Virtual Reality To Augment Robot-Assisted Gait Training in Non-Ambulatory Patients With A Subacute Stroke: A Pilot Randomized Controlled Trial

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COPYRIGHT 2018 EDIZIONI MINERVA MEDICA
© 2017 EDIZIONI MINERVA MEDICA European Journal of Physical and Rehabilitation Medicine 2018 June;54(3):397-407
Online version at http://www.minervamedica.it DOI: 10.23736/S1973-9087.17.04735-9
ORIGINAL ARTICLE
Virtual reality to augment robot-assisted gait training

in non-ambulatory patients with a subacute stroke:
a pilot randomized controlled trial
Jeannine BERGMANN 1, 2 *, Carmen KREWER 1, Petra BAUER 1, 3,
Alexander KOENIG 4, Robert RIENER 4, 5, Friedemann MÜLLER 1, 2
1Schoen Klinik Bad Aibling, Bad Aibling, Germany; 2German Center for Vertigo and Balance Disorders (DSGZ), Ludwig-Maximilians-
University of Munich, Munich, Germany; 3Faculty of Applied Healthcare and Social Sciences, University of Applied Sciences,
Rosenheim, Germany; 4Sensory-Motor Systems Lab, ETH Zurich, Zurich, Switzerland; 5Spinal Cord Injury Center, Balgrist University
Hospital, Zurich, Switzerland
*Corresponding author: Jeannine Bergmann, Schön Klinik Bad Aibling, Kolbermoorer Strasse 72, 83043 Bad Aibling, Germany.
E-mail: JBergmann@Schoen-Kliniken.de
ABSTRACT
BACKGROUND: Active performance is crucial for motor learning, and, together with motivation, is believed to be associated with a better re-
habilitation outcome. Virtual reality (VR) is an innovative approach to engage and motivate patients during training. There is promising evidence
for its efficiency in retraining upper limb function. However, there is insufficient proof for its effectiveness in gait training.
AIM: To evaluate the acceptability of robot-assisted gait training (RAGT) with and without VR and the feasibility of potential outcome measures
to guide the planning of a larger randomized controlled trial (RCT).
DESIGN: Single-blind randomized controlled pilot trial with two parallel arms.
SETTING: Rehabilitation hospital.
POPULATION: Twenty subacute stroke patients (64±9 years) with a Functional Ambulation Classification (FAC) ≤2.
METHODS: Twelve sessions (over 4 weeks) of either VR-augmented RAGT (intervention group) or standard RAGT (control group). Accept-
ability of the interventions (drop-out rate, questionnaire), patients’ motivation (Intrinsic Motivation Inventory [IMI], individual mean walking
time), and feasibility of potential outcome measures (completion rate and response to interventions) were determined.
RESULTS: We found high acceptability of repetitive VR-augmented RAGT. The drop-out rate was 1/11 in the intervention and 4/14 in the
control group. Patients of the intervention group spent significantly more time walking in the robot than the control group (per session and total
walking time; P<0.03). In both groups, motivation measured with the IMI was high over the entire intervention period. The felt pressure and
tension significantly decreased in the intervention group (P<0.01) and was significantly lower than in the control group at the last therapy session
(r=-0.66, P=0.005). The FAC is suggested as a potential primary outcome measure for a definitive RCT, as it could be assessed in all patients and
showed significant response to interventions (P<0.01). We estimated a sample size of 44 for a future RCT.
CONCLUSIONS: VR-augmented RAGT resulted in high acceptability and motivation, and in a reduced drop-out rate and an extended train-
ing time compared to standard RAGT. This pilot trial provides guidance for a prospective RCT on the effectiveness of VR-augmented RAGT.
CLINICAL REHABILITATION IMPACT: VR might be a promising approach to enrich and improve gait rehabilitation after stroke.
(Cite this article as: Bergmann J, Krewer C, Bauer P, Koenig A, Riener R, Müller F. Virtual reality to augment robot-assisted gait training in non-
ambulatory patients with a subacute stroke: a pilot randomized controlled trial. Eur J Phys Rehabil Med 2018;54:397-407. DOI: 10.23736/S1973-
9087.17.04735-9)
Key words: Robotics - Virtual reality - Motivation.
or other proprietary information of the Publisher.
R estoration of gait is a major objective for stroke re-

habilitation.1 The loss or impairment of ambulation
is one of the most devastating disabilities after stroke,
years, new technologies for gait training have been devel-
oped.4 For example, robot-assisted gait training (RAGT)
is a safe form of treadmill training which reduces physical
which limits a patient’s mobility and activity.2, 3 In recent demands on therapists, and allows highly repetitive gait
Vol. 54 - No. 3 European Journal of Physical and Rehabilitation Medicine 397

