Effects of Passive Bi-axial Ankle Movement Training with Electrical Stimulation on Ankle Sensorimotor Functions in Stroke Patients: A Randomized Controlled Pilot Study

Background: This study was conducted to investigate the effect of passive biaxial ankle movement training synchronized with electrical stimulation therapy (AMT-EST) on ankle proprioception, ankle strength, balance, and gait in chronic stroke patients. We observed the changes in ankle sensorimotor function after stroke. Methods: Thirty-ve stroke patients were randomized to an experimental or control group, and 30 patients completed the trials. The experimental group received AMT-EST on the affected ankle for 30 minutes a day, 5 times a week for 4 weeks, for a total of 20 sessions. The control group received electrical stimulation therapy on the affected ankle. The primary outcome measures were ankle proprioception, passive range of motion, and strength. The secondary outcome measures were balance and gait-related functional abilities. Results: Compared with those in the control group, the participants in the experimental group who received AMT-EST showed signicant post-training improvement in ankle proprioception of eversion (P<0.05). The ankle passive range of motion (inversion and eversion), ankle strength (dorsiexion, plantarexion, inversion, and eversion), and functional abilities (Fugl–Meyer Assessment, Berg Balance Scale, Timed Up and Go test, Fall Ecacy Scale, and walking speed) signicantly improved in the experimental group (P<0.05). Signicant group×time interactions were observed in ankle passive range of motion (inversion and eversion), ankle strength (dorsiexion), and Fugl–Meyer Assessment (P<0.05). All ankle proprioception moderately correlated with ankle passive range of motion (eversion), ankle strength (dorsiexion and eversion), the Berg Balance Scale, and Fugl–Meyer Assessment (P<0.05). Conclusions: Biaxial AMT-EST effectively increased ankle proprioception, range of motion, strength, and functional abilities in chronic stroke patients. These ndings suggest that AMT-EST can be proposed as a novel ankle rehabilitation program for chronic stroke patients with ankle sensorimotor impairment. Trial registration: This study ≥ AMT-EST: ankle movement training synchronized with electrical stimulation therapy; PROM: passive range of motion; K-MMES: Korean Version of the Mini-Mental State Examination; DF: dorsiexion; EV: eversion; PF: plantarexion; INV: inversion; FM-L: Fugl–Meyer Assessment for the lower extremity; BBS: Berg Balance Scale; TUG: Timed Up and Go test


Background
Somatosensory impairment in stroke patients is common and appears in approximately 89% of stroke survivors, and the damage to proprioception and tactile sensation is more pronounced in the lower extremities than in the upper extremities [1,2]. Proprioception provides self-information regarding position, movement, or force necessary for the body to make motor adjustments [3]. In the lower extremity, ankle proprioception provides essential information to enable the adjustment of ankle position and plays a key role in maintaining balance [4]. Furthermore, the sensory system, including ankle proprioception, plays an important role in both feedforward and feedback operations to achieve novel ankle motor tasks and motor learning [5]. Therefore, interventions to improve ankle proprioception potentially affect ankle motor control, balance, and daily functioning [6].
Considering the importance of the sensory system, studies have investigated interventions for sensory function and functional activity in stroke patients. Electrical stimulation (ES) aims to achieve sensorimotor integration, thereby ensuring better function and pain control in paraplegic individuals [7,8]. Furthermore, ES induces a sensory cue to activate motor neurons or re ex pathways via stimulation of sensory nerve bers [9]. These effects are related to sensory facilitation of neural plasticity by increasing the strength of afferent inputs to promote motor learning [10]. Therefore, ES is used frequently to improve performance in hemiparetic stroke patients who have di culty controlling ankle movements due to muscle weakness. Combination therapy with ES and other modalities (e.g., gait trainer, treadmill, rocker board, and cycling) has been found to modulate ankle spasticity [11], functional ability [11,12], gait characteristics [11][12][13], and recovery of physical condition [14]. However, as these modalities focused on the overall performance of the lower extremities, outstanding ankle impairment was unresolved. Therefore, the application of ES and functional movement training focused on the ankle is necessary to improve the ankle sensory function in stroke patients.
Understanding the ankle joint structure and movement is useful for re-education and effective training of functional ankle movement. The ankle is a biaxial structure with an obliquely aligned subtalar joint axis. As the movement of the subtalar joint signi cantly contributes to foot position, ankle inversion (INV) and eversion (EV) are important ankle function movements. The effects of a passive biaxial ankle training, including ankle INV and EV movement, on ankle functional ability and functional performance related to balance and gait in chronic stroke patients were reported previously [15]. Passive range of motion (PROM) exercise aims to maintain or increase joint mobility by in uencing the extensibility of the lower motor neurons as well as soft tissues, thereby reducing spasticity and directly or indirectly increasing muscle extensibility [16]. Moreover, PROM provides sensory information derived from muscle spindles, Golgi tendon organs, and joint and cutaneous receptors [17,18]. Thus, ES as an adjunct to ankle biaxial PROM exercise can effectively provide sensory information to stroke hemiparetic patients who have di culty with active ankle movements. A recent meta-analysis showed that a combination of PROM and ES was more effective for improving sensory impairment [19], and further research on the ankle is needed.
The aim of this study was to investigate the effects of passive biaxial ankle movement training synchronized with electrical stimulation therapy (AMT-EST) on the enhancement of ankle proprioception, PROM, strength, and other functional abilities. We hypothesized that AMT-EST would more signi cantly improve ankle sensorimotor function in chronic stroke patients than in the control group. The second hypothesis was that this ankle training would improve the ankle-joint-associated functional abilities, including gait and balance.

