Objective: To investigate the impact of GBA variants on the long-term outcome of deep brain stimulation (DBS) in a large cohort of Italian PD subjects who underwent DBS-surgery.

Background: GBA mutations are a well-known genetic risk factor for PD. Overall, GBA-PD patients had an earlier disease onset, more prevalent non-motor features and a greater risk of cognitive decline than non-mutated PD (NM-PD). DBS is considered nowadays one of the best therapeutic options for PD. However, is not fully understood what are the risk factors that can affect the DBS outcome in GBA-PD and data on long-term clinical outcome are still scarce.

Method: We retrospectively analysed clinical data from a multicentric Italian cohort of DBS-PD patients upon stratification for the presence/absence of GBA variants. Motor and non-motor features were recorded before surgery and after 1, 3 and 5 years.

Results: We recruited 296 DBS-PD patients, of whom 65 (22%) carried GBA variants (severe=29, mild=16, risk=12, unknown=8). At pre-DBS evaluation, GBA-PD had earlier age at onset, age at DBS implant and shorter disease duration than non-mutated PD (NM-PD) but showed similar clinical features except dyskinesias (more prevalent in GBA-PD). Up to 5-years post-DBS, both groups showed motor improvement with satisfactory control of fluctuations and dyskinesias; all non-motor symptoms were also comparable, except for cognitive scores, which worsened significantly faster in GBA-PD than NM-PD, already at 3 years from DBS. However, dementia was diagnosed only on 25 % of GBA-PD after 5 years of follow-up. Interestingly, all demented GBA-PD cases were female, while a prevalence of a specific GBA mutations class were not found.

Conclusion: This is the first report addressing the impact of GBA variants on DBS clinical outcomes in a large well-characterized Italian PD cohort with a relatively long follow-up. Our data, although preliminary, suggest that GBA-PD patients had a clinical motor benefit from DBS as much as NM-PD. Cognitive performance, although progressively worsening in both groups, shows a more rapid deterioration in GBA-PD, however only a small percentage of them developed dementia after 5 years from DBS surgery. Gender differences and its impact on the clinical outcome will be further investigated.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/are-gba-parkinson-disease-patients-good-candidates-for-deep-brain-stimulation-a-longitudinal-multicentric-study-on-a-large-italian-cohort/