Friday, November 5, 2010
Thursday, October 28, 2010
BOTOX (R) Injections
BOTOX (R) Injections
Eight serologically distinct botulinum neurotoxins exist, designated as A, B, C1, C2, D, E, F, and G. Seven are associated with paralysis. Types A, B, E and, rarely, F and G are associated with human botulism.
Botulism is a bilaterally symmetric descending neuroparalytic illness caused by botulinum neurotoxin. The German physician and poet Justinus Kerner published the first full description of clinical symptoms of food-borne botulism from 1817-1822.2 His observations followed an increase in food poisoning in Stuttgart from 1795-1813 caused by general economic hardship related to the Napoleonic wars and a decline in hygienic measures of food production and handling. The illness became known as "sausage poisoning" because it was observed to follow ingestion of spoiled sausage. The word botulism comes from the Latin botulus, meaning sausage.
Kerner deduced that the toxin acts by interrupting signal transmission within the peripheral and sympathetic nervous system, leaving sensory transmission intact. He also hypothesized possible therapeutic uses of the sausage toxin. In 1895, the microbiologist Emile-Pierre van Ermengen discovered the association with an anaerobic bacterium during an outbreak of botulism following a funeral ceremony in the Belgian village of Ellezelles.
When foods tainted with neurotoxin are ingested, the neurotoxin is absorbed and spread hematogenously to peripheral cholinergic nerve terminals, where it blocks the release of acetylcholine. The neurotoxin is heat labile and denatured by cooking. Sporadic outbreaks of botulism in the United States occur after ingestion of home-canned foods, meat products, and preserved fish. The incubation period following ingestion is 18-36 hours.
In contrast, infant botulism is caused by colonization of the gut by C botulinum, and subsequent production and absorption leads to absorption of the toxin. Honey consumption has been implicated in infant botulism, and microbiologic surveys have identified clostridial spores (mostly type B) in up to 25% of honey products.
Wound botulism may occur if the organism infects a wound and produces the toxin. The clinical syndrome of botulism is one of progressive muscle weakness, often beginning in the extraocular or pharyngeal muscles and becoming generalized. GI tract complaints may be prominent. Dilated unreactive pupils are common, and mucous membranes are often dry and erythematous. No sensory signs are associated, and alertness is maintained as long as respiration is adequate.
In 1946, Schantz helped isolate botulinum toxin type A in crystalline form. In the early 1970s, Scott experimented with botulinum toxin type A in monkeys for the treatment of strabismus. In 1977-1978, he performed trials in patients with strabismus. In the mid 1980s, he treated an individual with botulinum toxin for cosmetic reasons. Carruthers, Carruthers, Brin, and the Columbia University group noticed cosmetic improvement following botulinum toxin injection for facial dystonias and began pursuing this line of investigation in the late 1980s and early 1990s.3,4
Botulinum toxins currently are used to treat various disorders, including strabismus, hemifacial spasms, focal dystonias (eg, blepharospasm, torticollis, spasmodic dysphonia, limb dystonia, writer's cramp), spasticity, tremor, tics, synkinesis, hyperhidrosis, achalasia, and sphincter dysfunction. They are being evaluated to treat headaches and pain syndromes.
BOTOX® (botulinum toxin type A) is currently approved by the US Food and Drug Administration (FDA) for the treatment of blepharospasm and strabismus associated with dystonias (including benign essential blepharospasm or cranial nerve VII disorders) in patients aged 12 years or older, and for the treatment of cervical dystonia in adults. Myobloc (botulinum toxin type B) is currently FDA-approved for the treatment of cervical dystonia. Injection of botulinum toxins for cosmesis is currently considered off-label use but constitutes the most prevalent use of these injections.
Mechanism of action
Botulinum toxins block acetylcholine release, causing a chemical denervation. Neurotransmission at the neuromuscular junction involves the release of acetylcholine from the presynaptic nerve terminal. Acetylcholine release requires docking and binding of the neurotransmitter vesicles to the presynaptic membrane.
Several different proteins mediate this process. N -ethylmaleimide-sensitive fusion protein (NSF) is a cytoplasmic protein that is part of the fusion complex. Soluble N -ethylmaleimide-sensitive fusion–attachment proteins (SNAPs) are found in the cytoplasm and serve as attachment and stabilizing proteins for the NSF complex. SNAP receptors (SNAREs) are found on the vesicle and plasma membranes. SNAREs include vesicle-associated membrane protein (VAMP/synaptobrevin) and the plasma proteins SNAP-25 and syntaxin.
Botulinum toxin is a zinc-dependent endopeptidase made up of a light (50 kilodaltons [kDa]) and a heavy (100 kDa) chain linked by disulfide bonds.
The mechanism of action includes the following 4 key steps:
After several months, the inactivated terminals slowly recover function, and the new sprouts and end plates regress. Recovery of inactivated terminals appears to be the basis of the loss of clinical effect several months after injection.
The dose of botulinum toxin is expressed in mouse units. One unit is equal to the amount that kills 50% of a group of 18- to 22-g Swiss Webster mice when injected intraperitoneally. The human lethal dose (LD) for BOTOX® (botulinum type A purified neurotoxin complex) is estimated at approximately 3000 units. BOTOX® injections of less than 100 units usually are used for cosmetic purposes and of less than 300-600 units for other purposes, thereby allowing a wide safety margin. Recognizing that doses are not interchangeable among different formulations of botulinum toxin (BOTOX®, Dysport, Myobloc) is important; to achieve similar clinical effects, different doses are used.
Botulinum toxin formulations
BOTOX® is a sterile lyophilized form of botulinum toxin type A. It is produced from a culture of the Hall strain of C botulinum and purified by a series of acid precipitations to a crystalline complex containing the toxin and other proteins. The FDA approved BOTOX® in December 1989 as an orphan drug for the treatment of strabismus, hemifacial spasms, and blepharospasm. BOTOX® is distributed in 100-unit vials.
The original batch of neurotoxin prepared by Shantz in November 1979 (designated batch 79-11) constituted the original BOTOX® formulation and was used until December 1997. It was replaced by a new neurotoxin complex batch designated BCB 2024. The new bulk batch is 5-6 times more potent on a weight basis. In a 100-unit vial, only 4.8 ng of neurotoxin is needed compared to 25 ng of 79-11. The new BOTOX® is comparable in clinical efficacy and safety to the old, and a unit dose of new BOTOX® provides an equivalent response to the same unit dose of old BOTOX®. The reduced protein load of the new BOTOX® has been hypothesized to lead to reduced immunogenicity and a lower incidence of neutralizing antibody formation.
Dysport is another formulation of botulinum toxin type A available in Europe and a few other countries. It is prepared using column-based purification techniques and distributed in 500-unit vials that can be stored at room temperature. BOTOX® and Dysport are both botulinum toxin type A preparations but are quite distinct from one another. BOTOX® is approximately 4 times more potent on a per unit basis, and Dysport doses often are approximately 4 times the BOTOX® doses used to generate a similar clinical effect. Differences in these toxins may relate to differences in the strain of bacterium, preparation, diffusion, and potency testing.
Myobloc is a botulinum toxin type B preparation that is approved for the treatment of cervical dystonia. It is distributed as a solution. Little information is available concerning the cosmetic use of Dysport and Myobloc. The remainder of this article therefore focuses on BOTOX®, and all unit doses refer to BOTOX® unless otherwise specified.
Reconstitution and storage
Store BOTOX® in a freezer at or below -5°C. The package insert for BOTOX® recommends dilution with sterile nonpreserved saline. Studies have demonstrated that preserved saline provides increased patient comfort without decreasing efficacy.5 The practice of adding lidocaine to BOTOX® has been abandoned following an unrelated death.6 Topical anesthetics are dilators (with the exception of cocaine) and, therefore, may increase migration of BOTOX® to unwanted areas.7
For the purposes of this section, botulinum toxin is described in units of the BOTOX® brand type A toxin. Oculoplastic specialists use a 1-mL dilution per 100 units of BOTOX®. Dermatologists and plastic surgeons tend to use a range from 1-4 mL per 100 units. More dilute concentration is preferable in order to increase migration (as in the forehead), whereas lower volumes are preferred to avoid migration into unplanned areas.8,9
BOTOX® is denatured easily by bubbling or agitation; gently inject the diluent onto the inside wall of the vial. Discard the vial if a vacuum does not pull the diluent in. The final dilution of BOTOX® is mostly a matter of personal preference; 100 units commonly are reconstituted in 1-10 mL of diluent. Theoretically, more concentrated solutions reduce reliability in delivering a specific unit dose, and more dilute solutions lead to greater diffusion of the toxin. The authors prefer to use 2 mL of diluent to prepare a solution of 5 U/0.1 mL (50 U in a 1-mL tuberculin syringe if that much is to be used). Use a 30-gauge 1-inch needle to perform the injections.
Once reconstituted, keep BOTOX® refrigerated at 2-8°C. The package insert indicates that reconstituted BOTOX® should be used within 4 hours. One study found no loss of activity at 6 hours but a 44% loss after 12 hours and a 70% loss with refreezing at 1-2 weeks. Other authors report no substantial loss of potency in a 10 U/1 mL reconstituted solution kept refrigerated for 1 month. Most practitioners discard unused reconstituted BOTOX® after 1-7 days.
General considerations in cosmetic use of BOTOX®
Aging is associated with the development of lines and wrinkles caused by actinic damage, gravitational effect, sleep lines, and muscular action. Mimetic facial musculature may undergo hypertrophy secondary to hyperfunctional pull. BOTOX® injections reduce facial lines caused by hyperfunctional muscles. They also are used to contour aspects of the face such as the brows.
Injection of the lower face requires a precise technique, since any asymmetry may result in facial asymmetry and speech impediments. Injection of the mid and lower face and neck is best reserved for experienced injectors and patients who have had successful injections in the upper face.7
Pretreatment photography is highly recommended to document any preexisting asymmetry. Patients should be informed that cosmetic injection in any site other than the glabella constitutes an off-label indication in the United States.7 An informed consent form is required, with detailed mention of possible complications, such as headache, bruising, infection, eyelid drooping, facial asymmetry, speech changes, and dysphagia.
Injection techniques often vary among practitioners and over time. Patients usually notice a clinical effect 1-3 days following injection, and the effect is maximal by 1-2 weeks. Some diffusion of toxin occurs. A 10-unit injection into the frontalis muscle produces a circular area of paresis with a radius of approximately 1.5 cm. Space injections apart appropriately, and do not place injections too close to muscles in which weakness is to be avoided.
Adverse effects of injection include minimal ecchymosis and bruising. Applying ice to the injection sites before and after treatment may decrease the pain and the risk of swelling and bruising. When not contraindicated, patients should avoid platelet inhibitors, including aspirin and nonsteroidal anti-inflammatory drugs, for 1 week prior to injection.
Set realistic expectations. The benefits usually last 3-6 months and then resolve. A clear plan should be devised to address the individual's anatomy and areas to be injected.
Anatomy
The frontalis muscle elevates the eyebrows and the skin of the forehead. The fibers of the frontalis are oriented vertically, and wrinkles of the forehead are oriented horizontally. The frontalis muscle originates on the galea aponeurotica near the coronal suture and inserts on the superciliary ridge of the frontal bone and skin of the brow, interdigitating with fibers of the brow depressors (ie, procerus, corrugator supercilii, orbicularis oculi muscle).
The medial fibers usually are more fibrous than the lateral fibers, thus requiring less toxin for paralysis. Avoid total paralysis of the frontalis, since this is likely to cause brow ptosis and loss of expression. Injection too close to the lateral eyebrow can cause lateral eyebrow ptosis. Technique
Multiple injections of small amounts of toxin create weakness without total paralysis. Inject 3-5 sites on each side of the mid line, usually using 2 units (1-3 U) per site. Separate sites by 1-2 cm. Choose an initial injection site approximately 1 cm above the eyebrow vertical to the medial canthus. Additional sites diverge laterally and upward to the hairline in a "V" configuration, often for a total of 3 sites. Additional sites (1-3) can be added in the mid line or more laterally (1-2) depending on individual and clinical response.
