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. 2021 Sep 6;7(1):77.
doi: 10.1038/s41531-021-00223-5.

Subthalamic and pallidal deep brain stimulation for Parkinson's disease-meta-analysis of outcomes

M Lenard Lachenmayer  1 , Melina Mürset  2 , Nicolas Antih  3 , Ines Debove  2 , Julia Muellner  2 , Maëlys Bompart  3 , Janine-Ai Schlaeppi  4 , Andreas Nowacki  4 , Hana You  2 , Joan P Michelis  2 , Alain Dransart  3 , Claudio Pollo  4 , Guenther Deuschl  5 , Paul Krack  2
Affiliations

Subthalamic and pallidal deep brain stimulation for Parkinson's disease-meta-analysis of outcomes

M Lenard Lachenmayer et al. NPJ Parkinsons Dis. .

Abstract

Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) and the subthalamic nucleus (STN) has become an established treatment for Parkinson's disease (PD), a recent meta-analysis of outcomes is lacking. To address this gap, we performed a meta-analysis of bilateral STN- and GPi-DBS studies published from 1990-08/2019. Studies with ≥10 subjects reporting Unified Parkinson's Disease Rating Scale (UPDRS) III motor scores at baseline and 6-12 months follow-up were included. Several outcome variables were analyzed and adverse events (AE) were summarized. 39 STN studies (2035 subjects) and 5 GPi studies (292 subjects) were eligible. UPDRS-II score after surgery in the stimulation-ON/medication-OFF state compared to preoperative medication-OFF state improved by 47% with STN-DBS and 18.5% with GPi-DBS. UPDRS-III score improved by 50.5% with STN-DBS and 29.8% with GPi-DBS. STN-DBS improved dyskinesia by 64%, daily OFF time by 69.1%, and quality of life measured by PDQ-39 by 22.2%, while Levodopa Equivalent Daily Dose (LEDD) was reduced by 50.0%. For GPi-DBS information regarding dyskinesia, OFF time, PDQ-39 and LEDD was insufficient for further analysis. Correlation analysis showed that preoperative L-dopa responsiveness was highly predictive of the STN-DBS motor outcome across all studies. Most common surgery-related AE were infection (5.1%) and intracranial hemorrhage (3.1%). Despite a series of technological advances, outcomes of modern surgery are still comparable with those of the early days of DBS. Recent changes in target selection with a preference of GPi in elderly patients with cognitive deficits and more psychiatric comorbidities require more published data for validation.

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Conflict of interest statement

MLL reveived reimbursement of traveling expenses to scientific meeting by Medtronic and Teva Pharmaceutical Industries. JPM received royalties from Merz Pharma Germany and Ipsen Pharma Germany. ID received a research grant from Boston Scientific,as well as reimbursement of traveling from Zambon and Boston scientific, all support outside the submitted work. NA and MB are employees of Aleva Neurotherapeutics. AD is an employee and stockholder of Aleva Neurotherapeutics, and holds patents assigned to Aleva Neurotherapeutics in the field of neuromodulation. AN received travel grants from Boston scientific. He received a research grant from the Swiss Parkinson Foundation CP is co-founder of Aleva Neurotherapeutics and received consultancy fees from Boston Scientific. GD has served as a consultant for Boston Scientific, Aleva, Cavion and Functional Neuromodulation. He has received lecture fees from Boston Scientific and royalties from Thieme publishers. He is a government employee and receives funding for his research through his institution from the German Research Council, the German Ministery of Education and Research and Medtronic. PK reports grants from Swiss National Science Foundation, Roger de Spoelberch Foundation, Bertarelli Foundation, Michael J Fox Foundation, Annemarie Opprecht Foundation, Parkinson Schweiz, research grants from Boston Scientific, and Aleva, lecturing fees paid to employing institution from Boston Scientific and Bial, as well as reimbursement of traveling expenses to scientific meeting by Zambon, all support outside the submitted work. The remaining authors have nothing to disclose.

Figures

Fig. 1
Fig. 1. Estimated decrease in total UPDRS II score following STN-DBS.
Postoperative stimulation-ON/medication-OFF vs. preoperative OFF-medication state: UPDRS II Mean Difference. N = number of subjects at follow-up; FU = follow-up time; CI = confidence interval; RE Model = random-effects model.
Fig. 2
Fig. 2. Estimated decrease in total UPDRS II score following GPi-DBS.
Postoperative stimulation-ON/medication-OFF vs. preoperative OFF-medication state: UPDRS II Mean Difference. N = number of subjects at follow-up; FU = follow-up time; CI = confidence interval; RE Model = random-effects model.
Fig. 3
Fig. 3. Estimated decrease in total UPDRS-III score following STN-DBS.
Postoperative stimulation-ON/medication-OFF vs. preoperative OFF-medication state: UPDRS III Mean Difference. N = number of subjects at follow-up; FU = follow-up time; CI = confidence interval; RE Model = random-effects model.
Fig. 4
Fig. 4. Preoperative L-dopa response predicts STN-DBS motor outcome.
Dose-response relationship between preoperative L-dopa response and improvement in UPDRS-III after STN-DBS, considering average disease duration (color shade), study population size (circle diameter), and randomized controlled trials (red frame). Studies reviewed indicated by first author and year of publication.
Fig. 5
Fig. 5. Estimated decrease in total UPDRS-III score following GPi-DBS.
Postoperative stimulation-ON/medication-OFF vs. preoperative OFF-medication state: UPDRS III Mean Difference. N = number of subjects at follow-up; FU = follow-up time; CI = confidence interval; RE Model = random-effects model.
Fig. 6
Fig. 6. Change in motor complications following STN-DBS.
Postoperative vs. preoperative state: change in mean dyskinesia severity (A) and mean OFF time (B). N = number of subjects at follow-up; FU = follow-up time; CI = confidence interval; RE Model = random-effects model.
Fig. 7
Fig. 7. Change in total PDQ-39 summary index (SI) score following STN-DBS.
Postoperative vs. preoperative state: PDQ-39 (SI) Mean Difference. N = number of subjects at follow-up; FU = follow-up time; CI = confidence interval; RE Model = random-effects model.
See this image and copyright information in PMC

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