Central Effects of Botulinum Toxin: Neurophysiological Study in Stroke Patients With Spastic Lower Limb

Spasticity is a motor disorder characterized by a velocity-dependent increase in tonic stretch reflex with exaggerated tendon jerk (Lance 1980). Patients with brain lesion often display spasticity due to the interruption of the descending pathways that control the spinal reflex networks, which results in hyperexcitability of the monosynaptic reflex triggered by stretch of the muscle spindles. Spasticity in lower limb muscle impairs the gait, especially in strokes that are the main cause of neurological disability. While 80% of the stroke survivors recover the ability to walk, the poor quality of their gait constitutes a serious handicap in daily life (Bensoussan et al. 2004; Bensoussan et al. 2006). Local injection of Botulinum toxin (BTx) has become a mainstay of the treatment of focal spasticity, particularly in post-stroke patients. BTx weakens the excessive muscle contraction by blocking the release of acethylcholine from motoneuron terminals at the neuromuscular junction and transiently paralyzing the muscle for several months. Besides this peripheral action, BTx is assumed to have also a central effect (Curra et al. 2004; Gracies 2004; Krishnan 2005; Palomar and Mir 2012). In particular, by affecting also the fusimotor synapses on intrafusal muscles fibers (Rosales and Dressler 2010; Trompetto et al. 2008; Trompetto et al. 2006), BTx may reduce the discharge from muscle spindles, which may be indirectly responsible for functional changes in central motor mechanisms at both spinal and supraspinal levels. Animal experiments also suggested that BTx is carried by retrograde axonal transport to motoneuron soma and possibly transynaptically, and can affect the spinal cholinergic synaptic transmission in the spinal cord. Until now, electrophysiological findings are limited and controversial, probably due to the various motor disorders investigated, the physiological mechanisms tested and the different toxin injection protocols used in the few studies available (Frascarelli et al. 2011; Girlanda et al. 1997; Modugno et al. 1998; Naumann and Reiners 1997; Pauri et al. 2000; Priori et al. 1995; Wohlfarth et al. 2001). Hence, the central action of the toxin in spasticity remains uncertain.