If wrinkles extend to the temporal region, lateral injections can be performed. Use caution to prevent injecting lateral to the lateral canthus to avoid inhibiting temporalis function. Use caution when injecting patients in whom the hyperfunctional frontal lines support a ptotic upper eyelid.
Injections of the upper face and periocular region usually are performed with the patient seated, and the patient is asked to remain upright for 2-3 hours to prevent spread of toxin through the orbital septum.
Anatomy
Facial rhytides and folds in this area result from action of the depressor muscles (ie, corrugator supercilii, depressor supercilii, orbicularis oculi, procerus).
The corrugator superciliaris, medial orbital portion of the orbicularis oculi, and more vertically oriented fibers of the depressor supercilii produce the vertical lines of the glabella. The corrugator muscle is a brow adductor moving the eyebrow downward and medially. It arises from the nasal bone just above the rim of the orbit medially and extends laterally and upward, inserting in the skin above the middle of the eyebrow. It lies deep to the frontalis, procerus, and orbicularis oculi muscles. The medial fibers of the orbicularis oculi originate from the medial orbital rim anterior to the origin of the corrugator. The fibers interdigitate with fibers of the frontalis, procerus, and corrugator muscles. The depressor supercilii originates from the nasal process of the frontal bone and inserts into the skin at the medial aspect of the eyebrow.
The vertically oriented procerus muscle, which originates from the upper nasal cartilage and the lower nasal bone, produces the horizontal lines of the glabella and nasal root. It inserts into the skin between the brows and the frontal belly of the occipitofrontalis. Its fibers interdigitate with those of the orbicularis, frontalis, and corrugator muscles.
Technique
Usually, 5 sites are injected with 4-6 units each for an average total dose of approximately 25 units. One site on each side is used to inject the corrugator, one site on each side is used to inject the orbicularis oculi and depressor supercilii, and one site is used to inject the procerus in the mid line.
The patient is asked initially to frown and scowl, and the target muscles are palpated. Place the first injection into the belly of the corrugator muscle. Insert the needle at the origin of the corrugator fibers just above the medial canthus and superciliary arch until bone is felt, and then withdraw it slightly. Advance the needle within the belly of the muscle upward and lateral as far as the medial third of the eyebrow, 1 cm superior to the orbital rim. Inject 4-6 units as the needle is withdrawn.
The next site is approximately 1 cm above the upper medial aspect of the supraorbital ridge. Advance the needle slightly in a vertical direction toward the hairline. Inject 4-6 units into the orbicularis oculi and depressor supercilii as the needle is withdrawn. Repeat these injections on the contralateral side.
Place the last injection into the belly of the procerus to eliminate the horizontal lines at the root of the nose. Inject 4-6 units at a point where 2 lines drawn at 45° from the medial aspect of the eyebrows converge in the center of the nasal root, just superior to the horizontal plane of the medial canthi. To avoid resultant accentuation of eyebrow arching in men, inject an additional 4-6 units 1 cm above the supraorbital prominence vertical to the mid point of the eyebrow.
In 1998, a dose/response study by Hankins et al of 46 women receiving BOTOX® for glabellar wrinkles found an effective starting dose from 2.5-4 units per injection site (12.5-20 U total).10
A glabellar "spread test" may be performed prior to injection by spreading the glabellar wrinkles apart with the thumb and index fingers. This may allow an estimate of the expected benefit from BOTOX® injection. Patients with thick sebaceous skin and deep dermal scarring that are not improved with manual spreading usually respond poorly to botulinum toxin injections. EMG guidance may provide valuable information when initial injections prove unsatisfactory.
Some patients may need evaluation for medial recruitment from the mid brow. Medial recruitment is caused by hyperfunctional orbicularis oculi fibers just below the mid eyebrow. This population of patients may not favorably respond to BOTOX®, as the injection may lead to depression of the medial and lateral brow.7
A recent study has demonstrated that injecting 3 essential sites in the procerus and the corrugator muscles is essential for the treatment of glabellar wrinkles, while 2 additional forehead region injections did not significantly improve efficacy.11
One study has demonstrated that glabellar line treatment may help convey positive and relaxed emotions more accurately.12
Anatomy
The lateral fibers of the orbicularis oculi are arranged in a circular pattern around the eye. Contraction of these fibers produces wrinkles that extend radially from the region of the lateral canthus.
Technique
Perform 3 or 4 subcutaneous injections approximately 1 cm lateral to the lateral orbital rim using 2-3 units per injection site (for a total of 6-12 U per side). Space sites 0.5-1 cm apart in a vertical line or slightly curving arch. Doses that are too high or injections that are too medial can lead to eyelid ptosis or diplopia.
With age, the lateral eyebrow typically becomes ptotic before the medial aspect. The lateral brow is more affected by the gravitational descent of the temporal soft tissue mass and the downward force of the corrugator supercilii and orbicularis oculi muscles. Temporal brow lift can be achieved by BOTOX® injections into the lateral brow depressors. Ahn et al treated patients seeking elevation in eyebrow height with 7-10 units of BOTOX® injected into the superolateral portion of the orbicularis oculi below the lateral third of the brow. Mean brow height increased 1.0 mm at the mid pupil and 4.8 mm at the lateral canthus (P = 0.038 and 0.0001, respectively). Injecting superior and lateral to the orbital rim minimized the potential for ptosis.
Levator labia superioris
Contraction of this muscle is observed when an individual "scrunches" his or her nose, and hyperfunctional contraction often confers a "mad dog" appearance to the face. This muscle can be injected with 2-5 units of BOTOX® on each side of the nose lateral to the nasion.
Nasal flare
Several patients with undesirable nasal flare have been treated successfully with serial BOTOX® injections.
Mental crease
Reduction of a prominent mental crease can be achieved by injection of 5-10 units of BOTOX® into the point of the chin.
Facial asymmetry
Injections of BOTOX® can improve facial asymmetry and synkinesis. The asymmetry of residual unilateral paresis can be reduced by judicious injection of normal muscles on the unaffected side. Hyperkinesis from aberrant degeneration can be reduced by injection of hyperkinetic muscles.
Upper lip wrinkling
Optimally treat multiple fine wrinkles using a filler substance such as injectable collagen or by middepth or deeper resurfacing. These fine wrinkles do not respond well to BOTOX® injections, and the upper lip is sensitive to paresis. However, botulinum toxin injections may be used in individuals with 2 or 3 deep wrinkles. Small doses of botulinum toxin (0.5-1 U per wrinkle) may be administered, injected superficially rather than deeply. Avoiding weakness of the upper lip is important.
Depressor anguli oris
To weaken the depressor anguli oris, which is the underlying muscle of the downturn at the corner of the mouth, 2-3 units of botulinum toxin may be injected. Instruct the individual to forcibly pull down the corners of the mouth; the depressor anguli oris can be felt inferior to a point 1 cm lateral to the commissure.
Nasolabial folds
Carruthers and Carruthers, attempting to soften the nasolabial fold, injected low doses (2-3 U) of BOTOX® in the levator labii superioris alaeque nasi.4 EMG localization of the muscle was used. Some of the individuals who had softening of the folds showed lengthening of the upper lip. In general, achieving a good result in attempting to soften the nasolabial fold is difficult.
Adjunctive use of BOTOX® injections
BOTOX® injections may be used to provide presurgical chemodenervation of the brow depressor muscles, giving better results with surgical repositioning of the brow. Pretreatment of crow's feet allows the surgeon to better define the incision line within the confines of the bony orbital margin.
The platysma muscle originates inferiorly from the pectoralis and deltoid fascia. It crosses the sternocleidomastoid at the midlateral neck area at the Erb point. In 75% of individuals, the platysmal fibers interface with those on the opposite side 1-2 cm below the chin. In 15% of individuals, the fibers interdigitate at the level of the thyroid cartilage and cover the submental area confluently, forming one band. In 10% of individuals, the fibers do not decussate with those on the opposite side.
The lateral bands of the platysma muscle facilitate facial expression by lowering the corners of the lower lip. Its posterior fibers continue superiorly to join the superficial musculoaponeurotic system (SMAS) of the face. At the anterior chin, the deeper lower lip depressors are shaped like a large, split "M" formed by the depressor anguli inferioris, the mentalis, and the depressor anguli inferioris on the other side. A wider split M, representing the lateral commissure muscle and the depressor anguli oris, covers this split M.
Aging of the neck
Several factors affect aging of the neck, including heredity, actinic damage, and weight changes. Age-related downward pull of the platysma muscle creates vertical fibrous bands. The skin laxity over the platysma muscle produces horizontal rhytides. The inferior pull of the platysma-SMAS complex, together with the age-related skin and muscular degeneration, causes the largest submental fat pad to herniate between the 2 free borders of the platysma muscle.
Cosmetic BOTOX® injection of the neck
Injections generally are considered most appropriate for older patients who are not candidates for surgery, older patients who previously have had neck rejuvenation surgery without relapse or severe neck skin excess, and younger patients with strong platysmal bands who are not yet surgical candidates. They also can be used to improve the cosmetic outcome after rhytidectomy. Younger patients have a noticeably better result, as do older patients who have had prior surgery. Patients exhibit greater improvement during animation than in repose. Kane noted in 1999, "Although most of the patients were very happy with their results, even the best results in no way approached the most disappointing results obtained by means of surgical manipulation of the platysma and neck skin."13
Injection technique
After preparing the skin, ask the patient to contract the platysma muscle; this identifies its bands. Injection techniques vary among practitioners. Some use a few injections along the length of a band while others use many. Some practitioners use EMG guidance, although this usually is not necessary. One technique involves injecting each band at 1.0- to 1.5-cm intervals from the jawline to the lower neck. Approximately 3-10 units may be injected, depending on the thickness of the platysmal band.
Another technique involves injecting the bands at the following 3 sites: the curve between the horizontal submental surface and the vertical anterior surface, at points midway between this point and the anterior extent of the band on the submental surface, and the inferior extent of the band on the anterior neck. The 2 large bands can be injected with 20 units each and smaller bands with 5 units each.
Most patients require a total of 50-100 units, and some require as many as 200 units. Use caution to inject the platysma muscles and not the muscles beneath them, since this is more likely to cause swallowing weakness. Complications are minimal and may include transient edema and ecchymoses, hematoma formation, muscle soreness, and mild neck weakness.
Contraindications include prior allergic reaction, injection into areas of infection or inflammation, pregnancy (category C - safety for use during pregnancy has not been established), or breastfeeding. Women who inadvertently were injected during pregnancy thus far have had uneventful deliveries, and to date no teratogenicity has been attributed to botulinum toxin. Nonetheless, it is a category C medication, and delay of injections is recommended until pregnancy is complete and breastfeeding has ended.
Relative contraindications
Treat patients with diseases of the neuromuscular junction (eg, myasthenia gravis) cautiously because underlying generalized weakness can be exacerbated, and local weakness at injection sites can occur more than otherwise expected. Some medications decrease neuromuscular transmission and generally should be avoided in patients treated with botulinum toxin. These include aminoglycosides, penicillamine, quinine, and calcium channel blockers.
Other considerations
Single-fiber EMG studies have detected neuromuscular changes far removed from injection sites. This likely reflects hematogenous spread of a small amount of toxin and is not of known clinical significance. Avoid intravascular injections because diffuse spread of large amounts of toxin can mimic the symptoms of botulism.
Complications
Generalized idiosyncratic reactions are uncommon, generally mild, and generally transient. These include nausea, fatigue, malaise, flulike symptoms, and rashes at sites distant from the injections. Untoward sequelae caused by percutaneous injection include pain, edema, erythema, ecchymosis, headache, and hypesthesia. These also are generally mild and transient. The most common meaningful adverse effect is unwanted weakness. Fortunately, unwanted weakness caused by the action of the toxin usually resolves in several months and in some patients in a few weeks, depending on the site, strength of the injections, and the muscles made excessively weak.
Carefully counsel patients who depend on emotive expression, such as actors and politicians, about a potential reduction in facial expression. Excess weakness following frontalis injection may cause paralysis rather than weakening of the muscle. Patients report they appear masklike and their brow feels heavy. If brow ptosis occurs, a hooded appearance may be present, and occasionally vision may be partially obstructed. Therefore, avoiding use of overly large doses and restricting injections to 1 cm above the eyebrow are important. If the lateral fibers of the frontalis have not been injected appropriately, a quizzical appearance may result in which the lateral brow is pulled up while the central brow is lowered. Inject a small amount of toxin into the lateral fibers to treat this.