not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, log
©
BERGMANN VR TO AUGMENT RAGT IN NON-AMBULATORY PATIENTS WITH A SUBACUTE STROKE
training early in the rehabilitation process.5, 6 The treadmill Materials and methods
speed, the amount of body weight support, and the guid-
ance force can be adjusted to create an optimized training This study is a randomized, controlled pilot trial with
intensity. However, despite these advantages the evidence two parallel groups. The study was approved by the Eth-
on the effectiveness of RAGT is controversial.7 A critical ics Committee of the Bavarian State Chamber of Phy-
factor may be the passive assistance provided by the robot- sicians (reference number: 08103). All procedures were
ic device, which can lead to reduced effort and passive be- conducted according to the Declaration of Helsinki and
havior.8 It was shown that passive guidance during RAGT all patients or their legal representative gave written in-
results in decreased metabolic costs and lower muscle ac- formed consent.
tivity, compared to therapist-assisted treadmill walking.9 The trial is registered at the German Clinical Trials Reg-
Active performance is crucial for motor learning, and, to- ister (DRKS00003207).
gether with motivation, is believed to be associated with a Participants
better rehabilitation outcome.10, 11
Virtual reality (VR) is an innovative approach to engage All subjects included in the study were in an inpatient re-
and motivate patients during training and has the poten- habilitation setting at the Schön Klinik Bad Aibling. They
tial to apply relevant concepts of neuroplasticity, i.e. task- met the following inclusion criteria: hemiparesis after
oriented, repetitive and intensive training.12-15 It offers a first unilateral ischemic or hemorrhagic stroke, 3 weeks
novel possibility to provide feedback about a patient’s to 6 months since onset, age between 18 and 75 years,
performance by directly interlinking motor behavior with inability to ambulate without ambulation aid and manual
actions in the VR-scenario. The application of VR has be- assistance from another person (Functional Ambulation
come increasingly popular in rehabilitation, and there is Classification ≤2), cognitive abilities to understand and
promising evidence for its efficiency in retraining upper follow simple verbal instructions, and spatial orientation.
limb function.16-18 However, there is insufficient proof for Patients with excessive osteoporosis, unstable fracture,
its effectiveness in gait training.19-21 Brütsch et al.12, 22 and restricted Range of Motion, excessive spasticity, or con-
Schuler et al.15 implemented VR for RAGT with children. tractures of lower extremities were excluded from the
They compared the immediate effect of different support- study. Other exclusion criteria were acute diseases of
ive RAGT conditions (i.e., VR scenarios, therapist instruc- the cardiovascular or respiratory system, pressure sore
tions, watching a movie) on motor output during the train- of lower extremity, serious cognitive deficits or aphasia,
ing. The motor output increased during the VR-augmented and pregnancy. Body weight was limited to 130 kg, body
conditions, compared to standard RAGT. Moreover, the height to 200 cm, and the maximum leg length difference
children reported high motivation during VR-augmented was 2 cm.
RAGT. However, the different conditions they tested were
Study protocol
all scheduled within a single session and lasted only few
minutes. Therefore, it has yet to be determined whether Between June 2010 and September 2011 a scientific staff
VR-augmentation over an entire therapy phase leads to member scanned and identified potential participants that
increased motivation and a better functional outcome. met the study inclusion criteria. Patients who fulfilled all
According to the standards of the extension to the CON- inclusion and exclusion criteria were approached with the
SORT 2010 statement for randomized pilot and feasibil- study information. If the patient was interested in the study
ity trials,23 the present pilot trial guides the planning of a and agreed to participate, informed written consent was
larger randomized controlled trial (RCT) for investigation obtained. Patients included in the study were randomized
of the effectiveness of repetitive VR-augmented RAGT on using different block sizes of four and six by a computer-
walking function. The main aim of this pilot trial was to generated randomization to the intervention group (VR-
determine the acceptability of the interventions, patients’ augmented RAGT), or the control group (standard RAGT)
motivation during the interventions, the feasibility of the (1:1), stratified by age at study entry (>55 years or ≤55
potential outcome measures, and the estimation of the years). The allocation was done by a scientific staff mem-
treatment effect and the variance in order to inform sample ber not directly involved in the project to ensure conceal-
size calculation of a future RCT. ment of allocation.
398 European Journal of Physical and Rehabilitation Medicine June 2018

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VR TO AUGMENT RAGT IN NON-AMBULATORY PATIENTS WITH A SUBACUTE STROKE BERGMANN
Interventions VR was presented to patients of the intervention group on

