Project Grant R44HD112281

SPINAL CORD INNOVATION IN PEDIATRICS TO TREAT CEREBRAL PALSY (SCIP CLINICAL STUDY) - SUMMARY CEREBRAL PALSY (CP) IS THE MOST COMMON MOTOR DISABILITY IN CHILDHOOD. POPULATION-BASED STUDIES FROM AROUND THE WORLD REPORT PREVALENCE ESTIMATES RANGING FROM 1.5 TO 4 PER 1000 INDIVIDUALS. GLOBALLY, APPROXIMATELY 17 MILLION PEOPLE HAVE CP. IT IS A DIAGNOSIS THAT INCLUDES A WIDE RANGE OF SYMPTOMS WITH HETEROGENEOUS ETIOLOGIES OF NEURAL AND CARDIOVASCULAR ORIGINS. A WIDE RANGE OF FUNCTIONAL DISORDERS TYPICALLY BECOME OBVIOUS IN CP DURING EARLY DEVELOPMENT. FOR EXAMPLE, THE MAJORITY OF CHILDREN CLASSIFIED AS GROSS MOTOR FUNCTIONAL CLASSIFICATION SCALE (GMFCS) LEVEL I ARE EXPECTED TO REACH THEIR MOTOR POTENTIAL BETWEEN 7-9 YEARS AND REMAIN STABLE AFTER THAT UNTIL AGE 21 WHERE THEY MAY DECLINE DUE TO PAIN, WEAKNESS AND STIFFNESS. WHILE MOVEMENTS SUCH AS STEPPING AND POSTURE ARE AMONGST THE MOST RECOGNIZABLE IMPAIRMENTS, ABSENCE OR ABNORMAL SENSATIONS, PERCEPTION, IMPAIRED COGNITION, COMMUNICATION SKILLS, EPILEPSY, SPASTICITY, POOR CONTROL OF FINE MOVEMENTS AND MARKED SECONDARY MUSCULOSKELETAL PROBLEMS CAN EMERGE WITH TIME. PRESENTLY, ALL AVAILABLE INTERVENTIONS ARE DESIGNED TO MINIMIZE THE SEVERITY OF SYMPTOMS RATHER THAN CORRECTING THE NEUROLOGICAL ETIOLOGY. TWO COMMONLY PREFERRED TREATMENTS, SELECTIVE DORSAL ROOT RHIZOTOMY AND REPETITIVE ADMINISTRATION OF BOTULINUM TOXIN A (BOTOX) DIRECTLY TARGET THE NEUROMUSCULAR SYSTEM TO COUNTER SPASTICITY. WHILE THESE TWO STRATEGIES MINIMIZE SOME OF THE DISRUPTIVE MOVEMENTS ASSOCIATED WITH SPASTICITY; THE LONG-TERM BENEFITS OF THESE INTERVENTIONS ARE LESS CLEAR AND BOTH CAUSE IRREVERSIBLE CHANGES TO THE NEUROMUSCULAR SYSTEM THAT MAY BE DETRIMENTAL TO FUTURE FUNCTION. IN THE PRESENT PROPOSAL WE HAVE MERGED IDEAS AND CONCEPTS DERIVED FROM BOTH RECENT CLINICAL OBSERVATIONS OF CP AND DECADES OF STUDIES OF SPINAL CORD INJURY TO ARRIVE AT A SUBJECT-SPECIFIC REHABILITATION STRATEGY DRIVEN BY ACTIVITY- BASED MECHANISMS DURING TRANSCUTANEOUS SPINAL NEUROMODULATION. THE OBJECTIVES OF OUR NEUROMODULATION PROCEDURES ARE TO AMPLIFY THE PLASTICITY OF THE NEUROMUSCULAR SYSTEM AND HELP CHILDREN GAIN THE ABILITY TO PERFORM COORDINATED MOVEMENTS THROUGH ACTIVITY-DEPENDENT PLASTICITY. WE HYPOTHESIZED THAT TRANSCUTANEOUS SPINAL NEUROMODULATION DURING ACTIVITY-BASED NEUROREHABILITATION THERAPY (ABNT) CAN TRANSFORM THE NEURAL NETWORKS IN CHILDREN DIAGNOSED WITH SPASTIC CP TO IMPROVE VOLUNTARY POSTURAL AND LOCOMOTOR ACTIVITY AS CAPTURED ON THE GMFM88 SCORES. THIS STRATEGY COULD PROVIDE A SPECIFIC PHYSIOLOGICAL TARGET OF FUNDAMENTAL SIGNIFICANCE IN THE CONTROL OF MOVEMENT THAT CAN BE USED TO IMPROVE FUNCTION AND PROVIDE NEW CARE PATHWAYS FOR CHILDREN WITH CP.