Note the clear distinction between hyperfunctional brow lines with no underlying brow ptosis versus frontalis contraction to elevate ptotic brows. If botulinum toxin is used in the latter case, brow ptosis is likely. The brow depressors generally can be paralyzed to treat glabellar lines. However, ptosis of the upper eyelid is a common complication following injection in this region. This may occur as late as 2 weeks after injection. Ptosis is caused by migration of toxin through the orbital septum. Patients often are instructed to remain in an upright position for 3-4 hours following injection and to avoid manual manipulation of the area. Active contraction of the muscles under treatment may increase the uptake of toxin and decrease its diffusion.
To avoid ptosis, place injections 1 cm above the eyebrow and do not cross the midpupillary line. Ptosis can be treated with apraclonidine 0.5% eyedrops. This is an alpha2-adrenergic agonist, which causes Müller muscles to contract. Apraclonidine is contraindicated in patients with documented hypersensitivity. Phenylephrine (Neo-Synephrine) 2.5% can be used when apraclonidine is not available. Neo-Synephrine is contraindicated in patients with narrow-angle glaucoma and in patients with aneurysms. Use 1-2 drops 3 times daily until ptosis resolves.
Weakness of the lower eyelid or lateral rectus can occur following injection of the lateral orbicularis oculi. If severe lower lid weakness occurs, an exposure keratitis may result. If the lateral rectus is weakened, diplopia results. Treatment is symptomatic. Avoid these complications by injecting at least 1 cm lateral to the lateral canthus and above the zygomatic arch.
Injection of platysma muscles can result in dysphagia from diffusion of toxin into muscles of deglutition. When this occurs, it usually lasts only a few days or weeks. Some patients may require soft foods. Although swallowing weakness does not herald systemic toxicity, if it is severe, patients may be at risk of aspiration; seek consultation.
Some patients experience neck weakness, which is especially noticeable when attempting to raise the head from a supine position. This occurs after weakening of the sternocleidomastoid muscles, either from direct injection or diffusion. This is more common in women with long thin necks.
Avoid these adverse effects by using the lowest effective doses and precisely placing toxin into the platysma.
Therapeutic failure
Some patients do not respond to injections and, having never previously responded, are designated as primary nonresponders. Lack of response has many potential causes. Patients with rhytides that are not dynamic in origin (eg, photodamage, age-related changes) do not respond. Possibly, the injection technique was inadequate or the toxin denatured. Theoretically, some patients may have neutralizing antibodies from prior subclinical exposure, or individual variations in docking proteins may exist. A test dose of 15 units in the frontalis muscle should indicate whether the patient experiences a physiologic response (weakness) to toxin.
Secondary nonresponders respond initially but lose the response on subsequent injections. Most of these patients may have developed neutralizing antibodies.
Some patients injected for cosmetic purposes develop neutralizing antibodies. When a patient loses his or her response, serum can be tested for neutralizing antibodies, although this rarely is performed outside research settings. Alternatively, a patient's physiologic response can be evaluated with a single injection of 15 units into the frontalis on one side.
Limited information is available as to whether neutralizing antibodies resolve over time and, consequently, whether attempts at reinjection should be made after a prolonged period. Using the lowest dose of toxin necessary to achieve the desired clinical effect and avoiding reinjection within 1 month appear prudent in an effort to keep antibody formation as low and unlikely as possible.
For excellent patient education resources, visit eMedicine's Procedures Center. Also, see eMedicine's patient education article BOTOX® Injections.
Introduction
Botulinum neurotoxin is the most poisonous substance known. If inhaled, 1 ug would kill a person.1 It exerts its effect by paralyzing striated muscles or the autonomic-innervated muscles. The muscle paralyzing feature of botulinum toxin, when used beneficially, has proven to be useful in more than 50 pathological conditions, including cosmetic applications. Today, botulinum neurotoxin injection is the most commonly performed cosmetic procedure in the world.
Before BOTOX® treatment. Image courtesy of Allergan, Inc.
After BOTOX® treatment. Image courtesy of Allergan, Inc.
Botulism is a bilaterally symmetric descending neuroparalytic illness caused by botulinum neurotoxin. The German physician and poet Justinus Kerner published the first full description of clinical symptoms of food-borne botulism from 1817-1822.2 His observations followed an increase in food poisoning in Stuttgart from 1795-1813 caused by general economic hardship related to the Napoleonic wars and a decline in hygienic measures of food production and handling. The illness became known as "sausage poisoning" because it was observed to follow ingestion of spoiled sausage. The word botulism comes from the Latin botulus, meaning sausage.
Kerner deduced that the toxin acts by interrupting signal transmission within the peripheral and sympathetic nervous system, leaving sensory transmission intact. He also hypothesized possible therapeutic uses of the sausage toxin. In 1895, the microbiologist Emile-Pierre van Ermengen discovered the association with an anaerobic bacterium during an outbreak of botulism following a funeral ceremony in the Belgian village of Ellezelles.
When foods tainted with neurotoxin are ingested, the neurotoxin is absorbed and spread hematogenously to peripheral cholinergic nerve terminals, where it blocks the release of acetylcholine. The neurotoxin is heat labile and denatured by cooking. Sporadic outbreaks of botulism in the United States occur after ingestion of home-canned foods, meat products, and preserved fish. The incubation period following ingestion is 18-36 hours.
In contrast, infant botulism is caused by colonization of the gut by C botulinum, and subsequent production and absorption leads to absorption of the toxin. Honey consumption has been implicated in infant botulism, and microbiologic surveys have identified clostridial spores (mostly type B) in up to 25% of honey products.
Wound botulism may occur if the organism infects a wound and produces the toxin. The clinical syndrome of botulism is one of progressive muscle weakness, often beginning in the extraocular or pharyngeal muscles and becoming generalized. GI tract complaints may be prominent. Dilated unreactive pupils are common, and mucous membranes are often dry and erythematous. No sensory signs are associated, and alertness is maintained as long as respiration is adequate.
In 1946, Schantz helped isolate botulinum toxin type A in crystalline form. In the early 1970s, Scott experimented with botulinum toxin type A in monkeys for the treatment of strabismus. In 1977-1978, he performed trials in patients with strabismus. In the mid 1980s, he treated an individual with botulinum toxin for cosmetic reasons. Carruthers, Carruthers, Brin, and the Columbia University group noticed cosmetic improvement following botulinum toxin injection for facial dystonias and began pursuing this line of investigation in the late 1980s and early 1990s.3,4
Botulinum toxins currently are used to treat various disorders, including strabismus, hemifacial spasms, focal dystonias (eg, blepharospasm, torticollis, spasmodic dysphonia, limb dystonia, writer's cramp), spasticity, tremor, tics, synkinesis, hyperhidrosis, achalasia, and sphincter dysfunction. They are being evaluated to treat headaches and pain syndromes.
BOTOX® (botulinum toxin type A) is currently approved by the US Food and Drug Administration (FDA) for the treatment of blepharospasm and strabismus associated with dystonias (including benign essential blepharospasm or cranial nerve VII disorders) in patients aged 12 years or older, and for the treatment of cervical dystonia in adults. Myobloc (botulinum toxin type B) is currently FDA-approved for the treatment of cervical dystonia. Injection of botulinum toxins for cosmesis is currently considered off-label use but constitutes the most prevalent use of these injections.
Mechanism of action
Botulinum toxins block acetylcholine release, causing a chemical denervation. Neurotransmission at the neuromuscular junction involves the release of acetylcholine from the presynaptic nerve terminal. Acetylcholine release requires docking and binding of the neurotransmitter vesicles to the presynaptic membrane.
Several different proteins mediate this process. N -ethylmaleimide-sensitive fusion protein (NSF) is a cytoplasmic protein that is part of the fusion complex. Soluble N -ethylmaleimide-sensitive fusion–attachment proteins (SNAPs) are found in the cytoplasm and serve as attachment and stabilizing proteins for the NSF complex. SNAP receptors (SNAREs) are found on the vesicle and plasma membranes. SNAREs include vesicle-associated membrane protein (VAMP/synaptobrevin) and the plasma proteins SNAP-25 and syntaxin.
Botulinum toxin is a zinc-dependent endopeptidase made up of a light (50 kilodaltons [kDa]) and a heavy (100 kDa) chain linked by disulfide bonds.
The mechanism of action includes the following 4 key steps:
The 4-step process by which botulinum toxin reduces neuromuscular activity: (a) Normally functioning neuromuscular junction; (b) Binding step: The binding of botulinum dichain as the 100-kDa heavy chain binds to the cholinergic site on the cell membrane of the presynaptic cholinergic motor nerve terminal at a neuromuscular junction; (c) Internalization: The invagination of the cell membrane around the toxin molecule produces small endocytic vesicles within the cytoplasm of a motor nerve terminal; (d) Translocation step: Penetration and translocation of the neurotoxin 30-kDa light chain domain across the endosomal membrane of the endocytic vesicle into the cytosol of the motor nerve terminal; Blocking step: The neurotoxin 50-kDa light chain domain impedes the fusion of the acetylcholine vesicles on the inner side of the nerve terminal plasma membrane and the exocytosis of acetylcholine and its release into the synaptic cleft, preventing muscle contraction (Bendetto AV, 1999).
- The first step is binding of the toxin to specific receptors on the surface of the presynaptic cell surface, mediated by the C-terminal half of the heavy chain. This step occurs over approximately 30 minutes.
- The second step is internalization, an energy-dependent receptor-mediated endocytic process. In this step, the plasma membrane of the nerve cell invaginates around the toxin-receptor complex, forming a toxin-containing vesicle inside the nerve terminal.
- The third step is translocation. After internalization, the disulfide bond is cleaved, and the 50-kDa light chain of the toxin molecule is released across the endosomal membrane of the endocytic vesicle into the cytoplasm of the nerve terminal.
- The final step is blocking. The 50-kDa light chain of serotypes A and E inhibit acetylcholine release by cleaving a cytoplasmic protein (SNAP-25) required for the docking of acetylcholine vesicles on the inner side of the nerve terminal plasma membrane. Botulinum toxin type D is specific for VAMP/synaptobrevin. Botulinum toxin types B and F also affect the VAMP/synaptobrevin protein. These actions impede the release of acetylcholine into the synaptic cleft.
The development of extrajunctional acetylcholine receptors and expansion of the motor endplate occur after an injection of BOTOX®. (a) An axon terminal proliferating external collateral sprouts. (b) A single nerve sprout reestablishing a new neuromuscular junction results in the return of muscle activity (Bendetto AV, 1999).
After several months, the inactivated terminals slowly recover function, and the new sprouts and end plates regress. Recovery of inactivated terminals appears to be the basis of the loss of clinical effect several months after injection.
Botulinum Toxin
DoseThe dose of botulinum toxin is expressed in mouse units. One unit is equal to the amount that kills 50% of a group of 18- to 22-g Swiss Webster mice when injected intraperitoneally. The human lethal dose (LD) for BOTOX® (botulinum type A purified neurotoxin complex) is estimated at approximately 3000 units. BOTOX® injections of less than 100 units usually are used for cosmetic purposes and of less than 300-600 units for other purposes, thereby allowing a wide safety margin. Recognizing that doses are not interchangeable among different formulations of botulinum toxin (BOTOX®, Dysport, Myobloc) is important; to achieve similar clinical effects, different doses are used.
Botulinum toxin formulations
BOTOX® is a sterile lyophilized form of botulinum toxin type A. It is produced from a culture of the Hall strain of C botulinum and purified by a series of acid precipitations to a crystalline complex containing the toxin and other proteins. The FDA approved BOTOX® in December 1989 as an orphan drug for the treatment of strabismus, hemifacial spasms, and blepharospasm. BOTOX® is distributed in 100-unit vials.
The original batch of neurotoxin prepared by Shantz in November 1979 (designated batch 79-11) constituted the original BOTOX® formulation and was used until December 1997. It was replaced by a new neurotoxin complex batch designated BCB 2024. The new bulk batch is 5-6 times more potent on a weight basis. In a 100-unit vial, only 4.8 ng of neurotoxin is needed compared to 25 ng of 79-11. The new BOTOX® is comparable in clinical efficacy and safety to the old, and a unit dose of new BOTOX® provides an equivalent response to the same unit dose of old BOTOX®. The reduced protein load of the new BOTOX® has been hypothesized to lead to reduced immunogenicity and a lower incidence of neutralizing antibody formation.
