Botulinum Toxins: Ứng Dụng Trong Thẩm Mỹ Và Lâm Sàng Y Khoa


Botulinum Toxins
helps to minimize the risk of loss of function.
It should be noted that all of the above recom-
mended injection points are located either at
the central border or the peripheral border of
the perioral area (Figure 14.6). This location
helps to ensure that only certain fibers of the
targeted muscles are denervated. Because of
the critical function of the perioral muscu-
lature, this area should be treated by expe-
rienced injectors. Careful informed consent
and pretreatment photographs at rest, smil-
ing, and while pursing the lips should take
place prior to injection. Understanding the
anatomy, starting with lower doses and hav-
ing patients return for a touch up in 2 weeks
will help to ensure adequate treatment while
minimizing risks in this sensitive area.
Figure .Summary of recommended injection
points marked in white. Red circles indicate
additional alternative injection points to consider
with caution. Note that the white injection points are
at the periphery of the muscles in the perioral area.
Red injection points are more central and may carry
a higher risk of functional compromise.
References
Semchyshyn N, Sengelmann RD.
Botulinum toxin A treatment of perioral
rhytides. Dermatol Surg 2003 May;29(5):
490–495.
Cohen J, Dayan Sn. OnabotulinumtoxinA
dose-ranging study for hyperdynamic
perioral lines. Dermatol Surg 2012;38:
1497–1505.
Cohen J, Thomas J, Paradkar D, et al. An
interrater and intrarater reliability study of
2 photographic scales for the classification
of perioral aesthetic features. Dermatol
Surg 2014;40:663–670
Kane M, Donofrio L, Ascher B, et al.
Expanding the use of neurotoxins in facial
aesthetics: a consensus panel’s assessment
and recommendations. J Drugs Dermatol.
2010 Jan; 9;(1 Suppl);S7-S22, quiz S23–S25.
Carruthers J, Fagien S, Matarasso SL; Botox
Consensus Group. Consensus
recommendations on the use of botulinum
toxin type A in facial aesthetics. Plast
Reconstr Surg. 2004 Nov;114 (6 Suppl):
1S–22S.
Caruthers J, Carruthers A. Clinical
indications and injection technique for the
cosmetic use of botulinum A exotoxin.
Dermatol Surg 1998; 24:1189–1194.
Gray’s Anatomy: The Anatomical Basis of
Clinical Practice. 40th edition (2008).
Garber DA, Salama MA. The aesthetic
smile: diagnosis and treatment. Periodontol
2000 1996;11:18–28.
Mazzuco R. Hexsel D. Gummy smile and
botulinum toxin: A new approach based on
the gingival exposure area. J Am Acad
Dermatol 2010 Dec;63(6):1042–1051.
Hwang WS, Hur MS, Hu KS, et al. Surface
anatomy of the lip elevator muscles for
the treatment of gummy smile using
botulinum toxin. Angle Orthod 2009;79:
70–77.
Polo M. Botulinum toxin type A (Botox) for
the neuromuscular correction of excessive
gingival display on smiling (gummy smile).
Am J Orthod Dentofacial Orthop. 2008;
133:195–203.
Carruthers A, Carruthers J. Cosmetic uses
of botulinum A exotoxin. In: Klein AW,
eds. Tissue Augmentation in Clinical
Practice: Procedures and Techniques. New
York: Marcel Dekker; 1998:207–236.



