Quantifying upper limb motor impairment in people with Parkinson’s disease: a physiological profiling approach

Participants

Thirty-four people with Parkinson’s disease participated in the study (47 to 87 years, 22 males and 12 females). All participants provided written and verbal consent prior to participation. Participants were recruited from three Parkinson’s New South Wales support groups located on the Mid North Coast, New South Wales, Australia. For inclusion, participants had to be aged 18 years or older, and have had received a clinical diagnosis of PD by a neurologist with a score of 1–4 on the Hoehn and Yahr (HY) scale. Prospective participants were excluded if they could not provide verbal or written consent, were unable to follow test instructions, or have any concurrent musculoskeletal and/neurological condition that could affect test performance. Testing took place in March 2019 and was conducted at a testing facility or within participants’ homes.

For each participant with PD, two age- and gender-matched controls without PD were randomly selected from the database of a research study previously conducted at Neuroscience Research Australia (Ingram et al., 2019). Ethical approval was granted by the Human Research Ethics Committee, University of New South Wales (HC 15607). All assessments were conducted in accordance with the Declaration of Helsinki (2008).

Procedure

Each PD participant was tested twice, i.e., in their ‘on’ and ‘off’ medication states. The order in which this occurred was determined by participant convenience and logistics. At the beginning of the initial assessment, participants completed the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire (Hudak, Amadio & Bombardier, 1996). The DASH is a 30-item questionnaire used to measure upper-extremity function (Beaton et al., 2001). Participants are scored on a 100-point scale, with higher values indicating increased levels of self-reported upper limb impairment. DASH scores were not calculated until after the completion of testing. Visual acuity was screened using a Logarithmic Visual Acuity Chart (SLOAN Two Sided ETDRS Format Near Point Test) calibrated for testing at 40 cm (Precision Vision, USA). This was to ensure that each participant had satisfactory vision to complete the subsequent tests (Lovie-Kitchin, 2015). Visual aids were permitted where necessary. Participants then completed the upper limb tests (see below). A single examiner assessed all participants with each test session taking approximately 60 min.

The upper limb PPA consists of 13 tests (with a total of 16 test measures) classified into the physiological domains of muscle strength, unilateral movement and dexterity, position sense, skin sensation, bimanual coordination, arm stability and functional tasks. The tests have been shown to be sensitive in detecting motor impairments in people with compromised upper limb function from the general population. Age and gender normative scores are available for each test (Ingram et al., 2019). Each of the 13 tests are outlined briefly below, and have been described in detail previously (Ingram et al., 2019).

Measurements

Muscle strength was assessed at the elbow (isometric elbow flexion strength) and the hand (handgrip strength). Isometric elbow flexion strength was assessed using a digital hanging scale anchored to a portable wooden platform situated beneath the chair while participants were seated with the elbow joint flexed at 90° and forearm supinated. Handgrip strength was assessed with Jamar+ Digital Dynamometer. The best of three trials (measured in kilograms) was recorded as the test score. Unilateral movement and dexterity were assessed via finger-press reaction time, finger tapping, 9-hole peg test, and the loop & wire test. Finger-press reaction time was assessed in milliseconds using a modified computer mouse containing a light stimulus embedded in the left button, which participants responded to by pressing the right button. The number of times participants could tap their index finger on a touch pad over a 10-second period provided the test score for the finger tapping test. The 9-hole peg test (9-HPT) was measured (in seconds) as the time taken for the participant to pick up each peg individually, place them into each of the holes, and then return them to the molded dish (Kellor M, 1971; Mathiowetz et al., 1985). The average number of times the participant touched the copper wire maze on each of the two trials of the loop & wire test was recorded as the test score. Position sense was measured using an elbow matching test, where differences (in degrees) in aligning the index fingers was recorded using a clear acrylic sheet marked with a protractor that was vertically aligned to the participants midline, with the average error of 5 trials recorded as the test score. Tactile sensitivity, two-point discrimination and two-line discrimination were used to quantify skin sensation. For tactile sensitivity, von-Frey filaments were used to assess perceptual thresholds (measured in grams) to cutaneous stimuli at the hypothenar eminence. Static two-point discrimination was measured (in mm) using a small- (2–8 mm) and large-interval (9–20 mm) Mackinnon-Dellon Disk-Criminator applied along the mediolateral axis of the distal pad of the index finger. Two-line discrimination measured the smallest distance (in mm) that participants could accurately detect between two lines of 0.6 mm diameter as they progressively separated over a distance of 580 mm. Bimanual coordination was tested using the bimanual pole test where participants moved a screw embedded within a modified swivel stick back and forth through a maze as fast as possible by flexing and extending the wrists in a coordinated manner (measured in seconds). Arm stability was measured as the total path (in degrees) that the participants’ wrist moved as they sat with their outstretched arm held perpendicular to the floor over a period of 30 s. Participants completed four conditions (unweighted eyes open/closed; weighted eyes open/closed). The shirt task was used as a measure of functional performance. Here, participants were timed as they put on a long sleeve shirt and did up all six buttons (measured in seconds).

