Botulinum toxin A in facial plastics

KHAIRALLAH AOUCARPGY4 ENT

HISTORICAL ASPECT

A German poet, doctor and scientist , Dr. Justinus Kerner of Wurttemberg, first explained the disease called botulism (1817 to 1822) caused by ‘sausage poison’.

Already imagined that the toxin that caused such a serious disease, could be used to treat diseases like muscular spasms.

Dr Emile Pierre van Ermengem (belgium) in 1895 successfully isolated this bacterium, named it Bacillus botulinus.

Botulinum toxin was first used to treat human disease (1980) by Drs Alan Scott (opthalmologist) and Edward Schantz, in treating strabismus.

History

In 1987, ophthalmologist Jean Carruthers observed that frown lines disappeared after the use of botulinum toxin A for blepharospasm.

In 1996, they published the first paper on the use of Botox for cosmetic purposes.

In 2002, the FDA announced the approval of BOTOX® Cosmetic to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows (glabellar lines).

DERMATOLOGICAL INDICATIONS

AESTHETIC INDICATIONS horizontal forehead lines glabellar lines and vertical frown lines crow's feet bunny lines marionette lines dimpled chin platysmal bands.

Dynamic wrinkles respond better than fixed wrinkles.

CONTRAINDICATIONS

1. Patients afflicted with a preexisting motor neuron disease, myasthenia gravis, Eaton-Lambert syndrome, neuropathies, psychological unstability.

2. History of reaction to toxin or albumin.3. Pregnancy and lactating females.4. Infection at the injection site.

RELATIVE CONTRAINDICATIONS Some medications decrease neuromuscular transmission, generally should be avoided in

patients treated with botulinum toxin. Includes aminoglycosides (may increase effect of botulinum toxin) penicillamine, quinine, chloroquine and hydroxychloroquine (may reduce effect) calcium channel blockers, and blood thining agents eg. warfarin or aspirin (may result in bruising).

 Preoperative Counseling and Informed Consent Detailed counseling with respect to the treatment, desired effects, and

longevity of the results should be discussed . A detailed consent form needs to be completed by the patient. Should include the type of botulinum toxin, longevity expected, need

for repeated treatments and possible postoperative complications. Preoperative photography is mandatory.

Cronic UV-damage to the skin.◦ Photo-aging due to cumulative sun

exposure.◦ Glogau Wrinkle Scale:

Type 1: 'Early Wrinkles' Patient age: 20s to 30s Early photo-agingMild pigment changes Minimal wrinklesNo 'age spots'

Type 2: 'Wrinkles in Motion'Patient age: 30s to 40sEarly to moderate photo-aging Appearance of smile lines Early brown 'age spots'Skin pores more prominent Early changes in skin texture

Factors contributing to aging skin

Type 3: 'Wrinkles at Rest' Patient age: 50s & older Advanced photoaging Prominent brown pigmentationVisible brown 'age spots' Prominent, small blood vesselsWrinkles, even at rest

Type 4: 'Only Wrinkles' Patient age: 60s or 70s Severe photoaging Yellow-gray skin color Prior skin cancersPre-cancerous skin changes (actinic keratosis)

Loss of subcutaneous fat.◦ Loss of volume and fullness/roundness.◦ Flattened, sunken appearance.◦ Facial contours and mouth.

Hyperdynamic wrinkles due to repetitivefacial expression.◦ Smoking, frowning, squinting etc.◦ Muscles that insert into skin.

Frontal, glabellar, periocular, nasolabial, perioral◦ Initially only wrinkles with movement, later at

rest.

Loss of elasticity due to gravitational changes.◦ Facial soft tissues lose resiliency and can no

longerresist stretching forces and movement; no rebound.

◦ Facial soft tissues start to sag as a result of gravity.

Remodeling of bony and cartilaginousstructures.◦ Bone resorption results in decrease of facial

volume.◦ Stretching of cartilage as a result of gravitational

forces results in drooping of facial structures (nasal tip)

◦ Facial assymmetry may result.

Microbiology

Synthesized by a variety of Clostridial species, most commonly Clostridium botulinum, but also C. baratii or C. butyricum

BoNT is broken into 7 neurotoxins (labeled as types A, B, C [C1, C2], D, E, F, and G), which are antigenically and serologically distinct but structurally similar.

