We developed the ankle bracelet laser as a new closed-loop visual cueing device to improve gait performance in parkinsonism patients with FOG. Our study revealed the improvement of gait speed and stride length, and decrease in TUG time in the laser-on condition compared to the laser-off condition. None of the patients showed difficulty of walking or adverse effects while using the device.
The improvement of gait speed by an average of 0.07 m/s (95% CI: 0.04–0.09 m/s) reached the minimal clinically important difference (MCID) in parkinsonism for moderate change (0.06 m/s) in the UPDRS motor scale [25]. In patients with H&Y stage 3, gait speed was improved by an average of 0.1 m/s, reaching the MCID with a large effect [25]. The effect size also shown a large improvement in H&Y stage 3 group (Cohen’s d = 0.74). Gait speed is a key indicator for independent living, life in the community, and related to objective measures of the balance such as the Berg balance, TUG, and severity in H&Y [26]. Slow gait speed and short stride length are related to falling and fragility in Parkinson’s people [1]. Therefore, increasing gait speed is related to greater mobility, increased independence, and improved balance for parkinsonism patients. Stride length with laser-on showed a clinically significant average improvement of 0.17 m [1]. Increasing the stride length [1, 27] also improves walking performance and reduces shuffling gait in FOG, which might help reduce the risk of falls. This study also showed the improvement in gait speed and stride length, but decreased cadence after laser-on. These results are related to the walking characteristics of people with PD, in which gait speed is more related to stride length than cadence[1].
Our study found a clear change in these spatiotemporal parameters. In contrast, previous studies produced controversial or negative results [12, 14, 15, 28]. Most previous mobile cueing devices need manual control and require attention and cognitive function to use the devices effectively. These may be impractical to some patients, especially those with cognitive impairments, which are commonly found in parkinsonism. Our ankle bracelet laser could project cues that automatically follow each walking step. Therefore, the demands on executive function and attention are lower [10, 11] and may be the reason for the results in the present study. In addition, the movable laser line following tibial movement might increase sensory input and improve motor performance, especially by increasing stride length [29]. This device also acts as proof of concept for ease of use by leading to an immediate improvement in inexperienced participants, nine out of ten of whom had no experience with visual cues, and only one person had a history of unsuccessful using a self-made cue attached to a walking stick.
In the TUG test, the mean difference of 8.55 s reached the minimal detectable change in PD (3.5 s) [30, 31]. The TUG test is one of the tools used to evaluate the risk of falls with good reliability and validity [32]; however, there was less evidence regarding visual cues and the TUG test [33]. Some studies have focused on sit-to-stand ability [34, 35] and did not represent the dynamic balance in turning, which is usually impaired in parkinsonism patients with FOG. Therefore, the decreased TUG time suggests the benefits in improving balance and overall function from sitting to standing, walking, turning, and standing to sitting. In addition, reducing the turning time might help reduce the number of FOG episodes because impaired turning ability is also a common trigger of FOG and is related to falls [10, 36]. The improvement of TUG in this study is improved similar to that in previous studies using NW training [20].
The higher LRI represents the improvement of the metabolic economy [23]. The LRI in our study was also improved, similar to the NW training, and reflected that walking speed in laser-on is closer to OWS and has a lower metabolic cost. However, the degree of improvement in our study was less than the 6-week NW training. In our study, 80% of the participants were in H & Y stages 3–4 with FOG episodes. On the other hand, the people in NW training were in an average H & Y stage of 1.5 and evaluated the outcomes during the ON- period with fewer people (3 out of 16) having FOG. Therefore, the disease staging may affect in different degree of improvement. The ankle laser may be more suitable to the Parkinsonism at an advanced stage, while the NW training showed the best outcomes in saving the walking economy in the mildest degree of PD people [2]. Due to the small sample size in each stage, further study should be done with a larger sample size in different H&Y staging to prove this hypothesis. Further study should also include coordinating the exercise training with the device, adjusting to each stage to see the different effect.
