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

Karlo J Lizarraga; Bhairavei Gnanamanogaran; Tameem M Al-Ozzi; Melanie Cohn; George Tomlinson; Alexandre Boutet; Gavin J B Elias; Jürgen Germann; Derrick Soh; Suneil K Kalia; Mojgan Hodaie; Renato P Munhoz; Connie Marras; William D Hutchison; Andres M Lozano; Anthony E Lang; Alfonso Fasano

doi:10.1002/mdc3.14188

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

Mov Disord Clin Pract. 2024 Nov;11(11):1421-1426. doi: 10.1002/mdc3.14188. Epub 2024 Aug 13.

Authors

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.

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.

Publication types

Randomized Controlled Trial

MeSH terms

Aged
Deep Brain Stimulation* / methods
Female
Functional Laterality / physiology
Gait Disorders, Neurologic / etiology
Gait Disorders, Neurologic / physiopathology
Gait Disorders, Neurologic / therapy
Humans
Male
Middle Aged
Parkinson Disease* / physiopathology
Parkinson Disease* / therapy
Subthalamic Nucleus* / physiopathology
Treatment Outcome

Abstract

Publication types

MeSH terms

Grants and funding