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

Abstract

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 approximately 30% of the initial value at approximately 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 approximately 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.

Dose‐ and volume dependent‐response to intramuscular injection of botulinum neurotoxin‐A optimizes muscle force decrement in mice

“…19 Although histology may confirm the morphometric changes in the atrophied muscle and its neuromuscular junctions, alterations in neuromuscular junction remodeling, and muscle recovery are already well documented. 1,5,12,13,15,16,19,34,35 This study explores functional outcomes after varying injection dose and volume, and recognizes that it is limited to MFG testing, EMG testing, and muscle mass.…”

“…1,[11][12][13] Nerve growth factors, myonuclear addition, axonal sprouting, and motor end plate activity are increased within a week. [14][15][16][17] Muscle recover occurs within 3-6 months in humans which enables BoNTA to be a valuable tool in reversibly altering muscle tone. 8,18 Literature to date offers little information on a systematic approach to the effects of dose and volume on the neuromuscular physiology following intramuscular administration of the toxin.…”

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

“…[55][56][57][58] When exocytosis at the parent terminal eventually recovers, the nerves retract and endplate functioning returns to normal. 55,59 BTX-A administration has a similar effect on neuroeffector transmission in both smooth and striated muscle. When BTX-A is administered to the bladder wall there is an increase in bladder capacity, with a reduction in incontinence episodes and symptoms of urgency.…”

Neurophysiological effects of botulinum toxin type a

“…The reduced EMG recruitment pattern is followed by spontaneous denervation signs occurring in normal muscles about 20 days after BoNT-A injection (Van Putten et al, 2002) and in spastic muscles 10-20 days after injection (Frasson et al, 2005) and by the development of muscle atrophy (peaking at day 42) (Hamjian and Walker, 1994) with motor unit rearrangement. The definite relationship between changes in the pattern of muscle activity after BoNT-A injections and the clinical benefits is still an open question (Gelb et al, 1991).…”