Basis of movement control in dystonia and why botulinum toxin should influence it?

Abstract

Dystonia is a network disorder involving multiple brain regions, such as the motor cortex, sensory cortex, basal ganglia, and cerebellum. Botulinum toxin (BoNT) is the first-line therapy for treating focal dystonia and is a potent molecule that blocks the release of acetylcholine at the peripheral neuromuscular junction. However, the clinical benefits of BoNT are not solely related to peripheral muscle relaxation or modulation of afferent input from the muscle spindle. An increasing body of evidence, albeit in smaller cohorts, has shown that BoNT leads to distant modulation of the pathological brain substrates implicated in dystonia. A single treatment session of BoNT has been observed to reduce excessive motor excitability and improve sensory processing. Furthermore, owing to plasticity effects that are induced by botulinum, neural reorganization of pathological networks occurs, presumably leading to defective motor programs of dystonia replaced with normal movement patterns. However, longitudinal studies investigating the effects of multiple treatment sessions in large, well-characterized homogenous cohorts of dystonia will provide further compelling evidence supporting central botulinum mechanisms.