Nerve stimulation boosts botulinum toxin action in spasticity

Spasticity leads to functional and structural changes in nerves and muscles, which alter skeletal muscle function. To evaluate whether short-term electrical nerve stimulation (NS) improves the effect of botulinum toxin in spastic skeletal muscle, we studied changes in the amplitude of the compound muscle action potential (CMAP) recorded from the extensor digitorum brevis (EDB) muscle in response to peroneal nerve stimulation at the ankle after injection of botulinum toxin type A (BTXA) alone or combined with short-term NS. In paraparetic patients, both EDB muscles were injected with BTXA; and NS was applied to one EDB muscle alone. All patients received a 30-minute session of electrical NS once a day for 5 consecutive days after BTXA injection. We used two different stimulation frequencies (low-frequency, 4 Hz; and high-frequency, 25 Hz). EDB-CMAP amplitudes were evaluated before BTXA injection (day 0) and changes in CMAP amplitude, expressed as a percentage (CMAP%), were measured at various time points over a 30-day period after BTXA injection. We compared changes in the CMAP% amplitude on the stimulated and contralateral nonstimulated sides. We also studied the electromyographic activity recorded from EDB muscles over a 30-day period. CMAP% amplitudes measured at all time points after BTXA injections were significantly reduced in both EDB muscles. On days 4, 10, and 15, the CMAP% amplitude reduction was significantly greater for the low-frequency stimulated EDB than for the contralateral nonstimulated EDB. No significant differences in CMAP% were observed for the high-frequency stimulated and nonstimulated EDB. After BTXA injection, spontaneous activity appeared in both EDB muscles; but it appeared earlier and involved larger areas in the stimulated than in the nonstimulated EDB. In conclusion, short-term NS accelerates the effectiveness of intramuscular BTXA injections on the neuromuscular blockade in patients with spastic paraparesis and could induce a rapid and persistent improvement in spasticity. Its action probably arises mainly from low-frequency NS.