This study found significant improvements in patients with H&Y stages 2–4, with patients with H&Y stage 3 showing great improvement in gait speed, TUG test and the LRI with large effect size, shown in supporting table 15. After using the mixed linear model, adjusting the sequence and staging effects as shown in appendix table 13–14, the staging of H & Y showed significant differences between the patients in H & Y stage 3,4 compared to H & Y stage 2. Because of the small number of patients with each H & Y stage, future studies should examine these groups separately to identify any different outcomes, including long-term effects, between each stage. After calculating the sample size based on the data from this study, a further 39 subjects should be included for the cross-over trial study to compare the effects of this device for Parkinsonism in moderate to severe degrees, or H & Y stage 3–4.
Our device led to improvement in all four patients with atypical and secondary parkinsonism, which is very interesting because these patients have smaller responses to anti-parkinsonism drugs than patients with primary parkinsonism [37, 38], and there is less evidence on the use of cueing devices in these groups. We should conduct further studies with a larger sample size of patients with different types of parkinsonism.
Currently, the pathogenesis of FOG is still unclear. The basal ganglia are a group of nuclei that controlled the movement such as walking from initiation to walk and maintain the walking process, by providing the internal cue via the connection pathway with the supplementary motor area (SMA)[9]. It has been proposed that FOG is caused by frontal lobe dysfunction or a lack of connectivity between the supplementary motor area (SMA) and the basal ganglia [39]. Visual cues could activate the dorsolateral pre-motor control system by bypassing the brain network via the cerebello-parieto-premotor loops instead of the usual route via the hypoactive basal ganglia-supplementary motor area. The SPECT study[40] also showed more enhancement of cerebral blood flow in the right lateral pre-motor cortex (PMC), which is mainly influenced by cerebellar input [40], and middle frontal gyrus, as well as reduced left dorsolateral pre-frontal cortex (DLPFC) activity in PD patient with FOG while walking on treadmills with visual cues compared to control. The fronto-striatal pathways[41] that connect the shifting between cognitive and motor control are less efficient in freezers than in non-freezers[11]. Therefore, Parkinsonism with FOG has less cognitive reserve[16] and also the sequence learning deficits[18], leading to the difficulties of dual-task conditions and limited the motor relearning. Our ankle bracelet laser focuses on ease of use and natural walking to reduce brain overload, so the patients could focus on gait training. Regarding the limitations of this study, we did not compare the device directly with other visual cueing systems. In the future, we will compare their efficacies with other systems to identify differences or add on data values. The present study found an immediate and significant improvement with less than 5 minutes of trials, which suggests the ease and practical use of the ankle bracelet laser system. However, we still lack a study of using the device in a home-setting, which should be further done to prove this concept in daily living. Cognitive impairment is one important factor related not only to the efficacy of visual cues but also to the degree of FOG. Future studies should also investigate different degrees of cognitive impairment and evaluate correlations between gait improvement, benefits of visual cues, and cognitive function.
The closed-loop cueing system[11, 42] like in our device using wearable sensors to detect the leg motion and send the signal via a microcontroller to activate the laser cue. Through this process, the external (visual) cue was projected based on real-time movement, which was considered the motor feedback. The combination of the feedback from the user’s movement and the feedforward of the sensory stimuli may enhance the neuroplasticity and motor relearning. Therefore, the use of the ankle bracelet laser should be incorporated with a gait training or exercise program to evaluate training effects and whether this device could help in sensory feedback and motor relearning, as per the hypothesis.
The other limitation of using a visual cue is the need to look down at the laser line while walking, which the ankle bracelet laser projects continuously. This device could be programmed to project the laser cue on-demand (only when the FOG occurs) to send the feedback based on the user’s performance. However, there is still controversy when comparing the efficacy of continuous cueing with on-demand cueing. Although previous studies have reported better results with continuous cueing, the patients also reported greater fatigue while using continuous cues than when using on-demand cues [35]. Because the long-term effects of the two methods remain unknown, future studies should compare results using the ankle bracelet laser with on-demand cues, such as determining the time to project the laser line and comparing the results with continuous laser projection [43].