Dysport is another formulation of botulinum toxin type A available in Europe and a few other countries. It is prepared using column-based purification techniques and distributed in 500-unit vials that can be stored at room temperature. BOTOX® and Dysport are both botulinum toxin type A preparations but are quite distinct from one another. BOTOX® is approximately 4 times more potent on a per unit basis, and Dysport doses often are approximately 4 times the BOTOX® doses used to generate a similar clinical effect. Differences in these toxins may relate to differences in the strain of bacterium, preparation, diffusion, and potency testing.
Myobloc is a botulinum toxin type B preparation that is approved for the treatment of cervical dystonia. It is distributed as a solution. Little information is available concerning the cosmetic use of Dysport and Myobloc. The remainder of this article therefore focuses on BOTOX®, and all unit doses refer to BOTOX® unless otherwise specified.
Reconstitution and storage
Store BOTOX® in a freezer at or below -5°C. The package insert for BOTOX® recommends dilution with sterile nonpreserved saline. Studies have demonstrated that preserved saline provides increased patient comfort without decreasing efficacy.5 The practice of adding lidocaine to BOTOX® has been abandoned following an unrelated death.6 Topical anesthetics are dilators (with the exception of cocaine) and, therefore, may increase migration of BOTOX® to unwanted areas.7
For the purposes of this section, botulinum toxin is described in units of the BOTOX® brand type A toxin. Oculoplastic specialists use a 1-mL dilution per 100 units of BOTOX®. Dermatologists and plastic surgeons tend to use a range from 1-4 mL per 100 units. More dilute concentration is preferable in order to increase migration (as in the forehead), whereas lower volumes are preferred to avoid migration into unplanned areas.8,9
BOTOX® is denatured easily by bubbling or agitation; gently inject the diluent onto the inside wall of the vial. Discard the vial if a vacuum does not pull the diluent in. The final dilution of BOTOX® is mostly a matter of personal preference; 100 units commonly are reconstituted in 1-10 mL of diluent. Theoretically, more concentrated solutions reduce reliability in delivering a specific unit dose, and more dilute solutions lead to greater diffusion of the toxin. The authors prefer to use 2 mL of diluent to prepare a solution of 5 U/0.1 mL (50 U in a 1-mL tuberculin syringe if that much is to be used). Use a 30-gauge 1-inch needle to perform the injections.
Once reconstituted, keep BOTOX® refrigerated at 2-8°C. The package insert indicates that reconstituted BOTOX® should be used within 4 hours. One study found no loss of activity at 6 hours but a 44% loss after 12 hours and a 70% loss with refreezing at 1-2 weeks. Other authors report no substantial loss of potency in a 10 U/1 mL reconstituted solution kept refrigerated for 1 month. Most practitioners discard unused reconstituted BOTOX® after 1-7 days.
General considerations in cosmetic use of BOTOX®
Aging is associated with the development of lines and wrinkles caused by actinic damage, gravitational effect, sleep lines, and muscular action. Mimetic facial musculature may undergo hypertrophy secondary to hyperfunctional pull. BOTOX® injections reduce facial lines caused by hyperfunctional muscles. They also are used to contour aspects of the face such as the brows.
Injection of the lower face requires a precise technique, since any asymmetry may result in facial asymmetry and speech impediments. Injection of the mid and lower face and neck is best reserved for experienced injectors and patients who have had successful injections in the upper face.7
Pretreatment photography is highly recommended to document any preexisting asymmetry. Patients should be informed that cosmetic injection in any site other than the glabella constitutes an off-label indication in the United States.7 An informed consent form is required, with detailed mention of possible complications, such as headache, bruising, infection, eyelid drooping, facial asymmetry, speech changes, and dysphagia.
Injection techniques often vary among practitioners and over time. Patients usually notice a clinical effect 1-3 days following injection, and the effect is maximal by 1-2 weeks. Some diffusion of toxin occurs. A 10-unit injection into the frontalis muscle produces a circular area of paresis with a radius of approximately 1.5 cm. Space injections apart appropriately, and do not place injections too close to muscles in which weakness is to be avoided.
Adverse effects of injection include minimal ecchymosis and bruising. Applying ice to the injection sites before and after treatment may decrease the pain and the risk of swelling and bruising. When not contraindicated, patients should avoid platelet inhibitors, including aspirin and nonsteroidal anti-inflammatory drugs, for 1 week prior to injection.
Set realistic expectations. The benefits usually last 3-6 months and then resolve. A clear plan should be devised to address the individual's anatomy and areas to be injected.
Cosmetic BOTOX® Injections of the Face
Horizontal Forehead Lines
Performing BOTOX® injections to treat horizontal forehead lines is relatively easy, and the result usually is quite satisfying. Treatment can include injections for glabellar frown lines when appropriate.Anatomy
The frontalis muscle elevates the eyebrows and the skin of the forehead. The fibers of the frontalis are oriented vertically, and wrinkles of the forehead are oriented horizontally. The frontalis muscle originates on the galea aponeurotica near the coronal suture and inserts on the superciliary ridge of the frontal bone and skin of the brow, interdigitating with fibers of the brow depressors (ie, procerus, corrugator supercilii, orbicularis oculi muscle).
Anatomy of frontalis, corrugator supercilii, procerus muscles, and other facial muscles.
The medial fibers usually are more fibrous than the lateral fibers, thus requiring less toxin for paralysis. Avoid total paralysis of the frontalis, since this is likely to cause brow ptosis and loss of expression. Injection too close to the lateral eyebrow can cause lateral eyebrow ptosis. Technique
Multiple injections of small amounts of toxin create weakness without total paralysis. Inject 3-5 sites on each side of the mid line, usually using 2 units (1-3 U) per site. Separate sites by 1-2 cm. Choose an initial injection site approximately 1 cm above the eyebrow vertical to the medial canthus. Additional sites diverge laterally and upward to the hairline in a "V" configuration, often for a total of 3 sites. Additional sites (1-3) can be added in the mid line or more laterally (1-2) depending on individual and clinical response.
If wrinkles extend to the temporal region, lateral injections can be performed. Use caution to prevent injecting lateral to the lateral canthus to avoid inhibiting temporalis function. Use caution when injecting patients in whom the hyperfunctional frontal lines support a ptotic upper eyelid.
Injections of the upper face and periocular region usually are performed with the patient seated, and the patient is asked to remain upright for 2-3 hours to prevent spread of toxin through the orbital septum.
Glabellar Frown Lines
Glabellar frown lines are the most common reason for cosmetic injection of BOTOX®.
(1) Botulinum toxin dose used to treat glabellar frown lines in an individual with an arched brow. The arch represents the bony rim, not the eyebrow. (2) Botulinum toxin dose used to treat glabellar frown lines in a woman with a more horizontal-type brow.
Facial rhytides and folds in this area result from action of the depressor muscles (ie, corrugator supercilii, depressor supercilii, orbicularis oculi, procerus).
Anatomy of frontalis, corrugator supercilii, procerus muscles, and other facial muscles.
The corrugator superciliaris, medial orbital portion of the orbicularis oculi, and more vertically oriented fibers of the depressor supercilii produce the vertical lines of the glabella. The corrugator muscle is a brow adductor moving the eyebrow downward and medially. It arises from the nasal bone just above the rim of the orbit medially and extends laterally and upward, inserting in the skin above the middle of the eyebrow. It lies deep to the frontalis, procerus, and orbicularis oculi muscles. The medial fibers of the orbicularis oculi originate from the medial orbital rim anterior to the origin of the corrugator. The fibers interdigitate with fibers of the frontalis, procerus, and corrugator muscles. The depressor supercilii originates from the nasal process of the frontal bone and inserts into the skin at the medial aspect of the eyebrow.
The vertically oriented procerus muscle, which originates from the upper nasal cartilage and the lower nasal bone, produces the horizontal lines of the glabella and nasal root. It inserts into the skin between the brows and the frontal belly of the occipitofrontalis. Its fibers interdigitate with those of the orbicularis, frontalis, and corrugator muscles.
Technique
Usually, 5 sites are injected with 4-6 units each for an average total dose of approximately 25 units. One site on each side is used to inject the corrugator, one site on each side is used to inject the orbicularis oculi and depressor supercilii, and one site is used to inject the procerus in the mid line.
The patient is asked initially to frown and scowl, and the target muscles are palpated. Place the first injection into the belly of the corrugator muscle. Insert the needle at the origin of the corrugator fibers just above the medial canthus and superciliary arch until bone is felt, and then withdraw it slightly. Advance the needle within the belly of the muscle upward and lateral as far as the medial third of the eyebrow, 1 cm superior to the orbital rim. Inject 4-6 units as the needle is withdrawn.
The next site is approximately 1 cm above the upper medial aspect of the supraorbital ridge. Advance the needle slightly in a vertical direction toward the hairline. Inject 4-6 units into the orbicularis oculi and depressor supercilii as the needle is withdrawn. Repeat these injections on the contralateral side.
Place the last injection into the belly of the procerus to eliminate the horizontal lines at the root of the nose. Inject 4-6 units at a point where 2 lines drawn at 45° from the medial aspect of the eyebrows converge in the center of the nasal root, just superior to the horizontal plane of the medial canthi. To avoid resultant accentuation of eyebrow arching in men, inject an additional 4-6 units 1 cm above the supraorbital prominence vertical to the mid point of the eyebrow.
In 1998, a dose/response study by Hankins et al of 46 women receiving BOTOX® for glabellar wrinkles found an effective starting dose from 2.5-4 units per injection site (12.5-20 U total).10
A glabellar "spread test" may be performed prior to injection by spreading the glabellar wrinkles apart with the thumb and index fingers. This may allow an estimate of the expected benefit from BOTOX® injection. Patients with thick sebaceous skin and deep dermal scarring that are not improved with manual spreading usually respond poorly to botulinum toxin injections. EMG guidance may provide valuable information when initial injections prove unsatisfactory.
Some patients may need evaluation for medial recruitment from the mid brow. Medial recruitment is caused by hyperfunctional orbicularis oculi fibers just below the mid eyebrow. This population of patients may not favorably respond to BOTOX®, as the injection may lead to depression of the medial and lateral brow.7
A recent study has demonstrated that injecting 3 essential sites in the procerus and the corrugator muscles is essential for the treatment of glabellar wrinkles, while 2 additional forehead region injections did not significantly improve efficacy.11
One study has demonstrated that glabellar line treatment may help convey positive and relaxed emotions more accurately.12
Lateral Canthal Lines
Aging and photodamage cause much of the wrinkling in this area. However, the component of hyperfunctional contraction of the lateral aspect of the orbicularis oculi is targeted for improvement with BOTOX® injections.Anatomy
The lateral fibers of the orbicularis oculi are arranged in a circular pattern around the eye. Contraction of these fibers produces wrinkles that extend radially from the region of the lateral canthus.
Technique
Perform 3 or 4 subcutaneous injections approximately 1 cm lateral to the lateral orbital rim using 2-3 units per injection site (for a total of 6-12 U per side). Space sites 0.5-1 cm apart in a vertical line or slightly curving arch. Doses that are too high or injections that are too medial can lead to eyelid ptosis or diplopia.
Other Cosmetic Uses of BOTOX® Injections of the Face
Temporal brow liftWith age, the lateral eyebrow typically becomes ptotic before the medial aspect. The lateral brow is more affected by the gravitational descent of the temporal soft tissue mass and the downward force of the corrugator supercilii and orbicularis oculi muscles. Temporal brow lift can be achieved by BOTOX® injections into the lateral brow depressors. Ahn et al treated patients seeking elevation in eyebrow height with 7-10 units of BOTOX® injected into the superolateral portion of the orbicularis oculi below the lateral third of the brow. Mean brow height increased 1.0 mm at the mid pupil and 4.8 mm at the lateral canthus (P = 0.038 and 0.0001, respectively). Injecting superior and lateral to the orbital rim minimized the potential for ptosis.
