Effects of virtual reality-based motor control training on inflammation, oxidative stress, neuroplasticity and upper limb motor function in patients with chronic stroke: a randomized controlled trial

Abstract

Background: Immersive virtual reality (VR)-based motor control training (VRT) is an innovative approach to improve motor function in patients with stroke. Currently, outcome measures for immersive VRT mainly focus on motor function. However, serum biomarkers help detect precise and subtle physiological changes. Therefore, this study aimed to identify the effects of immersive VRT on inflammation, oxidative stress, neuroplasticity and upper limb motor function in stroke patients.

Methods: Thirty patients with chronic stroke were randomized to the VRT or conventional occupational therapy (COT) groups. Serum biomarkers including interleukin 6 (IL-6), intracellular adhesion molecule 1 (ICAM-1), heme oxygenase 1 (HO-1), 8-hydroxy-2-deoxyguanosine (8-OHdG), and brain-derived neurotrophic factor (BDNF) were assessed to reflect inflammation, oxidative stress and neuroplasticity. Clinical assessments including active range of motion of the upper limb and the Fugl-Meyer Assessment for upper extremity (FMA-UE) were also used. Two-way mixed analyses of variance (ANOVAs) were used to examine the effects of the intervention (VRT and COT) and time on serum biomarkers and upper limb motor function.

Results: We found significant time effects in serum IL-6 (p = 0.010), HO-1 (p = 0.002), 8-OHdG (p = 0.045), and all items/subscales of the clinical assessments (ps < 0.05), except FMA-UE-Coordination/Speed (p = 0.055). However, significant group effects existed only in items of the AROM-Elbow Extension (p = 0.007) and AROM-Forearm Pronation (p = 0.048). Moreover, significant interactions between time and group existed in item/subscales of FMA-UE-Shoulder/Elbow/Forearm (p = 0.004), FMA-UE-Total score (p = 0.008), and AROM-Shoulder Flexion (p = 0.001).

Conclusion: This was the first study to combine the effectiveness of immersive VRT using serum biomarkers as outcome measures. Our study demonstrated promising results that support the further application of commercial and immersive VR technologies in patients with chronic stroke.

Keywords: 8-hydroxydeoxyguanosine (8-OHdG); Brain-derived neurotrophic factor (BDNF); Heme oxygenase-1 (HO-1); Inflammation; Neuroplasticity; Oxidative stress; Stroke rehabilitation; Virtual reality (VR).

Fig. 1

Flow diagram of the participant inclusion

Fig. 2

Significant interaction effect between group and time in FMA-UE-Shoulder/Elbow/Forearm (a), FMA-UE-Total (b), and AROM-Shoulder Flexion (c)

Fig. 3

Range of FMA-UE-Total score and AROM-Shoulder Flexion score changes. AROM: active range of motion; FMA-UE: Fugl-Meyer Assessment for upper extremity

Fig. 4

Changes of BDNF levels in the two groups. COT: conventional occupational therapy; VRT: virtual reality training; BDNF: brain-derived neurotrophic factor

Fig. 5

Relationship between changes of motor performance and serum biomarkers. a Correlation between the change of FMA-UE-Shoulder/Elbow/Forearm score and HO-1. b Correlation between the change of FMA-UE-Wrist and 8-OHdG. (C) Correlation between the change of FMA-UE-Total and 8-OHdG. FMA-UE: Fugl-Meyer Assessment for upper extremity

Fig. 6

Results of the simulator sickness questionnaire (SSQ) and game-like rating. a Percentages of patients with uncomfortable symptoms. b Percentages of occurrence of SSQ symptoms. c Percentages of top favorite game rated by participants. d Percentages of top disliked game rated by participants