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Objective Neurorehabilitation that involves learning new motor skills is one of the promising clinical methods for motor recovery in people with multiple sclerosis (PwMS); therefore, factors that influence the acquisition of motor skills in PwMS need to be investigated. Sleep disturbances are common in PwMS; however, no study has investigated the effect of sleep and sleep-related biomarkers on skill acquisition in PwMS. This study aimed to examine the effect of sleep and sleep-related biomarkers on motor acquisition in PwMS. Methods Forty participants with MS and 40 controls were recruited in this study. To assess motor acquisition, each participant was asked to perform a novel game through a virtual reality (VR) system 5 times (blocks). The main outcome measures for each block were the required time to complete the VR game and the recorded errors. The difference in scores between Block 5 and Block 1 for both outcomes were considered to represent motor skill acquisition. Sleep was assessed by self-report using the Pittsburgh Sleep Quality Index (PSQI) and objectively using sleep monitor technology. Serotonin level was assessed using means of enzyme-linked immunosorbent assay using plasma samples. Results There were significant positive correlations in both groups between motor skill acquisition and PSQI score. In PwMS, significant negative correlation between motor skill acquisition and sleep efficiency and significant positive correlation between motor skill acquisition and sleep latency were also observed. Interestingly, a significant negative correlation was observed between motor skill acquisition and the plasma serotonin level in both groups. Most of these correlations remained significant after controlling for disease severity, fatigue, baseline performance, and cognitive status. Conclusion Sleep quality may influence motor skill acquisition in PwMS. Circulatory serotonin level might explain this relationship. Impact Physical therapists are encouraged to be aware of sleep quality and sleep assessment. Sleep management strategies should be considered when treating PwMS.

The Relationship Between Sleep Quality, Sleep-Related Biomarkers, and Motor Skill Acquisition in People With Multiple Sclerosis: A Pilot Study