a 42-inch screen in front of the subjects. Two VR-scenarios
Patients of both groups performed 12 sessions (4 weeks, 3 were used: the coin scenario, and the dog scenario (Figure
sessions per week) of RAGT, either standard RAGT (con- 1). Both scenarios took place in a forest, where subjects had
trol group) or VR-augmented RAGT (intervention group). to walk along a straight alley in the middle of the screen,
During the four-week intervention phase the amount of ad- and solve different tasks by controlling the avatar’s speed
ditional physiotherapy in the rehabilitation setting was con- by adapting their motor activity. Patients’ activity was quan-
trolled: all patients received 60 minutes of physiotherapy tified using weighted interaction torques (WIT) between the
on the two working days without study intervention and no robot and the patients, which was measured at the hip and
other physiotherapy was applied at the days with study inter- knee joints. WIT values were weighted for each step using
vention. After the 12th therapy session, patients performed the weighting function of Lünenburger et al.24 The resulting
an additional session of RAGT, but of the other therapy WIT values were considered high, if the patient performed
than during the intervention phase (crossover at last ses- an active movement, or low if the patient behaved passively
sion). This means, patients of the control group performed or resisted the walking pattern of the orthosis.25
a session of VR-augmented RAGT and patients of the inter- The dog scenario was performed, as described previ-
vention group performed a session of standard RAGT. This
ously.26, 27 Briefly, patients’ activity was displayed as a red
was done to directly compare the motivation of patients
dot on the path. With increasing activity the red dot moved
during the two interventions and their preference. During
faster, and with decreasing effort the red dot moved slow-
the follow-up phase following the crossover session, all pa-
er. A virtual dog walking on the path displayed the desired
tients continued their standard rehabilitation therapies and
activity level, and patients were instructed to place the red
the amount of therapy was not limited. Though, no RAGT
dot underneath the dog. For the coin scenario, patients had
or treadmill training was performed until the follow-up test.
to collect coins, and avoid rocks that were placed on the
The robotic-driven gait orthosis Lokomat (Hocoma
path. Patients had to increase or decrease their activity to
AG, Volketswil, Switzerland) was used for RAGT in both
catch or avoid the objects before they faded away. In order
groups. The Lokomat is an exoskeleton with linear drives
to get familiar with both scenarios, the dog scenario was
on hip and knee joints that assists locomotion on a tread-
applied in session 1 and 2, and the coin scenario in session
mill by guiding the subjects’ legs along a predefined trajec-
3 and 4. In the following sessions, patients were free to
tory. Patients were fixed into the gait orthosis with a har-
choose the scenario they preferred.
ness, which was attached to a body-weight support system,
and had cuffs placed around the legs. Elastic straps were Outcome measures
used to passively lift the subjects’ feet and prevent any foot
drop. Tension on the straps was steadily decreased as mo- The acceptability of the interventions was assessed in terms
tor recovery improved. Body weight support was individu- of the dropout rate in each group during the intervention
ally set for each patient, with no more than 50% of the pa- phase. The data sample included all patients who received
tient’s body weight. Therapists were instructed to keep the the allocated intervention. In addition, patients were asked
level of body weight support as constant as possible and
reduce guidance force of the orthosis as much as possible.
In both groups, patients were encouraged to behave ac-
tively during RAGT. A session of RAGT was one hour in
duration including pre- and postprocessing. Walking time
in the robot was individually determined. This means that
a minimal walking time of 20 minutes was given, but no
upper time limit, except for the length of a therapy session
(60 minutes). The therapy was stopped when the patient A B
indicated fatigue or wished to finish training. The train- Figure 1.—Virtual reality scenarios used in the study. A) Dog scenario:
ing was started with a warming-up of 3 to 5 minutes; sub- patient’s activity is displayed by the red dot. The patient is instructed to
place the dot underneath the dog and follow the dog; B) Coin scenario:
sequently the walking speed was increased up to 2.0-2.5 the patient has to collect coins (increase activity) and avoid rocks (de-
km/h. A trained therapist supervised the training. crease activity) before they fade away.

