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. 2021 Nov 19;137(1):184-191.
doi: 10.3171/2021.7.JNS21190. Print 2022 Jul 1.

Clinical profiles and outcomes of deep brain stimulation in G2019S LRRK2 Parkinson disease

Katherine Leaver  1 , Aaron Viser  2 , Brian H Kopell  1 , Roberto A Ortega  1 , Joan Miravite  1 , Michael S Okun  3 , Sonya Elango  1 , Deborah Raymond  1 , Susan B Bressman  1 , Rachel Saunders-Pullman  1 , Marta San Luciano  2
Affiliations

Clinical profiles and outcomes of deep brain stimulation in G2019S LRRK2 Parkinson disease

Katherine Leaver et al. J Neurosurg. .

Abstract

Objective: The objective of this study was to evaluate clinical features and response to deep brain stimulation (DBS) in G2019S LRRK2-Parkinson disease (LRRK2-PD) and idiopathic PD (IPD).

Methods: The authors conducted a clinic-based cohort study of PD patients recruited from the Mount Sinai Beth Israel Genetics database of PD studies. The cohort included 87 participants with LRRK2-PD (13 who underwent DBS) and 14 DBS participants with IPD enrolled between 2009 and 2017. The baseline clinical features, including motor ratings and levodopa-equivalent daily dose (LEDD), were compared among LRRK2-PD patients with and without DBS, between LRRK2-PD with DBS and IPD with DBS, and between LRRK2-PD with subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) DBS. Longitudinal motor scores (Unified Parkinson's Disease Rating Scale-part III) and medication usage were also assessed pre- and postoperatively.

Results: Compared to LRRK2-PD without DBS (n = 74), the LRRK2-PD with DBS cohort (n = 13) had a significantly younger age of onset, longer disease duration, were more likely to have dyskinesia, and were less likely to experience hand tremor at disease onset. LRRK2-PD participants were also more likely to be referred for surgery because of severe dyskinesia (11/13 [85%] vs 6/14 [43%], p = 0.04) and were less likely to be referred for medically refractory tremor (0/13 [0%] vs 6/14 [43%], p = 0.02) than were IPD patients. Among LRRK2-PD patients, both STN-DBS and GPi-DBS targets were effective, although the sample size was small for both groups. There were no revisions or adverse effects reported in the GPi-DBS group, while 2 of the LRRK2-PD participants who underwent STN-DBS required revisions and a third reported depression as a stimulation-related side effect. Medication reduction favored the STN group.

Conclusions: The LRRK2-PD cohort referred for DBS had a slightly different profile, including earlier age of onset and dyskinesia. Both the STN and GPi DBS targets were effective in symptom suppression. Patients with G2019S LRRK2 PD were well-suited for DBS therapy and had favorable motor outcomes regardless of the DBS target. LRRK2-DBS patients had longer disease durations and tended to have more dyskinesia. Dyskinesia commonly served as the trigger for DBS surgical candidacy. Medication-refractory tremor was not a common indication for surgery in the LRRK2 cohort.

Keywords: DBS; GPi; LRRK2; Parkinson’s disease; STN; deep brain stimulation; functional neurosurgery.

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Figures

FIG. 1.
FIG. 1.
Spaghetti plot of fitted (predicted) motor trajectories (UPDRS-III) of LRRK2-PD subjects. Blue lines represent individual subjects and the red line is average trend of all subjects. Left: Preoperative motor trajectories of LRRK2-DBS subjects. Right: Preoperative motor trajectories of LRRK2 non-DBS subjects.
FIG. 2.
FIG. 2.
Spaghetti plot of fitted (predicted) motor trajectories (UPDRS-III) of LRRK2 and IPD subjects undergoing DBS. Blue lines represent individual subjects and the red line is average trend of all subjects. Left: Preoperative motor trajectories by LRRK2 status. Right: Postoperative motor trajectories by LRRK2 status.
FIG. 3.
FIG. 3.
Spaghetti plot of fitted (predicted) motor trajectories (UPDRS-III) of LRRK2-PD subjects undergoing DBS. Blue lines represent individual subjects and the red line is average trend of all subjects. Left: Preoperative motor trajectories by brain target. Right: Postoperative motor trajectories by brain target.
See this image and copyright information in PMC

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