Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Dec 16:14:100417.
doi: 10.1016/j.prdoa.2025.100417. eCollection 2026.

Differentiating effects of levodopa and subthalamic nucleus deep brain stimulation on motor features in Parkinson disease

Tiffanie A Lee  1 , Deepa Ramesh  1 , Mwiza Ushe  2 , Scott A Norris  2   3 , Samer D Tabbal  2 , Joel S Perlmutter  2   3   4 , John R Younce  1
Affiliations

Differentiating effects of levodopa and subthalamic nucleus deep brain stimulation on motor features in Parkinson disease

Tiffanie A Lee et al. Clin Park Relat Disord. .

Abstract

Introduction: While deep brain stimulation of the subthalamic nucleus (STN DBS) is traditionally used to treat motor fluctuations in Parkinson disease (PD), recent progress in levodopa delivery systems may offer non-invasive alternatives to surgical options. To gain insight into symptoms more likely to be treated effectively by STN DBS or levodopa, we systematically compared the differential effects of levodopa and STN-DBS on specific parkinsonian motor components.

Methods: We retrospectively analyzed 395 PD patients who received bilateral STN-DBS at Washington University (1999-2020). UPDRS-III was obtained in three conditions: preoperative OFF-medication, preoperative ON-medication, and postoperative ON-DBS/OFF-medication. Exploratory factor analysis identified a consensus structure across conditions. Treatment responses by factor were compared using Wilcoxon rank-sum tests and correlations were assessed with Kendall's tau.

Results: Both treatments significantly improved all motor features. STN-DBS showed slightly superior efficacy for upper body tremor (mean change: -3.84 vs -3.43, p < 0.001), while levodopa demonstrated much greater effectiveness for axial symptoms (-5.41 vs -2.65, p < 0.001), and slightly greater effectiveness for lower body tremor (-1.25 vs -1.06, p < 0.001), and lower body bradykinesia (-1.18 vs -0.91, p = 0.005). Correlations between treatment responses were weak but statistically significant for rigidity (τ = 0.158), bradykinesia (hand: τ = 0.118; leg: τ = 0.179), and axial symptoms (τ = 0.207).

Conclusion: Levodopa and STN-DBS demonstrate similar but distinct therapeutic profiles across parkinsonian motor domains. However, weak correlations between treatment modalities for all motor features challenge the utility of levodopa responsiveness for DBS candidacy and support individualization of treatment selection based on symptom profile.

Keywords: Deep brain stimulation; Factor analysis; Levodopa; Parkinson disease.

PubMed Disclaimer

Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: John Younce reports financial support was provided by National Institutes of Health. Joel Perlmutter reports financial support was provided by National Institutes of Health. Joel Perlmutter reports financial support was provided by American Parkinson Disease Association. Joel Perlmutter reports financial support was provided by Saint Louis American Parkinson Disease Association. Joel Perlmutter reports financial support was provided by Foundation for Barnes-Jewish Hospital. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Relative response to levodopa and DBS for each parkinsonian factor composite score in percent change. Instances with baseline OFF score of zero were excluded. To facilitate visualization of overall trends, jitter of up to 2 percent was applied and outliers of over 100% change were not shown. Cluster at −100/-100 included 146 of 349 subjects for upper tremor, 112 of 173 subjects for lower tremor, and 55/376 subjects for rigidity.
See this image and copyright information in PMC

References

    1. Deep-Brain Stimulation for Parkinson’s Disease Study Group, Obeso JA, Olanow CW, et al. Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson’s disease. N. Engl. J. Med. [online serial]. 2001;345:956–963. Accessed at: http://www.ncbi.nlm.nih.gov/pubmed/11575287. - PubMed
    1. Rodriguez R.L., Fernandez H.H., Haq I., Okun M.S. Pearls in patient selection for deep brain stimulation. Neurologist [online Serial]. 2007;13:253–260. http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=0... Accessed at: - PubMed
    1. Welter M.L., Houeto J.L., Tezenas du Montcel S., et al. Clinical predictive factors of subthalamic stimulation in Parkinson’s disease. Brain [online Serial]. 2002;125:575–583. http://www.ncbi.nlm.nih.gov/pubmed/11872614 - PubMed
    1. Charles P.D., Van Blercom N., Krack P., et al. Predictors of effective bilateral subthalamic nucleus stimulation for PD. Neurology. 2002;59:932–934. - PubMed
    1. Zaidel A., Bergman H., Ritov Y., Israel Z. Levodopa and subthalamic deep brain stimulation responses are not congruent. Mov. Disord. [online Serial]. 2010;25:2379–2386. http://www.ncbi.nlm.nih.gov/pubmed/20824733 Accessed at: - PubMed

LinkOut - more resources