Quantitative clinical assessment of motor function during and following LSVT-BIG® therapy

The premise of the speed-amplitude relationship in healthy motor control is that larger amplitude movements are performed at proportionally higher speeds [1, 2]. The speed-amplitude relationship is disproportionately scaled in Parkinson’s disease (PD) [3, 4] and exercise interventions attempting to target this relationship have been shown to encourage natural mobility in individuals with PD [4‐6]. One therapy model incorporating this concept is Lee Silverman Voice Therapy – BIG (LSVT-BIG®), developed as a large-amplitude exercise for individuals with PD, incorporating stretching and stepping exercises in combination with functional tasks related to daily living [6‐12].

Research evaluating the clinical efficacy of LSVT-BIG® in individuals with PD has thus far been limited [13]. In a study of large amplitude therapy by Farley & Koshland, the first to reference ‘BIG’ exercises, significant increases in gait velocity, stride length, and wrist velocity were observed in 18 PD subjects following therapy [6]. A later study by Ebersbach et al., comparing LSVT-BIG® to a Nordic walking and a home exercise programme, reported significant improvements in MDS-UPDRS III motor scores and Timed-Up-and-Go times, whereas no significant differences were observed in the comparative therapies [9]. In a follow-on study examining cognitive aspects of motor preparation, LSVT-BIG® and Nordic Walking were both shown to improve cued reaction times, but not non-cued reaction times [14]. Despite the various benefits of LSVT-BIG® reported in the literature, issues remain regarding heterogeneity of UPDRS-III scores [13, 15], potentially reflecting the subjectivity or inconsistency of such scores. The disparities in clinical scoring emphasize the need for more objective, quantitative measures of motor function to accurately monitor and assess efficacy of therapeutic interventions in PD.

To obtain a more comprehensive depiction of patient motor function, recent studies have employed body-worn sensors to instrument standard clinical tests, such as the instrumented Timed-Up-and-Go [16‐21] and the instrumented Sit-to-Stand [22‐24]. These instrumented tests provide an array of quantitative features that can distinguish specific characteristics of motor function in individuals with PD [18, 25‐29]. Similarly, studies have used accelerometry (ACC) to analyse postural control in individuals with PD [30‐32], and to investigate differences in features of the gait cycle between PD and healthy control subjects, such as step time, swing time and stride time [27, 28, 33, 34]. While these studies highlight the advantages of instrumenting clinical tests to examine patient mobility, there remains a dearth of research incorporating body-worn sensors to monitor and quantitatively assess adaptations in motor function occurring at various stages of physical therapy. Furthermore, few studies have combined a range of instrumented tests to characterise separate aspects of motor function simultaneously.

Against this background, the present work aims to integrate a range of ACC-derived features to extensively examine motor function in individuals with PD, before, each week during, and up to 13 weeks after LSVT-BIG® therapy. Through instrumenting five standard clinical tests – instrumented Sit-to-Stand, instrumented Timed-Up-and-Go, quiet stance, instrumented 10 m walking test and finger tapping – a series of ACC-derived measures are used to examine adaptations in gait, posture, balance and fine motor control, which are then compared with those of healthy age-matched controls and non-exercising PD controls. Overall, this study aims to establish the feasibility of incorporating body-worn accelerometers to objectively monitor and assess adaptions in motor function in individuals with PD following large-amplitude exercise therapy.

Significant improvements in the i10MW walk time (F = 5.88; p <  0.001) and iTUG time (F = 13.94; p <  0.001) were observed in the PD_LSVT cohort over the course of LSVT-BIG® therapy, Figs. 3 & 5 and Table 3. Temporal parameters of the gait cycle steadily decreased throughout therapy in both the i10MW and iTUG tasks, with significant reductions observed in step time (i10MW: F = 9.12, p <  0.001; iTUG: F = 7.54, p <  0.001), stride time (i10MW: F = 8.63, p <  0.001; iTUG: F = 7.03, p <  0.001), swing time (i10MW: F = 5.34, p <  0.001; iTUG: F = 4.31, p <  0.001) and stance time (i10MW: F = 3.22, p = 0.037; iTUG: F = 3.23, p = 0.004), Fig. 4. Post-hoc analysis showed that significantly lower gait times predominantly occurred at follow-up stages (Post1 – Post3) when compared to pre-therapy (Pre1, Pre2), Figs. 4 & 6. No effect was observed for the stage of therapy on the gait asymmetry (p = 0.93), gait regularity (p = 0.32), or step time variance (p = 0.56) measures. While the time to first step did not change in the iTUG task (p = 0.501), the total step count significantly decreased with therapy (F = 2.86, p <  0.011), Fig. 6.