Levator labia superioris
Contraction of this muscle is observed when an individual "scrunches" his or her nose, and hyperfunctional contraction often confers a "mad dog" appearance to the face. This muscle can be injected with 2-5 units of BOTOX® on each side of the nose lateral to the nasion.
Nasal flare
Several patients with undesirable nasal flare have been treated successfully with serial BOTOX® injections.
Mental crease
Reduction of a prominent mental crease can be achieved by injection of 5-10 units of BOTOX® into the point of the chin.
Facial asymmetry
Injections of BOTOX® can improve facial asymmetry and synkinesis. The asymmetry of residual unilateral paresis can be reduced by judicious injection of normal muscles on the unaffected side. Hyperkinesis from aberrant degeneration can be reduced by injection of hyperkinetic muscles.
Upper lip wrinkling
Optimally treat multiple fine wrinkles using a filler substance such as injectable collagen or by middepth or deeper resurfacing. These fine wrinkles do not respond well to BOTOX® injections, and the upper lip is sensitive to paresis. However, botulinum toxin injections may be used in individuals with 2 or 3 deep wrinkles. Small doses of botulinum toxin (0.5-1 U per wrinkle) may be administered, injected superficially rather than deeply. Avoiding weakness of the upper lip is important.
Depressor anguli oris
To weaken the depressor anguli oris, which is the underlying muscle of the downturn at the corner of the mouth, 2-3 units of botulinum toxin may be injected. Instruct the individual to forcibly pull down the corners of the mouth; the depressor anguli oris can be felt inferior to a point 1 cm lateral to the commissure.
Nasolabial folds
Carruthers and Carruthers, attempting to soften the nasolabial fold, injected low doses (2-3 U) of BOTOX® in the levator labii superioris alaeque nasi.4 EMG localization of the muscle was used. Some of the individuals who had softening of the folds showed lengthening of the upper lip. In general, achieving a good result in attempting to soften the nasolabial fold is difficult.
Adjunctive use of BOTOX® injections
BOTOX® injections may be used to provide presurgical chemodenervation of the brow depressor muscles, giving better results with surgical repositioning of the brow. Pretreatment of crow's feet allows the surgeon to better define the incision line within the confines of the bony orbital margin.
Cosmetic Use of BOTOX® Injections for the Aging Neck
Anatomy of the platysma and lip depressor musclesThe platysma muscle originates inferiorly from the pectoralis and deltoid fascia. It crosses the sternocleidomastoid at the midlateral neck area at the Erb point. In 75% of individuals, the platysmal fibers interface with those on the opposite side 1-2 cm below the chin. In 15% of individuals, the fibers interdigitate at the level of the thyroid cartilage and cover the submental area confluently, forming one band. In 10% of individuals, the fibers do not decussate with those on the opposite side.
(A) The platysma muscle is joined together at the anterosuperior neck two thirds of the time. This crisscross or decussation usually covers approximately one half the distance from the chin to the hyoid bone. (B) One third of the time, the decussations are absent, or a complete separation occurs.
The anatomy of the muscles of the lower lip can be represented as 2 split Ms covering each other. These 2 Ms act in concert to open, contract, depress, and animate the lower lip. The deeper M is the central mentalis muscle that contracts the chin and helps raise it. This muscle responds well to botulinum A toxin injections. The lateral limb is the depressor labii inferioris (DLI). This lowers the lower lip. The more superficial and more widely split M represents the platysma muscle, which inserts into the lateral chin and commissure of the mouth. The depressor anguli oris (DAO) pulls down the corner of the mouth. EP - Topographic point to inject local anesthetic; PB - Platysma band injected in patients with hypertrophied or sagging muscle; SG - Submandibular gland; SN - Sternal notch; SCM - Sternocleidomastoid muscle; MB - Mandibular border.
Several factors affect aging of the neck, including heredity, actinic damage, and weight changes. Age-related downward pull of the platysma muscle creates vertical fibrous bands. The skin laxity over the platysma muscle produces horizontal rhytides. The inferior pull of the platysma-SMAS complex, together with the age-related skin and muscular degeneration, causes the largest submental fat pad to herniate between the 2 free borders of the platysma muscle.
Cosmetic BOTOX® injection of the neck
Injections generally are considered most appropriate for older patients who are not candidates for surgery, older patients who previously have had neck rejuvenation surgery without relapse or severe neck skin excess, and younger patients with strong platysmal bands who are not yet surgical candidates. They also can be used to improve the cosmetic outcome after rhytidectomy. Younger patients have a noticeably better result, as do older patients who have had prior surgery. Patients exhibit greater improvement during animation than in repose. Kane noted in 1999, "Although most of the patients were very happy with their results, even the best results in no way approached the most disappointing results obtained by means of surgical manipulation of the platysma and neck skin."13
Injection technique
After preparing the skin, ask the patient to contract the platysma muscle; this identifies its bands. Injection techniques vary among practitioners. Some use a few injections along the length of a band while others use many. Some practitioners use EMG guidance, although this usually is not necessary. One technique involves injecting each band at 1.0- to 1.5-cm intervals from the jawline to the lower neck. Approximately 3-10 units may be injected, depending on the thickness of the platysmal band.
Another technique involves injecting the bands at the following 3 sites: the curve between the horizontal submental surface and the vertical anterior surface, at points midway between this point and the anterior extent of the band on the submental surface, and the inferior extent of the band on the anterior neck. The 2 large bands can be injected with 20 units each and smaller bands with 5 units each.
Most patients require a total of 50-100 units, and some require as many as 200 units. Use caution to inject the platysma muscles and not the muscles beneath them, since this is more likely to cause swallowing weakness. Complications are minimal and may include transient edema and ecchymoses, hematoma formation, muscle soreness, and mild neck weakness.
Contraindications and Complications of BOTOX® Injections
Contraindications to BOTOX® injectionsContraindications include prior allergic reaction, injection into areas of infection or inflammation, pregnancy (category C - safety for use during pregnancy has not been established), or breastfeeding. Women who inadvertently were injected during pregnancy thus far have had uneventful deliveries, and to date no teratogenicity has been attributed to botulinum toxin. Nonetheless, it is a category C medication, and delay of injections is recommended until pregnancy is complete and breastfeeding has ended.
Relative contraindications
Treat patients with diseases of the neuromuscular junction (eg, myasthenia gravis) cautiously because underlying generalized weakness can be exacerbated, and local weakness at injection sites can occur more than otherwise expected. Some medications decrease neuromuscular transmission and generally should be avoided in patients treated with botulinum toxin. These include aminoglycosides, penicillamine, quinine, and calcium channel blockers.
Other considerations
Single-fiber EMG studies have detected neuromuscular changes far removed from injection sites. This likely reflects hematogenous spread of a small amount of toxin and is not of known clinical significance. Avoid intravascular injections because diffuse spread of large amounts of toxin can mimic the symptoms of botulism.
Complications
Generalized idiosyncratic reactions are uncommon, generally mild, and generally transient. These include nausea, fatigue, malaise, flulike symptoms, and rashes at sites distant from the injections. Untoward sequelae caused by percutaneous injection include pain, edema, erythema, ecchymosis, headache, and hypesthesia. These also are generally mild and transient. The most common meaningful adverse effect is unwanted weakness. Fortunately, unwanted weakness caused by the action of the toxin usually resolves in several months and in some patients in a few weeks, depending on the site, strength of the injections, and the muscles made excessively weak.
Carefully counsel patients who depend on emotive expression, such as actors and politicians, about a potential reduction in facial expression. Excess weakness following frontalis injection may cause paralysis rather than weakening of the muscle. Patients report they appear masklike and their brow feels heavy. If brow ptosis occurs, a hooded appearance may be present, and occasionally vision may be partially obstructed. Therefore, avoiding use of overly large doses and restricting injections to 1 cm above the eyebrow are important. If the lateral fibers of the frontalis have not been injected appropriately, a quizzical appearance may result in which the lateral brow is pulled up while the central brow is lowered. Inject a small amount of toxin into the lateral fibers to treat this.
Note the clear distinction between hyperfunctional brow lines with no underlying brow ptosis versus frontalis contraction to elevate ptotic brows. If botulinum toxin is used in the latter case, brow ptosis is likely. The brow depressors generally can be paralyzed to treat glabellar lines. However, ptosis of the upper eyelid is a common complication following injection in this region. This may occur as late as 2 weeks after injection. Ptosis is caused by migration of toxin through the orbital septum. Patients often are instructed to remain in an upright position for 3-4 hours following injection and to avoid manual manipulation of the area. Active contraction of the muscles under treatment may increase the uptake of toxin and decrease its diffusion.
To avoid ptosis, place injections 1 cm above the eyebrow and do not cross the midpupillary line. Ptosis can be treated with apraclonidine 0.5% eyedrops. This is an alpha2-adrenergic agonist, which causes Müller muscles to contract. Apraclonidine is contraindicated in patients with documented hypersensitivity. Phenylephrine (Neo-Synephrine) 2.5% can be used when apraclonidine is not available. Neo-Synephrine is contraindicated in patients with narrow-angle glaucoma and in patients with aneurysms. Use 1-2 drops 3 times daily until ptosis resolves.
Weakness of the lower eyelid or lateral rectus can occur following injection of the lateral orbicularis oculi. If severe lower lid weakness occurs, an exposure keratitis may result. If the lateral rectus is weakened, diplopia results. Treatment is symptomatic. Avoid these complications by injecting at least 1 cm lateral to the lateral canthus and above the zygomatic arch.
Injection of platysma muscles can result in dysphagia from diffusion of toxin into muscles of deglutition. When this occurs, it usually lasts only a few days or weeks. Some patients may require soft foods. Although swallowing weakness does not herald systemic toxicity, if it is severe, patients may be at risk of aspiration; seek consultation.
Some patients experience neck weakness, which is especially noticeable when attempting to raise the head from a supine position. This occurs after weakening of the sternocleidomastoid muscles, either from direct injection or diffusion. This is more common in women with long thin necks.
Avoid these adverse effects by using the lowest effective doses and precisely placing toxin into the platysma.
Therapeutic failure
Some patients do not respond to injections and, having never previously responded, are designated as primary nonresponders. Lack of response has many potential causes. Patients with rhytides that are not dynamic in origin (eg, photodamage, age-related changes) do not respond. Possibly, the injection technique was inadequate or the toxin denatured. Theoretically, some patients may have neutralizing antibodies from prior subclinical exposure, or individual variations in docking proteins may exist. A test dose of 15 units in the frontalis muscle should indicate whether the patient experiences a physiologic response (weakness) to toxin.
Secondary nonresponders respond initially but lose the response on subsequent injections. Most of these patients may have developed neutralizing antibodies.
Immunologic Considerations
An estimated 5-15% of patients injected serially with 79-11 BOTOX® developed secondary nonresponsiveness from the production of neutralizing antibodies. Risk factors associated with the development of neutralizing antibodies include injection of more than 200 units per session and repeat or booster injections given within 1 month of treatment. The newer BCB 2024 BOTOX® appears to have a lower potential to induce antibody production because of its decreased protein load. In rabbit studies, no antibody formation occurred with new BOTOX® after 6 months of treatment, while 79-11 old BOTOX® caused antibody formation in all rabbits by 5 months. Recent studies by Dressler et al suggest that the rate of developing neutralizing antibodies is substantially reduced with BSB 2024.14 In addition, Jankovic reported that the new formulation of BOTOX® reduced the frequency of antibodies 6-fold.15Some patients injected for cosmetic purposes develop neutralizing antibodies. When a patient loses his or her response, serum can be tested for neutralizing antibodies, although this rarely is performed outside research settings. Alternatively, a patient's physiologic response can be evaluated with a single injection of 15 units into the frontalis on one side.
Limited information is available as to whether neutralizing antibodies resolve over time and, consequently, whether attempts at reinjection should be made after a prolonged period. Using the lowest dose of toxin necessary to achieve the desired clinical effect and avoiding reinjection within 1 month appear prudent in an effort to keep antibody formation as low and unlikely as possible.
