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.

Operative technique

• My median dose for treating the corrugators and procerus muscles is 17.5 units for women and 20 units for men.

• After observing the patient through normal animation during the consultation, I ask them to frown, then relax, then frown again, then scrunch their nose as if smelling something unpleasant repeatedly. This allows me to gauge which sections of which muscles dominate and to target those areas specifically with Botox.

Horizontal frowners

• For a horizontal frowner, I displace the forehead and brow cephalad and then with my non-injecting hand fix it in position by placing pressure across the superior orbital rim.

• The patient is again asked to frown.

• This reveals an indentation in the skin corresponding to where the tail of the corrugator inserts into the dermis of the skin of the brow.

• I begin injecting in this area and progress medially with small injections to the procerus, which receives little Botox.

• The same procedure is repeated across the other brow, moving lateral to medial.

• Most men have significantly longer corrugators than women with the tail extending lateral to the mid-pupillary line.

Forehead

Operative Approach

The frontalis muscle is injected to partially weaken the forehead to relieve horizontal forehead rhytids. The frontalis has highly variable functional anatomy. Despite its appearance in most anatomy texts, the frontalis is usually continuous across the forehead, with muscle even in the midline.

Operative technique

• My dosage range for the frontalis is 3.75-30 units, though most injections fall within the range of 5-7.5 units.

• Observe patients in normal animation and then ask them to raise and lower their brows several times, almost to the point of exhaustion. Upon observation of this motion, the strongest portions of this muscle are targeted, not the rhytids. No standard pattern of injection is used and these are mentioned only to be condemned.¹³

Complications

Care must be taken to not overly denervate the frontalis, which can lead to an overly smooth, artificial appearance, brow ptosis, and eyelid ptosis in the patient who has been using his frontalis as an accessory eyelid elevator.

Crow’s Feet and Lower Eyelid

Operative Approach

The lateral and inferior orbicularis oculi is weakened to diminish crow’s feet and lower eyelid rhytids in selected patients. The effects of surgically weakening the lateral orbicularis had been known for several years prior to the cosmetic use of Botox injections.¹⁴

In my practice nearly all patients who have their crow’s feet treated have some injection into their lower lids as well.

The functional anatomy of this area leads to a classification of crow’s feet patterns.¹⁵ The most common pattern is the full fan pattern where the lateral orbicularis contracts and wrinkles the overlying skin from the lateral brow to the lower lid/upper cheek junction, yet even this pattern occurs in less than 50% of patients. The exact incidence of each pattern is not as important as the recognition of different patterns in different patients and asymmetry in individual patients. Treatment is based on the functional anatomy of the orbicularis oculi (Fig. 4.1A-D).

Fig. 4.1 Use of Botox for crow’s feet. A, Early static rhytids in the crow’s feet area. This patient has a full fan pattern of motion. B, Full effacement of these nondynamic rhytids in repose by injection of 5 units of Botox along the full pattern of motion with less injection along the lower eyelid/upper cheek border. C&D, The patient smiling before and after injection of 7.5 units to her left lateral periorbital area. Her primary complaint on this side was of the curl of muscle that raises up along the lower lid margin. If she were injected in a ‘standard’ pattern not only would this lump of muscle not have been addressed, but by weakening the rest of the lateral orbicularis oculi, it would have been made worse. Botox was injected directly into the very active area of muscle along the lower lid and in lesser doses radiating out from this point to create a gradient of motion.

Operative technique

• Although there are no standard doses or dosing patterns, most patients that I inject currently receive between 3.75 and 5 units per side.

• I try to not waste Botox on relatively adynamic sections of the muscle. To do this, it is necessary to recognize that the functional anatomy of the lateral periorbita varies widely. I inject the most dynamic area of the muscle first, followed by smaller injections radiating out from this point. The idea is to create a gradient of motion to avoid having an area of no motion directly bordering an area of extreme, compensatory hypermotility, which produces an unattractive line of demarcation.

