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Botulinum toxin injections reduce associative plasticity in patients with primary dystonia
Authors:Maja Kojovic MD  Antonio Caronni PhD  Matteo Bologna MD  John C Rothwell PhD  Kailash P Bhatia MD  Mark J Edwards PhD
Institution: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;3. Department of Human Physiology, University of Milan, Milan, Italy;4. Department of Neurology and Psychiatry and Neuromed Institute, “Sapienza” University of Rome, Rome, Italy
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.
Keywords:botulinum toxin  primary dystonia  cervical dystonia  cortical plasticity  paired associative stimulation  transcranial magnetic stimulation  TMS
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