Conclusion
To choose the most appropriate treatment for lines of the face, distinguish between rhytides created by loss of collagen or elastic fibers, loss of fat, redundant folds, and facial lines caused by hyperfunctional muscles. BOTOX® injected in small amounts into the face and neck muscles can improve the appearance of facial lines and platysma bands of the neck for several months. Adverse effects are usually mild and transient. The most common substantive complication is excessive or unwanted weakness, and this resolves as the action of the toxin is lost. Brow ptosis, eyelid ptosis, neck weakness, dysphagia, and diplopia may occur. Knowledge of the functional anatomy and experience with the procedure help injectors avoid complications. The clinical benefit is extremely gratifying, especially when used for hyperfunctional lines of the upper face.For excellent patient education resources, visit eMedicine's Procedures Center. Also, see eMedicine's patient education article BOTOX® Injections.
Multimedia
| | Media file 1: The 4-step process by which botulinum toxin reduces neuromuscular activity: (a) Normally functioning neuromuscular junction; (b) Binding step: The binding of botulinum dichain as the 100-kDa heavy chain binds to the cholinergic site on the cell membrane of the presynaptic cholinergic motor nerve terminal at a neuromuscular junction; (c) Internalization: The invagination of the cell membrane around the toxin molecule produces small endocytic vesicles within the cytoplasm of a motor nerve terminal; (d) Translocation step: Penetration and translocation of the neurotoxin 30-kDa light chain domain across the endosomal membrane of the endocytic vesicle into the cytosol of the motor nerve terminal; Blocking step: The neurotoxin 50-kDa light chain domain impedes the fusion of the acetylcholine vesicles on the inner side of the nerve terminal plasma membrane and the exocytosis of acetylcholine and its release into the synaptic cleft, preventing muscle contraction (Bendetto AV, 1999). |
| | Media file 2: The development of extrajunctional acetylcholine receptors and expansion of the motor endplate occur after an injection of BOTOX®. (a) An axon terminal proliferating external collateral sprouts. (b) A single nerve sprout reestablishing a new neuromuscular junction results in the return of muscle activity (Bendetto AV, 1999). |
| | Media file 3: The anatomy of the muscles of the lower lip can be represented as 2 split Ms covering each other. These 2 Ms act in concert to open, contract, depress, and animate the lower lip. The deeper M is the central mentalis muscle that contracts the chin and helps raise it. This muscle responds well to botulinum A toxin injections. The lateral limb is the depressor labii inferioris (DLI). This lowers the lower lip. The more superficial and more widely split M represents the platysma muscle, which inserts into the lateral chin and commissure of the mouth. The depressor anguli oris (DAO) pulls down the corner of the mouth. EP - Topographic point to inject local anesthetic; PB - Platysma band injected in patients with hypertrophied or sagging muscle; SG - Submandibular gland; SN - Sternal notch; SCM - Sternocleidomastoid muscle; MB - Mandibular border. |
| | Media file 4: (1) Botulinum toxin dose used to treat glabellar frown lines in an individual with an arched brow. The arch represents the bony rim, not the eyebrow. (2) Botulinum toxin dose used to treat glabellar frown lines in a woman with a more horizontal-type brow. |
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 | Media file 6: Diagram of the botulinum toxin injection points of the lateral canthus. |
 | Media file 7: (a) Diagram of the 7 sites into which botulinum toxin is injected into the glabella of men; (b) Diagram of the 5 sites into which botulinum toxin is injected into the glabella of women. |
| | Media file 8: (A) The platysma muscle is joined together at the anterosuperior neck two thirds of the time. This crisscross or decussation usually covers approximately one half the distance from the chin to the hyoid bone. (B) One third of the time, the decussations are absent, or a complete separation occurs. |
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| | Media file 10: After BOTOX® treatment. Image courtesy of Allerg |
Liposuction, Trunk
Liposuction, Trunk
Liposuction has become the most popular cosmetic procedure performed by board-certified plastic surgeons in the United States.1 Although liposuction is not a technically difficult procedure, it requires thoughtful planning and an artistic eye to achieve aesthetically pleasing postoperative results. The goal of the liposuction surgeon is to remove "target" fat, leaving the desired body contour and smooth transitions between suctioned and nonsuctioned areas. Careful selection of patients and proper surgical technique help avoid contour irregularity, and diligent perioperative care of the patient helps avoid postoperative complications.
In 1978, Kesselring and Meyer reported the use of a suction-assisted curettage method in which sharp curettage and strong suction were employed to remove fat.3 In the early 1980s, surgeons such as Illouz and Fournier began using suction cannulae without sharp curettage to remove subcutaneous fat.4,5 Illouz, in the early part of 1980, also introduced the concept of "wet" liposuction. This technique incorporates an injection of saline into the subcutaneous space before performing liposuction. He found this reduced blood loss and assisted in obtaining smoother, more satisfying results. This technique currently is used most often in liposuction procedures.
Traditional suction-assisted lipoplasty (SAL) became popular in the United States in the 1980s. It has a long track record and is considered the criterion standard tool for liposuction.6 Increased support for advancing this procedure to more complex cases has been demonstrated successfully when used in the proper patients. Ultrasound-assisted liposuction (UAL) was introduced in the United States in the mid 1990s to address some of the shortcomings of SAL. Interestingly, this procedure gained popularity quickly in the management of gynecomastia.
Ultrasonic medical devices have been used in other fields (eg, neurosurgery, otology, ophthalmology, urology) for a number of years and have proven to be extremely useful and safe. UAL has been used in tens of thousands of plastic surgery cases in Europe and in other countries outside of the United States for approximately 25 years. Plastic surgeons who have used these devices have been extremely enthusiastic about them,7 and they became more popular in the United States over the turn of the century. Some surgeons think that these devices are superior tools for sculpting and find less need for cross-tunneling compared with SAL.
A progressive accumulation of fat occurs intra-abdominally as a person ages. This intra-abdominal fat is not treated by liposuction, thus must be differentiated carefully from subcutaneous fat when evaluating a patient for surgery.
Modern liposuction techniques allow treatment of a much broader range of patients. New "super volume" liposuctions allow for treatment of patients with more generalized lipodystrophy. For more information, see eMedicine article Liposuction, Large Volume: Safety and Indications. In addition, ultrasound-assisted liposuction (UAL) has afforded good results in patients with fatty deposits that were poorly responsive to traditional liposuction. Although beyond the scope of this chapter, excisional surgery (eg, abdominoplasty or tummy tuck) has specific indications to treat problems such as severe skin laxity and truncal obesity in patients with poor skin elasticity. Excisional surgery and liposuction are often combined for an optimal result in certain patients.
Evaluation
A liposuction consultation should begin by asking the patient the following questions:
Liposuction has become the most popular cosmetic procedure performed by board-certified plastic surgeons in the United States.1 Although liposuction is not a technically difficult procedure, it requires thoughtful planning and an artistic eye to achieve aesthetically pleasing postoperative results. The goal of the liposuction surgeon is to remove "target" fat, leaving the desired body contour and smooth transitions between suctioned and nonsuctioned areas. Careful selection of patients and proper surgical technique help avoid contour irregularity, and diligent perioperative care of the patient helps avoid postoperative complications.
History of the Procedure
Accounts of human interest in body weight and contour can be found throughout history.2 Some of the simplest attempts to change body shape and appearance can be observed in the vast array of clothing used to hide, compress, and mold the human figure. Surgical procedures were devised to alter actual body shape permanently.2 In 1921, Dujarrier used an obstetric uterine curette to remove fat from the knees of a ballerina. The patient sustained irreparable injury and was left with the horrendous result of an eventual amputation.In 1978, Kesselring and Meyer reported the use of a suction-assisted curettage method in which sharp curettage and strong suction were employed to remove fat.3 In the early 1980s, surgeons such as Illouz and Fournier began using suction cannulae without sharp curettage to remove subcutaneous fat.4,5 Illouz, in the early part of 1980, also introduced the concept of "wet" liposuction. This technique incorporates an injection of saline into the subcutaneous space before performing liposuction. He found this reduced blood loss and assisted in obtaining smoother, more satisfying results. This technique currently is used most often in liposuction procedures.
Traditional suction-assisted lipoplasty (SAL) became popular in the United States in the 1980s. It has a long track record and is considered the criterion standard tool for liposuction.6 Increased support for advancing this procedure to more complex cases has been demonstrated successfully when used in the proper patients. Ultrasound-assisted liposuction (UAL) was introduced in the United States in the mid 1990s to address some of the shortcomings of SAL. Interestingly, this procedure gained popularity quickly in the management of gynecomastia.
Ultrasonic medical devices have been used in other fields (eg, neurosurgery, otology, ophthalmology, urology) for a number of years and have proven to be extremely useful and safe. UAL has been used in tens of thousands of plastic surgery cases in Europe and in other countries outside of the United States for approximately 25 years. Plastic surgeons who have used these devices have been extremely enthusiastic about them,7 and they became more popular in the United States over the turn of the century. Some surgeons think that these devices are superior tools for sculpting and find less need for cross-tunneling compared with SAL.
Problem
Fat is deposited in the subcutaneous layer in almost all areas of the body. Fat is a normal component of the subcutaneous tissue layer. Fat cells may not be distributed evenly, causing some areas to be more prominent than is ideal. Liposuction is a surgical procedure that attempts to contour specific areas of fat accumulation that patients see as undesirable.Frequency
According to the American Society for Aesthetic Plastic Surgery (ASAPS) 456,828 liposuction procedures were performed in the United States in 2007. Liposuction is the most commonly performed cosmetic procedure in the United States.1Pathophysiology
Patterns of fat distribution differ among races, ages, and sexes. The actual number of fat cells remains stable during adult life. The cells get larger with weight gain and smaller with weight loss. In general, women have a proportionately higher percentage of body fat than men. Women typically have a disproportionate number of fat cells in their hips, upper thighs, and buttock, while men tend to have a more even distribution of fat cells in the trunk. Also, liposuction is effective in changing contour because it permanently removes fat cells that are distributed unevenly. The remaining fat cells still can store fat. Therefore, liposuction affects weight distribution but cannot prevent further weight gain.A progressive accumulation of fat occurs intra-abdominally as a person ages. This intra-abdominal fat is not treated by liposuction, thus must be differentiated carefully from subcutaneous fat when evaluating a patient for surgery.
Indications
The ideal liposuction patient is healthy, eats a well-balanced diet, has good skin elasticity, desires treatment of minimal-to-moderate localized fat deposits, and is within 20-30% of ideal body weight. Note localized excess fat on the hips, inner thighs, and outer thighs in the image below.
Liposuction, trunk. Frontal view of patient before tumescent suctioning. Note the excess fat on the hips, inner thighs, and outer thighs.
Modern liposuction techniques allow treatment of a much broader range of patients. New "super volume" liposuctions allow for treatment of patients with more generalized lipodystrophy. For more information, see eMedicine article Liposuction, Large Volume: Safety and Indications. In addition, ultrasound-assisted liposuction (UAL) has afforded good results in patients with fatty deposits that were poorly responsive to traditional liposuction. Although beyond the scope of this chapter, excisional surgery (eg, abdominoplasty or tummy tuck) has specific indications to treat problems such as severe skin laxity and truncal obesity in patients with poor skin elasticity. Excisional surgery and liposuction are often combined for an optimal result in certain patients.
Evaluation
A liposuction consultation should begin by asking the patient the following questions:
- What would you like to change about your body?
- What is your current weight?
- How long have you been at this weight?
- Have you had any significant weight gains or losses?
- What is your current diet and exercise regimen?
- For how long have you maintained this regimen?
- Have you taken any diet pills to assist with weight reduction?
- Have you had previous liposuction?
- How will your life responsibilities allow for recovery time?
Relevant Anatomy
Two main layers of subcutaneous fat, deep and superficial, are present. Liposuction primarily is focused on the deeper layer of fat, since suctioning is safer and easier there. Suctioning in the superficial layer allows the surgeon to achieve subtle benefits in the procedure8 but, because of its superficial location, increases risks of contour irregularities and injury to the skin. Others claim that superficial liposuction enhances skin retraction.Contraindications
Liposuction carries greater risk for patients with significant medical problems. Heart disease, lung disease, diabetes, and peripheral vascular disease pose serous risk during any surgical procedure. Smoking or a recent history of smoking is a strong risk factor. Patients who have undergone previous surgery in the area to be contoured are at risk of surgical complications during liposuction. Surgery alters the local anatomy and distorts the normal subcutaneous planes in which liposuction is performed, increasing the chances of injury to local tissues.Brow Lift, Mid Forehead
Brow Lift, Mid Forehead
Introduction
Eyebrow ptosis is a result of gravitational and involutional changes defined by eyebrows that rest lower than their normal position. Other causes of brow ptosis include facial palsy, tumors, and asymmetry related to trauma. The patient may present complaining of difficulty with vision because of secondary dermatochalasis, irritation of the eyes from lash ptosis (again caused by secondary dermatochalasis), or cosmetic concerns.
