Botulinum toxin injections reduce associative plasticity in patients with primary dystonia§

Authors

  • Maja Kojovic MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom
    2. Department of Neurology, University of Ljubljana, Ljubljana, Slovenia
    Search for more papers by this author
  • Antonio Caronni PhD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom
    2. Department of Human Physiology, University of Milan, Milan, Italy
    Search for more papers by this author
  • Matteo Bologna MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom
    2. Department of Neurology and Psychiatry and Neuromed Institute, “Sapienza” University of Rome, Rome, Italy
    Search for more papers by this author
  • John C. Rothwell PhD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom
    Search for more papers by this author
  • Kailash P. Bhatia MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom
    Search for more papers by this author
  • Mark J. Edwards PhD

    Corresponding author
    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom
    • Sobell Department, Institute of Neurology, UCL, Queen Square, London, WC1N 3BG, UK

    Search for more papers by this author

  • Relevant conflicts of interest/financial disclosures: Maja Kojovic has received honoraria for conference travel from EFNS, Movement Disorders Society, Guarantors of Brain, Ipsen, and UCB; Grants from EFNS Scientific Fellowship Grant 2009 and a Lady Astor PhD Grant; and is employed by the Department of Neurology, University of Ljubljana, Slovenia. Antonio Caronni is employed by the Department of Human Physiology, University of Milan, Italy. Matteo Bologna has received an ENS Fellowship Grant 2009 and is employed by the “Sapienza” University of Rome, Italy. John C. Rothwell has received honoraria for conference travel and meetings from the Movement Disorders Society, grants from the Dystonia Medical Research Foundation, Tourette Syndrome Association, and the FP7 Collaborative Project (222918 and 223524), and is employed by University College London. Kailash P. Bhatia is a member of the Movement Disorders Society Scientific Advisory Board, has received honoraria from GSK, Boehringer-Ingelheim, Ipsen, Merz, and Orion pharmaceutical companies and grants from the Wellcome Trust and an MRC award (ref. WT089698), and a Halley Stewart Trust grant through the Dystonia Society UK, and is employed by University College London. Mark J. Edwards has received honoraria from Teva Pharmaceuticals and Orio, an NIHR Clinician Scientist Grant, is employed by University College London, and has received royalties from Oxford University Press for Oxford Specialist Handbook of Parkinson's Disease and Other Movement Disorders.

  • This work was undertaken at UCLH/UCL, which received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.

  • §

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

Abstract

Botulinum toxin injections ameliorate dystonic symptoms by blocking the neuromuscular junction and weakening dystonic contractions. We asked if botulinum toxin injections in dystonia patients might also affect the integrity of sensorimotor cortical plasticity, one of the key pathophysiological features of dystonia. We applied a paired associative stimulation protocol, known to induce long-term potentiation–like changes in the primary motor cortex hand area to 12 patients with cervical dystonia before and 1 and 3 months after botulinum toxin injections to the neck muscles. Primary motor cortex excitability was probed by measuring transcranial magnetic stimulation-evoked motor evoked potentials before and after paired associative stimulation. We also measured the input–output curve, short-interval intracortical inhibition, intracortical facilitation, short afferent inhibition, and long afferent inhibition in hand muscles and the clinical severity of dystonia. Before botulinum toxin injections, paired associative stimulation significantly facilitated motor evoked potentials in hand muscles. One month after injections, this effect was abolished, with partial recovery after 3 months. There were significant positive correlations between the facilitation produced by paired associative stimulation and (1) the time elapsed since botulinum toxin injections and (2) the clinical dystonia score. One effect of botulinum toxin injection treatment is to modulate afferent input from the neck. We propose that subsequent reorganization of the motor cortex representation of hand muscles may explain the effect of botulinum toxin on motor cortical plasticity. © The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Ancillary