21 Botulinum Toxin

Treatment of facial lines and wrinkles (also called rhytids) with botulinum toxin has become the most frequently performed cosmetic procedure in the United States, according to statistics from the American Society for Aesthetic Plastic Surgery.¹ It is also one of the most common entry procedures for health care professionals seeking to incorporate aesthetic procedures into their practice.²

As we age, the skin naturally thins, and repetitive contraction of the underlying facial musculature causes visible lines and wrinkles. Initially, these lines are seen only during facial expression with frowning, laughing, or smiling and are referred to as dynamic lines. Over time, however, dynamic lines may become etched into the skin, resulting in permanent or static lines. Botulinum toxin reduces unwanted dynamic lines, and to a lesser degree static lines, by relaxing hyperdynamic facial muscles and smoothing the overlying skin.

Botulinum toxin is a potent neurotoxin protein derived from the Clostridium botulinum bacterium. It reduces muscular contraction through inhibiting release of acetylcholine at the neuromuscular junction. Injection of small quantities of botulinum toxin into specifically targeted muscles causes localized, temporary chemical denervation with resultant muscle relaxation.³

Botulinum toxin has been used for more than 20 years to treat a variety of clinical conditions such as blepharospasm, strabismus, cervical dystonia, hyperhidrosis, migraines, and muscle spasticity.⁴^–⁶ Botulinum toxin is used in numerous facial aesthetic areas. However, treatment of the glabellar complex,⁷ frontalis⁸ and orbicularis oculi muscles,⁹ which contribute to formation of frown lines, horizontal forehead lines, and crow’s feet, respectively, offers the most predictable results, greatest efficacy, and fewest side effects.^10,¹¹ Botulinum toxin treatment of hyperdynamic muscles in the upper one-third of the face are a core aesthetic procedure for providers interested in incorporating aesthetic care into office practice.¹²

Cosmetic Indications

• FDA approved for the temporary improvement of moderate to severe dynamic glabellar frown lines.

• FDA approved for adults ages 18 to 65. It is commonly used in patients older than 65, but treatments may be less effective if severe static wrinkling is present.

• Other cosmetic uses include reduction of wrinkles in upper, mid and lower face, neck, and upper chest.

Alternative Therapies

Botulinum toxin is the only FDA-approved treatment for dynamic wrinkles. Static wrinkles can also be treated with chemical peels, microdermabrasion, topical products such as retinoids, nonablative lasers for soft-tissue coagulation and tightening using infrared and radio-frequency, nonablative lasers for collagen remodeling using 1320 and 1540 nm Q-switched lasers and others, and ablative and fractional ablative lasers using erbium and carbon dioxide. Limited data suggest that an acetylcholine blocker found in topical skin care products, acetyl hexapeptide-8, may reduce wrinkles.¹³ However, additional studies are necessary to support this finding.

Products Currently Available

Clostridium botulinum produces eight serotypes of botulinum toxin proteins (A, B, Cα, Cβ, D, E, F, and G). Once activated, the botulinum toxin protein cleaves a docking protein on the internal surface of the neuronal membrane, SNAP-25, thereby inhibiting fusion and release of acetylcholine vesicles in the neuromuscular junction. Botulinum toxin serotype A is the most potent and is used for cosmetic treatments; serotype B is used for therapeutic indications. As of 2011, two botulinum toxin serotype A products had been approved by the U.S. Food and Drug Administration (FDA) for cosmetic use to treat the glabellar complex muscles that form frown lines: onabotulinumtoxinA (trade name Botox^®) and abobotulinumtoxinA (trade name Dysport^®). Both of these were formerly known as botulinum toxin type A. Botulinum toxin products are not interchangeable because they vary in their formulation characteristics, dosing, response, and complications. All references in this chapter to botulinum toxin refer specifically to onabotulinumtoxinA manufactured by Allergan as Botox.

Contraindications

• Pregnancy or nursing

• Active infection in the treatment area (e.g., herpes simplex, pustular acne, or cellulitis)

• Hypertrophic or keloidal scarring

• Bleeding abnormality (e.g., thrombocytopenia or anticoagulant use)

• Impaired healing (e.g., due to immunosuppression)

• Skin atrophy (e.g., chronic oral steroid use or genetic syndromes such as Ehlers-Danlos syndrome)

• Dermatoses such as active psoriasis or eczema in the treatment area

• Uncontrolled systemic condition

• Sensitivity or allergy to constituents of Botox (i.e., botulinum toxin serotype A, human albumin, lactose, or sodium succinate)

• Gross motor weakness in the treatment area (e.g., due to a history of polio or Bell’s palsy)

• Neuromuscular disorder including, but not limited to, amyotrophic lateral sclerosis, myasthenia gravis, Lambert-Eaton syndrome, and myopathies

• Inability to actively contract muscles in the treatment area prior to treatment

• Periocular/ocular surgery within the previous 6 months (e.g., laser-assisted in situ keratomileusis [LASIK] or blepharoplasty)

• Medications that inhibit neuromuscular signaling and may potentiate botulinum toxin effects, such as aminoglycosides, penicillamine, quinine, and calcium channel blockers

• Body dysmorphic disorder

• Unrealistic expectations

• Dependency on facial expression for livelihood (e.g., actors, singers).

Advantages of Botulinum Toxin

• Technically straightforward with short procedure time

• Safe and effective, particularly in the upper one-third of the face

• High patient satisfaction.

