TY - JOUR
T1 - Subthalamic deep brain stimulation and levodopa in Parkinson’s disease
T2 - a meta-analysis of combined effects
AU - Vizcarra, Joaquin A.
AU - Situ-Kcomt, Miguel
AU - Artusi, Carlo Alberto
AU - Duker, Andrew P.
AU - Lopiano, Leonardo
AU - Okun, Michael S.
AU - Espay, Alberto J.
AU - Merola, Aristide
N1 - Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
KW - Deep brain stimulation
KW - Levodopa
KW - Parkinson
KW - Subthalamic nucleus
KW - Synergism
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U2 - 10.1007/s00415-018-8936-2
DO - 10.1007/s00415-018-8936-2
M3 - Review article
C2 - 29909467
AN - SCOPUS:85048554871
SN - 0340-5354
VL - 266
SP - 289
EP - 297
JO - Journal of Neurology
JF - Journal of Neurology
IS - 2
ER -