Protocol for a randomized controlled trial to evaluate a year-long (NICU-to-home) evidence-based, high dose physical therapy intervention in infants at risk of neuromotor delay.

INTRODUCTION: Developmental disabilities and neuromotor delay adversely affect long-term neuromuscular function and quality of life. Current evidence suggests that early therapeutic intervention reduces the severity of motor delay by harnessing neuroplastic potential during infancy. To date, most early therapeutic intervention trials are of limited duration and do not begin soon after birth and thus do not take full advantage of early neuroplasticity. The Corbett Ryan-Northwestern-Shirley Ryan AbilityLab-Lurie Children's Infant Early Detection, Intervention and Prevention Project (Project Corbett Ryan) is a multi-site longitudinal randomized controlled trial to evaluate the efficacy of an evidence-based physical therapy intervention initiated in the neonatal intensive care unit (NICU) and continuing to 12 months of age (corrected when applicable). The study integrates five key principles: active learning, environmental enrichment, caregiver engagement, a strengths-based approach, and high dosage (ClinicalTrials.gov identifier NCT05568264). METHODS: We will recruit 192 infants at risk for neuromotor delay who were admitted to the NICU. Infants will be randomized to either a standard-of-care group or an intervention group; infants in both groups will have access to standard-of-care services. The intervention is initiated in the NICU and continues in the infant's home until 12 months of age. Participants will receive twice-weekly physical therapy sessions and caregiver-guided daily activities, assigned by the therapist, targeting collaboratively identified goals. We will use various standardized clinical assessments (General Movement Assessment; Bayley Scales of Infant and Toddler Development, 4th Edition (Bayley-4); Test of Infant Motor Performance; Pediatric Quality of Life Inventory Family Impact Module; Alberta Infant Motor Scale; Neurological, Sensory, Motor, Developmental Assessment; Hammersmith Infant Neurological Examination) as well as novel technology-based tools (wearable sensors, video-based pose estimation) to evaluate neuromotor status and development throughout the course of the study. The primary outcome is the Bayley-4 motor score at 12 months; we will compare scores in infants receiving the intervention vs. standard-of-care therapy.

Targeted Muscle Reinnervation for the Upper and Lower Extremity.

Myoelectric devices are controlled by electromyographic signals generated by contraction of residual muscles, which thus serve as biological amplifiers of neural control signals. Although nerves severed by amputation continue to carry motor control information intended for the missing limb, loss of muscle effectors due to amputation prevents access to this important control information. Targeted Muscle Reinnervation (TMR) was developed as a novel strategy to improve control of myoelectric upper limb prostheses. Severed motor nerves are surgically transferred to the motor points of denervated target muscles, which, after reinnervation, contract in response to neural control signals for the missing limb. TMR creates additional control sites, eliminating the need to switch the prosthesis between different control modes. In addition, contraction of target muscles, and operation of the prosthesis, occurs in reponse to attempts to move the missing limb, making control easier and more intuitive. TMR has been performed extensively in individuals with high-level upper limb amputations and has been shown to improve functional prosthesis control. The benefits of TMR are being studied in individuals with transradial amputations and lower limb amputations. TMR is also being investigated in an ongoing clinical trial as a method to prevent or treat painful amputation neuromas.