Neck Rejuvenation
Koenraad De Boulle, MD,1 Lakhdar Belhaouari, MD,2 and Julia D. Kreger, MD3
1Aalst Dermatology Clinic, Aalst, Belgium
2Director, Centre de Chirurgie Esth´etique et Medecine Esth´etique Jules Guesde, Toulouse, France
3University of Colorado Dermatology, Colorado, USA
Throughout the ages, men and women
have wanted to make themselves attractive,
preserve the freshness of their youth, and
even to turn back time. 3500 years ago, an
Egyptian papyrus was already extolling the
virtues of an abrasive paste of milk and honey
with particles of alabaster for smoothing the
surface of the skin and removing imperfec-
tions. But humans, “late arrivals in an already
old world”, are subject to aging, defined
as the action of time on the body. This
physiological phenomenon is irreversible,
slowly progressive, and inevitable in all living
matter. From a morphological perspective,
its signs are revealed in their most obvi-
ous and irreversible form in the face and
neck.
The Anatomical and Functional
Basis of Aging
The signs of aging in the face and neck are
based on a trilogy: sagging, wrinkles and atro-
phy. Sagging in the neck occurs through loss
of elasticity, and manifests as loss of tension
and tone of the different components: skin,
subcutaneous fat, aponeurosis and muscle
[1,2].
The Skin of the Neck and Its Subcutaneous
Fatty Tissue
The skin loosens, thins, and becomes less
elastic through the loss of its mechani-
cal properties in the derma (fewer collagen
fibers, fewer elastic fibers). This explains the
loss of definition of the mandibular edge
and the cervicomental angle, and also the
shrivelled skin, more pronounced jowls, and
“turkey neck” appearance [3]. In short, the
laxity which explains why for ages men and
women have looked at themselves in a mirror,
or in a pool of water before mirrors existed,
said to themselves “wouldn’t it be good if …”
and pulled the skin of the face and neck
up and back, imitating the procedure of the
facelift. In fact, it was they who first imag-
ined the face lift, and not the brilliant and
dedicated surgeons – such as Charles Con-
rad Miller in the United States, the derma-
tologist Suzanne No¨el, Raymond Passot, and
Julien Bourguet in France, and Eugen Hollan-
der and Erich Lexer in Germany – who at
the beginning of the twentieth century had
the genius and daring to perform the first
procedures. These pioneers were followed by
many other outstanding surgeons throughout
the twentieth century, culminating in today’s
techniques [1,2].
Botulinum Toxins: Cosmetic and Clinical Applications, First Edition. Edited by Joel L. Cohen and David M. Ozog.
© 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.
Companion Website:

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Botulinum Toxins
The Muscles of the Neck
Above all else, it is vital for a doctor to
understand anatomy. Anatomy is essentially
a fundamental science and its knowledge is
indispensable to any doctor, regardless of spe-
cialty, for understanding a treatment physi-
ologically, functionally, and clinically, before
attempting its technical execution. This is
equally true whether the treatment is surgical
or nonsurgical, such as with the injection
of botulinum toxin.
The Platysma Muscle
Platysma means “flat plate” in Greek. It is
the cutaneous muscle of the neck: a thin,
flattened, very broad, quadrilateral, paired,
symmetric sheet. It covers the anterolateral
region of the neck but also the inferior part
of the face, passing above the horizontal
branch of the lower jaw, and stretches from
the thorax to the inferior maxilla and cheek
(Figure 15.1).
Its caudal origin is in the deep part of
the skin that covers the acromion and the
deltoid and subclavian regions, and it pro-
ceeds somewhat obliquely upward, forward
and medially in a splitting of the superficial
fascia covering the anterolateral region of the
neck [4–7].
The two parts of the platysma, which are
separated at their base, proceed upward and
come closer together on the upper cervical
median line. Their median, anterior edges
form the platysmal bands. These platysmal
bands interlace below the chin in 75% of cases
at a height of 1–2 cm; they remain separated
without decussation in 10% of cases, or in
15% of cases, they interlace and reconnect
further up and form a continuous muscular
sheet with the thyroid cartilage [8].
The upper insertion points are both bony
and cutaneous:
r After interlacing, the anterior fibers attach
to the skin of the mental eminence and the
mental protuberance.
r The middle fibers attach to the lower edge
of the mandible on the anterior part of
its external oblique line and the lateral
part of the mental protuberance. Some
of these fibers contract from adhesions
by entwining, proceeding and interlac-
ing with fibers of the depressor anguli
oris and the depressor labii inferioris
muscles.
r The posterior and lateral fibers cover the
gonion and extend to the labial commis-
sure and the skin of the cheek. At the cheek,
the most lateral fibers entwine with the
risorius muscle fibers (although accord-
ing to some anatomists this muscle may
only be an extension of the platysma)
[5,6].
(b)
(a)
Figure .(a) Source: Reprinted courtesy L. Belhaouari from Ref. [3]; © 2013, L. Belhaouari. (b) Dissection by L.
Belhaouari and F. Lauwers., Department of Anatomy Toulouse University, France. Source: Reproduced from
Ref. [3] courtesy L. Belhaouari; © 2013.

