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Multicenter Study
. 2024 Mar 13;95(4):309-315.
doi: 10.1136/jnnp-2023-332387.

Are patients with GBA-Parkinson disease good candidates for deep brain stimulation? A longitudinal multicentric study on a large Italian cohort

Micol Avenali  1   2 , Roberta Zangaglia  2 , Giada Cuconato  3 , Ilaria Palmieri  2 , Alberto Albanese  4 , Carlo Alberto Artusi  5   6 , Marco Bozzali  5   6 , Giovanna Calandra-Buonaura  7   8 , Francesco Cavallieri  9 , Roberto Cilia  10 , Antoniangela Cocco  4 , Filippo Cogiamanian  11 , Fabiana Colucci  10 , Pietro Cortelli  7   8 , Alessio Di Fonzo  12 , Roberto Eleopra  10 , Giulia Giannini  7   8 , Alberto Imarisio  3 , Gabriele Imbalzano  5   6 , Claudia Ledda  5   6 , Leonardo Lopiano  5   6 , Maria Chiara Malaguti  13 , Francesca Mameli  11 , Raffaella Minardi  7 , Pierfrancesco Mitrotti  1 , Edoardo Monfrini  12 , Francesca Spagnolo  14 , Cristina Tassorelli  1   2 , Francesca Valentino  2 , Franco Valzania  9 , Claudio Pacchetti  2 , Enza Maria Valente  15   3 ; PARKNET Study Group
Affiliations
Multicenter Study

Are patients with GBA-Parkinson disease good candidates for deep brain stimulation? A longitudinal multicentric study on a large Italian cohort

Micol Avenali et al. J Neurol Neurosurg Psychiatry. .

Abstract

Background: GBA variants increase the risk of developing Parkinson disease (PD) and influence its outcome. Deep brain stimulation (DBS) is a recognised therapeutic option for advanced PD. Data on DBS long-term outcome in GBA carriers are scarce.

Objective: To elucidate the impact of GBA variants on long-term DBS outcome in a large Italian cohort.

Methods: We retrospectively recruited a multicentric Italian DBS-PD cohort and assessed: (1) GBA prevalence; (2) pre-DBS clinical features; and (3) outcomes of motor, cognitive and other non-motor features up to 5 years post-DBS.

Results: We included 365 patients with PD, of whom 73 (20%) carried GBA variants. 5-year follow-up data were available for 173 PD, including 32 mutated subjects. GBA-PD had an earlier onset and were younger at DBS than non-GBA-PD. They also had shorter disease duration, higher occurrence of dyskinesias and orthostatic hypotension symptoms.At post-DBS, both groups showed marked motor improvement, a significant reduction of fluctuations, dyskinesias and impulsive-compulsive disorders (ICD) and low occurrence of most complications. Only cognitive scores worsened significantly faster in GBA-PD after 3 years. Overt dementia was diagnosed in 11% non-GBA-PD and 25% GBA-PD at 5-year follow-up.

Conclusions: Evaluation of long-term impact of GBA variants in a large Italian DBS-PD cohort supported the role of DBS surgery as a valid therapeutic strategy in GBA-PD, with long-term benefit on motor performance and ICD. Despite the selective worsening of cognitive scores since 3 years post-DBS, the majority of GBA-PD had not developed dementia at 5-year follow-up.

Keywords: COGNITION; ELECTRICAL STIMULATION; NEUROGENETICS; NEUROSURGERY; PARKINSON'S DISEASE.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Clinical motor and non-motor parameters at T1 of non-GBA-PD and GBA-PD groups. (A–B) Between-group comparison (GBA-PD vs non-GBA-PD) and within-group comparison (T0 vs T1) of clinical motor and non-motor parameters. (C) Between-group comparison (GBA-PD vs non-GBA-PD) of motor and non-motor complications at T1. *, p value<0.05 significance difference. FOG, freezing of gait; ICD, impulse control disorders; LEDD, levodopa equivalent daily dose; MDS-UPDRS-III, MDS-Unified Parkinson’s Disease Rating Scale part III; MDRS, Mattis Dementia Rating Scale; PD, Parkinson disease.
Figure 2
Figure 2
Evolution of clinical motor and non-motor parameters of non-GBA-PD and GBA-PD groups over time. The graphs show for GBA-PD (orange) and non-GBA-PD (blue) the mean of MDS-UPDRS-OFF med, MDRS and LEDD and the percentage of ‘yes’ of dyskinesias, on-off phenomenon, wearing-off, ICD and orthostatic hypotension at baseline (T0), T1, T3 and T5. *, p value<0.05 significance difference between-group comparison (GBA-PD vs non-GBA-PD) at T3 and T5. ICD, impulse control disorders; LEDD, levodopa equivalent daily dose; MDS-UPDRS-III, MDS-Unified Parkinson’s Disease Rating Scale part III; MDRS, Mattis Dementia Rating Scale; PD, Parkinson disease.
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