The mechanism of action of the toxin has been carefully researched, but is often misstated. Because botulism is still a serious health threat throughout undeveloped nations and because sporadic outbreaks still occur in the United States, hundreds of publications by many different specialties are generated each year concerning botulinum toxin. The toxin is a 1,295 amino acid chain that has been fully sequenced. It consists of a heavy chain of 97 kilodaltons (kDa) connected by a disulfide bond to a light chain of 52 kDa. The heavy chain binds to the neuronal cell membrane, allowing passage of the light chain into the cytoplasm of the nerve. The light chain is a metalloprotease that cleaves the protein known as SNAP-25 (synaptosomal-associated protein 25). SNAP-25 is necessary for the transmitter vesicle containing acetylcholine to fuse with the cell membrane. Without fusion of the vesicle to the cell membrane, the neurotransmitter cannot be released into the synapse and a presynaptic neural blockade is created. Consequently, the toxin does not directly affect the skin and only indirectly affects the muscle, which loses its stimulus. Properly stated, botulinum toxin A only directly affects the nerve.

Clinically, the beneficial effects of the toxin are apparent for 3 to 6 months. However, when carefully scrutinized, it typically takes 6 to 7 months for all of the clinical effects to disappear. As patients continue to have the toxin injected on a regular basis over 2 or more years, many note an increased duration of botulinum toxin (Botox) action.5

The fact that botulinum toxin A disrupts such a basic pathway leads to its efficacy in treating a wide range of pathologic states. Any pathologic condition mediated by acetylcholine release from a peripheral nerve has the potential to be treated. As of this writing, there are more than 300 different conditions reported in the scientific literature that can be treated with the toxin, including blepharospasm, strabismus, cervical dystonia, torticollis, achalasia, spasmodic dysphonia, anal fissure, writer’s cramp, parkinsonian tremor, spasm of sphincter of Oddi, synkinesis, hyperhidrosis, migraine headache, tetanus, and cerebral palsy.

Because the toxin acts on presynaptic nerve terminals, it is most commonly injected into the muscle where these terminals reside. It is not an all-or-nothing phenomenon. A certain amount of toxin will block a certain number of terminals. Thus, fine control over the amount of denervation desired is possible. Despite the common use of the word paralysis when discussing about the toxin, it is rare that this is the desired effect. Rather, a selective weakening of the musculature is performed to achieve a pleasant cosmetic effect.

Facial aging consists of many components. Thinning of the dermis, elastosis, loss of facial volume, genetic factors, gravity, skeletal changes, and smoking, all play a part in the aging process, so does facial animation. Certain rhytides are primarily caused by facial movement. As long as a wrinkle is caused or partially caused by muscular action, it can be treated with botulinum toxin A. This explains why nearly all facial rhytides are treatable by the toxin with varying degrees of success. For instance, a glabellar rhytid is nearly completely caused by the actions of the corrugator and procerus muscles and can be completely eradicated in a young patient. Vertical lip rhytides in an elderly woman with thin skin, sun damage, a history of smoking, and loss of lip volume can only be partially improved by careful injection of the toxin into the orbicularis oris muscle, which contributes to the accordionlike scrunching of the overlying lip skin. How well a rhytid responds to treatment with the toxin depends on how much of the rhytid is a result of factors other than animation. Although this chapter is primarily concerned with alterations in animation, it is the overlying skin’s ability to resist these forces that is paramount when discussing rhytides. Once facility is obtained treating simple rhytids, the toxin can then be used to restore the face to a more youthful and pleasing shape.

The Clostridium botulinum bacteria secretes eight distinguishable exotoxins.6 The most potent of these serotypes is A. Both toxins A (Botox, Allergan, Irvine, CA and Dysport, Medicis, Scottsdale, AZ) and B (Myobloc, Solstice, Louisville, KY) are available in the United States. Onabotulinum toxin A (Botox Cosmetic) is currently approved for the treatment of glabellar furrows in patients aged 65 years and younger. Another preparation of botulinum toxin type A, AbobotulinumtoxinA (Dysport), has been approved for the treatment of glabellar furrows in patients under 65 since 2009. All other applications described in this chapter are off-label uses. RimabotulinumtoxinB (Myobloc) is a type B toxin which is not approved for cosmetic purposes. It has a relatively minor role for cosmetic, off-label applications. Toxin B also exerts its effect via a presynaptic neural blockade but via a different mechanism. It does not act on SNAP-25; instead it acts on synaptobrevin. Although the onset of action is faster than that of Botox, the increased
pain on injection (it is supplied premixed in a vial with a relatively low pH of 5.6) and decreased duration of action limit its cosmetic usefulness. I currently use Myobloc in isolated instances such as when a patient has a social event within 1 or 2 days of injection. Myobloc has a much faster onset of action than both type A products, usually within 24 hours. By the time this chapter is printed, another type A toxin is likely to be on the market. Xeomin (Merz Aesthetics, San Mateo, CA) is a BoNTA that is free from complexing proteins and has a dosing regimen similar to Botox. Revance (Newark, CA) has a topically applied BoNTA currently in clinical trials for lateral canthal lines (crow’s feet).