Participants and Design
Participants were recruited from among inpatients at a rehabilitation hospital (National Rehabilitation Center, Seoul, South Korea) from January to May 2018. The eligibility criteria were as follows: (1) chronic post-stroke hemiparesis; (2) weakness of ankle muscles on the affected side (Medical Research Council Scale, ankle dorsi exion (DF) strength range, grades 1-4); (3) Modi ed Ashworth Scale score <3 for spasticity in the affected ankle; (4) impaired light touch sensation on the plantar aspect of the head of the rst metatarsal of the affected foot; and (5) Functional Ambulatory Category Score ≥3. Potential participants were excluded if they had complications of orthopedic disorders and cognitive impairment (Mini-Mental State Examination Score ≤24).
A double-blind, parallel-group, randomized controlled trial with blinding of assessors and concealed allocation was conducted. A person uninvolved in the trial created a blocked random allocation schedule for 35 participants using Microsoft Excel ® , and participants were divided accordingly into the experimental or control groups after the baseline assessment to receive AMT-EST or only ES, respectively, on the affected ankle for 4 weeks. All participants were reassessed at the end of the 4-week intervention period.

Ankle Movement Training System
The ankle-training device used in this study was developed for intensive and selective training on the paretic ankle in stroke patients. The main feature of the ankle training device was to reproduce the actual biaxial ankle movement that was applied by a seesaw-type foot cradle that pivoted along the transverse ankle axis, and the foot force plate was rotated along a 42°-tilted subtalar axis relative to the foot cradle. The improvement in ankle PROM, stiffness, and walking performance on uneven surface as a result of passive biaxial ankle training using this ankle device in chronic stroke patients has been reported previously [15]. In this study, an ankle function enhancement training protocol that applied ES in accordance with passive biaxial ankle movement was constructed and applied (more information about the ankle training system in Supplement I of the online-only Supplemental Material).

