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.

Effects of non-invasive brain stimulation in dystonia: a systematic review and meta-analysis

“…A total 642 participants were included across 51 studies, with ages ranging from 7 to 79 years ( M = 46.24, SD = 12.29). Four studies included patients with acquired dystonia, associated with Wilson’s disease 46 , 47 or cerebral palsy. 48 , 49 Twenty-two studies included participants who were not on oral medications (e.g.…”

“…A single study applied tACS, 50 and one applied high-frequency (10 Hz) rTMS. 46 Dystonia-specific motor training, kinesiotherapy or biofeedback was employed concurrently with NIBS in eight studies. 32 , 33 , 35 , 36 , 51 – 54 All study designs, participant demographics and characteristics are provided in Table 1 .…”

“…Prior to conducting the meta-analysis, a leave-one-out sensitivity analysis was performed, demonstrating the presence of two outliers 46 , 70 ( Supplementary File 3 ). These studies were therefore removed from all subsequent analyses.…”

Dysfunction of the Lenticular Nucleus Is Associated with Dystonia in Wilson’s Disease

“…On the one hand, these findings may be helpful for the clinical treatment of WD patients with dystonia. Previous studies have found that transcrania magnetic stimulation (TMS) can be used to alleviate and treat some neuropsychiatric disorders and Wilson's disease [30,54]. Other studies have also demonstrated that the dorsolateral prefrontal cortex and cerebellum can serve as targets to treat depression [55,56] and schizophrenia [57,58], respectively.…”

“…Previous studies have reported that the abnormal tension of the biceps brachii and medialis and lateralis gastrocnemius muscle is one of the commonly involved parts of extremities dystonia and can also reveal the degree of dystonia in upper and lower limbs, which can be indirectly reflected by measuring the muscle tension levels of biceps brachii and gastrocnemius muscle [22][23][24][25]. Furthermore, previous dystonia-related studies and our recent dystonia study of WD have shown that the digital muscle function assessment system (MyotonPRO) can reliably assess the degree of extremities dystonia by measuring the muscle tension levels of the biceps brachii and gastrocnemius [26][27][28][29][30]. Therefore, we selected the extremities to measure the biomechanical level of WD patients, and the muscle biomechanical level was assessed using the MyotonPRO by measuring the biceps brachii and medialis and lateralis gastrocnemius muscle on both sides to reflect the degree of dystonia.…”