Deep brain stimulation effects in dystonia: Time course of electrophysiological changes in early treatment§

Authors

  • Diane Ruge MD,

    Corresponding author
    1. Sobell Department of Motor Neuroscience and Movement Disorders, UCL–Institute of Neurology, University College London, London, United Kingdom
    • Sobell Department of Motor Neuroscience and Movement Disorders, UCL–Institute of Neurology, University College London, 33 Queen Square (Box 146), London WC1N3BG, UK
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  • Stephen Tisch MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, UCL–Institute of Neurology, University College London, London, United Kingdom
    2. Department of Neurology, St. Vincent's Hospital, Sydney, Australia
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  • Marwan I. Hariz MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, UCL–Institute of Neurology, University College London, London, United Kingdom
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  • Ludvic Zrinzo MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, UCL–Institute of Neurology, University College London, London, United Kingdom
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  • Kailash P. Bhatia MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, UCL–Institute of Neurology, University College London, London, United Kingdom
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  • Niall P. Quinn MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, UCL–Institute of Neurology, University College London, London, United Kingdom
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  • Marjan Jahanshahi PhD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, UCL–Institute of Neurology, University College London, London, United Kingdom
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  • Patricia Limousin MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, UCL–Institute of Neurology, University College London, London, United Kingdom
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  • John C. Rothwell PhD

    1. Sobell Department of Motor Neuroscience and Movement Disorders, UCL–Institute of Neurology, University College London, London, United Kingdom
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  • Funding agencies: This study was funded by the Dystonia Medical Research Foundation (DMRF) and Action Medical Research. This work was undertaken at UCLH/UCL which received a portion of the funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. The work was further supported by a grant from Medtronic, by the National Institutes of Health under grant RO1-NS40902 (PI:DC), and by the Medical Research Council UK.

  • Relevant conflicts of interest/financial disclosures: Diane Ruge was funded by Action Medical Research and the Dystonia Medical Research Foundation (DMRF). Stephen Tisch was funded by Action Medical Research, the Brain Research Trust, Medtronic UK, and the Parkinson's Appeal. Patricia Limousin, Ludvic Zrinzo, and Marwan I. Hariz were supported by the Parkinson's Appeal. Ludvic Zrinzo and Marwan I. Hariz also received occasional honoraria from industry for educational talks at meetings. Kailash P. Bhatia received honoraria/financial support to speak/attend meetings from GSK, Boehringer-Ingelheim, Ipsen, Merz, and Orion pharmaceutical companies and grants from the Dystonia Society UK and Halley Stewart Trust.

  • §

    Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Deep brain stimulation to the internal globus pallidus is an effective treatment for primary dystonia. The optimal clinical effect often occurs only weeks to months after starting stimulation. To better understand the underlying electrophysiological changes in this period, we assessed longitudinally 2 pathophysiological markers of dystonia in patients prior to and in the early treatment period (1, 3, 6 months) after deep brain stimulation surgery. Transcranial magnetic stimulation was used to track changes in short-latency intracortical inhibition, a measure of excitability of GABAA-ergic corticocortical connections and long-term potentiation-like synaptic plasticity (as a response to paired associative stimulation). Deep brain stimulation remained on for the duration of the study. Prior to surgery, inhibition was reduced and plasticity increased in patients compared with healthy controls. Following surgery and commencement of deep brain stimulation, short-latency intracortical inhibition increased toward normal levels over the following months with the same monotonic time course as the patients' clinical benefit. In contrast, synaptic plasticity changed rapidly, following a nonmonotonic time course: it was absent early (1 month) after surgery, and then over the following months increased toward levels observed in healthy individuals. We postulate that before surgery preexisting high levels of plasticity form strong memories of dystonic movement patterns. When deep brain stimulation is turned on, it disrupts abnormal basal ganglia signals, resulting in the absent response to paired associative stimulation at 1 month. Clinical benefit is delayed because engrams of abnormal movement persist and take time to normalize. Our observations suggest that plasticity may be a driver of long-term therapeutic effects of deep brain stimulation in dystonia. © 2011 Movement Disorder Society

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