15 Neck Rejuvenation
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Function: Its anterior fibers draw the skin of
the chin downwards, its middle fibers pulls
the angle of the mouth and lower lip down
by unfolding it, and its posterior fibers draw
the skin of the cheek downward and the labial
commissure laterally and down. It also tenses
and creases the skin of the neck and lifts the
skin of the pectoral region. It contracts dur-
ing exertion (forced inspiration) and in anger,
and it forms the platysma bands. Its atrophy
as a result of aging results in “turkey neck”:
unsightly vertical creases that affect elderly
people.
How Does the Platysma Age?
As with the skin of the neck and its subcuta-
neous tissue, the platysma atrophies and loses
its tone. It should logically become more flac-
cid and stretched out through the loss of its
mechanical and viscoelastic properties, but
unlike the skin, the muscle is a reactive tissue,
and responds to this stretching out by mus-
cular hypertonia. This contraction combats
the theoretical stretching of aging, resulting
in shortening of the muscle, giving a pseudo-
muscular resting tone [9].
As a result, this originally flat muscle loses
its homogeneity. Its fibers shrink up into
bundles (the platysmal bands), leaving empty
or loosely dense fiber spaces between these
bands, and thus genuine open gaps in the
flat surface of the platysma. This is an essen-
tial consideration, since if botulinum toxin is
injected subcutaneously in the neck and the
injected toxin encounters one of these open
spaces, it will inevitably diffuse deeper into
the neck, since there is no muscular barrier to
absorb it. If the doses are large, adverse effects
could result.
Consequently, the platysmal bands arise
from these two factors: shortening of the rest-
ing muscle and union with bundles of fibers
between them.
Muscles Associated with the Platysma
The Depressor Anguli Oris (DAO)
Triangular in shape (the origin of its “tri-
angular muscle” name in French), its infe-
rior base arises from the anterior third of
the external oblique line of the mandible. Its
fibers then proceed upward, by criss-crossing
and entwining with the anterior fibers of
the platysma, and continue upwards towards
the labial commissure. Some of these fibers
attach to the skin of the angle of the mouth
to transform the labial commissure, result-
ing in the expression of sadness. Other fibers,
after interlacing with the other muscles that
form the muscular knot termed the modio-
lus, go back up into the upper lip and (with
the upper fascias of the buccinator muscle)
form the external orbicularis oris muscle of
the lips before attaching beneath the skin of
the lips at the philtral ridge. These superficial
extrinsic fibers thus contribute to the relief of
the philtrum (said in folklore to be the indent
from God’s finger on the mouth of the new-
born child), and with the loss of tone and the
atrophy resulting from age, the relief of these
philtral ridges decreases, and the philtrum
becomes less well outlined and flattened.
Depressor Labii Inferioris (DLI)
Quadrilateral in shape, its inferior base arises
at the anterior third of the external oblique
line of the mandible, just above the line of
attachment of the depressor anguli oris mus-
cle. The DAO thus covers the DLI at this
level and is therefore more superficial (very
important when understanding the depth and
the level of injection needed for botulinum
toxin). As with the DAO, its fibers criss-cross
and entwine with the anterior fibers of the
platysma before inserting on the skin and the
red edge of the mucosa on nearly the entire
lower lip. As a transformer of the lower lip,
its free edge widens. It expresses disgust and
irony.
Risorius Muscle
According to some anatomists, the risorius,
an inconstant, very thin and very superficial
muscle, arises from fibers from the platysma.
It extends horizontally in a triangle, with
the posterior base on the middle part of the
cheek, and attaches at the modiolus and the
skin of the labial commissure. A superficial
adjunct of the buccinator, it draws the com-
missure laterally and can deepen the dimple


Botulinum Toxins
of the cheek by its mediojugal cutaneous
insertion.
Signs of Aging in the Neck
To recap, the three signs of aging in the neck
are:
1. Sagging, with loss of definition of the
mandibular edge and the cervicomental
angle, with cervical cutaneous ptosis.
2. Atrophy, in the form of platysmal bands.
3. Horizontal cervical wrinkles (also referred
to as horizontal necklace lines).
We have already discussed these first two
points in the preceding section.
Sagging, Ptosis of the Musculocutaneous
Integument
This explains the loss of definition of the
mandibular edge, with jowl formation, and
the loss of definition of the cervicomental
angle with ptosis of the integument. It con-
cerns the skin, subcutaneous fatty tissue, and
the platysma, and also explains the shrivelled
skin, jowls, and “turkey neck” (Figure 15.2).
The Platysmal Bands
The genesis of platysmal bands was described
in the preceding chapter: the result of changes
Figure .Jowl formation. Loss of definition of
cervicomental angle and loss of definition of jaw line.
Courtesy Dr. K. De Boulle, Belgium.
Figure .Prominent platysmal bands. Courtesy
Dr. K. De Boulle, Belgium.
in the platysma over time, with some fibers
among them forming clusters and shortening
of the muscle at rest. Atrophy over time, along
with the persistent platysmal activity to sup-
port the sagging neck and mouth floor struc-
tures leads to a more prominent appearance
(Figure 15.3).
Horizontal Cervical Wrinkles
The first question to ask is whether hori-
zontal cervical wrinkles are expression wrin-
kles. If they were, we would expect botulinum
toxin to be effective, as with frontal wrinkles.
But in fact botulinum toxin is not effective
in any way, because these horizontal cervi-
cal wrinkles are not expression wrinkles. As
a reminder, there are four types of wrinkles
in the neck: superficial photodamage wrin-
kles, dynamic expression lines, deep crum-
pling lines, and tissue accumulation wrinkles
(Figure 15.4).
Superficial Photodamage Wrinkles
These are superficial epidermal lines: peri-
oral wrinkles on the upper lip are another
example. This “barcode” is due to elastoly-
sis of the superficial stratum papillaris, which
loosens and becomes too baggy, compared to
the underlying dermis. It creases and it is this
fine creasing that creates the superficial wrin-
kles, as can also be noted in the neck area.

