Physiological anatomy of botulinum toxin effect on the spastic muscle of children with cerebral palsy

Abstract

Botulinum toxin is one of the treatments available to treat spasticity in patients with cerebral palsy (CP) from 2 years of age. The long-term action of the toxin on the neuromuscular junction (NMJ) and muscle structure is still unknown. We formulated the hypothesis that repeated injections of botulinum toxin could modify muscle structure. The main aim of our 3-year monocentric descriptive study is to evaluate the long-term effect of repeated injections of botulinum toxin on the muscle and the neuromuscular junction in patients with CP. Histopathological features and molecular biology were studied on muscle biopsies taken during scheduled orthopaedic surgeries. Evaluation criteria were the presence of fragmented neuromuscular junctions (both qualitative and quantitative) and axonal sprouting (qualitative). Two muscle biopsies were performed in 2 children aged respectively 7 and 10 years. The biopsies were located respectively in the right gracilis (after 1 injection) and in the right sural triceps (after 3 injections). Histological features found were fragmentated neuromuscular junctions (between 1 to 6), lack of axonal sprouting at the junction, the presence of CD56 satellite cells and presence of molecules suggesting the presence of denervated fibers. Whereas type I and type II fiber atrophy and fibrosis were found on the first biopsy, on the second were seen signs of atrophy of undifferentiated fibers without any sign of fibrosis. Additional results will be available soon. This study should improve knowledge about the effects of long-term botulinum toxin on muscle (and therefore its safety in use) on the NMJ and on the physiopathology of the muscle of children with CP.