Chemodenervation (Botulinum Toxin Type A [BoNT-A]) Flashcards
What are the different branded formulations of botulinum toxin type A (BoNT-A) currently available?
There are currently two available formulations of BoNT-A in the United States: Botox (onabotulinumtoxinA; Allergan Inc, Irvine, CA) and Dysport (abobotulinumtoxinA; Medicis Aesthetics Inc, Scottsdale, AZ). Two others are currently in the process of FDA approval in the USA, Xeomin (Merz Pharma) and PurTox (Mentor Corp, Santa Barbara, CA).
From what organism is BoNT-A made?
BoNT-A is the purified neurotoxin type A complex produced by fermentation of the bacterium Clostridium
botulinum type A, Hall strain.
What is the mechanism of action of BoNT-A?
It inhibits acetylcholine release at the neuromuscular junction and may inhibit neuropeptide neurotransmitter release. This blocks nerve stimulation of muscular activity and causes muscular paralysis. When applied to the mimetic muscles of the face in the proper dose, rhytids soften or disappear.
How long does BoNT-A take to act and how long does it last?
It induces partial chemical denervation resulting in reduced muscular activity. This is usually clinically evident within 24 to 72 hours depending on the type of BoNT-A used. The maximal clinical effect may take up to 14 days. The muscle may sustain atrophy, axonal sprouting may occur, and extrajunctional acetylcholine receptors may develop. Reinnervation of the muscle may occur, thus slowly reversing muscle denervation. On average the clinical effect on facial rhytids lasts 3 to 4 months. When used for hyperhydrosis the effect is much longer, on the order of 8 to 10 months.
What does a “unit” refer to when discussing the dose of BoNT-A?
One unit corresponds to the calculated median intraperitoneal lethal dose (LD50) in mice
What is the significance of final concentration when reconstituting BoNT-A?
BoNT-A comes in a powder form within a vacuum-sealed glass vial. It is typically reconstituted with preservative free sterile 0.9% saline prior to use. Depending on the volume of saline used differing concentrations can be developed. Using Botox as an example, a final concentration of 5.0 to 2.0 U per 0.1 mL is typically used. The more concentrated the toxin, the more potency per unit volume and thus per injection site can be achieved; however, this requires more precision in injection technique and a more dense tissue effect. With a more dilute injectate more volume needs to be injected, a slightly softer result can be achieved, but there is higher risk of diffusion away from the intended site of delivery.
What is the recommended means by which to store BoNT-A after it has been reconstituted?
Prescribing information states that BoNT-A should be used within 4 hours of reconstitution. However, published data suggest that potency can be maintained for up to 6 weeks with storage at 4◦C. Anecdotal reports state potency with even longer storage.
How many BoNT-A treatments were reported in 2008?
In the United States there were 2.5 million patients treated (including Botox and Dysport) for aesthetic purposes according to multispecialty data collected by the American Society for Aesthetic Plastic Surgery (ASAPS statistics 2009).
In addition to aesthetic purposes, for what other diagnoses has BoNT-A demonstrated treatment efficacy?
Besides aesthetic applications, BoNT-A has a wide range of on- and off-label applications including treatment of hyperhydrosis, cervical dystonia, muscular spasm associated with cerebral palsy, blepharospasm, spasmodic dysphonia, oromandibular dystonia, writer’s cramp, migraine headache, tennis elbow, Dupuytren contracture, chronic low back pain, poststroke spasticity, achalasia, and anal fissure.
How is a patient assessed in preparation for treatment with BoNT-A?
A full facial analysis is performed including the location and depth of facial rhytids. Asymmetries are identified before injection and noted to the patient. Particular attention is given to brow position and function, as well as eyelid position and function. The extent of sun damage and actinic change is also noted.
Describe the depressor muscles of the brow.
The depressors of the brow are the corrugator supercilii muscles (transverse and oblique heads), the procerus muscles, and the orbital portion of the orbicularis oculi and its associated depressor supercilii muscle medially. All these muscles act on the glabellar complex.
Describe the elevator muscles of the brow.
The elevator of the brow is the frontalis muscle. It had no true bony insertions but blends with the depressors of the brow. It also has dense dermal insertions responsible for transverse forehead rhytids.
Describe the constrictor muscles of the eyelids.
