Emerging concepts in the physiological basis of dystonia

Authors

  • Angelo Quartarone MD,

    Corresponding author
    1. Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York (CUNY), New York, NY, USA
    2. Department of Neurology, Division of Movement Disorders, New York University, New York, New York, USA
    3. Istituto Di Ricovero e Cura a Carattere Scientifico (IRCSS) Centro “Bonino Pulejo,”, Messina, Italy
    • Department of Neurosciences, Psychiatry, and Anaesthesiological Science, University of Messina, Messina, Italy
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  • Mark Hallett MD

    1. Human Motor Control Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland, USA
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  • Relevant conflicts of interest/financial disclosures: Full financial disclosures and author roles may be found in the Acknowledgments section online.

Correspondence to: Dr. Angelo Quartarone, Department of Neurosciences, Psychiatry & Anaesthesiological Science, University of Messina, Via Consolare Valeria 1, Messina 98125, Italy; angelo.quartarone@unime.it

ABSTRACT

Work over the past 2 decades has led to substantial changes in our understanding of dystonia pathophysiology. Three general abnormalities appear to underlie the pathophysiological substrate. The first is a loss of inhibition. This makes sense considering that it may be responsible for the excess of movement and for the overflow phenomena seen in dystonia. A second abnormality is sensory dysfunction which is related to the mild sensory complaints in patients with focal dystonias and may be responsible for some of the motor dysfunction. Third, evidence from animal models of dystonia as well as from patients with primary dystonia has revealed significant alterations of synaptic plasticity characterized by a disruption of homeostatic plasticity, with a prevailing facilitation of synaptic potentiation, together with the loss of synaptic inhibitory processes. We speculate that during motor learning this abnormal plasticity may lead to an abnormal sensorimotor integration, leading to consolidation of abnormal motor engrams. If so, then removing this abnormal plasticity might have little immediate effect on dystonic movements because bad motor memories have already been ‘‘learned'' and are difficult to erase. These considerations might explain the delayed clinical effects of deep brain stimulation (DBS) in patients with generalized dystonia. Current lines of research will be discussed from a network perspective. © 2013 Movement Disorder Society

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