©
a self-designed questionnaire after the crossover session Statistical analysis

about their preferential intervention. Motivation of pa-
tients during the respective interventions was assessed in Since this was a pilot trial, a sample size calculation was
terms of the individual mean walking time in the robot and not performed. The aim was to analyze 20 patients (10 per
by the Intrinsic Motivation Inventory (IMI). The IMI is group), who completed the intervention per protocol (at
a multidimensional questionnaire to assess motivational least 10 sessions of the respective intervention), in order
structures for target activities.28, 29 We used the following to determine feasibility of the potential outcome measures
five subscales: interest/enjoyment, value/usefulness, ef- and to estimate the treatment effect. Based on earlier stud-
fort/importance, perceived competence, pressure felt and ies with similar participants we proposed a dropout rate of
tension. Four items per subscale were included, and scored 20%. Consequently, we planned to include 24 patients in
on a Likert Scale from strongly disagree (1) to strongly the study.
agree (7). In the present study patients responded to the Demographic and clinical characteristics of patients,
IMI as self-assessment interviewed by a blinded neuropsy- and parameters of the RAGT were compared between
chologist or study nurse. To rate the patients’ motivation the intervention and the control group using the χ2 test
from a third person perspective, the therapist supervising (for comparison of proportions) or the Student’s t-test
the RAGT answered a rephrased version of the IMI. The (for continuous variables). Measures on the acceptability
IMI was assessed immediately after the 1st, the 6th, the 12th, of the interventions and the VR scenarios, the individu-
and the crossover therapy session. al mean walking time, and the frequency of use of the
In addition, the acceptability of the VR scenarios was scenarios are reported descriptively. Non-parametric sta-
determined by asking the patients a self-designed ques- tistics were used for analyzing the IMI. Between-group
tionnaire about the VR scenarios and by evaluating their comparisons for the IMI were performed for the assess-
frequency of use. ments after the 1st, the 6th, the 12th, and the crossover
To assess feasibility of potential outcome measures for a therapy session. Mann-Whitney U-tests were used for
future RCT, completion rate and response of the measures between-group comparisons, and for analyzing differenc-
to the interventions (within-group change) was assessed. es between the IMI self-assessment and IMI external as-
Therefore, a trained physiotherapist, who was blinded sessment. Within-group comparisons were performed us-
for treatment allocation, assessed the following measures ing Friedman-tests and if significant Wilcoxon matched-
before the intervention phase (baseline), at the end of the pairs tests applied. Bonferroni correction was applied for
4-week intervention phase (post), and at a follow-up two
multiple comparisons.
weeks after the end of the intervention phase: the Function-
For the potential outcome measures, medians and in-
al Ambulation Classification (FAC), the 10m walk test, a
terquartile ranges (Q1-Q3) are reported. Within-group
10-m dual task, the 6min walk test, and muscle strength of
changes were calculated for those measures which were
the lower extremity using the Medical Research Council
(MRC) Scale. The FAC distinguishes 6 levels of walking completed by at least half of the patients at follow-up test
ability on the basis of the amount of physical support re- (FAC, 10-m walk test, and muscle strength) using Fried-
quired.30, 31 Categories range from 0 (patient cannot walk, man-tests. For the FAC (suggested as primary outcome
or needs help from two or more persons), to 5 (patient can in a future RCT) Wilcoxon matched-pairs tests were per-
walk independently anywhere). For the 10-m walking test, formed for analysis of short-term effects (baseline – post)
the 10-m dual task, and the 6min walk test, patients used and long-term effects (baseline – follow-up). In addition,
their usual assistive or orthotic devices and a static start a Mann-Whitney U-Test was performed to compare FAC
was selected. Muscle strength was determined by manual baseline values between groups. Effect sizes (r) were cal-
muscle testing using the Medical Research Council (MRC) culated for the IMI and the FAC.33 Effect size of 0.1, 0.3,
scale.32 The following movements were tested: extension, and 0.5 represent a small, medium, and large effect respec-
flexion, abduction, and adduction of the hip, and extension tively.34 Missing values were not replaced. The statistical
and flexion of the knee. For the measure with the highest analyzes were performed using SPSS Statistics (Version
completion rate and response to interventions effect sizes 17.0). The significance level for alpha was set at 0.05.
for between group comparisons were calculated in order to Sample size calculation was performed using G*Power
inform the sample size calculation of a future RCT. 3.1.9.2.

©
Results Screened prior to eligibility assessment (N.=318)
During a period of 15 months, a total of 318 patients were

Randomized (N.=27)
screened for eligibility. Twenty-seven patients were in-
cluded in the study and randomly assigned to the interven-
tion or the control group. A flow chart of patients through Allocation
the study is shown in Figure 2. One of 11 patients of the Allocated to intervention group Allocated to control group
intervention group (9.1%) and 4 of 14 patient of the con- (RAGT + VR) (N.=13) (RAGT) (N.=14)
trol group (28,6%) were lost during the intervention phase. - Received allocated intervention - Received allocated intervention
(N.=11) (N.=14)
Reasons for dropping-out are given in Figure 2. - Did not receive allocated interven- - Did not receive allocated interven-
tion (N.=2) tion (N.=0)
Demographics and clinical characteristics of patients - Reason: FAC>4 at first therapy ses-
who finished the intervention per protocol can be found sion, technical problems with VR
in Table I. There were no significant differences between
Follow-up
the intervention, and the control group for any of the de-
mographic and clinical characteristics at the beginning of Lost to follow-up (N.=1) Lost to follow-up (N.=5)
- Finished intervention per protocol - Finished intervention per protocol
the intervention. (N.=10) (N.=10)
Table II shows therapy parameters, including average - Discontinued intervention (N.=1)
- Reason: refusal to continue study
- Discontinued intervention (N.=4)
- Reason: pain in foot or groin, refusal
walking time, for patients of the intervention and the con- to continue study, discharge for
replantation of cranial bone flap
trol group. Patients of the intervention group spent sig-
nificantly more time walking in the robot than the control
Assessment
group, both per session, and over the whole intervention
Acceptability of interventions Acceptability of interventions
period. No other therapy parameter showed significant dif- - dropout rate (N.=11) - dropout rate (N.=14)
ferences between groups. - self designed questionnaire (N.=9) - self designed questionnaire (N.=5)
Motivation Motivation
Answers to the self-designed questionnaire about the - IMI self assessment 1st, 6th, 12th ses- - IMI self assessment 1st, 6th, 12th ses-
interventions are shown in Figure 3. For the most part, pa- sion (N.=9) sion (N.=9)
- IMI external assessment 1st, 6th, 12th - IMI external assessment 1st, 6th, 12th
tients preferred the intervention they did during the inter- session (N.=9) session (N.=9)
vention period. - IMI self assessment crossover ses-
sion (N.=7)
- IMI self assessment crossover ses-
sion (N.=8)
IMI self-assessment and external assessment are shown - IMI external assessment crossover - IMI external assessment crossover
session (N.=8)
in Figures 4, 5 for the intervention and the control group. - average walking time (N.=10)
session (N.=8)
- average walking time (N.=10)
The IMI scores significantly differed between the self-as- Acceptability of VR scenarios Feasibility of potential
- self designed questionnaire (N.=9)
sessment and the external assessment (P≤0.015) in all sub- - frequency of use (N.=10) outcome measures
scales. The IMI scores were generally lower in the external Feasibility of potential
- completion rate (N.=10)
- response to interventions (N.=9)
assessment than in the self-assessment (vice versa for the outcome measures
Estimation of treatment effect
- completion rate (N.=10)
pressure/tension subscale). No significant difference was - response to interventions (N.=10) and variance (N.=9)
observed between groups in any subscale after the 1st, the Estimation of treatment effect
and variance (N.=10)
6th, and the crossover therapy session (P>0.05). However,
after the 12th session there was a significant difference Figure 2.—Flow diagram of the study.
Table I.—Demographics and baseline clinical characteristics of patients who finished the intervention per protocol.
RAGT+VR RAGT Between group comparisons
(N.=10) (N.=10)
Age [years] (mean±SD) 62±11 65±8 t(18)=-0.751, P=0.462
Sex (f/m) 5/5 1/9 χ2(1)=3.810, P=0.051
Ischemic/hemorrhagic stroke 7/3 5/5 χ2(1)=0.833, P=0.361
Side of lesion (right/left) 8/2 8/2 χ2(1)=0.000, P=1.000

