New Simulation Study Suggests BoNT/A Restrictions May Be Overly Conservative

A large-scale, simulation-based study challenges the long-standing 4-hour restriction on post-injection activity following botulinum neurotoxin A (BoNT/A) treatment, suggesting that everyday behaviors may have minimal impact on toxin spread. The study, published in Scientific Reports, employed a validated multiscale modeling platform to quantify the influence of post-injection behaviors on BoNT/A distribution and off-target binding.

Using the AesthetiSIM platform, researchers created a cohort of 10,000 paired digital twins—each subjected to a control (rest) condition and one of several post-injection scenarios: bending, light exercise, superficial rubbing, mild heat exposure, and a combined conservative case incorporating all behaviors. The model measured changes in effective spread radius (ΔR95) and off-target receptor binding (ΔFoff) at 4 hours post-injection.

Across all single behaviors, median ΔR95 values remained under 0.15 mm, with upper-tail values (Q95) staying below 0.52 mm. The combined scenario produced a slightly higher median ΔR95 of 0.22 mm and Q95 of 0.69 mm. The likelihood of spread exceeding a 1 mm margin remained low—≤1.2% for individual behaviors and 2.1% for the combined scenario.

Similarly, off-target binding changes (ΔFoff) remained small. Median changes ranged from 0.004 to 0.008 for single behaviors, with the combined scenario yielding a median ΔFoff of 0.012. Q95 values across all cases remained below 0.043, with exceedance of a 0.05 threshold ranging from 1.3% to 4.4%.

Global sensitivity analysis revealed that injection-specific factors—such as tissue diffusivity, internalization rate, and depth—had a far greater influence on toxin distribution than behavior-induced interstitial flow.

“These findings indicate that within the first 4 h after injection, the distribution of BoNT A is shaped primarily by injection geometry and rapid target binding and is only weakly affected by everyday movements or mild environmental exposures,” the authors wrote.