Axial Impairment Following Deep Brain Stimulation in Parkinson’s Disease: A Surgicogenomic Approach

Background: Postoperative outcome following deep brain stimulation (DBS) of the subthalamic nucleus is variable, particularly with respect to axial motor improvement. We hypothesized a genetic underpinning to the response to surgical intervention, termed “surgicogenomics”. Objective: We aimed to identify genetic variants associated with clinical heterogeneity in DBS outcome of Parkinson’s disease (PD) patients that could then be applied clinically to target selection leading to improved surgical outcome. Methods: Retrospective clinical data was extracted from 150 patient’s charts. Each individual was genotyped using the genome-wide NeuroX array tailored to study neurologic diseases. Genetic data were clustered based on surgical outcome assessed by comparing pre- and post-operative scores of levodopa equivalent daily dose and axial impairment at one and five years post-surgery. Allele frequencies were compared between patients with excellent vs. moderate/poor outcomes grouped using a priori defined cut-offs. We analyzed common variants, burden of rare coding variants, and PD polygenic risk score. Results: NeuroX identified 2,917 polymorphic markers at 113 genes mapped to known PD loci. The gene-burden analyses of 202 rare nonsynonymous variants suggested a nominal association of axial impairment with 14 genes (most consistent with CRHR1, IP6K2, and PRSS3). The strongest association with surgical outcome was detected between a reduction in levodopa equivalent daily dose and common variations tagging two linkage disequilibrium blocks with SH3GL2. Conclusion: Once validated in independent populations, our findings may be implemented to improve patient selection for DBS in PD.

Download Full-text

The trajectory of apathy after deep brain stimulation: From pre-surgery to 6 months post-surgery in Parkinson’s disease

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2010.12.011 ◽

2011 ◽

Vol 17 (3) ◽

pp. 182-188 ◽

Cited By ~ 43

Author(s):

L. Kirsch-Darrow ◽

L.B. Zahodne ◽

M. Marsiske ◽

M.S. Okun ◽

K.D. Foote ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Post Surgery ◽

Deep Brain

Download Full-text

Parkinson’s disease outcomes after intraoperative CT-guided “asleep” deep brain stimulation in the globus pallidus internus

Journal of Neurosurgery ◽

10.3171/2015.4.jns1550 ◽

2016 ◽

Vol 124 (4) ◽

pp. 902-907 ◽

Cited By ~ 44

Author(s):

Zaman Mirzadeh ◽

Kristina Chapple ◽

Margaret Lambert ◽

Virgilio G. Evidente ◽

Padma Mahant ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

General Anesthesia ◽

Globus Pallidus ◽

Brain Stimulation ◽

Globus Pallidus Internus ◽

Motor Score ◽

Levodopa Equivalent Daily Dose ◽

Deep Brain

OBJECT Recent studies show that deep brain stimulation can be performed safely and accurately without microelectrode recording ortest stimulation but with the patient under general anesthesia. The procedure couples techniques for direct anatomical targeting on MRI with intraoperative imaging to verify stereotactic accuracy. However, few authors have examined the clinical outcomes of Parkinson’s disease (PD) patients after this procedure. The purpose of this study was to evaluate PD outcomes following “asleep” deep brain stimulation in the globus pallidus internus (GPi). METHODS The authors prospectively examined all consecutive patients with advanced PD who underwent bilateral GPi electrode placement while under general anesthesia. Intraoperative CT was used to assess lead placement accuracy. The primary outcome measure was the change in the off-medication Unified Parkinson’s Disease Rating Scale motor score 6 months after surgery. Secondary outcomes included effects on the 39-Item Parkinson’s Disease Questionnaire (PDQ-39) scores, on-medication motor scores, and levodopa equivalent daily dose. Lead locations, active contact sites, stimulation parameters, and adverse events were documented. RESULTS Thirty-five patients (24 males, 11 females) had a mean age of 61 years at lead implantation. The mean radial error off plan was 0.8 mm. Mean coordinates for the active contact were 21.4 mm lateral, 4.7 mm anterior, and 0.4 mm superior to the midcommissural point. The mean off-medication motor score improved from 48.4 at baseline to 28.9 (40.3% improvement) at 6 months (p < 0.001). The PDQ-39 scores improved (50.3 vs 42.0; p = 0.03), and the levodopa equivalent daily dose was reduced (1207 vs 1035 mg; p = 0.004). There were no significant adverse events. CONCLUSIONS Globus pallidus internus leads placed with the patient under general anesthesia by using direct anatomical targeting resulted in significantly improved outcomes as measured by the improvement in the off-medication motor score at 6 months after surgery.

Download Full-text

Asymmetric Deep Brain Stimulation Electrodes for Parkinson's Disease: A Pilot Study of Symptom-Tailored Stimulation

Neurosurgery ◽

10.1093/neuros/nyz310_506 ◽

2019 ◽

Vol 66 (Supplement_1) ◽

Author(s):

Chencheng Zhang ◽

Linbin Wang ◽

Leonardo Almeida ◽

Bomin Sun ◽

Dianyou Li

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Bilateral Stimulation ◽

Nonmotor Symptoms ◽

Post Surgery ◽

Axial Symptoms ◽

Deep Brain

Abstract INTRODUCTION Bilateral subthalamic nucleus (STN) and globus pallidus interna (GPi) deep brain stimulation (DBS) are well established targets for the management of Parkinson's disease (PD). Each target has its own advantage, we presume the simultaneous unilateral STN and contralateral GPi DBS may compromise side effects of bilateral stimulation and keep each nucleus and its own efficacy on the motor and nonmotor symptoms. METHODS Eight patients with idiopathic PD with this kind of procedure were retrospectively reviewed. Motor, nonmotor symptoms, quality of life were measured before surgery, 6 mo, 1-yr post surgery under following conditions: medication on and off, bilateral stimulation on and off, unilateral STN stimulation on. Medication and stimulation parameters were noted. RESULTS Unilateral STN and contralateral GPi DBS significantly improved the UPDRS-? scores, with a 45% reduction at 6 mo and a 43% reduction at 1 yr. In total, 41% of levodopa equivalent daily dose was reduced at 1-yr follow-up. In the medication on condition, bilateral stimulation improved axial symptoms by 28.4% at 1-yr follow-up. In total, 3 m TUG (Time-Up Go test) improved by 41% at 6-mo follow-up compared to baseline, which lasts for 1 yr. In total, 64% reduction was found between baseline and 1-yr follow-up in gait and fall questionnaires. No deterioration was found in nonmotor measurements. No adverse events other than stimulation related were reported. CONCLUSION Our results provide the first evidence that supports unilateral STN and contralateral GPi DBS might be effective and safe in advanced PD patients. Future efforts are needed to explore the potential advantage in axial and cognitive symptoms in long term.

Download Full-text