Time since stroke [weeks] 11±5 11±3 t(18)=-0.200, P=0.843
ACE-R (median, IQR) 78±20 78±21 t(17)=0.190, P=0.851
Fugl-Meyer sensation touch (anesthesia/hypesthesia/normesthesia) 0/7/3 1/5/4 χ2(2)=1.476, P=0.478
Fugl-Meyer sensation position (missing/abnormal/normal) 0/6/4 1/7/2 χ2(2)=1.744, P=0.418

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Table II.—Therapy parameters of patients who performed the therapy per protocol (mean±SD).
RAGT+VR RAGT Between group comparison
Number of therapy sessions 11±1 12±1 t(18)=-0.246, P=0.809
Walking time per session (min) 28.3±3.5 24.0±3.7 t(18)=2.606, P=0.018
Total walking time (min) 325.8±34.2 281.2±47.0 t(18)=2.426, P=0.026
Distance per session (m) 1028.2±159.1 906.2±154.5 t(18)=1.739, P=0.099
Walking speed (km/h) 2.3±0.1 2.4±0.1 t(18)=-1.773, P=0.093
Guidance force paretic side (%) 70±15 78±18 t(18)=-1.064, P=0.301
Guidance force non-paretic side (%) 61±21 49±23 t(18)=1.796, P=0.247
Body weight support (%) 39±12 40±10 t(18)=-0.249, P=0.806
between groups for the subscale pressure/tension in the follow-up). At post-test, the FAC, the MRC, and the 10m
self-assessment (U=9.500, Z=-2.788, r=-0.66, P=0.005). walk test were done by at least half of the patients. Group
Specifically, the intervention group felt less pressure and values and within-group comparisons for these measures
tension during the therapy than the control group. With- are shown in Table IV. Walking speed was rated with 0 m/s
in-group comparisons revealed a significant change of if a patient was not able to do the 10-m walk test due to the
the pressure/tension subscale in the intervention group inability to walk. The FAC and the walking speed showed
for the self-assessment (χ2=11.167, P=0.011). No other significant improvements in both group, while muscle
within-group comparisons were significant (P>0.05). The
post-hoc analysis showed a significant reduction of the
pressure/tension subscale from the 1st to the 6th session 1st session
6th session
12th session
(Z=-2.399, r=-0.759, P=0.016), and from the 1st to the 12th crossover session
session (Z=-2.684, r=-0.895, P=0.007).

Answers to the self-designed questionnaire about the
VR scenarios are shown in Figure 6. Both scenarios were
IMI score
equally used (mean 6±2 times per patient).

Completion rates of the assessments are shown in Table
III. Very few patients were able to walk 10 meters at the
beginning of the study and no patient was able to do the
dual task or the 6-min walk test, while the FAC and muscle
strength could be assessed in all subjects who were avail- interest/enjoyment value/usefulness effort/importance perceived pressure/tension
able for testing (one patient of the control group was lost to A Subscale competence
1st session
6th session
12th session
crossover session
RAGT
RAGT & VR
no answer/undecided
none
IMI score
Question
interest/enjoyment value/usefulness effort/importance perceived pressure/tension

B
competence
Subscale
Number of answers
Figure 4.—Intrinsic Motivation Inventory self-assessment. A) Interven-
Figure 3.—Self-designed questionnaire about the patients’ preferential tion group; B) control group.
intervention (assessed after the crossover session). *P<0.05.