Human botulism is caused mainly by types A, B, E, and (rarely) F. Types C and D cause toxicity only in animals.

Microbiology

In nature, a single core neurotoxin (150-kD) is contained within a molecular complex that varies in size based on nontoxic, clinically inactive proteins classified as hemagglutinins or nonhemagglutinins.

These associated proteins serve as stabilizers to protect the neurotoxin molecule from pH, thermal stress, and enzymatic degradation

The BoNT molecule is synthesized as a single chain (150 kD) and then cleaved to form the dichain molecule with a disulfide bridge.

Fischer A, Montal M. Crucial role of the disulfide bridge between botulinum neurotoxin light and heavy chains in protease translocation across membranes. J Biol Chem. 2007;282:29604–29611.

1) the N-terminal (heavy chain) contains the translocation domain

2) the C-terminal (heavy) contains the binding domain that docks to the neuron

the light chain contains the catalytic portion responsible for cleavage of the intracellular BTX target

MECHANISM OF ACTION

Botulinum toxins act at four different sites in the body: The neuromuscular junction Autonomic ganglia Postganglionic parasympathetic nerve endings Postganglionic sympathetic nerve endings that release

acetylcholine.

Release of acetylcholine at the neuromuscular junction is mediated by the assembly of a synaptic fusion complex.

Allows the membrane of the synaptic vesicle containing acetylcholine to fuse with the neuronal cell membrane.

The synaptic fusion complex is a set of SNARE proteins, which include synaptobrevin, SNAP-25, and syntaxin.

After membrane fusion, acetylcholine is released into the synaptic cleft and then bound by receptors on the muscle cell.

The acidic pH within the endocytotic vesicle cleaves the disulfide bond

- types B, D, F, and G cleave synaptobrevin

-types A, C, and E cleave SNAP-25

-type C cleaves syntaxin. Without acetylcholine

release, the muscle is unable to contract.

The duration of action :inhibition of neurotransmitter release

varies among the serotypes based on the half-life of the light chain the time of the neuron to restore SNARE proteins. Studies suggest that botulinum toxin type A has the longest half-life, followed by

types CI, B, F, and E.

Elopra R, Tugnoli V, Quatrale R, et al. Different types of botulinum toxin in humans. Mov Disord. 2004;19(Suppl 8):S53–S59.

  Reconstitution and Handling

1. Follow all usual precautions of sterility and skin preparation before injection.

2. Seat the patient with chin down and head slightly lower than the physician's.

3. Plastic single use insulin syringes with 30-32 gauge needles are recommended, and toxin is injected into affected muscles or glands

4. Topical anesthetics are generally reserved for the very sensitive. Ice could be used as a numbing agent.

5. Doses are tailored according to the mode of use and individual patients, and the dose depends on the mass of muscle being injected: The larger the muscle mass the higher the dose required.

reconstitution

Unpreserved saline Preserved saline(with benzyl alcohol):1. less painful 2. Prefered method of reconstruction for botox

Lidocaine with epinephrine:1. enhance short term efficacy2. Accelarate onset of action3. Reduce discomfort with injections

reconstitution

Bupivacaine:1. faster onset of action 2. may be attributed to a synergistic effect between Botox® and bupivacaine-

induced myotoxicity

Sterile water: effective but associated with short-lived, intense pain at the injection site

Dilution

The package insert of onabotulinumtoxinA (Botox®) recommends dilution of 100 units in 1 to 8mL of saline (12.5 to 100 U/mL)

Three hundred units of abobotulinumtoxinA (Dysport®) may be diluted in 0.6 to 2.5mL of saline (120 to 500U/mL).

IMMUNOGENICITY/ALLERGY/RESISTANCE

Antibody formation may occur in response to botulinum toxin injections. when large doses of botulinum toxin are utilized (most frequently in

therapeutic, noncosmetic applications) The overall risk of antibody formation may be minimized by using low doses

with the longest feasible interval between injections Allergic reactions:1. exceedingly rare2. May range from non-serious skin rashes over more serious skin rashes and

granuloma formation 3. localized or even systemic anaphylactic reactions.

Glabella anatomy

The glabella is the most common and popular facial area treated with BoNT-A and the most studied aesthetic application.