With the exception of handgrip strength (Roberts et al., 2015) and the 9-hole peg test (Earhart et al., 2028; Shah et al., 2019), none of the upper limb PPA tests have previously been validated in the PD population. However, measures of finger tapping speed and amplitude, tremor and bimanual coordination are all included in the MDS-UPDRS (Movement Disorder Society Task Force on Rating Scales for Parkinson’s Disease, 2003), underscoring their importance in the overall assessment of upper limb function in people with PD. Participants performed each unilateral test with their dominant hand, and were seated for all tests with the exception of the shirt task. The number of trials for each test were based on standard protocols for previously validated tests, and restricted to one or a few trials for some of the novel test to facilitate quick administration and preclude leaning effects.

Data and statistical analysis

Continuous data are reported as mean ± SD or, if normality assumptions were violated, medians (interquartile range [IQR]). Independent t-tests and Mann–Whitney tests were used to contrast performances in each of the upper limb PPA tests between the PD group and the age- and gender-matched healthy controls. Correlations between test performance, age, duration of PD, HY scale and DASH scores were assessed using Pearson’s r and Spearman’s rho, and were interpreted as follows: <0.3 - negligible, 0.3–0.5 - small, 0.5–0.7 - moderate, and >0.7 - strong. Differences in test performance between the ‘off’ and ‘on’ medication states in the PD group were analysed using paired t-tests and Wilcoxon matched pairs tests. Finally, to highlight the degree to which test performances are impaired, test scores for the PD group during the ‘off’ and ‘on’ states were converted to standardised (z) scores based on data from a reference cohort of people without PD (Ingram et al., 2019). By doing so, a score of zero indicates average performance for healthy controls aged 50 years and over and each unit represents one standard deviation: positive and negative scores indicate above and below average performances respectively. The reference cohort was used to compile the profiles, as it is common to our proposed companion papers addressing other neurological conditions such as stroke, and thus provides a robust way to contrast upper limb impairments among clinical groups. For this analysis, variables were log₁₀ transformed if normality assumptions were violated.

For position sense, two-line discrimination and the shirt task, no scores were available for one, three and four participants, respectively, who could not complete the task. With the exception of the two-line discrimination test, these participants were assigned a maximum score, which was calculated as the mean + 3SD’s from data from 124 participants with neurological disorders: 34 participants with PD (the current sample), 50 stroke participants and 40 participants with multiple sclerosis. Maximum scores for these tests were calculated as 13.5° and 300 s for position sense and the shirt task, respectively. For the two-line discrimination test, these participants were assigned the maximum score available for this test: four mm. Furthermore, a small number of participants registered scores that were beyond those maximum scores that were calculated from the same database of 124 participants with neurological disorders (i.e., the mean + 3SD’s for each test). These included finger-press reaction time (n = 1, off state), 9-hole peg test (n = 1, on state), arm stability eyes closed (n = 1, off state; n = 1, on state), arm stability weight eyes open (n = 1, off state), arm stability weight eyes closed (n = 2, off state), and the shirt task (n = 1, off state). In each of these cases, the participant was assigned the maximum score for each of these tests, i.e., 500 ms, 180 s, 400° and 300 s, respectively.

All statistical analyses were performed using GraphPad Prism 7 software and Estimation Statistics Beta (Ho et al., 2019; Cumming & Calin-Jageman, 2016) with the level of significance set at p < 0.05. All data are presented in File S1.

