Advertisement

Efficacy of Virtual Reality Combined With Real Instrument Training for Patients With Stroke: A Randomized Controlled Trial

  • Young-Bin Oh
    Affiliations
    Department of Physical Medicine and Rehabilitation, Chonbuk National University Medical School, Jeonju, Republic of Korea

    Translational Research and Clinical Trials Center for Medical Devices, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea
    Search for articles by this author
  • Gi-Wook Kim
    Affiliations
    Department of Physical Medicine and Rehabilitation, Chonbuk National University Medical School, Jeonju, Republic of Korea

    Translational Research and Clinical Trials Center for Medical Devices, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea

    Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea
    Search for articles by this author
  • Kap-Soo Han
    Affiliations
    Translational Research and Clinical Trials Center for Medical Devices, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea

    Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea
    Search for articles by this author
  • Yu Hui Won
    Affiliations
    Department of Physical Medicine and Rehabilitation, Chonbuk National University Medical School, Jeonju, Republic of Korea

    Translational Research and Clinical Trials Center for Medical Devices, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea

    Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea
    Search for articles by this author
  • Sung-Hee Park
    Affiliations
    Department of Physical Medicine and Rehabilitation, Chonbuk National University Medical School, Jeonju, Republic of Korea

    Translational Research and Clinical Trials Center for Medical Devices, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea

    Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea
    Search for articles by this author
  • Jeong-Hwan Seo
    Affiliations
    Department of Physical Medicine and Rehabilitation, Chonbuk National University Medical School, Jeonju, Republic of Korea

    Translational Research and Clinical Trials Center for Medical Devices, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea

    Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea
    Search for articles by this author
  • Myoung-Hwan Ko
    Correspondence
    Corresponding author Myoung-Hwan Ko, MD, PhD, Department of Physical Medicine and Rehabilitation, Chonbuk National University Medical School, 20 Geonji-ro, Deokjin-gu, Jeonju, 54907 Republic of Korea.
    Affiliations
    Department of Physical Medicine and Rehabilitation, Chonbuk National University Medical School, Jeonju, Republic of Korea

    Translational Research and Clinical Trials Center for Medical Devices, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea

    Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea
    Search for articles by this author
Open AccessPublished:April 16, 2019DOI:https://doi.org/10.1016/j.apmr.2019.03.013

      Abstract

      Objective

      To investigate the efficacy of real instrument training in virtual reality (VR) environment for improving upper-extremity and cognitive function after stroke.

      Design

      Single-blind, randomized trial.

      Setting

      Medical center.

      Participants

      Enrolled subjects (N=31) were first-episode stroke, assessed for a period of 6 months after stroke onset; age between 20 and 85 years; patients with unilateral paralysis and a Fugl-Meyer assessment upper-extremity scale score >18.

      Interventions

      Both groups were trained 30 minutes per day, 3 days a week, for 6 weeks, with the experimental group performing the VR combined real instrument training and the control group performing conventional occupational therapy.

      Main Outcome Measures

      Manual Muscle Test, modified Ashworth scale, Fugl-Meyer upper motor scale, hand grip, Box and Block, 9-Hole Peg Test (9-HPT), Korean Mini-Mental State Examination, and Korean-Montreal Cognitive Assessment.

      Results

      The experimental group showed greater therapeutic effects in a time-dependent manner than the control group, especially on the motor power of wrist extension, spasticity of elbow flexion and wrist extension, and Box and Block Tests. Patients in the experimental group, but not the control group, also showed significant improvements on the lateral, palmar, and tip pinch power, Box and Block, and 9-HPTs from before to immediately after training. Significantly greater improvements in the tip pinch power immediately after training and spasticity of elbow flexion 4 weeks after training completion were noted in the experimental group.

      Conclusions

      VR combined real instrument training was effective at promoting recovery of patients’ upper-extremity and cognitive function, and thus may be an innovative translational neurorehabilitation strategy after stroke.

      Keywords

      List of abbreviations:

      9-HPT (9-Hole Peg Test), FMA-UE (Fugl-Meyer assessment upper-extremity scale), K-MMSE (Korean Mini-Mental State Examination), K-MoCA (Korean-Montreal Cognitive Assessment), MAS (modified Ashworth scale), MMT (Manual Muscle Test), VR (virtual reality)
      Stroke is currently the leading cause of disability and death worldwide, and stroke survivors often experience chronic functional impairment and cognition deficits, which are associated with a reduced quality of life including difficulties in social and personal relationships.
      • Nichols-Larsen D.S.
      • Clark P.C.
      • Zeringue A.
      • Greenspan A.
      • Blanton S.
      Factors influencing stroke survivors' quality of life during subacute recovery.
      • Kernan W.N.
      • Ovbiagele B.
      • Black H.R.
      • et al.
      Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.
      It is well known that patients with stroke have a limited use of their upper extremities owing to motor dysfunction, and such patients experience sensory-motor deficits that affect their ability to perform daily activities. Stroke increases the risk of dementia 4 to 12 times,
      • Khedr E.M.
      • Hamed S.A.
      • El-Shereef H.K.
      • et al.
      Cognitive impairment after cerebrovascular stroke: relationship to vascular risk factors.
      and up to 69% of subjects have a poststroke cognitive impairment.
      • Yu K.H.
      • Cho S.J.
      • Oh M.S.
      • et al.
      Cognitive impairment evaluated with Vascular Cognitive Impairment Harmonization Standards in a multicenter prospective stroke cohort in Korea.
      Consequently, the aims of the current rehabilitation strategies for these patients are to improve functional ability and cognitive impairments through optimal and comprehensive rehabilitation processes.
      Previous studies have reported that a considerable amount of practice using real instruments is required to stimulate functional improvement and neuroplastic changes.
      • Plautz E.J.
      • Milliken G.W.
      • Nudo R.J.
      Effects of repetitive motor training on movement representations in adult squirrel monkeys: role of use versus learning.
      • Kwakkel G.
      Impact of intensity of practice after stroke: issues for consideration.
      Conventional occupational therapies promote the recovery of upper-extremity dysfunction by utilizing task-oriented repetition training with real instruments.
      • Platz T.
      • van Kaick S.
      • Mehrholz J.
      • Leidner O.
      • Eickhof C.
      • Pohl M.
      Best conventional therapy versus modular impairment-oriented training for arm paresis after stroke: a single-blind, multicenter randomized controlled trial.
      • Samuelkamaleshkumar S.
      • Reethajanetsureka S.
      • Pauljebaraj P.
      • Benshamir B.
      • Padankatti S.M.
      • David J.A.
      Mirror therapy enhances motor performance in the paretic upper limb after stroke: a pilot randomized controlled trial.
      Conventional therapy using real instruments is essential for poststroke rehabilitation, but environmental, individual, and financial limitations are associated with it.
      • Foley N.C.
      • Teasell R.W.
      • Bhogal S.K.
      • Doherty T.
      • Speechley M.R.
      The efficacy of stroke rehabilitation: a qualitative review.
      • Langhorne P.
      • Coupar F.
      • Pollock A.
      Motor recovery after stroke: a systematic review.
      Over the past 2 decades, the advancement of computer technology has resulted in the development of interventions that involve virtual reality (VR) devices, which are defined as computer hardware and software systems that generate simulations of imagined environments via visual, auditory, and tactile feedback.
      • Holden M.K.
      Virtual environments for motor rehabilitation: review.
      VR environments may be perceptual, such as creating situations with multiple sensory feedback regarding the patients’ kinematic movements, which are passive or active assisted in a virtual environment, and providing high-intensity repetitive multisensory interaction and goal-oriented tasks.
      • Kwakkel G.
      • Kollen B.J.
      • Krebs H.I.
      Effects of robot-assisted therapy on upper limb recovery after stroke: a systematic review.
      Repetition and intensity are key factors for promoting neural plasticity in patients with brain damage.
      • Kleim J.A.
      • Jones T.A.
      Principles of experience-dependent neural plasticity: implications for rehabilitation after brain damage.
      Additionally, studies have reported that VR training promotes motor recovery and cognition by inducing experience-dependent neural plasticity through repetitive tasks of varying time, high intensity, and complexity levels.
      • Doyon J.
      • Benali H.
      Reorganization and plasticity in the adult brain during learning of motor skills.
      Various studies have revealed that adaptive neuroplasticity, defined as the reorganization of movement representation in the motor cortex, premotor cortex, supplementary motor area, and somatosensory cortex due to synaptic efficacy and remodeling of the dendritic spines, can be induced by conducting repetitive goal-oriented tasks in VR-based interventions after stroke.
      • Nudo R.J.
      Adaptive plasticity in motor cortex: implications for rehabilitation after brain injury.
      • Hallett M.
      Neuroplasticity and rehabilitation.
      • Jang S.H.
      • You S.H.
      • Hallett M.
      • et al.
      Cortical reorganization and associated functional motor recovery after virtual reality in patients with chronic stroke: an experimenter-blind preliminary study.
      Recently, various reports have highlighted the potential utility of VR-based rehabilitation strategies for improving upper-limb motor weakness,
      • Coupar F.
      • Pollock A.
      • Legg L.A.
      • Sackley C.
      • van Vliet P.
      Home-based therapy programmes for upper limb functional recovery following stroke.
      • Kwon J.S.
      • Park M.J.
      • Yoon I.J.
      • Park S.H.
      Effects of virtual reality on upper extremity function and activities of daily living performance in acute stroke: a double-blind randomized clinical trial.
      cognitive dysfunction, and balance in patients poststroke.
      • Brunner I.
      • Skouen J.S.
      • Hofstad H.
      • et al.
      Is upper limb virtual reality training more intensive than conventional training for patients in the subacute phase after stroke? An analysis of treatment intensity and content.
      • Carregosa A.A.
      • Aguiar Dos Santos L.R.
      • Masruha M.R.
      • et al.
      Virtual rehabilitation through Nintendo Wii in poststroke patients: follow-up.
      • Lledo L.D.
      • Diez J.A.
      • Bertomeu-Motos A.
      • et al.
      A comparative analysis of 2D and 3D tasks for virtual reality therapies based on robotic-assisted neurorehabilitation for post-stroke patients.
      Furthermore, research has shown that compared to conventional therapy, VR training can improve the quality of neurologic rehabilitation and enhance productivity.
      • Garcia N.
      • Sabater-Navarro J.M.
      • Gugliemeli E.
      • Casals A.
      Trends in rehabilitation robotics.
      Even more, it has more beneficial effects in poststroke rehabilitation, such as an increased motivation and engagement,
      • Putrino D.
      Telerehabilitation and emerging virtual reality approaches to stroke rehabilitation.
      cost, and usability.
      • Brunner I.
      • Skouen J.S.
      • Hofstad H.
      • et al.
      Virtual Reality Training for Upper Extremity in Subacute Stroke (VIRTUES): a multicenter RCT.
      • Lo W.L.
      • Mao Y.R.
      • Li L.
      • et al.
      Prospective clinical study of rehabilitation interventions with multisensory interactive training in patients with cerebral infarction: study protocol for a randomised controlled trial.
      • Schuster-Amft C.
      • Eng K.
      • Lehmann I.
      • et al.
      Using mixed methods to evaluate efficacy and user expectations of a virtual reality-based training system for upper-limb recovery in patients after stroke: a study protocol for a randomised controlled trial.
      In addition, VR training is able to facilitate an increased therapy time without necessarily having to rely on a therapist.
      • Laver K.E.
      • Lange B.
      • George S.
      • Deutsch J.E.
      • Saposnik G.
      • Crotty M.
      Virtual reality for stroke rehabilitation.
      For these reasons, the number of complex and realistic VR-based interventions is increasing in neurorehabilitation programs in order to enhance the variability and adaptability of the intervention, as well as patients’ motivation, after stroke. However, comparing the effects of VR training with conventional therapy is still unclear. According to previous mentions, the combination of VR and real instruments is expected to have a synergy effect rather than a conventional occupational therapy in patients with stroke, and we investigated to see the clinical effect by using actual devices combined with a VR system to perform numerous tasks related to real daily activities.
      In the present study, we developed a novel rehabilitation training that combined the benefits of real instrument training and VR-based intervention. The aim of this study was to investigate whether the VR combined with real instrument training would be an efficient translational intervention for improving the functional abilities of the upper-extremity and cognitive function in patients with stroke.

