Eight neurotoxins are secreted by Clostridium botulinum.¹ Type A is a fully sequenced 1295 amino acid chain surrounded by other hemagglutinin and nontoxic nonhemagglutinin proteins for stability.

All type A preparations have the exact same 1295 chain amino acid as their active ingredient, but their different complexing proteins give them different properties. All type A toxins, however, have the same mechanism of action. The heavy chain binds to receptors on the cell membrane of the nerve, which allows the light chain to enter the cytoplasm where it cleaves synaptosomal associated protein 25 (SNAP 25). Because SNAP 25 is essential for the exocytosis of the acetylcholine-containing vesicle, this cleavage results in a presynaptic nerve blockade.

Dr Alan Scott, an ophthalmologist, pioneered the use of botulinum toxin type A in humans. His first publication, detailing the toxin’s effect on Rhesus monkeys, appeared in 1973.² He first injected the toxin into humans in 1977 (Scott AB, personal communication). His first publication concerning the injection of the toxin into humans was published in 1980.³

For years, the toxin was an effective, though seldom used medication, limited to the field of investigational ophthalmology. Its primary uses were for blepharospasm and strabismus. There were rare anecdotal reports of its use for wrinkle reduction (Wyshynski PE, personal communication).⁴ The first comprehensive report detailing its cosmetic usefulness was published by the Carruthers, an ophthalmologist/dermatologist team, in 1992.⁵

Most patients have an initial excellent response for the first 3.5-4 months, with diminishing returns thereafter as the muscle regains its strength. However, when carefully scrutinized, it typically takes 6-7 months for all of the clinical effects to fade. As patients continue to have the toxin injected on a regular basis over 2 years, most begin to have an increased duration of action.⁶ Initially, recovery appears to be facilitated by neurite sprouting as early as 8 weeks after injection. It also appears that the initially blocked nerve terminals recover their function.⁷

Typically, after years of regular repeated injections the results last longer.

Anecdotally, and in one publication,⁸ it appears that reconstituted toxin that has been allowed to sit unused for weeks may have the same initial effect, but a possibly decreased duration of action.⁹

Botox is supplied as a freeze-dried crystalline complex in a vial containing 100 units. Although the package insert says to dilute the vial with 2.5 mL of non-preserved saline, I have used 4 mL of non-preserved saline to reconstitute a vial of Botox since 1991.

I use 4 mL of non-preserved saline to reconstitute a vial containing 100 units freeze-dried crystalline Botox, though the package insert says to dilute it with 2.5 mL of non-preserved saline.

Indications

The FDA cosmetic approval for Botox is only for glabellar rhytids in patients under 65 years of age, but I have used it in my practice for patients in their eighties and I have injected every muscle in the face.

Most Botox injections in my practice are off-label. Because the toxin acts upon presynaptic nerve terminals, it is most commonly injected into the muscle where these terminals reside. It is not an all or nothing phenomena. A certain amount of toxin will block a certain number of terminals. Therefore, fine control over the amount of denervation desired is possible. Despite the common use of the word paralysis when discussing the toxin, it is rare that this is the desired effect. Rather, there is a selective weakening of the musculature to achieve a pleasant cosmetic effect.

There are many components to facial aging including thinning of the dermis, elastosis, loss of facial volume, genetic factors, gravity, skeletal changes, smoking and facial animation. Certain rhytids are primarily caused by facial movement. Others are primarily caused by other factors as well as a component of animation. If a wrinkle is partially caused by muscular action, it can be treated with botulinum toxin A, which is why nearly all facial rhytids can be treated by the toxin with varying degrees of success. How well a rhytid responds to treatment with the toxin depends on how much of the rhytid results from factors other than animation.

Preoperative History and Considerations

Dosage

Just as all patients are different, so are their muscles. Having standard doses ignores these differences. Men typically require higher doses because their muscle mass tends to be larger. Despite these obvious truths, a constant request after presentations is for some ballpark dose as a good starting point for a neophyte injector. I will therefore refer to doses in this text with the reservation that it is up to each injector to determine the optimum dosage for their patient and that there are no true standard doses.

Although there are no true standard doses, doses are given in this text because I am often asked what is a good starting dose for a neophyte injector. It is, however, up to injectors to determine the optimum dosage for each patient.

Functional anatomy

The absolute key to becoming a proficient Botox injector rather than a technician is understanding the functional anatomy of the face.

Anatomy texts have shown us the location of the different muscles of the face and described their origins and insertions. However, although these texts allow for expected, slight anatomic variations, they do not prepare us for the overwhelming differences in functional anatomy between individuals.

A classic paper that deals with functional anatomy is Rubin’s description of the different smile patterns from 1974.¹² Although all individuals have the same mimetic muscles, their smile patterns are very different depending on which muscles dominate within the group. Even within a single muscle, different portions of that muscle can dominate and severely alter animation. The key is to analyze each patient’s face and discern which portions of which muscles dominate facial activity and cause wrinkles or unaesthetic shaping of the face.

Glabella

Operative Approach

The glabella was the first area to be treated cosmetically with Botox.⁶ Surgical debulking of the glabellar musculature is an established practice and chemodenervation of these muscles has much the same effect.

Even in a seemingly straightforward area of the face such as the glabella, there is a great deal of variation in functional anatomy. When frowning, most people primarily bring their brows together and depress them, whereas others primarily frown in a vertical pattern, dramatically depressing their brows and yet others actually raise their medial brows while moving them medially, resulting in a quizzical look. Despite minor anatomic variations, the functional anatomy is drastically different.