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J Neurol. 2019 Feb;266(2):289-297. doi: 10.1007/s00415-018-8936-2. Epub 2018 Jun 16.

Subthalamic deep brain stimulation and levodopa in Parkinson's disease: a meta-analysis of combined effects.

Author information

1
Department of Neurology, Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, 260 Stetson St, Suite 2300, Cincinnati, OH, 45267-0525, USA.
2
Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
3
Department of Neuroscience "Rita Levi Montalcini", University of Turin, via Cherasco 15, 10126, Turin, Italy.
4
Department of Neurology, Center for Movement Disorders and Neurorestoration, McKnight Brain Institute, Gainesville, FL, USA.
5
Department of Neurology, Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, 260 Stetson St, Suite 2300, Cincinnati, OH, 45267-0525, USA. merolaae@ucmail.uc.edu.

Abstract

INTRODUCTION:

While subthalamic nucleus deep brain stimulation (STN-DBS) and levodopa improve motor symptoms in Parkinson disease (PD) to a similar magnitude, their combined effect remains unclear. We sought to evaluate whether STN-DBS and levodopa yield differential effects on motor outcomes, dyskinesia, and activities of daily living (ADL) when combined compared to when administered alone.

METHODS:

We conducted a meta-analysis of all studies reporting motor, dyskinesia, and ADL outcomes after bilateral STN-DBS in PD with presurgical Unified Parkinson's Disease Rating Scale (UPDRS-III) in Medication-OFF and Medication-ON states and postsurgical assessments in four conditions: Stimulation-ON/Medication-ON, Stimulation-ON/Medication-OFF, Stimulation-OFF/Medication-ON, and Stimulation-OFF/Medication-OFF. Dyskinesia duration (UPDRS item 32) and ADL (UPDRS-II) were compared between high and low postsurgical levodopa equivalent daily dose (LEDD) reduction. Random-effects meta-analyses using generic-inverse variance were conducted. Confidence in outcomes effect sizes was assessed.

RESULTS:

Twelve studies were included (n = 401 patients). Stimulation-ON/Medication-ON was associated with an UPDRS-III improvement of - 35.7 points [95% confidence interval, - 40.4, - 31.0] compared with Stimulation-OFF/Medication-OFF, - 11.2 points [- 14.0, - 8.4] compared with Stimulation-OFF/Medication-ON, and - 9.5 points [- 11.0, - 8.0] compared to Stimulation-ON/Medication-OFF within 5 years. The difference was maintained beyond 5 years by - 28.6 [- 32.8, - 24.4], - 8.1 [- 10.2, - 5.9], and - 8.0 [- 10.3, - 5.6], respectively. No difference was observed between Stimulation-ON/Medication-OFF and Stimulation-OFF/Medication-ON within and beyond 5 years. Dyskinesia duration and ADL outcomes were similar in high vs. low postsurgical LEDD reduction.

CONCLUSION:

Subthalamic nucleus deep brain stimulation and levodopa independently lessened motor severity in PD to a similar magnitude, but their combined effect was greater than either treatment alone, suggesting therapeutic synergism.

KEYWORDS:

Deep brain stimulation; Levodopa; Parkinson; Subthalamic nucleus; Synergism

PMID:
29909467
DOI:
10.1007/s00415-018-8936-2
[Indexed for MEDLINE]

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