The iSTS count also significantly improved with therapy (F = 14.39; p <  0.001) matched by a significant reduction in the total average Sit-to-Stand time (F = 10.12, p <  0.001), Standing time (F = 8.36, p <  0.001), Sitting time (F = 10.06, p <  0.001), complete stance time (F = 5.63, p = 0.011), and complete sit time (F = 3.73, p = 0.046), Figs. 7 & 8 and Table 3. As observed in the i10MW and iTUG tasks, post-hoc comparisons showed significant differences in iSTS measures predominantly occurring between pre-therapy (Pre1, Pre2) and post-therapy (Post2, Post3) stages. The root-mean-square jerk of the first 5 Sit-to-Stand cycles significantly increased with therapy (F = 3.37, p = 0.032), whereas no difference was observed in the variance of the first 5 Sit-to-Stand cycles (p = 0.092). Despite the improved scores of the iTUG, i10MW, and iSTS tasks, LSVT-BIG® had no effect on any measure in the QS tasks (RMS Jerk: p = 0.84; Normalized Path Length: p = 0.18; Displacement: p = 0.51) or FT tasks (Tap Count: p = 0.42; Intertap Interval: p = 0.43; 10s/30s Count: p = 0.38), Table 3. The daily levodopa equivalent dosage (LED) did not change for any PD_LSVT subject during therapy, Table 1.

Total iSTS count was significantly lower (p = 0.006), and Sit-to-Stand time significantly higher (p = 0.014), in the PD_LSVT group at baseline than in the CON_Health group, Table 3. Following therapy, both measures converged towards values similar to those of CON_Health, Figs. 7 & 8. The temporal parameters of the gait cycle in the PD_LSVT group were comparable with those of CON_Health at baseline, with step and stride time significantly lower after therapy (Post3 - step time: p = 0.013, stride time: p = 0.011), Figs. 4 & 6 and Table 3.

When compared over a four-week period from the beginning of therapy (Pre2), PD_LSVT subjects showed a consistent weekly improvement in i10MW, iTUG and iSTS clinical scores, in contrast to the non-exercising CON_PD group over the same period, Fig. 9. Results of the mixed ANOVA showed a significant interaction effect between subject group and stage of therapy in the i10MW (F = 9.06, p <  0.001) and iTUG (F = 5.10, p = 0.004) tasks, indicating that weekly delivery of LSVT-BIG® therapy significantly improves functional mobility when compared to a non-exercising PD cohort examined over the same period. Although no interaction effect was observed for the iSTS count over the period examined, PD_LSVT subjects had significantly higher iSTS counts at S15 when compared to CON_PD subjects at Wk4 (two-sample T-test: p = 0.018). CON_PD subjects performing the same experimental protocol showed no within-group change in i10MW time (F = 2.44, p = 0.092), iTUG time (F = 1.16, p = 0.347) or iSTS count (F = 0.48, p = 0.694) over a four-week period, Fig. 9.

The stretching and stepping exercises that LSVT-BIG® incorporates are designed to enhance the speed-amplitude relationship that is disproportionately scaled by PD [4, 5]. By integrating these exercises with functional aspects of daily living, LSVT-BIG® also aims to improve the internal cueing mechanisms that regulate motor control in various environments. While several studies have previously investigated the effect of LSVT-BIG® on motor and non-motor symptoms in PD [6, 9‐11, 13, 14, 46, 47], no study has yet quantitatively evaluated motor function using wearable sensors at multiple stages before, throughout, and up to 13 weeks post LSVT-BIG® therapy. Additionally, this study provided an examination of balance, postural control and fine motor function through iSTS, QS and FT tasks respectively, and compared outcome measures from all tasks with data from healthy age-matched controls.