Participant characteristics

Table 1 shows demographic, visual acuity, disease duration, PD severity (HY scale), and self-reported upper limb function measures (DASH scores) for the PD group (n = 34). The mean age was 68.6 years (range = 47–87) with women making up 35% (n = 12) of the sample. All but five participants identified as right-hand dominant. The mean logMAR score was 0.26 (corresponding to a Snellen eye chart score of 6/12 –adequate for all tests in the assessment battery). Twenty-seven participants performed the initial round of testing during their ‘off’ medication phase, between the hours of 0800 and 1000 with no PD medication taken after retiring to bed the night before. The median time since diagnosis was 5.0 years (IQR = 3.0–10.0) and the mean HY scale score was 2.7 (range = 1–4), suggestive of bilateral symptoms with impaired postural reflexes but physically independent. The mean DASH score of 36 out of 100 exceeds the threshold of 15, which indicates self-reported upper limb function (Kennedy et al., 2011).

Demographic, visual acuity and DASH scores for the age- and gender-matched controls are also shown in Table 1 (n = 68). Both the mean logMAR (0.14) and DASH scores (6.6) were lower than in the PD group, indicating better visual acuity and lower levels of self-reported upper limb function, respectively.

For the reference cohort of people without PD (n = 176), the mean age was 70.1 years (range = 50–96) with a 53:47 ratio of females to males (Table 1). Visual acuity and DASH scores were comparable to that of the age- and gender-matched control group.

Comparison with age- and gender-matched controls without PD

During the ‘off’ state, the PD group performed worse than the healthy control group in all tests with the exception of isometric elbow flexion strength, two-point discrimination and two-line discrimination (Table 2 and Figs. 1–2). The same pattern of associations was evident in the ‘on’ state, with the exception that scores in bimanual pole test did not differ between the PD and healthy control participants (Figs. 3–4).

Comparison with normative values

Figure 5 presents test results as standardised (z) scores for the PD group during the ‘off’ and ‘on’ states referenced to the reference cohort without PD (Ingram et al., 2019). These profiles indicate that compared to healthy controls, the PD group was most impaired in the shirt task (z scores < −2), moderately impaired with respect to isometric elbow flexion strength (females, ‘off’ state only), finger-press reaction time, 9-hole peg test, loop and wire test (‘off’ state only), and all four conditions of the arm stability test (except for the two eyes open conditions during the ‘on’ state) (z scores between –1 and –2) and relatively less impaired with respect to the remaining tests (z scores > −1). Figure 6 highlights the inter-individual variability in the clinical presentation of upper limb motor impairments among four PD participants by contrasting their individual performance profiles, each derived from the reference cohort normative values.

Test performance in relation to age, PD duration, disease severity and upper limb function

In the ‘off’ state, poorer performance in the handgrip strength, two-point discrimination and bimanual pole test demonstrated small associations with increased age, while during the ‘on’ state, age showed small and moderate associations with poorer performance in both measures of muscle strength and the 9-hole peg test (Table 3 and Figs. 7 and 8). Finger-press reaction time and tactile sensitivity were the only tests associated with time since PD diagnosis during the ‘on’ medication state, with the direction of the relationship indicating worse performance with longer disease duration. The strengths of these associations were small (0.3–0.5). No tests were significantly associated with disease duration during the ‘off’ state.

During the ‘off’ state, poorer performance in the 9-hole peg test, loop and wire, and bimanual pole test demonstrated small associations with increased PD severity, as measured by the HY scale, while finger-press reaction time and shirt task performance were moderately associated with increased HY scale scores. During the ‘on’ state, finger tapping, loop and wire, arm stability (eyes closed, weight eyes open), and shirt task performance demonstrated small associations with the HY scale, while performance in finger-tapping and 9-hole peg test were moderately associated with the HY scale.

During the ‘off’ state, higher levels of self-reported deficits in upper limb function, as measured by the DASH questionnaire, demonstrated small associations with reduced performance in finger-press reaction time, 9-hole peg test, bimanual pole test, and the shirt task, while both tests of muscle strength and two-point discrimination were moderately associated with the DASH questionnaire scores. Lastly, poorer performance during the ‘on’ state in the 9-hole peg test, and bimanual pole test, arm stability (eyes closed), and the shirt task showed small associations with higher DASH questionnaire scores, while both tests of muscle strength and finger-press reaction time were moderately associated with the DASH.

Comparison of test scores between the ‘on’ and ‘off’ states

Mean (±SD) and median (IQR) test scores between the ‘on’ and ‘off’ medication states are presented in Table 4. Differences in performance were observed for isometric elbow flexion strength, 9-hole peg test, position sense, bimanual pole test and the two weighted conditions of the arm stability test. In each case, participants performed better during the ‘on’ state. There was no difference in performance between medication states for the remaining tests.

