In vivo analysis of end-plate noise of human extensor digitorum brevis muscle after intramuscularly injected botulinum toxin type A

To evaluate changes occurring in the neuromuscular junction after injection with botulinum neurotoxin type A (BoTx), three healthy volunteers were injected with 10 U BoTx in the right extensor digitorum brevis muscle. In agreement with previous observations, amplitude of compound muscle action potential (CMAP) decreased to ∼30% of the initial value at ∼day 8 and slowly returned to baseline values around day 250. Values of the acetylcholine receptor (AChR) open time were determined by spectral analysis of end-plate noise and from single exponential fits to the decay phase of individual miniature end-plate potentials (MEPPs). At baseline, the mean channel open times determined by end-plate noise analysis and the exponential fits were 1.1 ± 0.2 ms and 1.20 ± 0.04 ms, respectively. After BoTx injection, initially no end-plate noise could be recorded, From day 9 onwards, however, a gradual recurrence of end-plate noise was observed, with mean channel open times of ∼2-5 ms, being maximal between days 20 to 140. In addition, the shape of many recorded MEPPs was different from the typical fast rising MEPPs observed at baseline. After day 80, end-plate noise gradually returned to normal and mean channel open times decreased slowly to baseline values. Our findings reflect the changed AChR characteristics of newly formed neuromuscular junctions, which are created after BoTx injection and gradually removed after restoration of the original neuromuscular junctions.