.
• Deep brain stimulation (DBS) is a key therapy for advanced PD, but the impact of GBA status on its outcomes is not fully understood.

Purpose of the Study:

• To review the clinical significance of GBA genotyping before DBS.
• To assess GBA's role in decision-making, risk stratification, and long-term management for PD patients undergoing DBS.

Main Methods:

• A structured narrative review of existing literature.
• Examination of sequencing methods, variant interpretation, and outcomes in GBA-positive versus GBA-negative PD patients post-DBS.
• Focus on motor, cognitive, and neuropsychiatric outcomes, comparing trajectories based on GBA variant classes.

Main Results:

• GBA-associated PD patients show significant motor gains with DBS, similar to non-carriers.
• GBA carriers experience more rapid cognitive and neuropsychiatric decline, influenced by their genetic profile.
• Variant severity impacts postoperative trajectories; long-read sequencing enhances detection of recombinant alleles.

Conclusions:

• DBS is an effective motor therapy for GBA-associated PD.
• GBA genotyping should guide, not restrict, DBS candidate selection.
• Integrating clinical, cognitive, and genetic data enables personalized PD management and DBS planning.