Correlation of Botulinum Toxin Dose with Neurophysiological Parameters of Efficacy and Safety in the Glabellar Muscles: A Double-blind, Placebo-controlled, Randomized Study

Abstract

Despite the extensive use of botulinum toxin type A (BoNT-A) in treatments for glabellar frown lines, the dose-response effect in the glabellar muscles remains unknown. The aim of this randomized, double-blind, placebo-controlled prospective study was to characterize the neurophysiological parameters that correlate with the effect of BoNT-A in the glabellar muscles and its diffusion to surrounding ocular muscles. Sixteen healthy women were recruited and randomized to 3 different dose-groups of onabotulinumtoxin A (Vistabel®) or placebo and followed 24 weeks by neuro-physiological examinations. Efficacy of treatment on corrugator supercilii muscles was measured by compound motor action potential (CMAP) and electromyography (EMG). Photographs were used to score glabellar frown lines. Diffusion of the drug to surrounding muscles was assessed by CMAP of the nasalis muscle, EMG and concentric needle electrode jitter analysis (CNE) of the orbicularis oculi muscle. CMAP reduction correlated well with intramuscular BoNT-A dose. Muscle paralysis, measured by EMG, began from 2 weeks and was not entirely reversed at 24 weeks in individuals who received high dose of onabotulinumtoxin. Limited diffusion of orbicularis oculi was detected with CNE. In conclusion, we developed a novel neurophysiological strategy for effect evaluation of BoNT-A in glabellar muscles. CMAP and EMG correlated with given BoNT-A dose and are more defined effect measures than clinical glabellar photo scales.

A Randomized, Comparative Study to Evaluate Efficacy and Safety of Two Injection Volumes of AbobotulinumtoxinA in Treatment of Glabellar Lines

“…The CMAP amplitude has previously been reported to be an appropriate neurophysiological parameter for evaluation of the dose–response effect of botulinum toxin injections in the facial muscles of the glabellar area. 11 In our study, CMAP results also demonstrate that the twofold injection volume of 0.1 mL of abobotulinumtoxinA is noninferior to the 0.05 mL labeled injection volume in delivering the 10 sU fixed dose.…”

Jitter Evaluation in Distant and Adjacent Muscles after Botulinum Neurotoxin Type A Injection in 78 Cases

“…It is well known that the local effect of BoNT/A intramuscular injection either clinically (muscle paralysis) or through single-fiber electromyography (SFEMG) demonstrates very high jitter and impulse blocking [11][12][13][14]. The BoNT/A injection also may spread nearby, causing weakness, as seen in cervical dystonia (dysphagia) and in blepharospasm and hemifacial spasm (eyelid drop), that usually takes a few days to clear up [15]. Another defined point is the adjacent, and distant BoNT/A effect detected only through SFEMG with high jitter without or with sparse impulse blocking [11,[16][17][18][19][20][21][22][23][24][25][26].…”

Neurophysiological Measures of Efficacy and Safety for Botulinum Toxin Injection in Facial and Bulbar Muscles: Special Considerations

“…The first study found that reduction of the CMAP amplitude measured over the corrugator supercilii correlates well with intramuscular dose of onabotulinumtoxin A (Vistabel ® ) in the same muscle [ 50 ]. Further, electromyography (EMG) measurements revealed the onset of muscle paralysis after two weeks and effects (denervation) lasting as long as 24 weeks after injection in individuals receiving a high dose of onabotulinumtoxin [ 50 ]. Importantly, this study supports a novel neurophysiological strategy for effect evaluation of BoNT in glabellar muscles, since both CMAP and EMG parameters correlated with BoNT dose.…”

“…Following injections of the glabellar muscles for the indication glabellar lines, limited diffusion is known to occur to the surrounding extraocular muscle orbicularis oculi. This diffusion can be detected as slightly disturbed neuromuscular transmission (jitter) with single-fibre electromyography [ 50 ]. Diffusion has also been reported to contralateral facial muscles following unilateral BoNT application [ 74 ].…”