      Methods

      Patients

      This randomized controlled trial consisted of patients in the chronic phase of stroke who had previously undergone inpatient poststroke rehabilitation in the Physical Medicine and Rehabilitation Unit from June 2016 to July 2017. Thirty-one patients (21 men, 10 women) with stroke were enrolled in the study. Patients were randomly divided by a computer program to either the experimental group (n=17; 11 men, 6 women) or control group (n=14; 9 men, 5 women). All patients were randomized to either the experimental group or the control group, but 2 patients were lost to follow up (fig 1). Allocations were stored in numbered, sealed envelopes and opened only at the time of recruitment. One patient in the experimental group withdrew from the trial and 1 patient in the control group was discharged from the study due to an adverse event. Consequently, the data from 31 patients were included and analyzed at each time point. The inclusion criteria were as follows: (1) first-episode stroke, as demonstrated by brain computed tomography or magnetic resonance imaging; (2) evaluated for a period of 6 months after stroke onset; (3) age between 20 and 85 years; (4) patients with unilateral paralysis or paresis, with a Fugl-Meyer assessment upper-extremity scale (FMA-UE) score >18, indicating mild-to-moderate dysfunction; (5) substantial cooperation to complete the assessment. Patients were excluded if they had any of the following: (1) serious or unstable medical problems; (2) history of other neurologic diseases and/or psychiatric disorders; (3) insufficient cognitive and language functions, with a Korean Mini-Mental State Examination (K-MMSE) score <19. The demographics and clinical characteristics of the study patients were summarized at inclusion (table 1). No significant differences in the pretraining status of the control and experimental groups were noted. The study was approved by the Ethics Committee and all patients signed a written informed consent form before participation.
      Figure thumbnail gr1
      Fig 1Diagram describing the patient selection process and study flow.
      Table 1Demographic and clinical characteristics of the study participants
      CharacteristicsExperimental GroupControl GroupP Value
      Sex
       Male12 (38.7)9 (29.0)
       Female5 (16.1)5 (16.1)
       Total17 (54.8)14 (45.2)
      Age57.4±12.252.6±10.7.269
      Education11.7±2.812.0±3.5.896
      MMT
       Flexion
      Shoulder3.5±0.73.7±0.5.538
      Elbow3.7±0.53.5±0.5.347
      Wrist3.0±1.02.8±1.1.99
      Finger3.4±0.73.3±0.6.538
       Extension
      Shoulder3.4±0.73.6±0.5.538
      Elbow3.5±0.73.6±0.6.503
      Wrist2.8±0.92.6±1.3.979
      Finger2.4±1.12.2±1.1.538
      FMA-UM
       Shoulder/elbow24.4±7.523.8±8.4.979
       Wrist5.0±3.14.4±4.0.728
       Hand5.5±3.65.1±4.4.769
       Coordination2.7±1.73.1±1.7.769
       Total37.6±14.436.5±17.8.470
      Hand grip test
       Grip power22.4±18.824.4±22.1.671
       Lateral pinch4.1±1.97.6±5.8.833
       Palmar pinch2.7±1.05.8±7.0.724
       Tip pinch2.0±0.94.6±4.5.268
      Box and Block Test21.0±14.227.8±22.1.408
      MAS
      Flexion
       Shoulder0.2±0.50.1±0.4.979
      Elbow1.6±1.11.1±1.0.295
      Wrist0.2±0.60.4±0.8.99
      Finger0.2±0.60.1±0.3.99
      Extension
       Shoulder0.0±0.00.0±0.0.728
      Elbow1.5±1.11.1±1.0.728
      Wrist1.1±1.21.1±1.2.810
      Finger1.1±1.21.4±1.4.406
      K-MMSE27.3±3.027.9±1.5.270
      K-MoCA22.7±4.224.4±4.1.894
      NOTE. Values are given as means ± SD or n (%).
      Abbreviations: B&B, Box and Block Test; FMA-UM, Fugl-Meyer upper motor scale.

      Instrumentation

      The present study employed Joystima for the VR combined with real instrument training (fig 2). This 3-dimensional manipulator consists of a monitor, conventional computer, and various real instruments with 3 degrees of freedom, which patients with stroke can easily control with their upper extremities. The instrumental devices, such as a thumb pinch, doorknob, button, air tube, gas valve, tool turn, and steering wheel, are used to move and sustain the patient’s paretic upper extremities in relation to the realistic environment. The software consisted of 9 modules, 9 basic tools, 9 games, and 2 missions. The system is able to record information regarding the patient’s progress, and these data allow clinicians to perform objective assessments of the patient’s condition being helpful for designing optimal rehabilitation strategies.
      Figure thumbnail gr2
      Fig 2VR combined with real instrument (Joystim) in neurorehabilitation.