Experimental group
Before the training session, the participants were asked to comfortably sit on a height-adjustable chair with his/her knees exed at 90°, to place his/her paretic foot on the footplate of the ankle-training device, and to place his/her non-paretic foot on the height-matched footrest. The paretic foot was fastened to the force plate in the foot cradle using three length-adjustable straps ( Figure 1). The two electrode pairs (5×9 cm; RehaTrode, Hasomed, Germany) were placed over the common peroneal nerve as it passed over the head of bula and the motor point of the tibialis anterior. Other electrode pairs were placed slightly lateral to this and targeted toward the peroneus longus ( Figure 1). ES was applied to con rm that the location of the attached electrodes caused proper ankle DF (tibialis anterior) and EV (peroneus longus).
AMT-EST was performed for 4 weeks, with 5 sessions per week. All participants completed more than 90% of the training sessions. The duration of one training session was 40 minutes, which comprised a 5-minute warm-up, 30 minutes of ankle training, and a 5-minute cool-down. In the warm-up session, the PROM of ankle DF, plantar exion (PF), INV, and EV were measured, and all ankle training was performed within 80% of the full ankle range of motion. Subsequently, the participants performed a PROM exercise for each ankle direction along either talocrural or subtalar joint. In the ankle-training session, the simple and combined ankle PROM exercise with ES was performed along the ankle (talocrural) and subtalar (talocalcaneal) axes.
The simple movements consisted of 20 repetitions of DF-PF and INV-EV, and the combined movements consisted of 40 repetitions of inverted PF and everted DF (diagonal movements), which are more commonly used in actual movement. All ankle movement speed was slow, at 2.14°/s, to avoid ankle spasticity [15]. The timing of the starting and ending of the paretic ankle DF and EV movements was directly observed by the therapist who then applied ES (Microstim2, Medel GmbH, Germany) current with 0.28-ms pulses, at 35 Hz with pulse durations from 300 to 450 µs in alternating mode within the participants' tolerance level, via surface electrodes. The amplitude was adjusted to produce muscle contractions without causing patient discomfort [20]. In the last cool-down, 10 simple PROM exercises were performed for each ankle direction In the rst step, the ankle was moved passively from the initial angle (0°) to the randomly assigned 10 target angles (10°, 20°, and 30° of ankle PF and INV; 10° and 20° of ankle DF and EV; according to normal range of motion of the ankle), while asking the participant whether the ankle movement and the direction of movement were perceivable. After staying at the target position for 5 seconds, the ankle was returned to the initial angle. In the second step, the paretic ankle was moved toward the target angle again and the participant was asked to say "stop" when they felt that they had reached the target angle (actual angle). No feedback about results was provided to the participant during the task. The assessment began with a period of familiarization. Three ankle movements were evaluated per direction, and a total of 38 measurements including dummy trials (no movement) were performed. For statistical analyses, the proprioception ratio were calculated in relation to angular differences, which means that the difference between the target angle and actual angle was ascertained using the following equations [21]: Finally, the proprioception ratio for all four directions (DF, PF, INV, and EV) was calculated as the average value of the proprioception ratio that was measured three times for each angle. The larger the proprioception ratio value, the greater is the de cit.
The PROM of the paretic ankle was measured using a portable goniometer by a skilled physiotherapist. The average values of three measurements of maximum PROM of DF, PF, EV, and INV were recorded. To measure ankle strength, the isometric contraction force of the paretic ankle muscle was measured using a portable manual muscle strength tester (Lafayette, USA, 2018). The isometric strength of the ankle dorsi exor, plantar exor, invertor, and evertor was measured for 5 seconds, and the maximum value was recorded.
The secondary outcomes included motor, balance, and gait function, evaluated by the Fugl-Meyer Assessment for the lower extremity (FM-L), Berg Balance Scale (BBS), the Timed Up and Go test (TUG), the Korean version of the Fall E cacy Scale, and walking speed. A description of the assessment method is available in Supplement III of the online-only Supplemental Material.

Statistical Analyses
The sample size was calculated according to the study sample of a study that reported the effect of repeated passive exercises on the knee's proprioception in patients with hemiplegia [22]. Calculations were performed with a paired t-test value of the knee position sense for a comparison of the before and after intervention values, using an alpha of 0.05 at 95% power. The total sample size was determined to be 6 for each group (effect size: 1.744, actual power: 0.975). The G * Power 3.1.9.2 program was used.
The normative distribution was assessed using the Shapiro-Wilk test. Some sample characterization data did not show normative distribution, and the Mann-Whitney U test or chi-squaretest was conducted for comparing the groups at baseline. Within each group, the Wilcoxon signed rank test was used to compare data from the pre-and post-intervention tests. To examine the main effects of the interventions, a 2 (group)×2 (time) ANOVA with repeated measures was performed. The relationships between ankle proprioception and clinical outcomes were examined using Spearman's correlation coe cient (r). All statistical analyses were performed using SPSS ver. 22.0 (IBM, Armonk, NY, USA), and the signi cance level was set at P<0.05.

Participants
The participant's baseline characteristics are presented in Table 1. At the baseline, no signi cant betweengroup differences were found for demographics or measurements. Five individuals in the control group dropped out due to discharge from the hospital during the training. Therefore, the post-intervention testing and analysis were completed for 18 individuals in the experimental group and 12 in the control group. A CONSORT diagram is presented in Supplement II of the online-only Supplemental Material. The speci c values for ankle functions before and after the training are presented in Table 2 Table 2) were found. The relationship between ankle proprioception and clinical outcome measures at the baseline is presented in Table 3. A signi cant correlation was found between the post-stroke duration (months) and proprioception