The constrictor muscles of the eyelids are a complex array of concentrically oriented muscles with origins medial to the medial canthus and insertion lateral to the lateral canthus. Collectively, these muscles are referred to as the orbicularis oculi muscles. Further differentiation is made based on location relative to the underlying lid structures; oriented in a concentric manner from outside to inside they are the:
1. orbital orbicularis 2. preseptal orbicularis 3. pretarsal orbicularis
Further divisions (based on function) can be made, principally the innercanthal orbicularis and the extracanthal orbicularis. Understanding this anatomic and functional differentiation is critical when considering injections of BoNT-A in this area (for further description of the constrictor muscle function, see chapter on eyelid surgery).
Describe the elevator muscles of the upper eyelid.
The two primary muscles responsible for upper eyelid elevation are the levator palpebrae muscle (parasympathetic innervation) and Mueller’s muscle (sympathetic innervation); both insert onto the tarsal plate. A secondary effect on upper lid position is due to the frontalis muscle and brow position. Brow elevation will secondarily raise the eyelid. This is often evident as brow strain and chronic horizontal forehead rhytids in patients with dermatochalasis or upper lid ptosis.
What is the cause of ptosis after injection of BoNT-A, how long does it last, and how is it treated?
There are two potential etiologies of upper lid ptosis following BoNT-A injection. One is paralysis of brow elevation in the presence of brow strain compensating for preexisting lid ptosis. Second is migration of toxin to the lid retractors as a direct effect. This occurs if toxin is injected to close to the lid retractors, in the periosteum of the brow (facilitating migration), or toxin is massaged down to the eyelid after injection.
This effect can last up to a month and is managed with alpha-adrenergic agonist ophthalmic drops (eg, phenylephrine ophthalmic drops).
What are the two most common undesirable mimetic effects of BoNT-A injections of the glabella and forehead?
- The “Mephisto” eyebrow or the totally depressed eyebrow. The “Mephisto” or “Spock” brow is the result of medial brow depression and paralysis with preserved lateral brow function. This results in a severely angular appearance to the brow with medial depression and a severe upward lateral sweep. This is treated by a small dose administration to the lateral frontalis muscle responsible for preserved lateral brow elevation, resulting in lateral brow paralysis and resolution of the severe upward lateral sweep. This is avoided by uniform treatment of the forehead and/or conservative treatment of the glabella.
- Total brow depression is the result of excess toxin administration to the frontalis muscle in the presence of chronic frontalis stain in patients with dermatochalasis or upper eyelid ptosis. This is avoided by proper pretreatment assessment and conservative treatment of the forehead at least 2 cm above the level of the brow.
What are bunny lines? Which muscle is responsible for them?
Bunny lines are small obliquely oriented mimetic rhytids of the lateral nasal dorsum. These can be induced by asking the patient to simulate a deep sniff or sneer. The levator labii superioris alaeque nasi and nasalis muscles are responsible for theses lines. A low-dose–low-volume treatment of high concentration with BoNT-A is recommended here to minimize spread into local musculature, especially the medial head of the orbicularis oculi muscle.
What application does BoNT-A have in the chin?
An active mentalis muscle with thin skin coverage can result in a “peau d’orange” appearance. Small amounts of BoNT-A into the body of the mentalis muscle (low and close to center) can smooth this appearance. Care is taken to avoid unintentional injection into the depressor anguli oris (DAO).
What is the cause of vertical perioral rhytids?
Aging, smoking, and action of the orbicularis oris muscle.
What problems can be caused by overtreatment of the perioral area?
Difficulty in pursing the lips, sucking through a straw, speech impairment, difficulty eating, difficulty brushing teeth, and diminished proprioception. Excess injection of the DAO and associated lip depressors can cause oral incompetence, drooling, and asymmetrical smile.
What causes platysmal bands and can they be treated with BoNT-A?
Platysmal bands are the result of platysma muscle laxity and descent and thin coverage. Mild to moderate banding
can be improved with BoNT-A injections directly into the body of the band.
Why do men require a higher dose of BoNT-A?
In general the muscles of men are greater in mass and therefore require higher doses of BoNT-A to achieve a similar
clinical effect as seen in women with a lower dose.
What are the most common reported adverse events due to BoNT-A injections?
Bruising, swelling, and temporary skin irritation are common adverse events and mostly related to the use of a
needle for percutaneous injection.
How can the undesirable side effects of BoNT-A be minimized?
Proper patient selection and analysis is crucial. Use the smallest needle possible, minimize the number of percutaneous punctures, avoid known vessels, use ice packs after injection, avoid nonsteroidal anti-inflammatory drugs and aspirin prior to injection, and avoid vigorous activity immediately after injection.