Many surgical approaches to the ptotic brow are available, including the direct brow lift, mid forehead lift, pretrichial lift, temporal lift, coronal lift, and endoscopic lift. This article reviews the assessment and planning of brow lifts in general and indications for the mid forehead lift in particular.
Several different incisions for mid forehead lifts have been proposed. Here, incisions are placed at different heights to prevent a long horizontal scar.
History of the Procedure
Lexer provided the first documented discussion of a forehead lift in 1910. Hunt subsequently described a coronal resection of tissue for lifting the forehead. The first known documentation of the mid forehead lift was provided by Joseph in 1931; he described both pretrichial and lower forehead incisional lifts. Passot described excision of skin behind the hairline and in 1933 combined it with denervation of the temporal branch of the facial nerve. Edwards proposed isolated temporal neurectomy in 1957. Bames described a direct eyebrow lift via which he also excised the corrugators, undermined the forehead up to the hairline, and crosshatched the frontalis muscle. This was a variation of the mid forehead incisional approach in that essentially the same technique was performed via a lower incision.
Pangman and Wallace described modern approaches to forehead lifts in 1961. They described a hairline approach as well as a coronal approach with the incision 1 cm posterior to the hairline. In 1962, Gonzalez-Ulloa included the forehead lift as a part of his facelift procedure.
In the late 1960s and early 1970s, reports by surgeons suggested that coronal forehead lift results were temporary and the procedure lost favor. However, these earlier approaches consisted of excision of forehead or scalp skin, occasionally without undermining, but always without interruption of the frontalis muscle action. However, in 1957, Bames had bluntly crosshatched the frontalis through the superciliary incision.
Other authors incised the frontalis through different approaches. Subsequently, in the mid-1970s, Griffiths, Hinderer, Marino, Skoog, Vinas, and other authors demonstrated that excision of a strip of frontalis muscle eliminated the dynamic factors that contributed to the formation of horizontal wrinkles and permitted more stretching of the superficial tissues. In 1975, Washio studied cadaver foreheads and concluded that removal of a transverse segment of muscle allowed significant passive elevation of the forehead. Subsequently, Tessier (in 1968) and LeRoux and Jones (in 1974) advocated complete removal of the frontalis muscle.
More recently, endoscopic approaches have added much to the understanding of effective forehead lifting techniques with minimal incisions. The anatomy of eyebrow ptosis and the neurologic details of the sensory and motor innervation of the forehead were described in more detail in the 1990s, leading to more accurate approaches to eyebrow ptosis repair.
With recent advances in endoscopic approaches, procedures such as coronal forehead lifts, mid forehead lifts, and direct eyebrow lifts are performed less often. However, appropriately selected patients may benefit from these procedures, and the limits of minimally invasive endoscopic access should also be recognized.
Problem
Eyebrow ptosis is essentially a result of gravitational effects.1 Laxity of the forehead, eyebrows, and eyelids develops with time, resulting in inferior migration of the brow. With the downward movement of the eyebrows, the frontalis muscle attempts to compensate by elevating the brows, which results in horizontal furrows. Unlike the medial two thirds of the eyebrow, the lateral third does not have deep structural periosteal attachments, rendering it especially susceptible to temporal brow ptosis. In addition, the frontalis muscle fibers do not extend to the lateral brow, further contributing to the lack of lateral support. As a result of this underlying anatomic paradigm, observing severe temporal brow ptosis with secondary dermatochalasis causing hooding of the upper lid skin without any great medial brow ptosis is not uncommon.
Frequency
Objective criteria for brow ptosis remain ill-defined; no statistics are available for the incidence of significant brow ptosis. However, the authors contend that objective evaluation of brow position with aging would reveal a significant mischaracterization; almost every patient who presents with significant dermatochalasis has some degree of brow ptosis contributing to the problem. If one elevates the brows even moderately in a patient with a significant degree of dermatochalasis, one is struck by the contribution of brow ptosis. Even in relatively young patients in their 20s and 30s, brow ptosis is a common finding. This is especially so in patients leading an outdoors lifestyle, where constant use of the corrugator, procerus, and orbital orbicularis oculi muscles contributes to the decline of the brow.
When assessing aesthetic patients, note that brow ptosis results in horizontal as well as vertical redundancy of tissues. Every patient observed by the authors with upper eyelid ptosis or dermatochalasis, whether functional or cosmetic in nature, is assessed for brow ptosis. While not every patient is submitted to a brow lifting procedure or even given a recommendation to undergo a brow lift, the illustration of the effect of the brow on the upper eyelid helps to instill realistic expectations in the patient.
International frequency
No firm statistics are available regarding brow ptosis in different races. However, the authors have observed a vast difference in the degree of brow ptosis in different races. When operating in Africa, they note that while ptosis is as common as in Caucasians, dermatochalasis and significant brow ptosis are observed much less often, even though most of these individuals work and live without appropriate ocular protection. Indeed, even in elderly African men who have worked outdoors all their lives, forehead horizontal wrinkles are relatively uncommon.
Asian populations naturally have heavy brows; the low insertion of the orbital septum to the levator aponeurosis in the eyelid results in a low eyelid crease. The effect of the brow on upper eyelid dermatochalasis is usually obvious. Accordingly, forehead lifts are required less commonly in most of these patients.
Etiology
Forehead, eyebrow, and eyelid relationships
Facial expression and patient mood may be determined by positional and relational changes of the forehead, eyebrow, and eyelids. Forehead rhytides project tiredness, sleepiness, or worry. Eyebrow position and shape are particularly powerful determinants of interpersonal perception. Low lateral eyebrows reflect surprise or sadness, while low medial position may suggest anger. Flat brow shape may suggest tiredness, while appropriately shaped and positioned eyebrows may be perceived as expressing happiness.
Similarly, dermatochalasis can affect the visual field but also suggests tiredness because of the effect of the excess skin and the secondary compensatory brow elevation. If an upper blepharoplasty is performed in the presence of brow ptosis, the patient must understand that this results in further lowering of the brow. Indeed, when the excess skin has been removed from the upper eyelid, the impetus for the patient to keep the brows up is lost, and brow ptosis appears to be much worse than that expected simply by performing the blepharoplasty.
Pathophysiology
The development of brow ptosis is multifactorial. Review of patient photographs and patient family photographs may reveal a striking resemblance between the patient and his or her parent(s). A common refrain heard in the plastic surgery clinic is "I am becoming my mother!" The cause of brow ptosis may be genetic, with patients and their parents sharing similar familial characteristics, similar bony anatomy, and the "aging clock."
A second contributing factor is probably lifestyle. Patients who participate in sports or many outdoor activities often have marked overaction of the corrugator and procerus muscles and associated frontalis overaction. These patients constantly pull the brow and forehead downwards and inwards. They develop impressive corrugator and procerus lines (often described by patients as "elevenses" because of the vertical parallel lines) and horizontal frontalis forehead lines. The eyebrows seem to be closer together in these patients; they also have the horizontal nasal bridge line of central forehead collapse. The brows may appear increasingly closer together with age; this is demonstrated through comparison of current and less recent photographs of patients.
The lack of lateral support by the frontalis muscle results in an exaggerated lateral brow droop with secondary lateral upper eyelid dermatochalasis, hooding of skin laterally, and crow's feet.
Presentation
Physical
Patients with brow ptosis may present for functional or cosmetic reasons. Secondary dermatochalasis may result in a superior visual field defect. Brow ptosis and dermatochalasis may independently contribute to superior and superotemporal field defects.
Patients with brow ptosis may present for functional or cosmetic reasons. Secondary dermatochalasis may result in a superior visual field defect. Brow ptosis and dermatochalasis may independently contribute to superior and superotemporal field defects.
Cosmetic patients frequently focus on the dermatochalasis and must be educated on the contribution of brow ptosis to dermatochalasis. Complaints such as looking tired, angry, or unhappy and comments to that end from friends and colleagues are frequently causes for consultation. A patient presenting with a complaint that the brows are too low is uncommon. Corrugator and procerus muscle action leads to glabellar rhytides, again resulting in comments about anger and tiredness.
History
History
The preoperative workup of any surgical patient must be thorough. Specific details regarding forehead lifts are mentioned. Besides noting the patient's previous illnesses, medications, allergies, and history of unusual scarring, place emphasis on excluding thyroid disease, bleeding tendencies, and unusual edema. Patients with thyroid disease may require medical treatment, with surgical intervention reserved for when thyroid status has been stable for at least 6 months. Eyelid position, degree of fat herniation, and extent of eyelid edema fluctuates in patients with thyroid disease while they are undergoing treatment.
Examination of forehead and eyebrows
Examination of forehead and eyebrows
Whenever operating on any aspect of the face, examining the whole face and the relationship of relative structures is paramount. Even if the patient is specifically requesting eyebrow elevation or blepharoplasty, assessment of the relations of the various structures allows the surgeon to provide realistic expectations.
Examination of the forehead and brow includes assessment of the hairline, density of scalp hair, height of the forehead (distance between the brow and anterior scalp hairline), brow position and brow symmetry, upper eyelid skin crease and extent of dermatochalasis and fat herniation, individual brow malposition (eg, medial droop), extent of forehead rhytides (eg, transverse lines, glabellar lines, temporal lines, crow's feet), and position of the upper eyelid margin.
Determine if brow ptosis is present. No objective standard allows accurate assessment of the presence or absence of brow ptosis. However, a useful measurement is the distance between the inferior limbus of the cornea and the center of the brow. This distance is usually 22 mm or more. Anything less than 22 mm suggests brow ptosis, especially in women. The ideal brow position is very much an individual feature, determined best by the surgeon as well as the patient. The authors customarily review photographs of all patients from their younger days to see if an age exists when the brows were located in a position that the patient considers acceptable. Furthermore, the authors contend that brow shape may be the more critical determinant of brow ptosis, which is subjective.2
Measurement of brow ptosis
Measure the degree of brow ptosis medially, centrally, and temporally by holding a ruler with the zero mark at the upper border of the brow when it is relaxed and sequentially lifting the brow in the 3 positions until the desired position is achieved. Almost all patients have some degree of eyebrow ptosis asymmetry. This needs to be documented and shown to the patient in a mirror, since most patients are unaware of this fact. The surgeon can rest assured that postoperatively, the patient certainly notices any asymmetry, whether or not it was present preoperatively.3
Note the depth and distribution of the forehead, temporal, and glabellar rhytides. In particular, note the depth and distribution of the forehead rhytides when assessing a patient for a possible mid forehead lift. Note the density of the scalp hair and measure the distance between the brow and the anterior scalp hairline. Observing exact figures regarding the normal distance between the brows and the anterior hairline is difficult since a vast degree of racial and genetic variation is present. Whether a patient has a high forehead and whether the anterior hairline should be brought forward and downward should be determined for each patient individually. In general, men benefit from bringing their anterior hairlines forward, as do some women. Conversely, most women and many men do not do well with forehead scars that result from mid forehead lifts.
Inherent in the brow evaluation is an assessment of the upper eyelid. Assess the corneal reflex-lid margin distance, note the position of the upper eyelid skin crease, the extent of upper eyelid dermatochalasis that is not caused by brow ptosis, and the degree of upper fat herniation and lacrimal gland herniation.
Since most patients having a brow lift also undergo an upper eyelid blepharoplasty, possibly with correction of ptosis, lower eyelid (eg, laxity, snap back test, inferior scleral show) and cheek positions should be assessed on each patient.4 This is discussed elsewhere in this journal (see Blepharoplasty, Upper Lid). Similarly, assess the Bell phenomenon, corneal sensation, corneal staining, completeness of the blink, and tear film integrity.
