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  • Review Article
  • Published:

Axial disability and deep brain stimulation in patients with Parkinson disease

Nature Reviews Neurology volume 11, pages 98–110 (2015)Cite this article

Subjects

Key Points

  • Some patients with levodopa-responsive axial signs can benefit from deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi)

  • Postural instability and related falls are unlikely to respond to DBS, and can in fact worsen after surgery, particularly after STN procedures

  • STN DBS might provide greater alleviation of axial symptoms than GPi DBS; by contrast, GPi DBS might be associated with a milder long-term decline with regard to these symptoms

  • Worsening of axial disability after DBS is likely to be multifactorial, owing to progression of underlying pathology, adverse effects of surgery and/or stimulation, changes in medications, and comorbidities

  • DBS of the pedunculopontine nucleus area is still an experimental procedure, and further studies on the selection of patients, optimal target and programming are necessary before it can be recommended

Abstract

Axial motor signs—including gait impairment, postural instability and postural abnormalities—are common and debilitating symptoms in patients with advanced Parkinson disease. Dopamine replacement therapy and physiotherapy provide, at best, partial relief from axial motor symptoms. In carefully selected candidates, deep brain stimulation (DBS) of the subthalamic nucleus or globus pallidus internus is an established treatment for 'appendicular' motor signs (limb tremor, bradykinesia and rigidity). However, the effects of DBS on axial signs are much less clear, presumably because motor control of axial and appendicular functions is mediated by different anatomical–functional pathways. Here, we discuss the successes and failures of DBS in managing axial motor signs. We systematically address a series of common clinical questions associated with the preoperative phase, during which patients presenting with prominent axial signs are considered for DBS implantation surgery, and the postoperative phase, in particular, the management of axial motor signs that newly develop as postoperative complications, either acutely or with a delay. We also address the possible merits of new targets—including the pedunculopontine nucleus area, zona incerta and substantia nigra pars reticulata—to specifically alleviate axial symptoms. Supported by a rapidly growing body of evidence, this practically oriented Review aims to support decision-making in the management of axial symptoms.

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Figure 1: Simplified anatomical structures and pathways of subcortical nuclei involved in the basal ganglia circuitry.
Figure 2: Factors contributing to axial disability.
Figure 3: Timescale of gait problems in Parkinson disease.

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Acknowledgements

C.C.A. has received support from CAPES Foundation, Ministry of Education of Brazil, Brasília-DF 07.040-020, Brazil (proc. 10.139-13-3). B.B. has been supported by the Stichting ParkinsonFonds (SPF) and the National Parkinson Foundation (NPF).

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Authors and Affiliations

  1. Division of Neurology, Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, UHN, University of Toronto, 399 Bathurst Street, 7 Mc412, Toronto, M5T 2S8, ON, Canada

    Alfonso Fasano & Camila C. Aquino

  2. Department of Neurosurgery, Medical School Hannover, Carl-Neuberg Straße 1, Hannover, 30625, Germany

    Joachim K. Krauss

  3. Division of Neurosurgery at the University of British Columbia, 8105–2775 Laurel Street

    Christopher R. Honey

  4. Vancouver General Hospital, Vancouver, V5Z 1M9, BC, Canada

    Christopher R. Honey

  5. Department of Neurology, Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, PO Box 9101, Nijmegen, 6500, HB, Netherlands

    Bastiaan R. Bloem

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  1. Alfonso Fasano
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  2. Camila C. Aquino
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  4. Christopher R. Honey
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  5. Bastiaan R. Bloem
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Contributions

A.F. and C.C.A. researched data for the article and wrote the text. A.F., J.K.K., C.R.H. and B.R.B. reviewed and/or edited the manuscript before submission, and J.K.K. and B.R.B. provided substantial contributions to discussion of the content.

Corresponding author

Correspondence to Alfonso Fasano.

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Competing interests

A.F. has received speaker's fees and research funds from Boston Scientific and Medtronic. J.K.K. is a consultant to Medtronic and has received speaker's fees from St. Jude. C.R.H. has received consultant and speaker fees from Medtronic and research funds from Medtronic and St. Jude. C.C.A. and B.R.B. declare no competing interests.

Supplementary information

Supplementary Table 1

Motor effects of STN and GPi stimulation on axial symptoms in controlled (all available studies) and uncontrolled open-label studies (with a follow-up longer than 5 and 3 years, respectively) (DOC 195 kb)

Supplementary Table 2

Effect of levodopa and DBS on specific gait parameters in gait analysis studies performed in PD patients with bilateral implant targeting STN or GPi (DOC 192 kb)

Supplementary Table 3

Published outcomes of patients with Parkinson disease and camptocormia who received deep brain stimulation of the STN or GPi (DOC 120 kb)

Supplementary Table 4

Available trials of PPN DBS in PD cohorts (DOC 126 kb)

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Fasano, A., Aquino, C., Krauss, J. et al. Axial disability and deep brain stimulation in patients with Parkinson disease. Nat Rev Neurol 11, 98–110 (2015). https://doi.org/10.1038/nrneurol.2014.252

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