Glabella lines are created by the action of 3 muscles: the corrugator supercilli; the procerus; and the depressor superciliis.

Glabellar lines

Contracting the corrugator supercilii =>vertical lines

Contracting the depressor supercilii will draw the eyebrows down=>menacing expression.

Contracting the procerus =>horizontal line

Glabellars anatomy

Glabellar lines

The typical approach consists of injections into the corrugator (red and blue circles) and procerus (green circle) muscles:

Procerus => 1 injection point Corrugator => 1 injection point, .5 to 1 cm above

the medial orbital rim (total of 2 injections) Corrugator =>1 lateral injection point, 1 cm

above the orbital rim (total of 2 injections).

Glabellar lines

Younger patients typically require a less aggressive treatment approach and are often looking for prophylaxis instead of correction of deep wrinkles.

In summary, patients should be assessed individually to determine muscle mass, optimal injection sites and variable dosages.

Static versus dynamic enhancement is the basis for patient goals and injection technique is linked to clinical outcome.

Eye Lid Droop

Apraclonidine 0.5%(iopidine) naphazoline phenylephrine2.5% 2 drops tid till resolution of ptosis

Forhead anatomy

The forehead muscle(frontalis) is an elevator. Overtreating will result in brow ptosis The frontalis antagonists are the corrugators, procerus, and the

orbicularis oculi. Action of the frontalis forms horizontal forehead lines(HFL)

HFL

raise the eyebrows in the expression of surprise and even higher with fright

furrow the forehead with transverse lines with thought.

HFL BoNT-A is an effective treatment for

horizontal forehead lines and the forehead is often treated in conjunction with the glabella.

Keep injections 1-2 cm above eye brows to minimize eye brow ptosis

Start at low doses since frontalis is very responsive to treatment and encourage follow up at 2weeks to reevaluate

HFL

Predisposing factors for eyebrow ptosis:

Age >50 Mild eyebrow ptosis dermatochalasis

Individualized injection techniques for tall(>2 horizontal line injection) or short forheads(1 horizontal line)

Consensus Recommendations:Treating Horizontal Forehead Lines

Target MusclesUsual Number of

Injection Points (Range)

Total Starting Dose

(Usual Range) Frontalis, but consider interactions with procerus, corrugators, and orbicularis oculi in overall facial shape

4 to 8; but more or fewer may be required based on anatomic and aesthetic evaluations

Women: 15 U10 to 20 U

Men: 20 to 30 U

HFL

Use fillers rather than toxin to treat the first horizontal rhytid above the eyebrow

Helps soften the prominence without affecting the frontalis muscle

Suddenly Sinister: The Evil, Arched Brow

The Quizzical Brow

one brow is arched more than the other.  This usually happens when the Botox is

either unevenly applied, or natural asymmetry is underestimated (usually the case)

The Iron Forehead, Low Brow

Unfortunately: only solution here is Father Time.

Brow lift anatomy

Multiple muscles, shaded in yellow, have an impact on brow position:

the frontalis corrugators, procerus, and the orbicularis

oculi

Brow lift

The aging process often renders a gradual descent of the forehead and brow in the upper third of the face (from the hairline to the top of the eyebrows).

Aging and muscle activity contribute to1. lateral brow ptosis 2. upper eyelid fullness3. tired or sad look4. horizontal forehead lines due to compensation.

Brow lift

Lateral brow lift

Gender, personal preference, age, and current brow position impact the desired brow aesthetic and treatment approach

Injection:superior and lateral aspect of orbicularis oculi

1 per side(2U) 0.5 cm above orbital rim

Lateral brow lift

The peak effect occurs at 12 weeks post injection as opposed to the usual 4 weeks in skeletal muscle Due to slower adjustments in the resting tone of the untreated portion of the frontalis muscle

It is important to leave the lateral frontalis untreated since its responsible for brow elevation

Crows feet

Crow's feet are lines that form in the lateral canthal region and are caused by contraction of the orbicularis oculi muscle.

skin changes from aging and contraction of the zygomaticus may contribute.

Crows feet

source of the wrinkles :orbicularis oculi vs zygomaticus major. Evaluation should include a "snap test" to measure skin laxity along the lower lid margin.

