Intrafusal effects of botulinum toxin injection in patients with upper motor neuron syndrome

Objective: To evaluate the role of intrafusal chemodenervation in the treatment of post-stroke upper limb spasticity with botulinum toxin type A (BoNT-A). Background: Evidences from animal and human studies suggest that BoNT-A, besides its effect on extrafusal motor fibres, can act also on gamma motor endings thus modifying spindle afferent discharges from the injected muscles. This effect can be studied in humans by investi- gating BoNT-A induced changes of the tonic vibration reflex (TVR). Methods: In 7 patients (4 men, aged 64⫾17 years) with upper motor neuron syndrome due to stroke and never treated with BoNT-A, we measured the maximal M-wave (Mmax), the H/M ratio, the maximal voluntary contraction (MVC) and the TVR in the injected wrist and finger flexor muscles before (T0), 1 month (T1) and 4 months (T2) after injection. The ratio between pre- and post-injection values was calcu- lated. Muscle tone was clinically evaluated using the Modified Ash- worth Score (MAS). In two subjects, the physiological assessment was performed also 8 months after the treatment. Results: The TVR was significantly more inhibited than Mmax and MVC at T1 (p ⬍ 0.05). At T2, Mmax and MVC reached the pre- injection values, while the TVR remained depressed. The H/M ratio, slightly decreased at T1, regained the pre-injection value at T2. After BoNT-A injection muscle tone was reduced both at T1 and T2. In the two subjects studied 8 months after treatment, the TVR resulted still depressed, while the MAS value matched that at T0 and the H/M ratio was found to be increased compared to pre-injection values. Conclusions: The special sensitivity of TVR to suppression by BoNT-A depends on the chemodenervation of intrafusal muscle fibers, leading to a reduced spindle inflow to the central nervous system during vibration. This effect possibly explains the residual clinical benefit at T2. The lack of clinical evidence of increased spasticity at T3, in spite of the raised H/M ratio, suggests that the chemodenervation of intra- fusal fibers could counteract the progressive increase of spinal excit- ability, thus preventing further development of spasticity.