title: Abnormalities in motor cortical plasticity differentiate manifesting and nonmanifesting DYT1 carriers.
abstract: A mutation in the DYT1 gene causes dominantly inherited childhood-onset primary dystonia, but intriguingly, only 30 to 40% of those who carry the mutation ever develop symptoms. We have used the unique model provided by this group of patients to investigate the hypothesis that abnormalities in brain plasticity underlie the pathophysiology of primary dystonia. We recruited 8 DYT1 gene carriers with dystonia, 6 DYT1 gene carriers without dystonia, 6 patients with sporadic primary dystonia (torticollis), and 10 healthy control subjects. Groups were age-matched. We compared the effect in these groups of subjects of repetitive transcranial magnetic stimulation (rTMS) delivered to the motor cortex, by assessing changes in corticospinal excitability following rTMS. rTMS was given in the form of theta burst stimulation (TBS) using the inhibitory protocol "cTBS" (total of 300 pulses in 50-Hz bursts given every 5Hz). DYT1 gene carriers with dystonia and subjects with torticollis had a significantly prolonged response to rTMS in comparison with healthy subjects. In contrast, DYT1 gene carriers without dystonia had no significant response to rTMS. These data demonstrate an excessive response to an experimental "plasticity probing protocol" in subjects with dystonia, but a lack of response in genetically susceptible individuals who have not developed dystonia. These preliminary data suggest that the propensity to undergo plastic change may affect the development of symptoms in genetically susceptible individuals and that this may be an important mechanism in the pathogenesis of primary dystonia in general.
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, UCL, Queen Square, London, United Kingdom.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Edwards
authors.forename: Ying-Zu
authors.initials: YZ
authors.lastname: Huang
authors.forename: Pablo
authors.initials: P
authors.lastname: Mir
authors.forename: John C
authors.initials: JC
authors.lastname: Rothwell
authors.forename: Kailash P
authors.initials: KP
authors.lastname: Bhatia
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D004421:Dystonia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D004558:Electric Stimulation / Q000379:methods; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D009044:Motor Cortex / Q000473:pathology* / Q000503:physiopathology* / Q000528:radiation effects; D009473:Neuronal Plasticity / Q000502:physiology* / Q000528:radiation effects; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation / Q000379:methods
chemical_list: D018832:Molecular Chaperones; C108175:TOR1A protein, human