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Is deep brain stimulation neuroprotective if applied early in the course of PD?

Nature Clinical Practice Neurology volume 4, pages 424–426 (2008)Cite this article

Parkinson's disease (PD) is a progressive and disabling disorder that affects millions worldwide and is characterized by tremor, bradykinesia, rigidity and balance difficulties. Nonmotor features, including cognitive decline, autonomic disorders and sleep disruption, are present in a considerable minority of individuals with PD and dramatically increase disability. Although PD was first described 200 years ago, we have not yet identified the cause or developed a cure or treatment to slow progression. Hundreds of putative neuroprotective agents have been tested in clinical trials over the past two decades, but none of these agents has been successful at preventing the progression of PD. Deep brain stimulation (DBS) of the bilateral subthalamic nucleus (B-STN) is a safe, effective and cost-effective treatment for the motor symptoms of advanced PD,1,2 and recent literature has suggested that DBS may also provide a neuroprotective benefit.3,4 We believe that DBS will be the first therapy proven to slow PD progression, and that it must be applied in the earliest stages of the disease to have such an effect.

Pioneered at the University of Grenoble in the 1980s, B-STN DBS provides long-term symptomatic benefit and improves quality of life for many patients with PD.2,5 However, despite the technique's widespread use, we do not fully understand its mechanism of action—neither the proven symptomatic benefit nor the potential neuroprotective effect. Several theories have been proposed to explain the neuroprotective properties of DBS. One such theory is based on the idea that PD develops after initial injury to the substantia nigra, mainly its pars compacta, causing the substantia nigra to become hypoactive. Other areas of the basal ganglia, including the STN, become hyperactive as a result of loss of inhibition. The STN is the main relay of the indirect pathway of the basal ganglia; it influences motor output through the globus pallidus internus and substantia nigra. The hyperactive STN may promote glutamate excitotoxicity, further accelerating dopaminergic cell death in the substantia nigra. It has been proposed that high-frequency B-STN DBS alters STN activity, resulting in the removal of a source of toxic glutamate input to the substantia nigra, which in turn leads to the preservation of dopaminergic cells.

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Authors and Affiliations

  1. CE Gill is a Research Coordinator in the Division of Movement Disorders, TL Davis is Associate Professor of Neurology and Director of the Division of Movement Disorders, PD Charles is Associate Professor and Vice Chairman of Neurology for Education and Development, and PE Konrad is Associate Professor of Neurosurgery and Biomedical Engineering and Director of Functional Neurosurgery, all at Vanderbilt University School of Medicine, Nashville, TN, USA.,

    P David Charles, Chandler E Gill, Thomas L Davis & Peter E Konrad

  2. A-L Benabid is Professor Emeritus of Biophysics and Neurosurgery at Joseph Fourier University and Professor at CEA Minatec Leti, Grenoble, France.,

    Alim-Louis Benabid

Authors
  1. P David Charles
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  2. Chandler E Gill
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  3. Thomas L Davis
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  4. Peter E Konrad
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  5. Alim-Louis Benabid
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Correspondence to P David Charles.

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Competing interests

Drs Charles, Davis, Konrad and Benabid have received support from Medtronic, Inc in the form of research grants, honoraria or personal compensation. CE Gill declared no competing interests.

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Charles, P., Gill, C., Davis, T. et al. Is deep brain stimulation neuroprotective if applied early in the course of PD?. Nat Rev Neurol 4, 424–426 (2008). https://doi.org/10.1038/ncpneuro0848

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