©
dog scenario
1st session coin scenario
6th session
12th session no decison
crossover session
Question
IMI score
Number of answers
interest/enjoyment value/usefulness effort/importance perceived pressure/tension
A Subscale competence
Figure 6.—Self-designed questionnaire about the virtual reality sce-
1st session
6th session narios.
12th session
crossover session
short-term effects (intervention group: Z=-2.070, r=-0.46,

p=0.038; control group: Z=-2.000, r=-0.45, p=0.046), and
IMI score
long-term effects (intervention group: Z=-2.555, r=-0.57,

P=0.011; control group: Z=-2.060, r=-0.46, P=0.039).
Sample size for a definitive RCT was calculated in
G*Power 3.1.9.2 with the null hypothesis that there is no
difference in the FAC improvement (pre – follow-up) be-
tween the intervention group and the control group. The
interest/enjoyment value/usefulness effort/importance perceived pressure/tension mean FAC differences 2 and 1 and a standard deviation
B Subscale competence
SD=1 were assumed in the intervention and the control

Figure 5.—Intrinsic Motivation Inventory external assessment. A) inter- group, respectively, to calculate effect size. Sample size
vention group; B) control group.
estimation for a two-sided Mann-Whitney U-test with a
power of 0.80 and an alpha value of 0.05 resulted in a to-
force improved mainly in the intervention group. As the tal sample size of 36 subjects (18 per group). Assuming
FAC was completed in all patients and showed significant the average drop-out rate of 20% which we found in the
response to interventions, we suggest the FAC as a primary present pilot trial, a sample of 44 subjects is needed for a
outcome measure for a future RCT on the effectiveness definitive RCT.
of VR-augmented RAGT on walking function. The FAC An ancillary analysis was performed, because we were
showed no significant difference between groups at base- interested whether the acceptability and the patients’ ben-
line (U=40.00, Z=-1.453, r=-0.32, p=0.146). Both groups efit from the interventions depend on cognitive function.
significantly improved over time and showed significant The Addenbrooke’s Cognitive Examination (ACE-R) was
Table III.—Completion rate of the potential outcome measures (number of patients who performed the assessment/total number of sub-
jects).
Baseline Post Follow-up
RAGT+VR RAGT RAGT+VR RAGT RAGT+VR RAGT
FAC (completed/total) 10/10 10/10 10/10 10/10 10/10 9/9
MRC 10/10 10/10 10/10 10/10 10/10 9/9

10-m walking test 1 3/10 0/10 6/10 4/10 6/9 5/9
10-m walking test 2 1/10 0/10 3/10 3/10 6/9 2/9
Dual task 10-m 0/10 0/10 1/10 0/10 5/9 2/9
6-min walking test 0/10 0/10 1/10 0/10 4/9 1/9

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Table IV.—FAC, walking speed (10-m walk test), and muscle strength at baseline, postintervention and follow-up: median (Q1-Q3).
Baseline Post Follow-up Within group comparison
RAGT+VR RAGT RAGT+VR RAGT RAGT+VR RAGT RAGT+VR RAGT
FAC 0 (0-0) 0 (0-0) 1 (0-2) 0 (0-1) 1.5 (1-3) 1 (0-2) χ2(2)= 13.556, χ2(2)= 9.000,
p=0.001 p = 0.011
Number of patients within each FAC 0=8 FAC 0=10 FAC 0=4 FAC 0=6 FAC 0=2 FAC 0=4
FAC category FAC 1=2 FAC 1=3 FAC 1=4 FAC 1=3 FAC 1=1
FAC 2=3 FAC 2=2 FAC 2=3
FAC 3=2 FAC 3=1
FAC 4=1
Walking speed (m/s) 0.00 0.00 0.09 0.00 0.16 0.08 χ2(2)=11.565, χ2(2)=6.632,
(0.00-0.00) (0.00-0.00) (0.00-0.19) (0.00-0.17) (0.00-0.34) (0.00-0.16) P=0.003 P=0.036
Muscle strength
Hip extension 1 (0-2) 1 (1-2) 2 (1-3) 2 (1-2) 3 (2-3) 2 (1-3) χ2(2)=8.615, χ2(2)=4.000,
P=0.013 P=0.135
Hip flexion 2 (0-2) 2 (0-3) 2 (2-3) 2 (1-3) 3 (2-3) 2 (1-3) χ2(2)=5.448, χ2(2)=3.500,
P=0.066 P=0.174
Hip abduction 2 (0-2) 1 (0-2) 2 (1-3) 2 (1-3) 3 (2-4) 1 (1-2) χ2(2)=13.471, χ2(2)=2.867,
P=0.001 P=0.239
Hip adduction 2 (0-3) 2 (1-2) 2 (1-3) 2 (1-3) 3 (2-4) 3 (1-3) χ2(2)=7.000, χ2(2)=7.760,
P=0.030 P=0.021
Knee extension 2 (0-2) 2 (0-2) 3 (1-3) 2 (1-2) 4 (2-4) 2 (1-3) χ2(2)=7.800, χ2(2)=4.526,
P=0.020 P=0.104
Knee flexion 1 (0-2) 2 (0-2) 2 (1-3) 2 (1-2) 3 (1-3) 2 (1-3) χ2(2)=8.857, χ2(2)=4.174,
P=0.012 P=0.124
FAC: Functional Ambulation Classification.
assessed in all patients at study enrolment. The ACE-R Acceptability of interventions and patient’s motivation
scores of patients who dropped out during the intervention
phase was similar to the ACE-R scores of patients who fin- The present study showed high acceptability of repetitive
ished the intervention per protocol (U=35.500, Z=-0.856, VR-augmented RAGT. The drop-out rate was lower in the
P=0.406). This means, acceptability and adherence to the group which performed VR-augmented RAGT than in the
interventions was not affected by the patients’ cognitive group with standard RAGT. Importantly, of those patients
function. In addition we correlated the improvements in who completed the study per protocol (minimum 10 ses-
the FAC (difference baseline – post and difference base- sions), patients who trained with VR spent significantly
line – follow-up) with the ACE-R score. We found a sig- more time walking in the robot than patients of the control
nificant correlation for the changes in the FAC between group (per therapy session and total walking time). This
baseline and follow-up and the ACE-R score (rSp=0.407, indicates that VR enhances motivation in patients to con-
P=0.047): patients with better cognitive function showed tinue exercising for longer time periods. Extended training
larger long-term improvement of their walking function. time might lead to greater improvements in activity of dai-
ly living and in walking speed.35 Overall, patients favored
RAGT with VR over standard RAGT. However, patients
Discussion
for most instances preferred the intervention they did dur-
VR is a promising approach to engage and motivate sub- ing the intervention phase, i.e. patients of the intervention
jects during training. Recent studies on VR in motor re- group favored mostly RAGT with VR and patients of the
habilitation have focused primarily on upper limb recov- control group standard VR.
ery, but there is insufficient proof for its use in gait train- Results of the IMI show that all patients in this study
ing.19, 20 In the present study, we conducted a randomized, were highly motivated during the entire intervention pe-
controlled pilot trial which guides the planning of a larger riod, independent of the therapy they performed. Patients
RCT investigating the effectiveness of VR-augmented rated their intrinsic motivation significantly higher than
RAGT on motivation and walking function. therapists did, but, in general, the external assessments

