Authors: Mohamed Badie Ahmed, MD, PhD , Mariam Al Aloosi, MD Candidate , Jeffrey A Cohen, MD , Mitchell A Stotland, MD
Abstract: Botulinum neurotoxin A (BoNT-A) is widely used clinically; yet, its temporary effects require repeated injections that increase cost and inconvenience. There is limited rigorous evidence to support claims that repeated BoNT-A use alters efficacy. Unlike peripheral nerve transection, which causes irreversible denervation after 12 to 24 months, the long-term physiological effects of BoNT-A chemodenervation remain unclear. Using electromyography (EMG), we investigated whether prolonged short-interval BoNT-A administration induces irreversible paralysis of glabellar muscles. Twenty-one Caucasian female participants aged 35 to 60 years with at least moderate glabellar lines were recruited and randomized to receive BoNT-A injections either every 6 weeks (Group I), every 9 weeks (Group II), or every 12 weeks (Group III). Each session consisted of 5 injections totaling 20 U of onabotulinumtoxinA to the glabellar muscles. The 3-year study included a 108-week treatment phase and then a 48-week follow-up, with serial corrugator electromyographic recordings undertaken over the course of the 156-week period. The EMG data were analyzed using linear regression models. Analysis demonstrated a consistent, statistically divergent reduction in corrugator EMG activity across all posttreatment time points, with maximal suppression at 108 weeks, indicating a durable neuromodulatory effect. Predictive-margins analysis showed sustained suppression from baseline through 156 weeks in all groups, with only a late increase remaining well below pretreatment levels. Relative to the 9-week group, the 12-week group exhibited higher EMG activity, while no meaningful difference was observed for the 6-week group. In this 3-year study, including 2 years of short-interval BoNT-A injections and 3 years of electromyographic (EMG) assessment, prolonged intermittent BoNT-A administration produced a sustained chemodenervation effect that persisted beyond treatment cessation and exceeded the duration typically observed with standard clinical dosing intervals. Larger studies with longer follow-up are required to confirm these findings.
