Botulinum toxin changes intrafusal feedback in dystonia: A study with the tonic vibration reflex

Abstract

To investigate the possible role of botulinum toxin (BT-A) injection in reducing muscle afferent feedback, we evaluated electrophysiologically 10 right-handed patients with writer's cramp before and 3 weeks after treatment. The ratio between pre- and postinjection values of maximal M-wave (M-max), maximal voluntary contraction (MVC), and tonic vibration reflex (TVR) were measured in the injected muscles (wrist flexors or extensors). In all the subjects, BT-A injection reduced the TVR more than the M-max and MVC (mean ratio +/- SD: TVR, 0.24 +/- 0.22; MVC, 0.59 +/- 0.32; M-max, 0.68 +/- 0.24; P = 0.003). Long-term evaluation of 2 patients disclosed that, after 7 months, when some clinical benefits persisted, M-max and MVC had fully recovered, whereas the TVR was still depressed. This special sensitivity of the TVR to suppression by BT-A injection could be mediated by the chemodenervation of intrafusal muscle fibers, leading to a reduction in spindle inflow to the central nervous system during vibration. The action on intrafusal fibers could alter sensorimotor integration, thus contributing to the clinical benefits of BT-A injection.

Movement-induced uncoupling of primary sensory and motor areas in focal task-specific hand dystonia

“…Between the currently available symptomatic treatment strategies, botulinum toxin injections represent the best chance for patients affected by focal task-specific hand dystonia (Tintner and Jankovic, 2001;Jankovic, 2006;Simpson et al, 2008;Albanese et al, 2011). Recent items of evidence suggest that botulinum toxin modulates the intrafusalmediated sensorimotor feedback, thus underlying the clinical importance of this mechanism (Trompetto et al, 2006).…”

Neurophysiological effects of botulinum toxin type a

“…Because vibration applied to a muscle mainly excites the primary spindle endings (Burke et al, 1976a,b), Urban and Rolke (2004) attributed the reduced MEP to a BoNT-A-induced muscle spindle denervation. To investigate the possible role of BoNT-A injection in reducing muscle afferent feedback, in a group of patients with focal hand dystonia (WC) we recently measured the ratio between the pre-and post-injection values of the maximal M-wave (M max ), the maximal voluntary contraction (MVC) and the tonic vibration reflex (TVR) in the injected muscles (Trompetto et al, 2006). The TVR mainly reflects the activation of muscle spindle Ia afferents through both monosynaptic and polysynaptic circuits (Matthews, 1966;Burke et al, 1976a,b), whereas the M max and MVC are independent of muscle spindle afferents.…”

Botox produces functional weakness in non-injected muscles adjacent to the target muscle

“…Botulinum type-A (BTX-A) neurotoxin, produced by Clostridium botulinum, exerts a paralytic effect on muscles by preventing the release of acetylcholine at the neuromuscular junction (Brin, 1997), thereby limiting force in muscle fibres and affecting movement control through its action on the gamma efferent motor nerve terminal (Rosales et al, 1996;Trompetto et al, 2006;Curra et al, 2004). This is of particular interest therapeutically as the neurotoxin is used in the temporary treatment of a variety of muscle spasticity disorders such as cervical and hemifacial dystonia and cerebral palsy (Brin, 1997).…”