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

o 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. © 2006 Movement Disorder Society Writer's cramp (WC) is a focal task-specific dystonia of the upper limb characterized by excessive muscular activation only during writing (simple WC) or also with other tasks (dystonic WC).1 Although the exact pathophysiology is unknown, focal dystonia is considered as a basal ganglia disorder2 and several lines of evidence support the role of sensory inputs in the pathophysiology of focal dystonia.3–5 Local injection of botulinum toxin type A (BT-A) has become a mainstay of therapy for focal dystonia.6–8 BT-A is a metalloproteinase that, when injected intramuscularly, prevents the release of acetylcholine from presynaptic vesicles on the neuromuscular junctions, causing the denervation of extrafusal motor fibers.9, 10 Several findings both from animal and human studies8 suggest that BT-A can act also on gamma motor endings, thus modifying spindle afferent discharges from the injected muscle and producing indirect changes at a central level. Others nonetheless failed to confirm that BT-A produces a central effect by altering peripheral feedback.11 Because muscle afferents may play a pivotal role in producing dystonic contractions in patients with WC,3 growing interest has centered on the role of reduced muscle afferent feedback in the therapeutic effects of botulinum toxin.12 One approach for studying muscle afferents in humans is to elicit the tonic vibration reflex (TVR), which mainly reflects the activation of muscle spindle Ia afferents through both monosynaptic and polysynaptic circuits.13–17 Conversely, EMG parameters considered independent of muscle spindle afferents are the maximal voluntary contraction (MVC) and maximal M-wave (M-max).18 To seek evidence of a BT-A–induced fusimotor block in dystonia, we studied the TVR before and 3 weeks after BT-A injection in 10 patients with WC and compared these changes with those induced in the MVC and M-max responses. Understanding how BT-A acts on intrafusal motor fibers could help to explain the role of peripheral input in the pathophysiology of dystonia.