©
also revealed a high motivation. There might be a potential estimation revealed a sample size of 44 subjects which
study bias, as all patients participated voluntarily in this would be required to detect differences between groups
study, and, therefore, might have been highly interested in a definitive RCT investigating the effectiveness of VR-
and motivated for the therapy. Consequently, the patients augmented RAGT on walking ability.
in this study might not be representative of the broader For gait speed, a change of 0.16 m/s was estimated as
stroke population. We found no significant differences be- minimal clinically important difference among patients
tween groups for any subscale of the IMI, except for the with subacute stroke and severe gait impairments.36 Pa-
subscale pressure/tension in the self-assessment. The per- tients who increase their gait speed ≥0.16 m/s are more
ceived pressure and tension decreased in the intervention likely to experience a meaningful improvement in disabil-
group over the intervention period, and was significantly ity level than those who do not. Only four patients of the
lower than in the control group at the last therapy session. intervention group, and three patients of the control group
This means that VR-augmented RAGT caused more pres- showed a change ≥0.16 m/s from baseline to follow-up.
sure and tension than standard RAGT at the first therapy These rather low numbers might be due to the severe initial
session, but as patients got familiar with the VR-scenari- walking impairment of the patients, as well as the short du-
os and learned to control them, the pressure significantly ration of the study period. In the future, it will be important
decreased and was marginal by the end of the interven- for studies to include a longer follow-up period to detect
tion period. Additionally, compared with the patients of potential clinically relevant changes in walking capacity.
the intervention group who received feedback about their Muscle strength was measured using the MRC scale.
performance, patients of the control group had fewer op- Several studies have reported a correlation between gait
portunities to follow their progress. This might have had a speed and strength measures of muscular groups of the pa-
negative influence on the level of pressure and tension in retic limb in stroke patients.37, 38 Similar to the FAC, mus-
the control group. cle strength could be tested in all patients and we found
Acceptability of VR was good and no negative side ef- significant changes in muscle strength of the paretic leg
fects were observed. One patient could not perform the al- in the intervention but not in the control group. Likewise,
located VR-augmented RAGT because there were techni- changes in walking speed were larger in the intervention
cal problems with the VR software. This was the only case than in the control group.
with major technical problems. Although the coin scenario The IMI was used to test motivation. The significant
was a little bit more difficult to understand and to perform differences we found between the self-assessment and the
than the dog scenario, both scenarios were similar favored external assessment might indicate some problems in the
and equally used. self-assessment or speech comprehension in this patient
population. The questionnaire may be of limited feasibility
Feasibility of the potential outcome measures in stroke patients. However, there is a lack of alternative
The potential outcome measures were only partly feasible instruments to assess motivation. The IMI has the advan-
for the present patients’ population. At study entry, all pa- tage that it assesses different aspects of motivation, and
tients were severely affected, and mainly unable to am- can be adapted to the target activity. The questionnaire has
bulate. The 10-m walk test, the 6-min walk test, and the previously been used to evaluate VR-augmented motor re-
10m dual task could not be done by most of the patients habilitation.39, 40
and resulted in a walking speed of 0 m/s for the analysis. Additional suggestions for future studies
After the intervention phase, half of the patients were still
unable to ambulate (FAC=0). Consequently, the walk tests VR-augmented RAGT can be applied in a similar setting
demonstrated floor effects in several patients and may not as in the present pilot trial to a definitive RCT. It was well
be adequately responsive to changes in the study sample. accepted and resulted in a reduced dropout rate compared
As the FAC could have been assessed in all patients and to standard RAGT. We would suggest adapting some is-
resulted in significant improvements over the study period sues in the study design such as a longer follow-up period
in both groups, it might be suggested as a primary outcome and possibly a longer intervention period. So far, the opti-
measure for a future RCT. The FAC has good responsive- mum amount of RAGT is unclear.7 A longer intervention
ness in severely affected stroke patients.30 Sample size period might improve the effectiveness of the intervention.