Complications

Mild overzealous injection can yield an unpleasant deer-in-the-headlights look and cheek ptosis at the opposite end of the spectrum.

Although most plastic surgeons are aware that the upper lateral orbicularis oculi is a brow depressor, many fail to realize that the lower lateral portion is an important cheek elevator. Over-denervation in its lower lateral section, can therefore result in malar flattening as well as an extra ‘roll’ of skin between the lower lid and cheek.

Injection of elevator muscles should either be eschewed or done extremely conservatively or done in combination with their counterpart depressors.

Excessive chemodenervation of the orbicularis oculi across the lower lid can have several unaesthetic results:

• in the patient with a relatively lax lower eyelid, frank ectropion or lower lid retraction may result;

• in the patient with minimal to borderline orbital fat prolapse, weakening the middle lamella can exaggerate and hasten the appearance of fat ‘bags’ of the lower lids;

• because this sheet of muscle also functions as a pump, extreme denervation can result in lymphedema.

Brow Elevation

Operative Approach

Brow elevation by the injection of Botox was once considered controversial, with publications in both the plastic surgical and dermatologic press saying that Botox could only depress the brows or at best tha it was an illusory brow lift created by dropping the medial brow.

Botox can easily and reliably lift the brows in excess of 6 mm in my practice.

The concept is remarkably easy. To lift the brows, one concentrates on injecting muscle segments that actively and even at rest depress the brows, allowing the brows to raise.

The other concept of increasing the lift of the brows by weakening the only muscle that lifts them is not so frequently understood. This seeming paradox is explained by the simple observation that non-weakened sections of muscle react to weakened sections by increasing their pull in compensatory fashion. This explains why:

• when the lateral orbicularis is strongly injected, lower lid rhytids increase – this is not simply an illusion caused by smoothing of the skin laterally, but results from an increase in resting tone of the non-injected portion of the muscle across the lower lid.

• when the central frontalis is injected strongly, the lateral brows often peak in an unattractive ‘Mr. Spock’ appearance with concomitant worsening of lateral suprabrow rhytids.

When portions of the frontalis are weakened, the other portions of the frontalis lift more strongly. To maximize brow lift, injecting the portions of the frontalis not responsible for raising brows, will induce the frontalis responsible for brow elevation to pull harder. Usually this means injecting the frontalis strongly centrally, in the zone above and medial to the brows. The frontalis lateral to the brows is also injected, causing the frontalis directly over the brows to lift more strongly.

Eleven muscle segments can depress the medial brow:

• the procerus;

• transverse heads of the corrugator;

• oblique heads of the corrugator;

• depressor supercilii;

• medial orbicularis oculi;

• and in some patients, the nasalis muscles.

In most patients, the effect of the nasalis on brow position is negligible. However, in a small number of patients I have fully injected the other medial brow depressors and been disappointed in the ensuing brow elevation. With the other segments completely non-functional, these patients were able to depress their brows by wrinkling their nasalis. Subsequent nasalis injection gave the brows additional elevation.

There is no standard pattern of injection for brow elevation. The key is individualizing treatment based on each patient’s functional anatomy.

The lateral brow is depressed by the cephalad portion of the lateral orbicularis oculi. The dynamics of this differ greatly among patients, and there is no single point that can be injected to reliably elevate the lateral brow.

Some patients who do not depress their brows when smiling will not reliably achieve brow elevation by simply injecting the upper lateral orbicularis.

The key is individualizing treatment based on each patient’s functional anatomy. There is no standard pattern of injection for brow elevation.

For a unilateral brow lift (Fig. 4.2A-F), in addition to the zones directly over the brows, weaken the frontalis slightly over the higher brow, inducing the frontalis over the lower brow to pull harder.