Botox injection is contraindicated in disorders of neuromuscular transmission, such as myasthenia gravis and Lambert-Eaton syndrome. It should not be used in patients taking aminoglycoside antibiotics whose use may potentiate the effects of the toxin. Although there is no evidence to suggest teratogenicity, I do not treat pregnant women, women actively attempting to become pregnant, or those who are breast-feeding. The toxin does not cross the blood-brain barrier. Complications occur from drift of the toxin to adjacent muscles, thereby weakening them. This is especially hazardous when injecting the perioral musculature. Other complications include headache, ecchymosis, and eyelid ptosis.

OnabotulinumtoxinA and abobotulinumtoxinA are supplied as vacuum dried and lyophilized complexes in glass vials. Complexing proteins, which in nature protect the toxin from stomach acid, are also present with onabotulinumtoxinA having more complexing protein present. Both preparations also contain varying amounts of excipients such as human serum albumin and sodium chloride. To be injectable, each preparation is reconstituted with normal saline. The label indicates that onabotulinumtoxinA be reconstituted with 2.5 cc of nonpreserved saline and abobotulinumtoxinA with 2.5 or 1.5 cc of non-preserved saline. However, common usage for both products is primarily off-label. Reconstitution varies among providers from 1 to 10 cc dilution. Preserved saline due to its mild anesthetic agent (benzyl alcohol) is the preferred diluent for most injectors. Time period after reconstitution for use is 24 and 4 hours on label but most practitioners use the product within 5 to 7 days after reconstitution. There is one article in the literature which supports use up to 6 weeks after reconstitution. Both products are labeled as single patient use but I have been a chairman and participant at many expert consensus panels but almost no experts follow this guideline. I have used 4 cc of non-preserved saline to reconstitute onabotulinumtoxinA since 1991 and 3 cc of non-preserved saline to reconstitute abobotulinumtoxinA since 2009.

Just as dilution of BoNTA is a personal choice, so is dosage in most circumstances. Different muscles in different people have different strengths. To have a standard dose per area or muscle group makes about as much sense as having a standard amount of fat to remove during liposuction. Every patient is different and requires a different dose placed differently across the muscle being treated. For example, most practitioners inject about 25 Botox units or 60 Dysport units, on average, per glabella. Some dermatologists advocate as much as 80 Botox units. My median dose is 17.5 Botox units or 50 Dysport units, but some patients have excellent results with as little as 5/10 units. Men typically require higher doses as the muscle mass tends to be greater.¹ I refer to doses in the following text with the reservation that it is up to each injector to determine the optimum dosage for an individual patient.

The difference between a proficient BoNTA injector and a technician is an understanding of the functional anatomy of the face. Anatomy texts demonstrate the location of the facial muscles. Although these texts allow for anatomic variations, they do not prepare us for the overwhelming differences in functional anatomy between individuals. A classic example is Rubin’s description of the different smile patterns.7 Even though all individuals have the same mimetic muscles, their smile patterns vary tremendously, depending on which muscles dominate within the group. Even within a single muscle, different portions of that muscle may dominate and alter animation. The key is a careful analysis of each patient’s face to discern which muscles cause unaesthetic lines or shaping of the face.

The glabella was the first area to be treated cosmetically with Botox (Figure 43.1). As with the other areas of the upper face to be treated with Botox, there was a longstanding surgical procedure upon which this treatment was based. The glabellar musculature is commonly debulked during brow lift procedures to ease glabellar furrowing and to reduce downward pull on the brow. Chemodenervation of these muscles has the same effect. My median dose for treating the corrugator and procerus muscles is 17.5 Botox/50 Dysport units for women and 20/60 units for men.

Even in a relatively straightforward area of the face such as the glabella, there is a great deal of variation in functional anatomy. When most people frown, they bring their brows together and down. In some patients, however, the brow’s movement is mostly vertical, whereas in others it is mostly horizontal.

After observing a patient through normal animation, I ask the patient to frown, relax, frown again, and then scrunch the nose as if smelling something unpleasant. The injection pattern varies depending on the frowning pattern. Horizontal frowners are not injected in the procerus muscle. Vertical frowners are injected in the medial portion of the corrugator and procerus muscles with the nasalis muscles injected as well.

The frontalis muscle is injected to weaken the forehead to relieve horizontal forehead rhytides (Figure 43.1). The frontalis also has highly variable functional anatomy. My dosage range for the frontalis is 3.75 to 30 Botox/7.5 to 60 Dysport units, although most fall within the range of 5.0 to 7.5/15 to 20 units. Care must be taken to not overly denervate the frontalis because it can lead to an overly smooth, artificial appearance, brow ptosis, and eyelid ptosis in the patient who has been using the frontalis as an accessory eyelid elevator. Despite its appearance in most anatomy texts, the frontalis is usually continuous across the forehead, with muscle present even in the midline.