Parkinson Disease

We recruited 101 people with stroke (58 male, 43 female) from a local self-help group via poster advertisements. People with stroke were included in the study if they: (1) were 50–80 years old; (2) suffered a single stroke that was confirmed by magnetic resonance imaging or computed tomography at least 1 year before the start of the study; (3) scored 7 or higher in the Chinese version of the Abbreviated Mental Test (27 (link)); (4) could speak Chinese (Cantonese); (5) had volitional control of their non-paretic arm; (6) could induce at least minimal anti-gravity movement in the shoulder of their paretic arm; (7) had at least 5° of wrist extension in the anti-gravity position; and (8) could walk independently for at least 10 m with or without an assistive device. People with chronic stroke were excluded if they: (1) had any other unstable medical conditions (e.g., angina pectoris, pain, or arthritis) or other conditions with medications that may intervene the upper limb function (e.g., Parkinson's disease or Multiple Sclerosis); and (2) had any aphasia or hearing impairment that would affect the data collection procedure.
We recruited 50 healthy older adults (14 male, 36 female) aged 50–80 years with stable health as the control group. People with any comorbid neurological, cardiovascular, or musculoskeletal disease that might affect the assessment were excluded.
The 15-item UEFI has demonstrated excellent test–retest reliability (ICC_{2, 1} = 0.95) in people with upper extremity musculoskeletal disorders (19 (link)). However, its reliability in people with stroke has not been evaluated. Assuming that an ICC value for assessing test–retest reliability of the 15-item UEFI in people with stroke was 0.9, a sample size of ≥46 subjects was required to achieve 80% power to detect an ICC of 0.9 with a null hypothesis ICC of 0.8 and a significance level of 0.05. To evaluate the ability of the C-UEFI to discern differences between different groups, ≥50 people with chronic stroke and ≥50 healthy controls were required with a CA₀ value of 0.3 and CA₁ value of 0.7 (28 (link)). A sample of >100 people with chronic stroke were regarded as reasonable based on the exploratory factor analysis (EFA) estimation (29 (link)). Thus, 101 people with stroke were recruited for this study.

The full UPDRS is a standardized evaluation test for both motor and non-motor deficits of Parkinson's disease (Goetz et al., 2008 (link)) and was utilized in this experiment to assess the baseline of subjects. Since this research mainly focused on the symptom of tremor, a subscale consisting of Part III in UPDRS (UPDRS-III, Motor Examination) was used instead after intervention. The excluded parts were: (Part I) Non-motor Experiences of Daily Living, (Part II) Motor Experiences of Daily Living and (Part IV) Motor Complications, which were less associated with the immediate response of tremor.
FTMTRS is a tool used to evaluate tremor severity in human body (Fahn et al., 1993 ). The full scale was used in the pre-intervention evaluation to assess baseline. A subscale comprising Part A and Part B in FTMTRS was used as a corresponding post-intervention evaluation. We excluded Part C: Functional Disabilities Resulting from Tremor for it had less relevance with the short-term response in tremor.
PPT is a tool for manipulative dexterity evaluation and requires the subject to place the specific small objects as many as possible in the limited time (Tiffin and Asher, 1948 (link)). Since upper limb tremor was one of the factors that affect subject's hand dexterity, we assumed any change in subject's performance in PPT manifested the change in tremor severity. The scale consists of four parts: (1) moving pins with the right hand, (2) moving pins with the left hand, (3) moving pins with both hands and (4) assembling pins, collars and washers with both hands. We followed the standard procedure to implement PPT over subjects. Subjects were instructed to practice the tasks before the evaluation and afterwards underwent a three-trial PPT in both the pre- and post-evaluation.

The research has been approved by the Chinese Clinical Trial Registry (Registration No.: ChiCTR2100054804) and the local Ethics Committee of Shanghai Jiao Tong University, China (Approved No. of Ethic Committee: 2019 Clinical Trial No. 136). All subjects provided written consent after being informed of the purpose and the procedures of the experiment. The overall experiment was strictly performed in accordance with all relevant guidelines and regulations of the institutional review board and the Declaration of Helsinki. Patients were recruited by the department of neurology of Rui Jin Hospital (Shanghai, China). All of them were out-patients with upper limb tremor resulted from Parkinson's disease (Excluded N = 11; Not meeting the inclusion criteria N = 7; Declined to participate N = 4) (Figure 1).
The inclusion criteria for subjects were: (1) age between 50 and 80 years old, (2) confirmed diagnosis of idiopathic Parkinson's disease according to the MDS clinical diagnostic criteria for PD (Postuma et al., 2015 (link)), (3) symptom of upper limb tremor (rest tremor or postural tremor) resulted from PD, and (4) modified Hoen & Yahr (H&Y) Stage 1 to 3 (Hoehn and Yahr, 1967 (link)). The exclusion criteria included: (1) history of other diseases that may lead to pathological tremor, such as essential tremor (Deuschl et al., 1998 (link)), (2) under the treatment of other neuromodulation therapy, such as DBS, within recent 1 month, (3) history of mental problems, including anxiety, dementia, hallucination or delusion etc., (4) strong reliance on anti-Parkinson medications, or (5) history of cognitive disorder [Mini-mental State Examination (MMSE) score ≤ 16] (Tombaugh and McIntyre, 1992 (link)).
The average disease duration of PD among all subjects [7M/6F, all right-handed, aged 67.5 ± 4.9 (mean ± SD)] were 4.38 ± 1.86 (mean ± SD) years. The Unified Parkinson's Disease Rating Scale (UPDRS) score ranged from 20 to 78 [31.7 ± 15.4 (mean ± SD)] while the modified H&Y stage ranged from 1.0 to 3.0 [1.8 ± 0.8 (mean ± SD)]. The tremor was found to be lateralized in all subjects. Throughout the manuscript, we refer to the more-affected side (MAS) as the side of body exhibiting more severe tremor, which was determined visually by an experienced physician, while the less-affected side (LAS)was defined as the other. Of all subjects, about half (n = 7) were found to be more-affected by tremor on the left side with the other half (n = 6) on the right side. The average levodopa-equivalent daily dose (LEDD) among all subjects was 278.8 ± 203.3 (mean ± SD) mg according to the calculation protocol provided by Tomlinson et al. (2010 (link)). In order to exclude drug effects, all subjects were told to discontinue anti-Parkinson medications on the day of the experiment, which ensured a withdrawal period of more than 12 h. Anti-Parkinson medications were resumed immediately after the experiment session of the day.