Are LRRK2 p.G2019S or GBA1 variants associated with long-term outcomes of deep brain stimulation for Parkinson's disease?

Saar Anis; Tomer Goldberg; Ethan Shvueli; Yuval Kozlov; Yonatan Redlich; Naama Lavi; Inbar Lavie; Yuri Ludwig Sosero; Ziv Gan-Or; Lior Ungar; Zion Zibly; Lior Greenbaum; Tsvia Fay-Karmon; Sharon Hassin-Baer

doi:10.1016/j.parkreldis.2024.106008

Are LRRK2 p.G2019S or GBA1 variants associated with long-term outcomes of deep brain stimulation for Parkinson's disease?

Parkinsonism Relat Disord. 2024 Jan 12:106008. doi: 10.1016/j.parkreldis.2024.106008. Online ahead of print.

Authors

Affiliations

¹ Movement Disorders Institute and Department of Neurology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: aniss2@ccf.org.
² Movement Disorders Institute and Department of Neurology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
³ Movement Disorders Institute and Department of Neurology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Arrow Project for Medical Research, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Faculty of Medicine, Hebrew University, Jerusalem, Israel.
⁴ Movement Disorders Institute and Department of Neurology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Faculty of Medicine, Hebrew University, Jerusalem, Israel.
⁵ Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁶ The Neuro (Montréal Neurological Institute-Hospital), McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada.
⁷ Department of Neurosurgery, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
⁸ Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.

PMID: 38242744
DOI: 10.1016/j.parkreldis.2024.106008

Abstract

Background: Deep brain stimulation (DBS) is a well-established treatment option for individuals with advanced Parkinson's disease (PD). The potential influence of the LRRK2 p.G2019S or GBA1 variants on its lasting efficacy and adverse effects should be better characterized.

Methods: We conducted a retrospective single-center case-control study involving PD patients who were carriers of a GBA1 variant (GBA1-PD), the LRRK2 p.G2019S variant (LRRK2-PD), and non-carriers (Nc-PD). All participants underwent DBS and were followed up for at least a year. Assessments before surgery and at 1, 2, 3, 5, and 10 years post-DBS included the following: the Movement Disorder Society's Unified PD Rating Scale (MDS-UPDRS) Part III, Hoehn and Yahr scale, Levodopa Equivalent Daily Dose (LEDD) and non-motor symptoms (psychotic episodes, depressive symptoms, and cognitive decline).

Results: The sample was composed of 103 patients (72 males, mean age at DBS surgery 61.5 ± 8.7 years, mean postoperative follow-up 7.0 ± 4.1 years). Of these, 19 were LRRK2-PD, 20 GBA1-PD, and 64 were Nc-PD. No significant differences in motor outcomes were observed between the groups. Compared to the Nc-PD patients, the GBA1-PD patients were at increased risk of both psychotic episodes [hazard ratio (HR) 2.76 (95 % CI: 1.12-6.80), p = 0.027], and cognitive decline [HR 2.28 (95 % CI: 1.04-5.00), p = 0.04].

Conclusion: LRRK2 and GBA1 variant status did not affect the motor outcomes of DBS in PD patients. However, GBA1-PD patients were at increased risk for psychosis and cognitive decline. Further studies are required to determine the role of genetic stratification in referral to DBS.

Keywords: Cognitive decline; Deep brain stimulation; GBA1; LRRK2; Motor symptoms; Parkinson's disease; Psychotic episodes.