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. 2023 Dec;38(12):2155-2162.
doi: 10.1002/mds.29647. Epub 2023 Nov 2.

Cognitive Effects of Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease with GBA1 Pathogenic Variants

Gian D Pal  1 , Daniel M Corcos  2 , Leo Verhagen Metman  3 , Zvi Israel  4   5 , Hagai Bergman  4   6   7 , David Arkadir  4   8
Affiliations

Cognitive Effects of Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease with GBA1 Pathogenic Variants

Gian D Pal et al. Mov Disord. 2023 Dec.

Abstract

Genetic subtyping of patients with Parkinson's disease (PD) may assist in predicting the cognitive and motor outcomes of subthalamic deep brain stimulation (STN-DBS). Practical questions were recently raised with the emergence of new data regarding suboptimal cognitive outcomes after STN-DBS in individuals with PD associated with pathogenic variants in glucocerebrosidase gene (GBA1-PD). However, a variety of gaps and controversies remain. (1) Does STN-DBS truly accelerate cognitive deterioration in GBA1-PD? If so, what is the clinical significance of this acceleration? (2) How should the overall risk-to-benefit ratio of STN-DBS in GBA1-PD be established? (3) If STN-DBS has a negative effect on cognition in GBA1-PD, how can this effect be minimized? (4) Should PD patients be genetically tested before STN-DBS? (5) How should GBA1-PD patients considering STN-DBS be counseled? We aim to summarize the currently available relevant data and detail the gaps and controversies that exist pertaining to these questions. In the absence of evidence-based data, all authors strongly agree that clinicians should not categorically deny DBS to PD patients based solely on genotype (GBA1 status). We suggest that PD patients considering DBS may be offered genetic testing for GBA1, where available and feasible, so the potential risks and benefits of STN-DBS can be properly weighed by both the patient and clinician. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; cognition; deep brain stimulation; glucocerebrosidase.

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Conflict of interest statement

Relevant financial disclosure or conflict of interest: GP-None, LVM-None, DC-None, ZI-None, HB-None, DA-None

Figures

Figure 1:
Figure 1:
Parkinson’s patient with mutation in GBA1 (GBA-PD) cognitively deteriorated faster following subthalamic deep brain stimulation (STN-DBS) compared to non-operated GBA-PD patients. Linear fit with 95% confidence interval bands is shown. Figure modified from Pal et al. 2022 with permission.
See this image and copyright information in PMC

References

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    1. Salles PA, Mata IF, Fernandez HH. Should we start integrating genetic data in decision-making on device-aided therapies in Parkinson disease? A Point of View. Parkinsonism & Related Disorders 2021. - PubMed
    1. Pal G, Mangone G, Hill EJ, et al. Parkinson Disease and Subthalamic Nucleus Deep Brain Stimulation: Cognitive Effects in GBA Mutation Carriers. Ann Neurol 2022;91(3):424–435. - PMC - PubMed
    1. Alcalay RN, Levy OA, Waters CC, et al. Glucocerebrosidase activity in Parkinson’s disease with and without GBA mutations. Brain 2015;138(Pt 9):2648–2658. - PMC - PubMed
    1. Pal G, Cook L, Schulze J, et al. Genetic Testing in Parkinson’s Disease. Mov Disord 2023;38(8):1384–1396. - PMC - PubMed

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