Joaquin A Vizcarra1, Miguel Situ-Kcomt2, Carlo Alberto Artusi3, Andrew P Duker1, Leonardo Lopiano3, Michael S Okun4, Alberto J Espay1, Aristide Merola5. 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.
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.
Entities:
Keywords:
Deep brain stimulation; Levodopa; Parkinson; Subthalamic nucleus; Synergism
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