      Intervention

      Patients in both groups trained for 30 minutes per day, 3 days a week, for 6 weeks, with the experimental group performing the VR combined real instrument training and the control group performing conventional occupational therapy. The patients in the experimental group underwent real instrument training in a VR environment and were supervised by an occupational therapist. The patients in the control group were seated at a table and were subjected to a standardized treatment program, which included upper-extremity range of motion exercises, active and/or active-assisted functional training with task-related exercises and activity of daily living board, fine motor training of the hand with various pegboards, and perception and cognition training using a pencil and paper with table activities. Training was performed by the same occupational therapist to minimize bias. The training in both groups was balanced in terms of intensity, and the level of difficulty could be adapted to each subject’s performance during the training period.

      Outcome measurements

      We utilized a standard evaluation procedure for all patients that consisted of various scales of proven sensitivity, validity, and reliability. The same clinician, who was trained to use the clinical scales and who was blinded to the treatment type, performed all the assessments. Assessments were done before starting the training (pretraining), after the 6-week training period (posttraining), and 4 weeks after training completion (follow-up). The following evaluations were employed and analyzed at each time point: FMA-UE, Manual Muscle Test (MMT), hand grip test, Box and Block Test, 9-Hole Peg Test (9-HPT), modified Ashworth scale (MAS), K-MMSE, and the Korean-Montreal Cognitive Assessment (K-MoCA).

      Statistical analysis

      The statistical analyses were performed using SPSS version 18.0,b and the results are presented as the mean ± SD. We compared the demographic and clinical information between the groups with independent t tests, 2-tailed Mann-Whitney U tests, chi-square tests, and Fisher exact tests, as appropriate. The pretraining, posttraining, and follow-up differences within individuals were evaluated using paired t tests and Wilcoxon signed-rank tests, while the differences between groups were assessed by independent t tests and Mann-Whitney U tests. Comparisons of the scores at the various time points between the groups were determined with Friedman tests and repeated-measures analyses of variance, with time (pretraining, posttraining, follow-up) as the within-subjects factor and training (experimental vs control group) as the between-subjects factor. For all analyses, statistical significance was set at P<.05.

