Genetic Influences in DBS: Motor and Cognitive Outcomes by Genetic Profile in Parkinson’s Disease
Viviana Torres Ballesteros1, Claire Alcus2, Matthew Feldman2, Marina Sarno3, Aidan Kunju2, Lucila Hernandez2, Ihtsham Haq4, Danielle S. Shpiner2, Corneliu Luca2
1Movement Disorders Fellowship - University of Miami, 2University of Miami, 3University of Miami Department of Neurology, 4University of Miami Miller School of Medicine
Objective:
To explore motor and neuropsychological outcomes in Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS), with a focus on genetic variability.
Background:
Deep brain stimulation (DBS) effectively manages motor symptoms in advanced Parkinson’s disease (PD), but cognitive effects may vary by genetic subgroup.
Design/Methods:
We analyzed 11 PD patients with pathogenic variants from the PDgene database who underwent DBS at our center. Assessments included the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) post-DBS (meds on, stim on) and Levodopa Equivalent Daily Dose (LEDD) pre/post-DBS. We conducted six-month pre/post neuropsychological evaluations of mental status, executive function, attention, processing speed, and language.
Results:
Motor improvements were noted across all genetic groups post-DBS. LRRK2 patients (N=3;median age:55.5 for females,78 for males) with STN targets had a 31.5% LEDD reduction and an 81.4% MDS-UPDRS improvement (44.7 to 8.33). Variants included G2019S (2 patients) and R1441C (1 patient). GBA patients (N=4;median age:66 for females, 53 for males) also with STN showed a 52.1% LEDD reduction and a 53.1% MDS-UPDRS improvement (52.8 to 24.8). Variants included L444P, E326K, N370S, and p.Trp420. PRKN patients (N=3; ages:47 for females, 59.5 for males), with one STN and two GPi targets, had a 33.8% LEDD reduction and a 70.3% MDS-UPDRS improvement (66.7 to 19.8). Variants included two with Exon 2 deletions and one with p.N52Mfs*29.
Cognitive outcomes were assessed in three patients. The LRRK2 patient’s MMSE remained at 29, while a male GBA patient’s MMSE declined (26 to 16). A female GBA patient showed declines in phonemic fluency and abstract reasoning, but both improved in depressive symptoms and anxiety
Conclusions:
These findings suggest that DBS may improve motor symptoms in genetic subgroups, while cognitive outcomes vary. The small sample size and short follow-up limit generalizability. Further research is needed to understand the long-term impacts of DBS on genetic profiles.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.