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General Commentary ARTICLE

Front. Syst. Neurosci., 14 April 2015 | https://doi.org/10.3389/fnsys.2015.00057

A Commentary on: “Preserving cortico-striatal function: Deep Brain Stimulation in Huntington's disease”

  • Department of Neurology, Vanderbilt University, Nashville, TN, USA

A commentary on
Preserving cortico-striatal function: Deep Brain Stimulation in Huntington's disease

by Nagel, S. J., Machado, A. G., Gale, J. T., Lobel, D. A., and Pandya, M. (2015). Front. Syst. Neurosci. 9:32. doi: 10.3389/fnsys.2015.00032

I read Nagel et al. with interest (Nagel et al., 2015). In theory, the potential to modify cognitive function in Huntington's disease (HD) with electrical stimulation or specifically Deep Brain Stimulation (DBS) is exciting. HD is a devastating and terminal disease in need of better treatments, both symptomatic and neuroprotective. Cognitive dysfunction itself is becoming more recognized as a severely disabling aspect of the disease as well (Paulsen and Long, 2014). Nagel et al. outline an intriguing argument for pursuing the globus pallidus externa as a DBS target for cognitive improvement while also acknowledging that the current evidence is based on a small number of animal models and very limited human (n = 2) experience.

In actuality, the practical nature of pursing DBS for the treatment of cognition in HD is more complicated. The ethics of pursuing DBS for new indications is a hotly debated topic (Unterrainer and Oduncu, 2015). We still do not yet fully understand the mechanism of DBS in treating disorders where its efficacy is established. Trialing it for other neurologic conditions without sound rational can be unnecessarily dangerous and not in the best interest of those we are trying to treat. While DBS was relatively free of complications in limited trials for HD chorea, it is not a benign procedure. It is a brain surgery with known irreversible surgical complications including infection, stroke, intracranial bleeding and even death (Bronstein et al., 2011). Some authors cite complication rates in Parkinson's disease as high as 10% for hemorrhage, 2% for stroke, 15% for infection and death rates up to 4.5% (Bronstein et al., 2011). Hardware complications requiring repeat surgery also occur. Finally, cognition and behavior have also been known to be negatively impacted after DBS surgery, albeit more often cited in the subthalamic target for Parkinson's disease. Still, there are accounts of cognitive decline and even mania after pallidal DBS as well (Miyawaki et al., 2000; Rothlind et al., 2014). Considering these known potential neuropsychiatric complications, trials of DBS for HD would need to proceed very cautiously given the high incidence of pre-existing cognitive dysfunction and increased risk for suicide.

Lastly, I would caution against making any statements alluding to slowing disease progression or neuroprotection given the current data, especially to perspective future participants in any DBS trials. This is too premature. This is indeed a desperate population and the ability to identify subjects early in the prodromal stage of the disease increases the potential for inappropriate and improper recruitment to any future trials. Any research using DBS in this population needs to be done slowly with the highest ethical standards and rigorous consenting protocols. Personally, while I commonly recommend DBS for my patients for treatment of currently approved indications and participate in a high volume of surgeries, I am still holding out hope for a medicinal, neuroprotective therapy that would have reversible adverse effects and not carry the risk of a brain surgery.

Conflict of Interest Statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

Bronstein, J., Tagliati, M., Alterman, R., Lozano, A., Volkmann, J., Stefani, A., et al. (2011). Deep brain stimulation for Parkinson's disease. Arch. Neurol. 68, 165–170. doi: 10.1001/archneurol.2010.260

PubMed Abstract | Full Text | CrossRef Full Text | Google Scholar

Miyawaki, E., Perlmutter, J. S., Troster, A. L., Videen, T. O., and Koller, W. C. (2000). The behavioral complications of pallidal stimulation: a case report. Brain Cogn. 42, 417–434. doi: 10.1006/brcg.1999.1113

PubMed Abstract | Full Text | CrossRef Full Text | Google Scholar

Nagel, S. J., Machado, A. G., Gale, J. T., Lobel, D. A., and Pandya, M. (2015). Preserving cortico-striatal function: deep brain stimulation in Huntington's disease. Front. Syst. Neurosci. 9:32. doi: 10.3389/fnsys.2015.00032

PubMed Abstract | Full Text | CrossRef Full Text | Google Scholar

Paulsen, J. S., and Long, J. D. (2014). Onset of Huntington's Disease: can it be purely cognitive? Mov. Disord. 29, 1342–1350. doi: 10.1002/mds.25997

PubMed Abstract | Full Text | CrossRef Full Text | Google Scholar

Rothlind, J., York, M., Carlson, K., Luo, P., Marks, W., Weaver, F., et al. (2014). Neuropsychological changes following deep brain stimulation surgery for Parkinson's disease: comparisons of treatment at pallidal and subthalamic targets versus best medical therapy. Neurol. Neurosurg. Psychiatry. doi: 10.1136/jnnp-2014-308119. [Epub ahead of print].

PubMed Abstract | Full Text | CrossRef Full Text | Google Scholar

Unterrainer, M., and Oduncu, F. (2015). The ethics of deep brain stimulation (DBS). Med. Health Care Philos. doi: 10.1007/s11019-015-9622-0. [Epub ahead of print].

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Keywords: Huntington's disease, Deep Brain Stimulation, electrostimulation, neuroprotection, globus pallidus

Citation: Tolleson CM (2015) A Commentary on: “Preserving cortico-striatal function: Deep Brain Stimulation in Huntington's disease.” Front. Syst. Neurosci. 9:57. doi: 10.3389/fnsys.2015.00057

Received: 27 February 2015; Accepted: 25 March 2015;
Published: 14 April 2015.

Edited by:

Mikhail Lebedev, Duke University, USA

Reviewed by:

Zoltan Nadasdy, NeuroTexas Institute and Research Foundation, USA
Saul Martinez-Horta, Hospital de la Santa Creu i Sant Pau, Spain

Copyright © 2015 Tolleson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Christopher M. Tolleson, christopher.tolleson@vanderbilt.edu