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

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  • 1 Department of Neurology, Mount Sinai Beth Israel, and Icahn School of Medicine, Mount Sinai, New York, New York;
  • | 2 Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, California; and
  • | 3 Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida
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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.

ABBREVIATIONS

CI = confidence interval; DBS = deep brain stimulation; GPi = internal segment of the globus pallidus; IPD = idiopathic PD; IQR = interquartile range; LEDD = levodopa-equivalent daily dose; MoCA = Montreal Cognitive Assessment; OR = odds ratio; PD = Parkinson disease; STN = subthalamic nucleus; UPDRS = Unified Parkinson’s Disease Rating Scale.

Supplementary Materials

    • Supplementary Tables 1-5 (PDF 529 KB)

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