      Results

      Treatment effects

      In this study, the experimental group, but not the control group, exhibited significant improvements in the MMT (P=.039) and MAS (P=.041) for wrist extension, MAS for elbow flexion (P=.022), and Box and Block Test (P=.002) scores in a time-dependent manner. However, both control and experimental groups showed significant improvements in the MMT for finger extension (P=.039 and P=.048, respectively), FMA-UE (P<.001 for both), grip power (P<.001 for both), lateral pinch power (P=.026 and P<.001, respectively), palmar pinch power (P=.008 and P=.024, respectively), and tip pinch power (P=.014 and P=.002, respectively), 9-HPT (P=.008 and P=.001, respectively), K-MMSE (P=.001 and P=.038, respectively), and K-MoCA (P<.001 for both) scores over time (table 2).
      Table 2Time-course effect of outcome measures within each group.
      OutcomesPrePostFollow-upP
      MMT
      Wrist (F)
       Control2.8±1.13.0±1.23.1±1.1.039
      P<.05.
       Experiment3.0±1.03.2±0.93.4±0.8.021
      P<.05.
      Wrist (E)
       Control2.6±1.32.8±1.12.8±1.1.135
       Experiment2.8±0.93.00±0.83.1±0.8.039
      P<.05.
      Finger (E)
       Control2.2±1.12.4±1.32.5±1.3.039
      P<.05.
       Experiment2.4±1.12.5±1.32.7±1.2.048
      P<.05.
      MAS
      Elbow (F)
       Control1.1±1.01.2±1.31.3±1.2.526
       Experiment1.6±1.11.3±1.11.3±1.1.022
      P<.05.
      Elbow (E)
       Control1.1±1.00.8±0.80.7±0.8.015
      P<.05.
       Experiment1.5±1.11.3±1.11.2±1.0.039
      P<.05.
      Wrist (E)
       Control1.1±1.20.9±1.20.9±1.2.050
       Experiment1.1±1.20.9±1.10.9±1.1.041
      P<.05.
      FMA-UM
      Shoulder/Elbow
       Control23.8±8.424.9±8.824.9±8.7.001
      P<.01.
       Experiment24.4±7.525.2±7.426.4±7.3.001
      P<.01.
      Wrist
       Control4.4±4.04.9±3.85.0±3.9.023
      P<.05.
       Experiment5.0±3.15.1±3.35.7±3.1.006
      P<.01.
      Hand
       Control5.1±4.45.7±4.75.8±4.7.003
      P<.01.
       Experiment5.5±3.66.2±4.36.5±4.0.004
      P<.01.
      Coordination
       Control3.1±1.73.1±1.83.1±1.8-
       Experiment2.7±1.72.9±1.73.0±1.8.039
      P<.05.
      Total
       Control36.5±17.838.6±18.538.8±18.5.001
      P<.01.
       Experiment37.6±14.439.5±15.141.5±14.8.001
      P<.01.
      Hand grip
      Grip
       Control24.4±22.130.6±22.537.0±25.2.001
      P<.01.
       Experiment22.4±18.829.5±23.333.2±23.1.001
      P<.01.
      Lateral pinch
       Control7.6±5.87.4±6.48.3±7.1.026
      P<.05.
       Experiment4.1±1.95.4±2.56.1±2.3.001
      P<.01.
      Palmar pinch
       Control5.8±7.05.6±7.06.6±6.8.008
      P<.01.
       Experiment2.7±1.003.6±1.63.7±1.8.024
      P<.05.
      Tip pinch
       Control4.6±4.54.6±4.45.8±4.9.014
      P<.05.
       Experiment2.0±0.93.5±1.33.5±1.9.002
      P<.01.
      B&B
       Control27.8±22.129.7±21.230.5±24.3.057
       Experiment21.0±14.225.1±15.426.2±18.3.002
      P<.01.
      9-HPT
       Control30.4±8.625.2±6.122.4±5.8.008
      P<.01.
       Experiment86.2±65.762.1±50.557.8±43.4.001
      P<.01.
      K-MMSE
       Control27.9±1.528.9±1.629.2±1.1.001
      P<.01.
       Experiment27.3±3.027.9±3.228.2±3.2.038
      P<.05.
      K-MoCA
       Control24.4±4.126.1±3.427.4±2.8.001
      P<.01.
       Experiment22.7±4.224.5±4.224.9±3.3.001
      P<.01.
      NOTE. Values are given as means ± SD.
      Abbreviations: B&B, Box and Block Test; E, extension; F, flexion; FMA-UM, Fugl-Meyer upper motor scale.
      P<.05.
      P<.01.
      Table 3 reveals the differences in the clinical assessment scale scores among the pretraining, posttraining, and follow-up points within each group. Interestingly, the experimental group, but not the control group, showed significant improvements in the Box and Block Test (P=.010) and 9-HPT (P=.025) scores, as well as in the lateral (P=.005), palmar (P=.012), and tip pinch (P=.006) power scores at the posttraining period when compared to the pretraining period. Moreover, the significant improvement in lateral pinch power was maintained at the follow-up period (P=.002) in the experimental group, but not in the control group, when compared with the scores from the pretraining period. In both groups, the FMA-UE, grip power, K-MMSE, and K-MoCA scores were significantly improved at the posttraining and follow-up evaluations. The follow-up scores for the MMT for finger extension (P=.046) and MAS for elbow extension (P=.034) significantly improved compared to the pretraining scores in the experimental group.
      Table 3Improvement of outcome measures within each group
      OutcomesPrePostD1P1Follow-upD2P2
      FMA-UM
       Control36.5±17.838.6±18.52.1±2.00.002
      P<.01.
      38.8±18.52.3±2.30.003
      P<.01.
       Experiment37.6±14.439.5±15.11.9±3.00.014
      P<.05.
      41.5±14.83.9±4.90.001
      P<.01.
      Hand grip
      Grip
       Control24.4±22.130.6±22.56.2±4.60.000
      P<.01.
      37.0±25.212.6±6.60.000
      P<.01.
       Experiment22.4±18.829.5±23.38.4±10.20.005
      P<.01.
      33.2±23.112.1±9.10.000
      P<.01.
      Lateral pinch
       Control7.6±5.87.4±6.40.4±1.10.2988.3±7.10.9±1.90.128
       Experiment4.1±1.95.4±2.51.2±1.40.005
      P<.01.
      6.1±2.32.0±1.90.002
      P<.01.
      Palmar pinch
       Control5.8±7.05.6±7.00.3±0.50.0596.6±6.80.9±1.60.026
      P<.05.
       Experiment2.7±1.03.6±1.60.7±1.00.012
      P<.05.
      3.7±1.81.2±1.60.026
      P<.05.
      Tip pinch
       Control4.6±4.54.6±4.40.3±0.60.1095.8±4.91.0±1.70.043
      P<.05.
       Experiment2.0±0.93.5±1.31.1±1.30.006
      P<.01.
      3.5±1.91.5±1.90.018
      P<.05.
      B&B
       Control27.8±22.129.7±21.23.5±7.20.12930.5±24.36.3±9.10.030
      P<.05.
       Experiment21.0±14.225.1±15.43.4±4.90.010
      P<.01.
      26.2±18.34.3±8.30.047
      P<.05.
      9-HPT
       Control30.4±8.625.2±6.12.2±4.00.06822.4±5.83.3±5.10.043
      P<.05.
       Experiment86.2±65.762.1±50.513.6±22.80.012
      P<.05.
      57.8±43.416.0±23.50.010
      P<.05.
      K-MMSE
       Control27.9±1.528.9±1.61.0±1.60.032
      P<.05.
      29.2±1.51.3±1.30.004
      P<.01.
       Experiment27.3±3.027.9±3.20.6±1.10.046
      P<.05.
      28.2±3.20.9±1.30.015
      P<.05.
      K-MoCA
       Control24.4±4.126.1±3.41.6±1.60.005
      P<.01.
      27.4±2.82.9±2.60.001
      P<.01.
       Experiment22.7±4.224.5±4.21.8±1.60.003
      P<.01.
      24.9±3.32.2±1.70.000
      P<.01.
      NOTE. Values are given as means ± SD.
      Abbreviations: B&B, Box and Block Test; D1, difference between pretraining and posttraining; D2, difference between pretraining and follow-up; FMA-UM, Fugl-Meyer upper motor scale; N/S, no significant difference; P1, significance of difference between pretraining and posttraining; P2, significance of difference between pretraining and follow-up.
      P<.01.
      P<.05.
      To gain an understanding of the differential effects of the 2 training types at the posttraining and follow-up time points, we compared the change rate in the outcome measures between the groups at each time point. We found that the improvement rate in the tip pinch power (P=.036) scores between the pretraining and posttraining periods was significantly higher in the experimental group than in the control group. Moreover, the improvement rate in the MAS for elbow flexion (P=.041) scores was significantly higher in the experimental group than in the control group between the pretraining and follow-up period (fig 3). These findings demonstrate that the scores of fine motor function tests were significantly improved by the real instrument training with VR environment and that the recovery of the fine motor function was maintained until the follow-up period at 4 weeks after training completion.
      Figure thumbnail gr3
      Fig 3Comparison of improvements in the tip pinch power and MAS for elbow flexion scores between the real instrument training in a VR environment (experimental) group and conventional occupational therapy (control) group. The experimental group shows significant improvements in the tip pinch power scores (A) at the posttraining period and in the MAS for elbow flexion scores (B) at follow-up period compared with the control group. NOTE. Values are presented as the mean ± SD. P<.05.

      Discussion

      To the best of our knowledge, ours is the first study that was designed specifically to elucidate the potential effects of real instrument training combined with a VR system on the recovery of the upper-extremity functional ability and cognitive impairment in patients with stroke. We recruited patients with chronic stroke who had a clinically mild to moderate dysfunction of the upper extremities (FMA-UE>18), a level of dysfunction at which significant improvements are difficult to achieve with conventional occupational therapy and focused on the recovery of fine motor function. The present study revealed that VR combined with real instrument training had relatively better effects on the recovery of upper-extremity dysfunction than did conventional occupational therapy. The scores for the lateral, palmar, and tip pinch power; Box and Block Test; and 9-HPT significantly improved at the posttraining vs pretraining evaluation by the VR combined with real instrument training but not by conventional occupational therapy. Moreover, the effects of the VR combined with real instrument training were more powerful in the posttraining period and were maintained through the follow-up assessment. Collectively, our findings support that real instrument training in a VR environment is a powerful therapeutic tool for improving the fine motor function of paretic upper extremities in patients with stroke.
      Studies conducted over the past few decades have established that conventional occupational therapies promote the recovery of upper-extremity dysfunction by utilizing task-oriented repetition training with real instruments.
      • Platz T.
      • van Kaick S.
      • Mehrholz J.
      • Leidner O.
      • Eickhof C.
      • Pohl M.
      Best conventional therapy versus modular impairment-oriented training for arm paresis after stroke: a single-blind, multicenter randomized controlled trial.
      • Samuelkamaleshkumar S.
      • Reethajanetsureka S.
      • Pauljebaraj P.
      • Benshamir B.
      • Padankatti S.M.
      • David J.A.
      Mirror therapy enhances motor performance in the paretic upper limb after stroke: a pilot randomized controlled trial.
      Here, we developed a VR intervention that was more complex and realistic than conventional therapy, as it combined a VR environment with real instrument training and focused on improving the fine motor function. The mechanisms of VR intervention therapy involve the principle of behavior-dependent neuroplasticity, whereby the VR system creates a realistic virtual environment that requires patients to use their paretic extremities to perform active or passive movements based on multisensory feedback.
      • Subramanian S.K.
      • Massie C.L.
      • Malcolm M.P.
      • Levin M.F.
      Does provision of extrinsic feedback result in improved motor learning in the upper limb poststroke? A systematic review of the evidence.
      Several recent studies reported that various types of VR interventions improved gross motor function and cognition deficits in patients with stroke.
      • Held J.P.
      • Ferrer B.
      • Mainetti R.
      • et al.
      Autonomous rehabilitation at stroke patients home for balance and gait: safety, usability and compliance of a virtual reality system.
      • Faria A.L.
      • Andrade A.
      • Soares L.
      • I Badia S.B.
      Benefits of virtual reality based cognitive rehabilitation through simulated activities of daily living: a randomized controlled trial with stroke patients.
      Additionally, several studies suggested that VR training is more effective and intensive than conventional therapy for improving gross motor function in patients with mild to moderate paresis.
      • Brunner I.
      • Skouen J.S.
      • Hofstad H.
      • et al.
      Is upper limb virtual reality training more intensive than conventional training for patients in the subacute phase after stroke? An analysis of treatment intensity and content.
      • Levin M.F.
      • Weiss P.L.
      • Keshner E.A.
      Emergence of virtual reality as a tool for upper limb rehabilitation: incorporation of motor control and motor learning principles.
      According to various neurophysiological studies, the highly repetitive practice and task-oriented processes by device-assisted task-specific training and VR training in poststroke rehabilitation improve the functional recovery of the upper extremities owing to neuroplasticity.
      • Kwakkel G.
      Impact of intensity of practice after stroke: issues for consideration.
      • Saleh S.
      • Fluet G.
      • Qiu Q.
      • Merians A.
      • Adamovich S.V.
      • Tunik E.
      Neural patterns of reorganization after intensive robot-assisted virtual reality therapy and repetitive task practice in patients with chronic stroke.
      • Wilkins K.B.
      • Owen M.
      • Ingo C.
      • Carmona C.
      • Dewald J.P.A.
      • Yao J.
      Neural plasticity in moderate to severe chronic stroke following a device-assisted task-specific arm/hand intervention.
      The results of the present study are consistent with the findings of previous studies, as the VR environment combined with real instrument training led to better neurologic recovery of paretic upper-extremity function by enhancing the efficacy of repetition of task-oriented exercise and motivation of training compared to conventional therapy for patients with stroke. This is likely because the VR system provided a multisensory perceptual feedback and used real instruments that were associated with a realistic environment, which together promoted neural networking in cortical and subcortical areas to better control the position and orientation of body segment.
      • Lord S.E.
      • Rochester L.
      • Weatherall M.
      • McPherson K.M.
      • McNaughton H.K.
      The effect of environment and task on gait parameters after stroke: a randomized comparison of measurement conditions.
      In VR combined real instrument training system, feedback was provided in a multimodal pathway, since the patients could feel a vibration via tactile feedback and confirm reached score via visual feedback. Also, training reported progress over a series of sessions regarded as auditory feedback. Moreover, regular real instrument training controlled by a computerized VR system can provide more sophisticated intensity and repetition to enhance feedback than conventional therapy. This study suggests that real instrument training in a VR environment may be able to replace conventional occupational therapy for patients in the chronic phase of stroke who are seeking to recover upper-extremity and cognitive function.
      The present study revealed that patients with stroke who performed real instrument training in a VR environment showed significantly greater improvements and conserved therapeutic effects, especially fine manual dexterities, than did patients who performed conventional therapy until 4 weeks after training completion. Unfortunately, the present study did not examine the long-term effects of real instrument training in a VR environment. However, some studies have shown that patients who trained with VR devices exhibited significantly greater improvements in their FMA-UE scores at the long-term follow-up assessment than did patients who underwent conventional therapy.
      • Housman S.J.
      • Scott K.M.
      • Reinkensmeyer D.J.
      A randomized controlled trial of gravity-supported, computer-enhanced arm exercise for individuals with severe hemiparesis.

      Study limitations

      Several limitations of the present study need to be considered. First, our study utilized a relatively small sample size of 31 participants. Moreover, the sample had relatively heterogeneous characteristics, such as the time since stroke, lesion characteristics, and motor function, which could restrict the generalizability of the results. Second, as mentioned above, we did not evaluate the long-term effects of the intervention, only the effects at 1 month after training. However, we think that the results of follow up after a month can suggest the long-term effect to some extent. Third, unfortunately several baseline parameters were not set closely between the experimental and control group due to the small sample size of this trial. Fourth, there is a possibility that the conditions comparison was not exact. Although, there was a limit to quantifying the 2 groups to the exact same conditions, we tried to set the intensity and repetition of tasks equally between the conventional occupational therapy and VR combined with real instrument training groups. Even though the number of treatment repetitions was not precisely controlled between the 2 groups, the control group also performed optimal occupational therapy during the same time by an expert occupational therapist. So, further large-scale, randomized controlled trials are needed to clarify this limitation and to confirm our findings regarding the efficacy of VR combined with real instrument training on the neurorehabilitation of patients with stroke.

      Conclusions

      In conclusion, our findings suggested that both VR combined with real instrument training and conventional therapy improved the functional ability of the upper extremities in the chronic phase of stroke. However, the VR intervention that used real instruments was more effective at promoting the recovery of the fine motor function compared to conventional therapy. A VR intervention after stroke provides the opportunity to encourage and motivate patients to perform rehabilitation training through a variety of challenging tasks and purposeful and task-oriented exercises, which are regarded as the most beneficial for upper-extremity motor function and cognitive function.
      • Llorens R.
      • Noe E.
      • Colomer C.
      • Alcaniz M.
      Effectiveness, usability, and cost-benefit of a virtual reality-based telerehabilitation program for balance recovery after stroke: a randomized controlled trial.
      Despite the previously mentioned limitations, the results of the present study imply that using a VR combined with real instrument training is an effective treatment option that could replace conventional therapy for patients with stroke. Therefore, we believe that real instrument training in a VR environment is an innovative translational intervention option for the comprehensive rehabilitation of patients in the chronic phase of stroke.

      Suppliers

      • a.
        Joystim; CyberMedic, Iksan, Korea.
      • b.
        SPSS, version 18.0; IBM.

