Antonino Errante, Donatella Saviola, M. Cantoni, Katia Iannuzzelli, Chiara Rubertelli, Settimio Ziccarelli, Fabrizio Togni, Marcello Simonini, Carolina Malchiodi, Debora Bertoni, Maria Grazia Inzaghi, Francesca Bozzetti, Annamaria Quarenghi, Paola Quarenghi, Daniele Bosone, Leonardo Fogassi, G. Salvi, Antonio De Tanti
BACKGROUND: Action observation treatment and virtual reality are established approaches for upper limb rehabilitation after stroke. This study investigated whether combining action observation with virtual reality improves hand dexterity and upper limb motor recovery compared with virtual reality alone. METHODS: In this multicenter, assessor-blinded randomized controlled trial conducted in inpatient rehabilitation centers in Italy between January 2022 and September 2024, poststroke adults with hemiplegia (n=48) were assigned to the experimental or to the control group. Both underwent 20 one-hour sessions over 5 weeks. Participants of the experimental group observed goal-directed daily actions before replicating them in virtual reality, whereas participants of the control group viewed nature scenes before performing the same virtual reality tasks without action observation. Motor function was evaluated at baseline, postintervention, and 6-month follow-up using the Box and Block Test, with the primary estimand defined as the between-group difference in change in paretic hand scores. Secondary outcomes included measures of muscle strength, spasticity, global disability, and functional independence. RESULTS: Both groups showed improvement in Box and Block scores for both hands. However, the experimental group demonstrated a greater gain in paretic hand function, with a between-group difference in change of 7.8 blocks at posttreatment (95% CI, 7.1-7.9) and 10.8 blocks at 6-month follow-up (95% CI, 10.6-10.9). Improvements in the nonparetic hand were comparable between groups. Similar improvements across both groups were observed in secondary outcome measures. A significant treatment×age×time-from-stroke interaction was observed for paretic hand dexterity, indicating that treatment effects varied according to these covariates. CONCLUSIONS: Action observation combined with virtual reality appears to be more effective than virtual reality alone for promoting upper limb motor recovery after stroke, particularly in enhancing fine motor function of the paretic hand. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05163210.