A summary of patient evaluation for forehead and brow elevation is as follows:
- Hair - Density and distribution
- Hairline - Frontal and temporal
- Forehead height relative to facial proportions
- Forehead height - Eyebrows to anterior scalp hairline
- Forehead transverse rhytides - Distribution and depth
- Forehead temporal rhytides
- Crow's feet
- Skin thickness, quality, and sebaceous quality
- Eyebrow shape and symmetry
- Eyebrow position (degree of medial, central, and lateral ptosis)
- Eyebrow hair distribution - Evidence of plucking, loss, other changes
- Eyebrow mobility (eg, paralysis, scarring, tumor)
- Severity and distribution of glabellar and nasal root rhytides
- Degree of dermatochalasis, hooding, and eyelid ptosis
Indications
- Brow ptosis leading to secondary dermatochalasis with visual field restriction
- Brow ptosis presenting together with significant upper dermatochalasis
- Temporal brow ptosis causing temporal hooding of the skin
- Brow ptosis resulting in a cosmetic deformity (eg, angry, sad appearance)
- Brow ptosis from facial palsy
- Patients who already have had upper dermatochalasis and who still complain of visual compromise, usually as a result of previously unrecognized brow ptosis
Specific indications for performing a mid forehead brow lift are as follows:
- Men who have prominent forehead furrows
- Patients, particularly men, in whom lowering the frontal hairline is desirable (because the procedure lowers the frontal hairline)
- Patients with a high, sparse, or receding frontal hairline
Relevant Anatomy
Surface anatomy
The surface anatomy of the male and female brow differs. However, generally, the medial eyebrow is approximately 1 cm above the superior orbital rim in both sexes. In women, the eyebrow arches more dramatically, with the apex approximately over the lateral limbus. In men, the eyebrow curve is more subtle, with a straighter and gentler arch, but again, the maximal height is approximately at the lateral limbus. Manual elevation of the medial, central, and lateral portion of the eyebrow during examination allows determination of the best position of the eyebrow and of the contribution of eyebrow ptosis to dermatochalasis. Specifically, the redundant upper eyelid tissues over the medial canthus, the center of the eyelid, and the lateral canthus are assessed.
Scalp and forehead
The scalp has 5 layers: skin, superficial fascia (which is a fibrofatty layer adherent to the skin and to the underlying muscle and its aponeurosis), tendinous galea aponeurotica (and its associated occipitofrontalis muscle), loose areolar tissue that occupies the subaponeurotic space, and periosteum. The galea splits to form a sheath around the muscles. The fourth layer, the loose areolar tissue, contains small arteries and emissary veins.
Muscles
The forehead and eyebrow regions are composed of 5 major muscles: the occipitofrontalis, orbicularis oculi, depressor superciliaris, corrugator supercilii, and procerus. The occipitofrontalis has 4 bellies, 2 occipital and 2 frontal, connected by the epicranial aponeurosis, also termed the galea aponeurotica. The occipital bellies arise from the highest nuchal line on the occipital bone and pass forward to insert on the galea. The frontal portion has no bony insertion but arises from the skin and superficial fascia of the eyebrow, passes through the orbital orbicularis oculi muscle, and inserts on the galea approximately midway between the coronal suture and the brow.
The orbicularis oculi muscle has 3 parts, the orbital, preseptal, and pretarsal orbicularis oculi muscle. The orbital portion overlies the orbital rim and arises from the anterior limb of the medial canthal tendon and the surrounding periosteum. The fibers sweep superiorly and inferiorly around the eye and meet laterally over the zygoma. The preseptal portion of the orbicularis oculi has superficial heads from the medial canthal tendon and deep heads from the posterior lacrimal crest. The fibers that sweep laterally form the lateral palpebral raphe.
The pretarsal fibers arise from the medial canthal tendon and Horner muscle. These fibers pass laterally to unite at the lateral canthal tendon. The orbicularis oculi muscle closes the eyelids, thereby pulling the skin of the forehead, temple, and cheek toward the eyes. The superior orbital portion of the orbicularis oculi muscle is a particularly powerful depressor of the brow, as is evident in patients with blepharospasm.
The frontalis muscle inserts into the eyebrow where it interdigitates with the corrugator supercilii muscles. The corrugator supercilii muscles originate from the nasal process of the frontal bone at the superomedial orbital rim. The muscle inserts into the medial cutaneous portion of the eyebrow, interdigitating with the frontalis muscle. The corrugator muscles produce vertical glabellar furrows.
The procerus muscle appears as a continuation of the inferior medial end of the frontalis muscle. It arises from the lower part of the nasal bone, and its action pulls down the medial end of the eyebrow and produces horizontal wrinkles of the skin. Some surgeons have suggested that the medial part of the corrugator muscle is an elevator of the medial brow, although this view is not accepted widely.
Several recent studies have demonstrated the presence of a distinct layer of fibroadipose tissue posterior to the orbicularis oculi and frontalis muscles and anterior to the orbital septum. This retro-orbicularis oculi fat (ROOF) tissue is best developed in the eyebrow but may continue inferiorly into the eyelid, nearly to the point where the orbital septum joins the levator aponeurosis. The ROOF is more fibrofatty than postseptal eyelid fat. It gives temporal eyelid and brow fullness, which persists after upper blepharoplasty and trimming of postseptal fat. Sculpting of the fibrofatty ROOF gives sharper orbital margin definition than simply elevating the brow and removing orbital fat. However, this must be performed judiciously to avoid an excessively harsh skeletonized look.
Although only recently stressed in the literature, this retro-orbicularis fat first was described in 1909 by Charpy, who mistook it to be a lateral orbital fat pocket. Eyebrow fat pads are larger in patients with thyroid orbitopathy and require particular attention when performing cosmetic upper eyelid and brow surgery.
The muscle plane of the eyebrow is secured to the frontal bone periosteum by a firm attachment on the underside of the fat pad, often known as the deep galeal insertion, particularly over the medial two thirds of the orbit. The submuscular fibroadipose layer appears to enhance eyelid and eyebrow mobility. This allows wide excursion of the eyebrow above and below the orbital rim with appropriate muscular contracture. A constant artery and vein are found in the mid forehead area, just above the brow. These are branches of the temporal artery and temporal vein, respectively. These vessels are encountered within the deeper part of the brow fat pad.
Motor nerves
The facial nerve emerges from the stylomastoid foramen and enters the anteromedial surface of the parotid gland. It then passes forward within the gland, superficial to the retromandibular vein and external carotid artery, and divides into 5 terminal branches. The frontal branch of the facial nerve emerges from the upper border of the gland and supplies the anterior and superior auricular muscles, the frontal belly of the occipitofrontalis, the orbicularis oculi, and the corrugator supercilii. The frontal branch travels superiorly in the musculoaponeurotic layer. Temporal to the nerve in this layer are the superficial temporal artery and vein. The surface markings of the frontal branch are 1.5 cm above the lateral eyebrow and 2 cm lateral to the lateral orbital rim.
The nerve actually divides into several branches over the zygomatic arch and it is safer to assume that the nerve occupies a width of approximately 2 cm of the arch approximately 2 cm from the lateral orbital rim. Branches of the frontal nerve enter the corrugator supercilii muscle at its lateral end just before the muscle passes into the frontalis and orbicularis muscles.
Sensory nerves
The supraorbital nerve runs cephalad, deep to the corrugator supercilii muscle immediately after exiting the supraorbital rim, either from a foramen just superior to the orbital rim or from a notch in the middle third of the rim. The supraorbital nerve is shown in anatomy textbooks to run over the frontalis muscle to the occipital area. In cadaver studies, Knize recently has shown that this is not the case.6 He found that the supraorbital nerve divides into the medial (superficial) and lateral (deep) divisions.6
The superficial division divides into multiple branches that penetrate the frontalis muscle and pass cephalad over the frontalis muscle to supply at most 3.5 cm of the frontal scalp. The deep division courses laterally between the periosteum and the galea aponeurotica. The deep division has few fine branches and runs up to the coronal suture.
The supratrochlear nerve exits the orbit just lateral to the corrugator supercilii muscle's bony origin, enters the muscle, and divides into 3-4 smaller branches. These branches course cephalad on or just deep to the anterior surface of the corrugator supercilii muscle and then penetrate the frontalis muscle and run on its medial ipsilateral surface toward the scalp.
Multiple fine branches of the infratrochlear nerve are present on the medial side of the corrugator supercilii muscle near its origin, although they generally do not enter the corrugator supercilii muscle. The supratrochlear nerve supplies a mid line vertical strip approximately 1 cm wide. The infratrochlear nerve innervates the skin between the medial canthus and the nasal bridge. Blocking this nerve during a forehead lift is important, since dissecting in this region is necessary to correct the horizontal nasal furrows.
The location of the supraorbital nerve and the supratrochlear nerve with respect to the mid line is approximately 2.7 cm and 1.7 cm, respectively. Marker sutures may be placed at these points to identify these nerves in brow lifts.
Fascia
The relation of the frontal nerve to the various forehead fascial planes is important to understand. Three fascial layers within the temporal region are in close relation to the frontal branch of the facial nerve: the temporoparietal fascia (superficial temporal fascia) and the deep temporal fascia, which consists of a superficial and a deep layer. The temporoparietal fascia represents a cephalad extension of the superficial musculoaponeurotic system (SMAS) across the zygomatic arch and is in continuity with the galea above, the frontalis anteriorly, and the occipitalis posteriorly. This fascial layer is either superficial or lies superficially to the zygomatic arch and encompasses the frontal branch of the facial nerve and superficial temporal vessels.
The frontal branch of the facial nerve lies on the undersurface of this layer. The nerve is superficial in its course across the zygomatic arch and is separated from the underlying zygomatic arch by the superficial layer of the deep temporal fascia and the loose areolar plane.
The temporoparietal fascia is separated from the superficial and deep layers of the deep temporal fascia by a loose areolar plane, which is termed the subaponeurotic plane. This loose areolar layer is the level of dissection commonly used when operating within the temporal region, and its degree of thickness is generally not appreciated. Dissection is possible beneath the undersurface of the temporoparietal fascia or directly on top of the surface of the superficial layer of the deep temporal fascia. The subaponeurotic plane is avascular and contains no crossing blood vessels. It is continuous superiorly with the subgaleal plane, which extends inferiorly to overlie the zygomatic arch.
The deep temporal fascia is a thick, dense, connective-tissue layer overlying the temporalis muscle. Superiorly it is in intimate contact with the temporalis muscle and exists as a single layer. Although it is a single sheet of fascia, it can be split by careful dissection into two separate layers.
Below the level of the superior orbital margin is the temporal line of fusion where the deep temporal fascia splits into two separate sheets of fascia, a thick outer layer and a thinner deep layer. Continuing inferiorly to the zygomatic arch, the two layers of deep temporal fascia remain separated from each other by a fat pad. This fat pad is the superficial temporal fat pad or Yasargil fat pad. The Yasargil fat pad is enveloped by the two layers of the deep temporal fascia and extends from the temporal line of fusion down to the zygomatic arch and as far forward as the lateral orbital wall.
The temporalis is covered by the deep layer of the deep temporal fascia. The buccal fat pad traverses upward beneath the zygomatic arch and extends as the deep temporal fat pad, overlying the inferior portion of the temporalis muscle and its tendon over approximately 2-4 cm above the zygomatic arch.
The deep temporal fascia is adherent to the periosteum at the superficial temporal crest line. At this point, the superficial temporal fascia joins the galea. This fascial junction is termed the conjoint fascia or the conjoint tendon and needs to be divided effectively by sharp or blunt dissection when performing a forehead elevation in the subperiosteal plane.7
Contraindications
Patients without forehead furrows may be poor candidates for the mid forehead approach. Furthermore, even in the presence of reasonably impressive mid forehead furrows, scars can be significant, and before and after photographs must be shown to the patient to ensure that he or she is willing to accept the ensuing scars. The procedure is also contraindicated in patients with low frontal hairlines.
Finally, with advances in endoscopic techniques, many patients who would previous have undergone mid forehead lifts now are operated on using modified endoscopic techniques.8 The aim in all functional or cosmetic forehead lifts is to achieve the desired repositioning of the brows and the forehead with minimal visible scarring.
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