Randomized Controlled Trial

. 2024 Nov;11(11):1421-1426.

doi: 10.1002/mdc3.14188. Epub 2024 Aug 13.

Lateralized Subthalamic Stimulation for Axial Dysfunction in Parkinson's Disease: Exploratory Outcomes and Open-Label Extension

Karlo J Lizarraga^{1

2}, Bhairavei Gnanamanogaran^{1

3}, Tameem M Al-Ozzi^{3

4

5

6}, Melanie Cohn^{4

7}, George Tomlinson^{8

9}, Alexandre Boutet^{7

10

11}, Gavin J B Elias^{9

11}, Jürgen Germann^{9

11}, Derrick Soh^{1

12}, Suneil K Kalia^{4

11

13}, Mojgan Hodaie^{4

11}, Renato P Munhoz^{1

4}, Connie Marras^{1

4}, William D Hutchison^{4

5

11

13}, Andres M Lozano^{4

11}, Anthony E Lang^{1

4}, Alfonso Fasano^{1

4

13}

Affiliations

¹ The Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Hospital Network and Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
² Motor Physiology and Neuromodulation Program, Division of Movement Disorders, Department of Neurology, University of Rochester, Rochester, NY, USA.
³ University of Toronto, Toronto, ON, Canada.
⁴ Krembil Research Institute, Toronto, ON, Canada.
⁵ Departments of Surgery and Physiology, Toronto Western Hospital and University of Toronto, Toronto, ON, Canada.
⁶ Graduate Training Center of Neuroscience, Universitätsklinikum Tübingen, Tübingen, Germany.
⁷ Department of Psychology, University of Toronto, Toronto, ON, Canada.
⁸ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁹ University Health Network, Toronto, ON, Canada.
¹⁰ Joint Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.
¹¹ Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, ON, Canada.
¹² Alfred Hospital, Melbourne, VIC, Australia.
¹³ CenteR for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, ON, Canada.

PMID: 39136363
PMCID: PMC11542286
DOI: 10.1002/mdc3.14188

Randomized Controlled Trial

Lateralized Subthalamic Stimulation for Axial Dysfunction in Parkinson's Disease: Exploratory Outcomes and Open-Label Extension

Karlo J Lizarraga et al. Mov Disord Clin Pract. 2024 Nov.

. 2024 Nov;11(11):1421-1426.

doi: 10.1002/mdc3.14188. Epub 2024 Aug 13.

Authors

Affiliations

¹ The Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Hospital Network and Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
² Motor Physiology and Neuromodulation Program, Division of Movement Disorders, Department of Neurology, University of Rochester, Rochester, NY, USA.
³ University of Toronto, Toronto, ON, Canada.
⁴ Krembil Research Institute, Toronto, ON, Canada.
⁵ Departments of Surgery and Physiology, Toronto Western Hospital and University of Toronto, Toronto, ON, Canada.
⁶ Graduate Training Center of Neuroscience, Universitätsklinikum Tübingen, Tübingen, Germany.
⁷ Department of Psychology, University of Toronto, Toronto, ON, Canada.
⁸ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁹ University Health Network, Toronto, ON, Canada.
¹⁰ Joint Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.
¹¹ Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, ON, Canada.
¹² Alfred Hospital, Melbourne, VIC, Australia.
¹³ CenteR for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, ON, Canada.

PMID: 39136363
PMCID: PMC11542286
DOI: 10.1002/mdc3.14188

Abstract

Background: A randomized trial suggested that reducing left-sided subthalamic stimulation amplitude could improve axial dysfunction.

Objectives: To explore open-label tolerability and associations between trial outcomes and asymmetry data.

Methods: We collected adverse events in trial participants treated with open-label lateralized settings for ≥3 months. We explored associations between trial outcomes, location of stimulation and motor asymmetry.

Results: 14/17 participants tolerated unilateral amplitude reduction (left-sided = 10, right-sided = 4). Two hundred eighty-four left-sided and 1113 right-sided stimulated voxels were associated with faster gait velocity, 81 left-sided and 22 right-sided stimulated voxels were associated with slower gait velocity. Amplitude reduction contralateral to shorter step length was associated with 2.4-point reduction in axial MDS-UPDRS. Reduction contralateral to longer step length was associated with 10-point increase in MDS-UPDRS.

Conclusions: Left-sided amplitude reduction is potentially more tolerable than right-sided amplitude reduction. Right-sided more than left-sided stimulation could be associated with faster gait velocity. Shortened step length might reflect contralateral overstimulation.

Keywords: Parkinson's disease; asymmetry; axial motor function; deep brain stimulation; lateralization.

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Figures

**Figure 1**
Summary of the blinded and open‐label phases of the lateralized STN‐DBS study. Dashed red line: Average values of the bilateral‐STN‐DBS periods. White arrows: Medication adjustments. Black arrows: Treatment failures. Green arrows: Left‐sided amplitude reduction beneficial. Blue arrows: Right‐sided amplitude reduction beneficial.

**Figure 2**
Voxels associated with gait velocity changes when stimulated (P < 0.05, uncorrected) are projected on high‐resolution T1‐weighted template slices (A: axial, B: coronal). Warm colors: Faster gait velocity. Cool colors: Slower gait velocity. Green outlines: STN. Pink outlines: Zona incerta.

See this image and copyright information in PMC

References

1. Lizarraga KJ, Gnanamanogaran B, Al‐Ozzi TM, et al. Lateralized subthalamic stimulation for axial dysfunction in Parkinson's disease: a randomized trial. Mov Disord 2022;37(5):1079–1087. 10.1002/mds.28953. - DOI - PubMed
1. Plotnik M, Giladi N, Balash Y, Peretz C, Hausdorff JM. Is freezing of gait in Parkinson's disease related to asymmetric motor function? Ann Neurol 2005;57(5):656–663. 10.1002/ana.20452. - DOI - PubMed
1. Fasano A, Herzog J, Seifert E, et al. Modulation of gait coordination by subthalamic stimulation improves freezing of gait. Mov Disord 2011;26(5):844–851. 10.1002/mds.23583. - DOI - PubMed
1. Castrioto A, Meaney C, Hamani C, et al. The dominant‐STN phenomenon in bilateral STN DBS for Parkinson's disease. Neurobiol Dis 2011;41(1):131–137. 10.1016/j.nbd.2010.08.029. - DOI - PubMed
1. Lizarraga KJ, Jagid JR, Luca CC. Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation on gait kinematics in Parkinson's disease: a randomized, blinded study. J Neurol 2016;263(8):1652–1656. 10.1007/s00415-016-8191-3. - DOI - PubMed

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Lateralized Subthalamic Stimulation for Axial Dysfunction in Parkinson's Disease: Exploratory Outcomes and Open-Label Extension

Affiliations

Lateralized Subthalamic Stimulation for Axial Dysfunction in Parkinson's Disease: Exploratory Outcomes and Open-Label Extension

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous