Effects of High-Frequency Repetitive Transcranial Magnetic Stimulation on Upper Limb Dystonia in Patients With Wilson's Disease: A Randomized Controlled Trial

Abstract

Background: Upper limb dystonia is a frequent complication of Wilson's disease (WD). It can lead to poor quality of life and disability. Currently, no effective treatment for it exists. Therefore, we carried out a clinical trial to determine whether high frequency repetitive transcranial magnetic stimulation (rTMS) on the primary motor cortex alleviates upper limb dystonia in WD patients. Methods: This study was a single-center, double-blind, randomized clinical study, included 60 WD patients with upper limb dystonia from a research base of WD in Hefei, China. Participants were randomly divided into a treatment group (TG) and a control group (CG). The TG received rTMS at 10 Hz, while the CG received sham stimulation for 7 consecutive days. Participants were assessed at baseline, after the seventh treatment session, and at 2 and 4 weeks after the seventh treatment session. The primary outcomes included patients' objective muscle tension and stiffness as measured with the MyotonPRO device. The secondary results were scores on clinical scales assessing muscle spasm and motor symptoms, which included the Modified Ashworth Scale (MAS), Unified Wilson's Disease Rating Scale (UWDRS), Burke Fahn Marsden Scale (BFM), and the Activities of Daily Living (ADL) scale. Results: The analysis revealed that after 10 Hz rTMS, muscle tension (P < 0.01) and stiffness (P < 0.01) as measured by the MyotonPRO device decreased significantly in the TG compared to the CG. Moreover, clinically relevant scale scores, including the MAS (P < 0.01), UWDRS (P < 0.01), BFM (P < 0.01), and ADL (P < 0.01) were also significantly reduced. Conclusion: High-frequency rTMS over the primary motor cortex may be an effective complementary and alternative therapy to alleviating upper limb dystonia in WD patients. Clinical Trial Registration: http://www.chictr.org.cn/, identifier: ChiCTR2100046258.

Keywords: Wilson's disease; primary motor cortex; randomized controlled trial; repetitive transcranial magnetic stimulation; upper limb myotonia.

Figure 1

Flow chart of the study design.

Figure 2

Flow chart of the study design.

Figure 3

Changes in clinical efficacy after rTMS. (A) The change of the F value. (B) The change of the S value. (C) The change of the UWDRS scores. (D) The change of the AS scores. (E) The change of the BFM scores. (F) The change of the ADL scores. Red: TG; blue: CG. Error bars represent SD; *represent significant difference between TG and CG at the same time point.