©
However, this remains to be investigated in further stud- 3. Schmid A, Duncan PW, Studenski S, Lai SM, Richards L, Perera S,
et al. Improvements in speed-based gait classifications are meaningful.
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vices. J Rehabil Med 2012;44:193-9.
the study design. In the present pilot trial we assessed the
5. Freivogel S, Schmalohr D, Mehrholz J. Improved walking ability and
ACE-R at study enrolment and found that a higher initial reduced therapeutic stress with an electromechanical gait device. J Reha-
ACE-R score resulted in a better long-term improvement bil Med 2009;41:734-9.
of walking function. Consequently, future trials might use 6. Horn SD, Dejong G, Smout RJ, Gassaway J, James R, Conroy B.
Stroke rehabilitation patients, practice, and outcomes: Is earlier and more
an established measure, such as the ACE-R, as stratifica- aggressive therapy better? Arch Phys Med Rehabil 2005;86:S101-S14.
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For walking function, we selected an FAC≤2 as an in- mechanical-assisted training for walking after stroke. Cochrane Database
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9. Israel JF, Campbell DD, Kahn JH, Hornby TG. Metabolic costs and
able to ambulate at all. 18 of 20 patients included in this muscle activity patterns during robotic- and therapist-assisted treadmill
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While previous pilot studies focused on the immediate
12. Brutsch K, Schuler T, Koenig A, Zimmerli L, Koeneke SM, Lunen-
effect of different supportive RAGT conditions on active burger L, et al. Influence of virtual reality soccer game on walking perfor-
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Conflicts of interest.—The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.
Authors’ contributions.—Jeannine Bergmann designed and coordinated the study, recruited the participants, performed analyses, interpreted the data, and
drafted the manuscript. Carmen Krewer participated in the design of the study, collected data, and contributed to data analysis and interpretation. Petra Bauer
contributed to recruitment of the patients, acquisition of data, and revised the article. Alexander Koenig participated in the conception of the study, provided
technical support, and revised the article. Robert Riener contributed to the conception of the study, and revised the article. Friedemann Müller participated
in the conception and design of the study, contributed to the interpretation of the results, and revised the article. All authors read and approved the final
manuscript.
Funding.—This work was supported by the EU Project MIMICS funded by the European Community’s Seventh Framework Program (FP7/2007-2013, grant
agreement no. 215756).
Acknowledgments.—The authors thank Lukas Zimmerli for programming the VR-scenarios, and Silke Heller and the team of physiotherapists for assistance
with therapies.
Article first published online: December 21. 2017. - Manuscript accepted: December 20, 2017. - Manuscript revised: November 17, 2017. - Manuscript
received: March 13, 2017.

Virtual Reality To Augment Robot-Assisted Gait Training in Non-Ambulatory Patients With A Subacute Stroke: A Pilot Randomized Controlled Trial

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Virtual Reality To Augment Robot-Assisted Gait Training in Non-Ambulatory Patients With A Subacute Stroke: A Pilot Randomized Controlled Trial

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Virtual reality to augment robot-assisted gait training

R estoration of gait is a major objective for stroke re-

Vol. 54 - No. 3 European Journal of Physical and Rehabilitation Medicine 397

398 European Journal of Physical and Rehabilitation Medicine June 2018

Interventions VR was presented to patients of the intervention group on

Vol. 54 - No. 3 European Journal of Physical and Rehabilitation Medicine 399

a self-designed questionnaire after the crossover session Statistical analysis

400 European Journal of Physical and Rehabilitation Medicine June 2018

Results Screened prior to eligibility assessment (N.=318)

During a period of 15 months, a total of 318 patients were

Side of lesion (right/left) 8/2 8/2 χ2(1)=0.000, P=1.000

Vol. 54 - No. 3 European Journal of Physical and Rehabilitation Medicine 401

session (Z=-2.684, r=-0.895, P=0.007).

equally used (mean 6±2 times per patient).

interest/enjoyment value/usefulness effort/importance perceived pressure/tension

402 European Journal of Physical and Rehabilitation Medicine June 2018

short-term effects (intervention group: Z=-2.070, r=-0.46,

long-term effects (intervention group: Z=-2.555, r=-0.57,

SD=1 were assumed in the intervention and the control

MRC 10/10 10/10 10/10 10/10 10/10 9/9

Vol. 54 - No. 3 European Journal of Physical and Rehabilitation Medicine 403

404 European Journal of Physical and Rehabilitation Medicine June 2018

Vol. 54 - No. 3 European Journal of Physical and Rehabilitation Medicine 405

406 European Journal of Physical and Rehabilitation Medicine June 2018

Vol. 54 - No. 3 European Journal of Physical and Rehabilitation Medicine 407

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