Skin that does not snap back into place after downward tugging may not respond well to neurotoxin treatment and be at higher risk for ectropion.

A beginning approach entails 3 injections of 3 to 4 units each Centered around a point 1.5cm lateral to the latheral canthus and separated by 1 to 1.5cm

Crow’s feet

Never inject crows line while patient is smiling: affects zygomaticus and cause ptosis of upper lip

Crow’s feet

Bunny lines anatomy Several muscles contribute to bunny

lines, but the nasalis is the most significant.

Patients should be asked to laugh, sniff, and to squint intensely as if a very bright light is before their eyes.

Usually, bunny lines are not present in kinetic patients with a mild smile.

They only become evident when smiling at maximum contraction.

In hyperkinetic patients, bunny lines are found with a mild smile and worsen at maximum contraction

Bunny lines

Injections should be limited to the levator labii superioris alequae nasi to avoid lip ptosis

Bunny lines

Masseter reduction

Bulky masseter squares the face Very common in East Asians 3-5 injections centered on maximum bulk

assessed by palpation or clenching(lower half) Deep and below a line drawn from tragus to

angle of the mouth

1 cm from the borders of the muscle

15-40 units per side

Masseter reduction

patients with only bony mandibular prominence are not candidates for Botox reduction

Muscular hypertrophy is thought to cause secondary bony enlargement of the mandibular angle from functional remodeling where the muscle inserts on bone

Lipstick lines or smoker’s wrinkles

Lipstick lines

Lipstick lines

Hypertrophic orbicularis oris; intensified by age, sun expore and smoking

BTX is good treatment for mild wrinkles; for moderate wrinkles use bTX in combination with fillers, chemical peels and/or laser resurfacing.

staying in close proximity (within 5mm) to the vermilion border. Results are generally not as dramatic as those in the upper face and

last approximately 10 weeks. The risk of dysarthria and oral incompetence should be discussed with

the patient prior to administration

Lip lengthening (gummy smile)

Lip lengthening

1 unit into levator at nasofacial complex just inferior to nasomaxillary groove

Client who already exhibits drooped mouth corners! ◦Asymmetry. ◦Too high dose may cause:1. Upper lip ptosis (takes longer to dissolve: 6 weeks).2. Excessive lengthening.3. Lower lip protrusion.

Marionette lines DAO anatomy Marionette lines are caused by contraction of

the depressor anguli oris or DAO, a triangular muscle that inserts in the fibers of the mouth corners

give the impression of being unhappy

Marionette lines DAO

Marionette lines are typically treated via 1 injection(2U) point into the posterior aspect of each DAO.

Injections should be at least 1 cm lateral to the mouth corner to avoid adverse outcomes.

A second injection site may be added laterally to target the platysma

DAO

The goal of treatment is to reduce the action of the DAO and lift the corners of the mouth.

Treatment of DAO (depressor anguli oris) allows zygomaticus muscles to elevate mouth corners.

DAO Neurotoxin treatment

effectively softens marionette lines, although most dramatic and rejuvenating results in lower face treatment are best seen in combination therapy with injectable fillers

Titrating the dose, starting with a low dose and titrating up, is advised.

 

Cobblestone anatomy mentalis muscle

Contraction of the mentalis causes a "cobblestone" appearance of the skin and possible deepening of the mentolabial crease.

Dimpled chin Typical treatment of the chin is via 1 central

or 2 lateral injections, about one half to 1 cm above the chin

Injections should be kept at least 1 cm from the lower lip(below transverse mental crease)

Dimpled chin

Due to the risk of oral incompetence, BTX-A should not be used in the perioral region in singers, musicians, or scuba divers.

Turkey neck(Nefrtiti lift) :platysma muscle

Platysmal bands occur due to diastasis of the midline platysmal muscle and loss of submental fat

Nefrtiti lift

Nefertiti lift

The number of injection points depends on length of each band.

Grasping the band with the noninjecting hand might be helpful while injecting very superficially in the contracted muscle

Nefrtiti lift To minimize adverse events ecchymosis, difficulty swallowing, neck

weakness, asymmetric smile from inadvertent diffusion into DAO, treatment approach should be conservative and conducted by experienced practitioners. Titrating the dose, with trial and follow-up, is recommended

Thank you