The present study showed that gait speed increased in subjects undergoing LSVT-BIG®, demonstrated by significantly lower i10MW and iTUG times at follow-up compared to baseline (p <  0.001; Figs. 3, 4, 5 and 6 and Table 3) and to a non-exercising PD cohort (i10MW: p <  0.001; iTUG: p = 0.004; Fig. 9). These results are consistent with those reported in previous studies where i10MW and Timed-Up-and-Go times decreased with LSVT-BIG® [6, 9, 13, 14, 47, 48]. By employing wearable sensors to detect gait events, the gait cycle was deconstructed into its constituent time phases, collectively showing significant reductions in step, stride, swing and stance times with therapy (Figs. 4 & 6, Table 3). As these times were also accompanied by significantly lower step counts (p = 0.010), these results provide further evidence that PD subjects undergoing LSVT-BIG® develop longer step lengths with faster step time [6, 10], suggesting a rescaling of the speed-amplitude relationship. Despite these outcomes, no change was observed in step time variance, gait asymmetry or gait regularity, measures. These features have been shown to be independent of gait speed [49] and related to attentional demand in PD [50, 51]. While LSVT-BIG® is not specifically designed to address gait variability, these measures are important due to their association with increased risk of falls [27, 50, 51]. The lack of any observable improvement in these measures with therapy may also be confounded by effects due to levodopa, shown to reduce gait variability [52].

Improvements in functional mobility with LSVT-BIG® were observed in the iSTS task, where the number of Sit-to-Stand cycles performed significantly increased with therapy (p <  0.001), Fig. 7 and Table 3. Similar to the gait cycle, the duration of each phase of the Sit-to-Stand cycle significantly decreased with therapy (Fig. 8), particularly in the standing and sitting phases where the average time pre-therapy reduced by approximately a third at post-therapy, potentially indicating enhanced muscular strength, greater effort, and improved balance. To the best of the authors’ knowledge, this is the first study to use the iSTS task to assess subject mobility in response to LSVT-BIG®, and as evidenced by the faster Sit-to-Stand times, demonstrates that the benefits of LSVT also translate to the iSTS task.

Although the mean value of i10MW, iTUG and iSTS outcome measures indicated an overall improved performance between Pre1 and Pre2 (Fig. 9), on an individual level this was not necessarily the case. For example, five of the twelve PD_LSVT subjects took longer to perform the iTUG task at Pre2 than at Pre1, while a third of subjects had slower step and swing times at Pre2 in the i10MW task. Data collection at Pre2 occurred on the first day of each subject’s LSVT-BIG® therapy. Therefore, it is possible that participants, eager to start therapy, may have been more motivated than usual at Pre2 compared to Pre1. Alternatively, the improvements observed at Pre2 may be associated with familiarisation of the experimental protocol at Pre1. However, it is evident from Fig. 9 that the non-exercising CON_PD subjects, performing the same weekly experimental protocol as those in the PD_LSVT group, did not show any consistent improvement in their i10MW, iTUG or iSTS clinical scores. This observation was supported by a RANOVA analysis of each clinical score, where no significant weekly change was observed in i10MW time, iTUG time or iSTS count, indicating that practice or familiarisation with the experimental protocol does not by itself influence subject performance on a week-to-week basis. Thus, the changes observed in PD_LSVT subject performance from Pre1 to Pre2 were likely due to a separate factor. The average values of the clinical scores for the CON_PD subjects were slightly lower than for PD_LSVT subjects, HY (1.25 ± 0.46) and MDS-UPDRS (22.75 ± 11.56). To check whether the difference in clinical scores could account for the different progression observed in the two groups, the mixed-ANOVA was reevaluated comparing the CON_PD group against the eight PD_LSVT subjects with the lowest MDS-UPDRS Total scores. The analysis confirmed a significant interaction effect between subject group and stage of therapy in the i10MW (p = 0.001) and iTUG (p = 0.011), with no significant difference in clinical scores between groups (MDS-UPDRS Total: p = 0.16; MDS-UPDRS III: p = 0.19). These results demonstrate that the disparity in initial clinical scores between the PD subject groups does not influence the overall findings of the study.

While the average iSTS count and stand-to-sit transition time were significantly different between CON_Health and PD_LSVT groups at baseline, the i10MW time, iTUG time, and the respective gait cycle features were initially comparable with CON_Health values, a potential consequence of several factors. Firstly, most PD_LSVT subjects reported being moderately active, with several walking regularly. Secondly, it has been demonstrated that PD subjects walk faster and with larger steps in the clinical environment due to a ‘performance effect’, where concentration is elevated and peripheral distraction is attenuated [10, 28]. Comparing gait in PD and healthy control subjects, Del Din et al., showed that measures of gait asymmetry and gait rhythm increased in PD subjects under free-living conditions, when no difference between groups was identified under laboratory conditions [28]. Hence, the relatively active nature of the PD_LSVT subjects, combined with a potential performance effect in the clinical environment may explain the similar i10MW and iTUG times between the CON_Health and PD_LSVT groups pre-therapy. An important element of LSVT-BIG® is adherence to a home exercise regimen in addition to one-to-one therapy received within the clinic. The homework protocol consists of four repetitions of each core LSVT-BIG® exercise, as well as large-amplitude walking and practice of functional tasks identified by the therapist. Although beyond the scope of the present study, future studies could extend the data analysis employed here to examine functional mobility from the same tasks performed at home, where the performance effect observed in the clinic may be absent.