      References

        • Nichols-Larsen D.S.
        • Clark P.C.
        • Zeringue A.
        • Greenspan A.
        • Blanton S.
        Factors influencing stroke survivors' quality of life during subacute recovery.
        Stroke. 2005; 36: 1480-1484
        • Kernan W.N.
        • Ovbiagele B.
        • Black H.R.
        • et al.
        Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.
        Stroke. 2014; 45: 2160-2236
        • Khedr E.M.
        • Hamed S.A.
        • El-Shereef H.K.
        • et al.
        Cognitive impairment after cerebrovascular stroke: relationship to vascular risk factors.
        Neuropsychiatr Dis Treat. 2009; 5: 103-116
        • Yu K.H.
        • Cho S.J.
        • Oh M.S.
        • et al.
        Cognitive impairment evaluated with Vascular Cognitive Impairment Harmonization Standards in a multicenter prospective stroke cohort in Korea.
        Stroke. 2013; 44: 786-788
        • Plautz E.J.
        • Milliken G.W.
        • Nudo R.J.
        Effects of repetitive motor training on movement representations in adult squirrel monkeys: role of use versus learning.
        Neurobiol Learn Mem. 2000; 74: 27-55
        • Kwakkel G.
        Impact of intensity of practice after stroke: issues for consideration.
        Disabil Rehabil. 2006; 28: 823-830
        • Platz T.
        • van Kaick S.
        • Mehrholz J.
        • Leidner O.
        • Eickhof C.
        • Pohl M.
        Best conventional therapy versus modular impairment-oriented training for arm paresis after stroke: a single-blind, multicenter randomized controlled trial.
        Neurorehabil Neural Repair. 2009; 23: 706-716
        • Samuelkamaleshkumar S.
        • Reethajanetsureka S.
        • Pauljebaraj P.
        • Benshamir B.
        • Padankatti S.M.
        • David J.A.
        Mirror therapy enhances motor performance in the paretic upper limb after stroke: a pilot randomized controlled trial.
        Arch Phys Med Rehabil. 2014; 95: 2000-2005
        • Foley N.C.
        • Teasell R.W.
        • Bhogal S.K.
        • Doherty T.
        • Speechley M.R.
        The efficacy of stroke rehabilitation: a qualitative review.
        Top Stroke Rehabil. 2003; 10: 1-18
        • Langhorne P.
        • Coupar F.
        • Pollock A.
        Motor recovery after stroke: a systematic review.
        Lancet Neurol. 2009; 8: 741-754
        • Holden M.K.
        Virtual environments for motor rehabilitation: review.
        Cyberpsychol Behav. 2005; 8 (discussion 212-9): 187-211
        • Kwakkel G.
        • Kollen B.J.
        • Krebs H.I.
        Effects of robot-assisted therapy on upper limb recovery after stroke: a systematic review.
        Neurorehabil Neural Repair. 2008; 22: 111-121
        • Kleim J.A.
        • Jones T.A.
        Principles of experience-dependent neural plasticity: implications for rehabilitation after brain damage.
        J Speech Lang Hear Res. 2008; 51: S225-S239
        • Doyon J.
        • Benali H.
        Reorganization and plasticity in the adult brain during learning of motor skills.
        Curr Opin Neurobiol. 2005; 15: 161-167
        • Nudo R.J.
        Adaptive plasticity in motor cortex: implications for rehabilitation after brain injury.
        J Rehabil Med. 2003; : 7-10
        • Hallett M.
        Neuroplasticity and rehabilitation.
        J Rehabil Res Dev. 2005; 42 (xvii-xxii)
        • Jang S.H.
        • You S.H.
        • Hallett M.
        • et al.
        Cortical reorganization and associated functional motor recovery after virtual reality in patients with chronic stroke: an experimenter-blind preliminary study.
        Arch Phys Med Rehabil. 2005; 86: 2218-2223
        • Coupar F.
        • Pollock A.
        • Legg L.A.
        • Sackley C.
        • van Vliet P.
        Home-based therapy programmes for upper limb functional recovery following stroke.
        Cochrane Database Syst Rev. 2012; : CD006755
        • Kwon J.S.
        • Park M.J.
        • Yoon I.J.
        • Park S.H.
        Effects of virtual reality on upper extremity function and activities of daily living performance in acute stroke: a double-blind randomized clinical trial.
        NeuroRehabilitation. 2012; 31: 379-385
        • Brunner I.
        • Skouen J.S.
        • Hofstad H.
        • et al.
        Is upper limb virtual reality training more intensive than conventional training for patients in the subacute phase after stroke? An analysis of treatment intensity and content.
        BMC Neurol. 2016; 16: 219
        • Carregosa A.A.
        • Aguiar Dos Santos L.R.
        • Masruha M.R.
        • et al.
        Virtual rehabilitation through Nintendo Wii in poststroke patients: follow-up.
        J Stroke Cerebrovasc Dis. 2018; 27: 494-498
        • Lledo L.D.
        • Diez J.A.
        • Bertomeu-Motos A.
        • et al.
        A comparative analysis of 2D and 3D tasks for virtual reality therapies based on robotic-assisted neurorehabilitation for post-stroke patients.
        Front Aging Neurosci. 2016; 8: 205
        • Garcia N.
        • Sabater-Navarro J.M.
        • Gugliemeli E.
        • Casals A.
        Trends in rehabilitation robotics.
        Med Biol Eng Comput. 2011; 49: 1089-1091
        • Putrino D.
        Telerehabilitation and emerging virtual reality approaches to stroke rehabilitation.
        Curr Opin Neurol. 2014; 27: 631-636
        • Brunner I.
        • Skouen J.S.
        • Hofstad H.
        • et al.
        Virtual Reality Training for Upper Extremity in Subacute Stroke (VIRTUES): a multicenter RCT.
        Neurology. 2017; 89: 2413-2421
        • Lo W.L.
        • Mao Y.R.
        • Li L.
        • et al.
        Prospective clinical study of rehabilitation interventions with multisensory interactive training in patients with cerebral infarction: study protocol for a randomised controlled trial.
        Trials. 2017; 18: 173
        • Schuster-Amft C.
        • Eng K.
        • Lehmann I.
        • et al.
        Using mixed methods to evaluate efficacy and user expectations of a virtual reality-based training system for upper-limb recovery in patients after stroke: a study protocol for a randomised controlled trial.
        Trials. 2014; 15: 350
        • Laver K.E.
        • Lange B.
        • George S.
        • Deutsch J.E.
        • Saposnik G.
        • Crotty M.
        Virtual reality for stroke rehabilitation.
        Cochrane Database Syst Rev. 2017; 11: CD008349
        • Subramanian S.K.
        • Massie C.L.
        • Malcolm M.P.
        • Levin M.F.
        Does provision of extrinsic feedback result in improved motor learning in the upper limb poststroke? A systematic review of the evidence.
        Neurorehabil Neural Repair. 2010; 24: 113-124
        • Held J.P.
        • Ferrer B.
        • Mainetti R.
        • et al.
        Autonomous rehabilitation at stroke patients home for balance and gait: safety, usability and compliance of a virtual reality system.
        Eur J Phys Rehabil Med. 2018; 54: 545-553
        • Faria A.L.
        • Andrade A.
        • Soares L.
        • I Badia S.B.
        Benefits of virtual reality based cognitive rehabilitation through simulated activities of daily living: a randomized controlled trial with stroke patients.
        J Neuroeng Rehabil. 2016; 13: 96
        • Levin M.F.
        • Weiss P.L.
        • Keshner E.A.
        Emergence of virtual reality as a tool for upper limb rehabilitation: incorporation of motor control and motor learning principles.
        Phys Ther. 2015; 95: 415-425
        • Saleh S.
        • Fluet G.
        • Qiu Q.
        • Merians A.
        • Adamovich S.V.
        • Tunik E.
        Neural patterns of reorganization after intensive robot-assisted virtual reality therapy and repetitive task practice in patients with chronic stroke.
        Front Neurol. 2017; 8: 452
        • Wilkins K.B.
        • Owen M.
        • Ingo C.
        • Carmona C.
        • Dewald J.P.A.
        • Yao J.
        Neural plasticity in moderate to severe chronic stroke following a device-assisted task-specific arm/hand intervention.
        Front Neurol. 2017; 8: 284
        • Lord S.E.
        • Rochester L.
        • Weatherall M.
        • McPherson K.M.
        • McNaughton H.K.
        The effect of environment and task on gait parameters after stroke: a randomized comparison of measurement conditions.
        Arch Phys Med Rehabil. 2006; 87: 967-973
        • Housman S.J.
        • Scott K.M.
        • Reinkensmeyer D.J.
        A randomized controlled trial of gravity-supported, computer-enhanced arm exercise for individuals with severe hemiparesis.
        Neurorehabil Neural Repair. 2009; 23: 505-514
        • Llorens R.
        • Noe E.
        • Colomer C.
        • Alcaniz M.
        Effectiveness, usability, and cost-benefit of a virtual reality-based telerehabilitation program for balance recovery after stroke: a randomized controlled trial.
        Arch Phys Med Rehabil. 2015; 96: 418-425