Disadvantages of Botulinum Toxin

• Short duration of action relative to other cosmetic procedures, although effects are cumulative over time with recurring treatments.

Anatomy

A thorough understanding of facial anatomy in the treatment areas is essential prior to performing botulinum toxin procedures (Figure 21-1). The muscles of facial expression are unique because, unlike most muscles, which have bony attachments, they have soft tissue attachments to the skin through the superficial muscular aponeurotic system. When a muscle contracts, the overlying skin moves with it and wrinkles are formed perpendicular to the direction of the muscle contraction. Figure 21-2 shows lines and wrinkles in the upper one-third of the face and the corresponding underlying musculature.

FIGURE 21-1 Musculature of the face.

FIGURE 21-2 Musculature and wrinkles of the upper face.

Glabellar wrinkles, or frown lines, are vertical lines that occur between the medial aspects of the eyebrows. The muscles that contribute to formation of frown lines are the glabellar complex depressor muscles, which pull the brows medially and inferiorly and include the corrugator supercilii, procerus, depressor supercilii, and medial orbicularis oculi (Figures 21-1, 21-2 and 21-3).

FIGURE 21-3 Functional anatomy of the upper face.

Horizontal forehead lines result from contraction of the broad frontalis muscle, which spans the forehead between the temporal fusion lines (see Figures 21-1, 21-2 and 21-3). The muscle fibers are vertically oriented and contraction of this levator muscle raises the eyebrows. The inferior 2-cm portion has the most marked effect on eyebrow height and shape. The goal of treatment in this area is to partially inhibit activity of the frontalis muscle to reduce horizontal forehead lines while maintaining a desirable eyebrow shape and height.

Periorbital wrinkles, commonly known as crow’s feet, result from contraction of the lateral portion of the orbicularis oculi, a thin, superficial muscle that encircles the eye (see Figures 21-1, 21-2 and 21-3). Contraction of the palpebral portion of the orbicularis oculi muscle results in closure of the eyelid. The goal of treatment in this area is to focally inhibit the lateral orbicularis oculi to reduce crow’s feet without excessive orbicularis oculi muscle relaxation.

Many of the muscles of facial expression interdigitate with one another and, while providing treatment with botulinum toxin to one area in isolation will often provide adequate wrinkle reduction results, in some cases an adjacent muscle group may require concomitant treatment to achieve the desired results. For example, the glabellar complex muscles interdigitate to a greater or lesser degree with the frontalis muscle, and treatment of the frontalis in addition to treatment of the glabellar complex muscles may be required to smooth frown lines in some cases ¹⁴.

Reconstitution

Botox Cosmetic^® is supplied as a powder which is reconstituted using saline. The manufacturer recommends using nonpreserved saline for reconstitution because it is alcohol free; however, some providers used preserved saline.

Injectors reconstitute Botox with differing amounts of saline and there is no standardized reconstitution protocol. Botox efficacy is based on the number of units injected rather than the dilution. However, diffusion and the risk of complications are related to greater dilution volumes.¹⁵ The author’s reconstitution technique is outlined below.

Reconstitute a 100-unit vial of Botox with 4.0 mL of 0.9% nonpreserved sterile saline. Using an 18-gauge needle with a 5.0-mL syringe, draw up 4.0 mL of saline. Insert the needle at a 45-degree angle into the Botox vial and inject saline slowly, maintaining upward plunger pressure so that the diluent runs down the sides of the vial. Gently swirl the reconstituted Botox vial and record the date and time of reconstitution on the vial. Note that alcohol can denature botulinum toxin and, therefore, bottle stoppers must be fully dry. Reconstitution of Botox powder using 4.0 mL of saline results in a concentration of 100 units of botulinum toxin per 4 mL (100 units/4 mL) or 2.5 units botulinum toxin per 0.1 mL increment on the 1.0-mL treatment syringe.

Handling and Storage

Botox is shipped frozen, on dry ice. Prior to and after reconstitution it should be stored in the refrigerator at a temperature of 2 to 8°C (35.6 to 46.4°F). Prior to reconstitution it may be stored for 24 months. While the manufacturer recommends using Botox within 24 hours of reconstitution, the American Society for Plastic Surgery Botox Consensus Panel recommends using Botox within 6 weeks and notes no loss of potency during that time.^3,¹⁶

Procedure Preparation

1. Perform an aesthetic consultation and review the patient’s medical history (see Chapter 19, Aesthetic Principles and Consultation).

2. Formulate a cosmetic treatment plan and record in the chart (see Chapter 19).

3. Obtain informed consent (see Chapter 19; also see Appendix A for an informed consent form and patient information handout titled Botulinum Toxin Treatments).

4. Take pretreatment photographs with the patient actively contracting the muscles in the intended treatment area and with the muscles at rest.

5. Document and discuss any notable asymmetries prior to treatment.

6. Minimize bruising by discontinuation of aspirin, vitamin E, St. John’s wort, and other dietary supplements including ginkgo biloba, evening primrose oil, garlic, feverfew, and ginseng for 2 weeks prior to treatment. Discontinue other nonsteroidal anti-inflammatory medications and alcohol consumption 2 days prior to treatment.

7. Position the patient comfortably in a reclined position for the procedure, at about 65 degrees.

8. Cleanse the treatment areas with alcohol prior to injection and allow the alcohol to dry.

9. Anesthesia is not typically required for botulinum toxin treatments. If necessary, ice may be used prior to injections in all treatment areas except the crow’s feet, because this makes identification and avoidance of veins more difficult.