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Dystonia is characterized by abnormal posturing due to sustained muscle contraction, which leads to pain and significant disability. New therapeutic targets are needed in this disorder. The objective of this randomized, sham-controlled, blinded exploratory study is to identify a specific motor system target for non-invasive neuromodulation and to evaluate this target in terms of safety and tolerability in the cervical dystonia (CD) population. Eight CD subjects were given 15-minute sessions of low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (MC), dorsal premotor cortex (dPM), supplementary motor area (SMA), anterior cingulate cortex (ACC) and a sham condition with each session separated by at least two days. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score was rated in a blinded fashion immediately pre- and post-intervention. Secondary outcomes included physiology and tolerability ratings. The mean change in TWSTRS severity score by site was 0.25 ± 1.7 (ACC), -2.9 ± 3.4 (dPM), -3.0 ± 4.8 (MC), -0.5 ± 1.1 (SHAM), and -1.5 ± 3.2 (SMA) with negative numbers indicating improvement in symptom control. TWSTRS scores decreased from Session 1 (15.1 ± 5.1) to Session 5 (11.0 ± 7.6). The treatment was tolerable and safe. Physiology data were acquired on 6 of 8 subjects and showed no change over time. These results suggest rTMS can modulate CD symptoms. Both dPM and MC are areas to be targeted in further rTMS studies. The improvement in TWSTRS scores over time with multiple rTMS sessions deserves further evaluation.

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The research was supported by the Dystonia Coalition (Grant Number U54NS065701) which is a part of the National Institutes of Health (NIH) Rare Disease Clinical Research Network (RDCRN), supported through a collaboration between the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), and the National Institute of Neurological Diseases and Stroke (NINDS). This research was also supported (in part or in full) by the National Center for Research Resources and National Center for Advancing Translational Science (NCATS) through Grant Number KL2TR000089 and Grant Number 8UL1TR000041. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


Trial Registration NCT01859247