Fig. 4.2 Use of Botox for brow lift. A, Relatively strong but short corrugators. B, After treatment with a total of 17.5 units injected into the medial brow depressors. No fillers were used. Note the partial recruitment of the left orbicularis oculi in an attempt to frown. C, The frontalis pre-treatment. D, The frontalis was treated with a total of 5 units strategically placed in the strongest parts of the muscle not directly over the brows. A small amount (<1 unit) was placed over the right brow. Note the peaking of the left brow. E&F, The patient at rest showing that due to the differential injection of her frontalis based on her functional anatomy, she has a left-sided brow lift stronger than on her right side. The glabella and forehead are also rejuvenated. The patient had a left pre-injection brow and borderline eyelid ptosis. If given a ‘standard’ frontalis injection, she would have gone on to develop frank eyelid ptosis.

Neck

Operative Approach

Platysmal bands are another area where Botox injections can yield excellent results. Two articles on neck injection were published simultaneously in 1999 with drastically different dosage, patient populations, results, and complications.16,17 One paper advocated up to 250 units to be injected, had better results in patients with greater skin laxity, and reported dysphagia as a complication.¹⁶ I would caution against injecting such high doses in the neck. In addition to dysphagia, high doses can also lead to dry mouth by affecting the salivary glands.

The key to evaluating the neck as a potential site for cosmetic improvement lies in the relative contributions of the skin and the platysma to banding. The best patients have minimal skin excess and relatively strong bands. Despite the results (based on 1500 patients) of the aforementioned paper,¹⁶ the patient with lax neck skin is a poor candidate for injection. Even with the bands completely paralyzed, the lax neck skin will continue to hang.

Good candidates for injection fall into two basic categories. The relatively young (35-45 years) patient with strong bands and minimal skin laxity is an excellent patient (Fig. 4.3A&B). Likewise the patient of any age who has had a surgical procedure on the neck and has relatively little excess skin and recurrent bands is a good candidate. A smaller class of patients, but one that is seen more frequently is the young patient who has had an aggressive fat removal procedure in the neck and now has visible bands.

Fig. 4.3 Use of Botox for strong platysmal bands. A, Patient in her mid 30s with strong platysmal bands and minimal excess skin. This large amount of muscle mass in a young patient required a high dose. B, She was treated with 20 units to her right primary band and 7.5 units to her right secondary (lateral) band.

Operative technique

• My current dose range is 15-30 units for the neck, with around 20 units for most patients.

• Ask the patient to show the lower teeth with the teeth clenched.

• The platysma band becomes apparent and is grasped between the thumb and index finger of the non-injecting hand.

• The patient is told to relax and the muscle is injected starting just below the mandibular border and progressing inferiorly to the point at which the band is visible.

• The horizontal ‘necklace’ rhytids can also be very mildly improved by injecting toxin just above and below them.

Nasolabial Fold

Operative Approach

The nasolabial fold is an excellent area for injection in the right patient who has been instructed what to expect.

The levator labii superioris alaeque nasi muscle is the muscle mainly responsible for the medial nasolabial fold and the final 3-4 mm of central upper lip elevation.¹⁸ Weakening of this muscle smoothes the medial nasolabial fold and changes the smile pattern of the patient.

Rubin described the three major smiling patterns in 1974.

• The most common or ‘Mona Lisa’ smile pattern is dominated by the zygomaticus muscle and elevates the oral commissures to the highest point of the smile.

• The canine smile pattern is dominated by the levator labii superioris and the highest part of the smile is the central upper lip. This pattern occurs in 35% of the population and these people are the potential candidates for this procedure. Because injection of this muscle results in a drop of the central upper lip upon smiling, it converts canine smilers into Mona Lisa smilers. Injecting Mona Lisa smile patients results in an exaggerated Mona Lisa smile that most patients find unattractive.

• Patients with gummy smiles are basically extreme canine smile pattern patients. This group benefits the most from Botox injection¹⁹ (Fig. 4.4A&B). Gummy smilers often smile asymmetrically, requiring asymmetric injection. They also tend to have deeper medial nasolabial folds, which is the area of primary improvement with this technique. The resulting drop of the upper lip hides the gingiva and results in a more pleasing smile.