In contrast to the large amplitude tests (i10MW, iTUG, iSTS), LSVT-BIG® showed no effect on any measure of the QS or FT tasks. Two meta-analyses of postural stability in PD have suggested that without specific balance-oriented training, only minor improvements in postural stability can be achieved [53, 54]. Furthermore, it has been recommended that a minimum of 8 weeks training is necessary to achieve substantial improvement in balance in PD [55], twice the duration of LSVT-BIG®. Thus, measures of balance during the QS task are unlikely to improve with LSVT-BIG®, as the focus of the therapy is on amplitude and not postural stability. Alternatively, the absence of any significant improvement in QS with LSVT-BIG® may relate to the type of measure, and how it is derived using ACC. Using the Berg Balance Test, Millage et al. have been the only researchers to specifically evaluate postural balance in individuals undergoing LSVT-BIG® therapy, but their findings were limited as four out of nine subjects achieved maximum scores prior to therapy, leaving a sample size of just 5 subjects [47].

Janssens et al., hypothesized that the finger-spreading exercises of LSVT-BIG® may help to improve manual dexterity, evaluated using the nine peg hole test [46]. Although a slight improvement was observed in the non-dominant hand, dexterity in the dominant hand did not benefit from LSVT-BIG®. In contrast, Ebersbach et al. have reported significantly improved manual dexterity with LSVT-BIG®, assessed using the box-block test [10, 56]. Given the lack of any observable improvement in FT measures, it remains unclear whether or not LSVT-BIG® benefits upper limb motor function in PD. However, the disparate type of motion assessed in the nine-peg-hole test, box-block test, and FT tasks may account for the inconsistency among studies. As the goal of LSVT-BIG® is to reinforce large amplitude movements, it is expected that such a therapy will have minimal impact on FT, which involves small amplitude movements, or QS, where the aim of the task is to minimize sway.

Many of the studies reporting on the efficacy of LSVT-BIG® that have been performed to date, although insightful as to the benefits of therapy, are limited by low subject numbers [11, 13, 46, 47], the absence of a PD or healthy control group [6, 9‐11, 13, 14, 46, 47], or a lack of detail on specific aspects of kinematic improvements [9‐11, 13, 14, 46, 47]. These shortcomings have been commonly observed across a spectrum of physical therapy studies in PD [15, 57], where it is unclear if improved mobility is a result of enhanced muscle mass or whether positive effects wear off post-therapy [13, 58]. The present work has addressed some of these issues by continually recording patients throughout therapy, by quantifying functional mobility at each stage and by comparing results with controls, yet there are several limitations which remain. Firstly, subjects remained on their prescribed levodopa medication which did not change throughout the course of therapy. Levodopa has been shown to affect various aspects of balance [59] and gait [52] in individuals with PD, which may mask the true effect of LSVT-BIG® on parkinsonian symptoms, or introduce behaviour in the ACC signal that obfuscates the measures derived. Secondly, no alternative therapy was examined against which to compare the effect of LSVT-BIG®. Thus, it cannot be stated whether LSVT-BIG® is more beneficial than other exercise-based therapies. However, consistent with the present findings, results from the Berlin BIG [9, 14] and JFK BIG [48] studies have shown LSVT-BIG® to benefit individuals with PD, helping to reduce bradykinesia and ameliorate the speed-amplitude relationship of large-amplitude movement.

Features derived from body-worn accelerometers showed that subjects undergoing LSVT-BIG® develop enhanced functional mobility which remains sustained up to 13 weeks post therapy. Although no significant effect was observed in measures of postural or fine motor control, temporal parameters of the gait and Sit-to-Stand cycles significantly reduced with therapy. The results indicate that LSVT-BIG® helps to partially restore the speed-amplitude relationship for large amplitude movement, matching that of age-matched controls. These findings are consistent with those of previous studies and extend previous findings by employing wearable ACC sensors to provide insight into specific features of movements performed during clinical tests.

The insights gained from the objective, quantifiable measures can provide clinicians with information about the efficacy of high-amplitude movement therapies, such as LSVT-BIG®, and can be used to target patients with specific subtypes of Parkinson’s Disease that are more likely to respond to a high-amplitude therapy programme.