Neuromuscular Junction Changes in Spastic Cerebral Palsy

Abstract

Spastic cerebral palsy (CP) is associated with deficits in the central nervous system; however, the major symptoms of CP involve movement, movement control, and musculoskeletal changes indicating that patients with CP have disruptions in the peripheral neuromotor system as well. The neuromuscular junction (NMJ) is the site of communication between motor nerves and muscle fibers. The coordination of NMJ structure and function and the colocalization of junctional components in NMJs are highly controlled, and the development of the NMJ requires signaling between motor neurons, skeletal muscle fibers, and perisynaptic Schwann cells. Patients with CP demonstrate sensitivity to depolarizing neuromuscular blocking agents and resistance to nondepolarizing neuromuscular blocking agents which target the NMJ; therefore, knowledge of NMJ organization in CP is critical to assure safe management of patients. Additionally, individuals with CP demonstrate alterations in the localization of NMJ proteins, increased primary postsynaptic fold length, increased distance between synaptic folds, reduction in mitochondrial load in the nerve terminal, and increased expression of the COL4A3, LAMB2, and KCNN3 genes. These defects appear to be distinct from those due to immaturity, denervation, or other pathologic conditions. Knowledge of the NMJ deficits and abnormal neuromotor function in CP is critical to understand the pathways contributing to disordered movement in CP.