Abstract
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease (PD). The G2385R variant of LRRK2 is a risk factor for PD in Han Chinese individuals. We retrospectively compared the clinical outcomes of STN-DBS surgery between PD Han Chinese G2385R variant carriers and non-carriers. Fifty-seven PD patients with bilateral STN-DBS were enrolled, including 8 G2385R+ variant carriers (G2385R+ group) and 49 non-carriers (G2385R– group). Clinical data included Unified Parkinson's Disease Rating Scale (UPDRS) parts I to IV, levodopa equivalent daily dose (LEDD), Mini-Mental State Examination Scale (MMSE) score, and Hamilton Depression Rating Scale (HAMD) score measured prior to DBS and 12 months post-DBS. DBS settings were also recorded. All PD patients benefited from STN-DBS surgery. There were no statistical differences between the two groups in terms of motor function, daily living activities, and LEDD reductions at 12 months post-DBS. The rigidity of the post-surgical G2385R+ group was significantly improved compared with that of the G2385R– group (P = 0.045). Post-surgical voltage in the G2385R+ group was significantly higher than that in the G2385R– group (P = 0.033). STN-DBS outcomes were not influenced by the LRRK2 G2385R variant in Han Chinese patients.
Highlights
Parkinson’s disease (PD) is a common and chronic neurodegenerative disorder characterized clinically by movement impairments including resting tremor, bradykinesia, rigidity, and postural instability, as well as a variety of non-motor symptoms
There were no significant differences in Unified Parkinson’s Disease Rating Scale (UPDRS) parts I to IV, levodopa equivalent daily dose (LEDD), Mental State Examination Scale (MMSE), and Hamilton Depression Rating Scale (HAMD) between the two groups in presurgical baseline characteristics (Table 2)
8 G2385R+ PD patients and 49 G2385R– PD patients with bilateral subthalamic nucleus (STN)-Deep brain stimulation (DBS) who were similar in ethnicity (Han Chinese), age, gender, age at PD onset, age at DBS surgery, duration of disease, and other clinical features were included
Summary
Parkinson’s disease (PD) is a common and chronic neurodegenerative disorder characterized clinically by movement impairments including resting tremor, bradykinesia, rigidity, and postural instability, as well as a variety of non-motor symptoms. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common mutations in sporadic and familial PD. G2385R and R1628P are the two most common LRRK2 variants in Asian patients with PD [1,2,3]. The G2385R variant increases the risk of PD in the Han Chinese population by nearly 2-fold [4]. The LRRK2 protein is integrated with GTP and protein kinase enzymes and is widely expressed in various tissues and involved in central nervous system functioning, including in the nigrostriatum and caudate nucleus [5]. G2385R is located on the C-terminal of the LRRK2’s WD40 domain, which is involved in the interaction of LRRK2 with other proteins [1]
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