Key tests for assessing upper limb function in people with PD

Table 5 presents a weighting system based on validity, reliability and feasibility for determining optimal tests of upper limb function in people with PD. Modelled on a scale devised to identify useful mobility tests for predicting falls in older people (Tiedemann et al., 2008), equal weights were allocated to (i) ability to differentiate between people with PD during their ‘on’ state and healthy controls, (ii) significant correlations with self-reported upper limb function (DASH scores), (ii) ability to detect differences between ‘off’/‘on’ medication states, (iv) feasibility with respect to test administration and (v) demonstrated reliability across the adult lifespan (Ingram et al., 2019). As indicated in Table 5, the handgrip strength, finger-press reaction time, 9-hole peg, bimanual pole, and arm stability tests along with the functional shirt task were identified as key tests.

Clinical implications

The study reveals the extent to which people with PD are impaired across the physiological domains necessary for adequate upper limb function: muscle strength, reaction time, fine motor control and dexterity, bimanual coordination, arm stability and functional tasks. Furthermore, as most of the tests demonstrate good criterion validity against the DASH questionnaire, and are simple and quick to administer, they constitute an excellent assessment battery for assessing upper limb for people with PD in the clinical setting. Here, they may play a valuable role in identifying specific motor impairments, monitoring disease progression and evaluating rehabilitation strategies designed to improve upper limb function. A number of the tests discriminate test performance between the “off” and “on” medication states, and offer scope for evaluating the efficacy of drug therapies and additional assessments to identify people with PD who do and do not respond to levodopa. The greatest asset that the upper limb PPA offers alongside the currently available tests is that it enables clinicians to quantify performance across multiple physiological domains necessary for independence of everyday activities with the upper extremities—each of which will be compromised to various degrees between patients with PD (Jankovic, 2008; Politis et al., 2010). This will allow the development of a performance profile that identifies the specific deficits (and their magnitude) in each individual, thereby tailoring rehabilitation and treatment to each patient’s specific needs.

Strengths and limitations

Strengths of the study included the comprehensive range of upper limb function tests, the assessments undertaken in both the on and off medication states, and the inclusion of participants across a broad age and PD severity ranges (1–4 on the HY scale). We also acknowledge some limitations. First, the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) was not administered in our PD sample, so we are not able contrast upper limb PPA scores with this established PD severity rating scale. However, our analyses contrasted upper limb PPA performances with PD severity as assessed with the HY scale and it is important to note the upper limb PPA was not designed as an alternative to the MDS-UPDRS scale, but rather a complementary quantitative battery of clinical tests that can identify specific sensory and motor impairments in individual patients. Second, due to logistical constraints, some participants may not have been in a complete ‘off’ state for their ‘off’ assessments, as it was not possible to withhold all PD medication for at least 12 h in all participants (McKay, Harrigan & Brašić, 2019). However, the majority of participants would have met this condition as they withheld their first daily PD medication dose till after their ‘off’ assessment. Therefore, if anything, our results may underestimate the ability of the upper limb PPA to document the effects of PD medication on upper limb function. For similar practical reasons, the assessor could not be blinded to medication status and the testing session order could not be randomised, and 27 of the 34 participants completed the initial session in their ‘off’ state and the second session in their ‘on’ state. Consequently, it is possible that learning effects may have influenced the ‘on’ assessments. This may be particularly the case for the bimanual pole test due to the novel nature of this task. Another limitation is that to minimize participant burden, participants performed the unilateral tests with the dominant hand only. However, given that 30 out of the 34 participants included in the current sample scored 2 or more on the HY scale (indicating bilateral involvement of PD-related symptoms), our results should still largely represent the sensorimotor impairments experienced by people with PD when performing everyday activities with their upper limbs. While we did not screen participants for cognitive impairment prior to participation, all included participants were able to follow the test instructions for each test without difficulty. Finally, although previous studies have reported good test-retest reliability for handgrip strength and the 9-hole peg test in people with PD (Villafañe et al., 2016; Proud et al., 2019) and we have reported acceptable test-rest reliability for all measures in a large sample of people without neurological conditions (Ingram et al., 2019), we did not assess test-retest reliability in the current study sample.