Discussion
The ndings of this study suggest that AMT-EST has several key advantages for proprioception of ankle EV, To restore sensorimotor function and functional abilities in stroke patients, ES has been used commonly in the clinical setting. Recently, the effect of ES combined with functional motion has been reported to further enhance afferent inputs to promote motor performance [23]. For example, the application of ES on ankle muscles during gait and everyday activities signi cantly increased ankle proprioception and ankle strength, balance, and gait speed [24]. However, such a performance includes complex movement of the entire lower extremity. Because ankle impairment is more prominent and voluntary ankle motor control is more di cult than the movement of other lower extremities in stroke patients, a focus on ankle training with ES while excluding other lower extremity movement is required. In this study, the application of ES to the ankle dorsi exor (tibialis anterior) and evertor (peroneus longus) along with functional ankle training was associated with signi cant improvements in ankle PROM and strength, as well as in the ankle proprioception of ankle EV and DF. When ES is applied with a focus on ankle function movement, it can enhance the generation of cortical brain perfusion to the ipsilesional sensorimotor cortex for restoring ankle sensorimotor function [25]. Furthermore, the repeated ankle movement training provides sensory input for muscle extensibility, which is responsible for the maintenance of stretch receptors of the muscle spindle.
Moreover, ankle movement training with simultaneous ES is effective in promoting ankle proprioception that recognizes the positional sense of joints with respect to changes in muscle length [26]. Sensory information from the ankle has been demonstrated to be associated with the perception of verticality [27], which in turn is related to balance [28]. More importantly, because the planning and execution of voluntary movement requires sensory information on body position and the prediction of future position, activities such as balancing can be di cult with severe impairment of ankle sensation. Therefore, the impaired ankle sensory function is considered important in the recovery of physical function in stroke patients. Recent studies have found that ankle proprioceptive de cits have signi cant relationships with mobility, balance, balance con dence, physical functions, and activities of daily living [29,30]. The results of this study showed that ankle proprioception had a moderate correlation with PROM, strength, BBS, and FM-L. Furthermore, the signi cant improvements in ankle proprioception and improved FM-L, BBS, and TUG in this study support the earlier evidence. Nonetheless, the role of sensory function in complex performance is somewhat different from that of balance. The performance of complex functions, such as walking, involves various factors including muscle strength [31][32][33], spasticity [32], cognition [34], motor function [33,34], and balance [31,33], as well as sensory information. A recent meta-analysis showed that leg somatosensory retraining after stroke signi cantly improved the somatosensory function and balance but not the gait [35].
However, this meta-analysis included only a few ankle proprioception-related training, and a 2-week proprioception training of the big toe and ankle was reported to be effective for improving light touch, postural control, and gait but not proprioception [36]. This study performed perception training consisting only of reposition training of the foot and ankle. Therefore, the evidence for effective proprioception training methods and their effect on functional ability is still insu cient. Nevertheless, it is clear that sensory impairments play an important role in motor recovery and physical function in stroke patients. Depending on the lesion location, strokes can damage both the motor and sensory neural systems, block the closed loop between the brain and body, and thus lead to neurological impairment that is associated with signi cant physical dysfunction [37,38]. Further studies on brain plasticity for sensory function recovery in brain lesions should be considered.
Individuals with proprioception de cits experience low balance con dence as well as impaired balance and lack of independence in daily living [29]. Balance con dence, which is signi cantly correlated with balance (BBS, r=0.44) and mobility (TUG, r=-0.43) of stroke patients [39], is closely related to fall e cacy. This study did not show a signi cant correlation between ankle proprioception and fall e cacy, but showed a signi cant improvement in fall e cacy after AMT-EST. Moreover, the participants in the experimental group reported a markedly positive improvement in con dence than those in the control group. We believe that AMT-EST of paretic ankle promotes psychological factors that are related to balance con dence as well as balance ability, and related research should be conducted.
To our knowledge, this is the rst randomized controlled trial that applied intensive passive biaxial ankle movements with ES for improving ankle sensorimotor function. The novelty of this study is that the ankle training and proprioceptive measurements in this study were performed in the biaxial ankle direction and at a subdivided angle. Nonetheless, this study has several limitations. First, the small sample size, insu cient intervention intensity, and intervention period detract from the strength of the ndings. Second, the long-term effects of the training could not be con rmed. Third, we could not exclude a learning effect for each evaluation system. Finally, ankle motor control and ankle muscle activity could not be directly determined.
Future studies need to study the optimal intensity and duration of this ankle intervention for participants with ankle sensorimotor impairment. The evidence of brain plasticity for sensory recovery should be investigated.

Conclusions
This study provided evidence that AMT-EST signi cantly enhanced ankle proprioception, PROM, strength, and functional abilities related to balance and gait. Thus, AMT-EST can be provided as part of an ankle rehabilitation program in hemiparetic stroke patients.