Introduction and History
One of the safest, simplest, and most satisfying methods of elective cosmetic reduction of facial rhytides is by the injection of botulinum neurotoxin Type A (BoNT-A, BOTOX® (Allergan, Irvine, CA)). Dysport® (Medicis, Scottsdale, AZ) is another formulaion of BoNT-A which is nearing FDA approval. Doses in this chapter are specific to BOTOX®, and Dysport® doses are approximately 2.5–3 times those for BOTOX®. BoNT-A is currently injected into selected superficial musculo-aponeurotic system (SMAS)-type facial muscles to temporarily reduce associated static and dynamic wrinkles. BoNT-A relaxes muscles by preventing the presynaptic release of the neurotransmitter acetylcholine at the peripheral cholinergic motor neuron endplate ( Fig. 13.1A & B ).
Acetylcholine (Ach) is stored in vesicles residing in the motor nerve ending. Docking is a necessary step prior to release of ACh into the neuromuscular junction. BoNT-A prevents the docking and exocytosis of these acetylcholine vesicles to the nerve endplate. In order for BoNT-A to exert this effect, it must first be absorbed into the nerve ending by a process termed receptor-mediated endocytosis. After BoNT-A is internalized within a cytoplasmic vesicle, the light chain is released into the cytoplasm. The light chain cleaves a protein known as SNAP-25A which must be functional in order for acetylcholine vesicles to dock prior to release into the neuromuscular junction ( Fig. 13.1C–F ).
Several distinct immunological BoNT serotypes exist (A, B, C1, D, E, F, G) which vary from approximately 300 to 900kD size. All BoNT serotypes target one or more specific intracellular proteins necessary for synaptic release of neurotransmitter. Proteins targeted by different serotypes include SNAP-25, syntaxin, and vesicle-associated membrane protein (VAMP, also known as synaptobrevin). Over time, the nerve ending may sprout additional axons, which establish new motor endplates ( Fig. 13.1G ). This results in a gradual return of motor function. Clinically, muscle function returns in 3–4 months. Skin testing for allergy to BoNT-A is not necessary, although blocking antibodies may occur in patients who receive high doses repeatedly.
In 1895, Emile Pierre van Ermengem, of Belgium identified Bacillus botulinus
In the 1920s, botulinum toxin type A isolated in purified form by Dr Herman Sommer at the University of California, San Francisco, USA
In 1946, Edward J. Schantz and colleagues purified botulinum toxin type A in crystalline form
In the 1960s and 1970s, Alan B. Scott tested botulinum toxin type A in monkeys to determine if the drug might be an effective therapy for strabismus
1978, Dr Scott received permission from the Food and Drug Administration (FDA) to test botulinum toxin type A in human volunteers
2002, FDA approval of BOTOX® for cosmetic treatment of the glabella (Dysport® approved 2009)
The facial mimetic muscles are specialized for several functions including facial signaling and communication. Most of the muscles of facial expression are part of a continuous interconnected layer of muscle and connective tissue known as the SMAS layer ( Fig. 13.2 ). While these muscles are specialized for facial expression, there is also a decline with age in the accuracy with which these muscles convey facial expression. Hence, the age-related development of standing glabellar furrows may create a mistaken expression of disapproval. It is often the goal of BOTOX® injection to reduce the facial ‘miscues’ through selective pharmacologic denervation of the offending muscles. The common target muscles are summarized in Table 13.1 .
|Muscle||Action||Clinical effect and wrinkle(s) produced|
|Orbicularis oculi (orbital portion)||Forced eyelid closure, lateral eyebrow depression||Crow’s-feet, eyebrow depression|
|Corrugator supercilii||Depresses and adducts medial half of eyebrow||Glabellar frown Lines|
|Procerus||Depresses medial eyebrow||Horizontal nasal bridge lines|
|Depressor supercilii||Depresses head of eyebrow||Depresses head of eyebrow|
|Frontalis (occipitofrontalis)||Furrows forehead, elevates eyebrows||Horizontal forehead lines|
|Orbicularis oris||Purses and puckers lips||Vertical lip lines|
|Depressors of mouth: depressor labii inferioris depressor anguli oris||Depresses lateral angle of mouth||Ptosis of lateral commissure|
|Platysma||Depresses lower jaw and lip||Vertical neck bands|
Clinical Indications and Patient Selection
BoNT-A injection works well and reliably in the crow’s-feet, glabella, and forehead ( Fig 13.3 ). With experience, the eyebrows may be repositioned through treatment of the adjacent orbicularis oculi, procerus, corrugator supercilii, and depressor supercilii. BoNT-A may also be used with caution and experience to reduce the perioral rhytides and to improve the lateral angle of the mouth. However, the risk of perioral treatment resides in the possibility of inducing a neurolytic incompetence of the oral sphincter which may result in temporary drooling, difficulty in pronouncing some sounds (P or B), or inability to whistle, and difficulty playing wind instruments. BoNT-A is not helpful in the treatment of the nasolabial and marionette lines because such treatment results in facial ptosis. Dose is often individualized and may be related to muscle mass such that relatively smaller doses are sometimes used in females and Asians ( Tables 13.2 & 13.3 ). BOTOX® injection is contraindicated in the presence of infection at the injection site or in patients with known hypersensitivity to BOTOX® or any of its components. Caution should be used in treating patients with pre-existing neuromuscular disorders. BoNT-A treatment is contraindicated in women who are pregnant or nursing.
|Type I||No wrinkles|
|Type II||Wrinkles in motion|
|Type III||Wrinkles at rest|
|Type IV||Only wrinkles|
|Site||Dose per site||Number of injections per side||Total dose per side||Spacing of ipsilateral injection||Recommended initial dose per side/ #injection sites per side/ distance between injections|
|Upper lip||1-1.5u||1-2||1-2u||1.5cm||1u/ 1/ na|
|Lower lip||1-1.5u||1-2||1-2u||1.5cm||1u/ 1/ na|
|Lateral Commisure||5-10u||1-2||5-10u||1-1.5cm||5u/ 1/ na|
|Platysma||5u||variable||15-50+||1-3cm||5u/ variable/ 1.5+cm|