Botulinum toxin A is used for both cosmetic and dermatological indications to temporarily improve the appearance of wrinkles and lines. It works by blocking the release of acetylcholine at the neuromuscular junction, preventing muscle contraction. Common areas treated include the glabellar region, forehead, crow's feet, and bunny lines. Proper injection technique and dosage tailored to the individual are important to achieve the desired aesthetic results while avoiding complications.

1. Botulinum toxin A in facial
plastics
KHAIRALLAH AOUCAR
PGY4 ENT

2. 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.

3. 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).

4. 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.

7. 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).

8. 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.

9.  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-aging
Mild pigment changes
Minimal wrinkles
No 'age spots'
Type 2: 'Wrinkles in Motion'
Patient age: 30s to 40s
Early 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

10. Type 3: 'Wrinkles at Rest'
Patient age: 50s & older
Advanced photoaging
Prominent brown
pigmentation
Visible brown 'age spots'
Prominent, small blood
vessels
Wrinkles, even at rest
Type 4: 'Only Wrinkles'
Patient age: 60s or 70s
Severe photoaging
Yellow-gray skin color
Prior skin cancers
Pre-cancerous skin changes (actinic keratosis)

11.  Loss of subcutaneous fat.
◦ Loss of volume and fullness/roundness.
◦ Flattened, sunken appearance.
◦ Facial contours and mouth.
 Hyperdynamic wrinkles due to repetitive
facial expression.
◦ Smoking, frowning, squinting etc.
◦ Muscles that insert into skin.
 Frontal, glabellar, periocular, nasolabial, perioral
◦ Initially only wrinkles with movement, later at rest.

12.  Loss of elasticity due to gravitational
changes.
◦ Facial soft tissues lose resiliency and can no longer
resist stretching forces and movement; no rebound.
◦ Facial soft tissues start to sag as a result of gravity.
 Remodeling of bony and cartilaginous
structures.
◦ 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.

13. 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.

14. 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

15.  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.

16.  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

17. 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.

18.  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.

19.  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.

20. 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.

23. 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.

24. 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 efficacy
2. Accelarate onset of action
3. Reduce discomfort with injections

25. 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

26. 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).

27. 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 rare
2. May range from non-serious skin rashes over more serious skin rashes and granuloma
formation
3. localized or even systemic anaphylactic reactions.

29. 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.

30. Glabellar lines
 Contracting the corrugator supercilii
=>vertical lines
 Contracting the depressor supercilii will
draw the eyebrows down=>menacing
expression.
 Contracting the procerus =>horizontal
line

31. Glabellars anatomy

32. 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).

33. 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.

35. Eye Lid Droop
 Apraclonidine 0.5%(iopidine)
 naphazoline
 phenylephrine2.5%
 2 drops tid till resolution of ptosis

36. 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)

37. HFL
 raise the eyebrows in the expression
of surprise and even higher with
fright
 furrow the forehead with transverse
lines with thought.

38. 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

39. 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)

40. Consensus Recommendations:
Treating Horizontal Forehead Lines
Target Muscles
Usual 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 U
10 to 20 U
Men: 20 to 30 U

41. HFL
Use fillers rather than toxin to treat the
first horizontal rhytid above the eyebrow
Helps soften the prominence without
affecting the frontalis muscle

42. Suddenly Sinister: The Evil, Arched Brow

43. 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)

44. The Iron Forehead, Low Brow
 Unfortunately: only solution here is Father Time.

45. Brow lift anatomy
 Multiple muscles, shaded in yellow, have an
impact on brow position:
 the frontalis
 corrugators, procerus, and the orbicularis oculi

46. 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 to
1. lateral brow ptosis
2. upper eyelid fullness
3. tired or sad look
4. horizontal forehead lines due to compensation.

47. Brow lift

48. 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

49. 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

50. 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.

51. 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.

52. 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

53. Crow’s feet
Never inject crows line while patient is smiling: affects
zygomaticus and cause ptosis of upper lip

54. Crow’s feet

55. 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

56. Bunny lines
 Injections should be limited to the levator labii superioris alequae
nasi to avoid lip ptosis

57. Bunny lines

58. 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

59. 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

60. Lipstick lines or smoker’s wrinkles

61. Lipstick lines

62. 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

63. Lip lengthening (gummy smile)

64. 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.

65. 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

66. 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

67. 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.

68. 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.

69. Cobblestone anatomy mentalis muscle
 Contraction of the mentalis causes a "cobblestone"
appearance of the skin and possible deepening of the
mentolabial crease.

70. 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)

71. 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.

72. Turkey neck(Nefrtiti lift) :platysma muscle
 Platysmal bands occur due to diastasis of the midline
platysmal muscle and loss of submental fat

73. Nefrtiti lift

74. 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

75. 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

76. Thank you