15 Neck Rejuvenation

Figure .Deep crumpling horizontal lines and
superficial photodamage wrinkles. Courtesy Dr. K. De
Boulle, Belgium.
Dynamic Expression Lines
These are due, as is well known, to the influ-
ence of the cutaneous muscles on the skin
to which they are attached; however, the
platysma is attached very low on the skin
that covers the acromion, and the deltoid
and subclavicular regions. Above, although
some fibers attach at the inferior edge of the
mandible on the anterior part of its exter-
nal oblique line, it is essentially inserted at
the skin of the cheek and the labial com-
missure. At the neck therefore, the platysma
covers only the anterolateral region of the
neck in a split superficial fascia, and without
inserting in the cervical skin as such. Thus,
on the neck itself, one can hardly expect to
find real expression wrinkles, which would
have been the main reason for recommend-
ing botulinum toxin treatment [10,11].
Deep Crumpling Lines
Horizontal cervical wrinkles are in fact
permanent elastic creases, as are mediojugal
wrinkles and vertical frontal wrinkles. These
are “accordion wrinkles” caused by positional
constraints of the neck and multiple flexion–
extension movements of the head on the
neck. The head is raised and lowered many
times each day, folding the cervical skin like
an accordion in a horizontal direction. These
folds become perennial with the loss of cuta-
neous plasticity as the cervical skin loosens
with age, and becomes stretched compared
to the subjacent neck. It also becomes less
elastic, less plastic, thinner, more pliable,
and more prone to creasing. The skin thus
remains fixed in the position in which it is
folded: it is a false fold, a permanent elastic
wrinkle. These effects are exacerbated by
the weight of this cutaneous tissue, which
has loosened with age, and the fixed night-
time position, often with the head slightly
bent, which fixes these folds like a nearly-
closed accordion. It thus becomes clear why
botulinum toxin cannot have an effect on
these wrinkles, which are elastic creases and
not dynamic expression lines of muscular
origin.
Neck Rejuvenation
From the earlier text, we could state that four
signs characterize the aging neck are:
r Platysmal bands
r Loss of definition of the cervicomental
angle with laxity and cervical cutaneous
ptosis
r Loss of definition of the mandibular edge
r Horizontal cervical wrinkles.
So, is botulinum toxin effective on these
four clinical signs? And, at this time, is there
competition between botulinum toxin and
the other techniques, especially surgical ones,
for these four indications [11,12]?
We have just seen in the Chapter 14 that:
r Horizontal cervical wrinkles are elastic
creases and not dynamic expression lines of
muscular origin; consequently, botulinum
toxin is not effective and there is no indica-
tion for its use [13–16].
r Concerning cervical sagging with cuta-
neous ptosis, it is completely unrealistic to
expect a real facelift effect. The “Botulinum
Toxin Facelift” is a dream today.
Injections with botulinum toxin are com-
pletely ineffective in patients presenting with
cervical sagging and cutaneous ptosis. This
has been stated in many publications and


Botulinum Toxins
most of the authors experienced in their prac-
tices no real evidence of lifting, and it is def-
initely not a substitute for long-term surgi-
cal results. Current thought is that botulinum
toxin can be effective on hyperactive muscle
lines (i.e., platysmal bands) in the appropri-
ate patient, though there has been no well-
described, proven effect on facial contour or
improving horizontal neck wrinkles or laxity
[15,17,18].
Phillip Levy deserves all the credit for hav-
ing described the “Nefertiti Neck” concept
and brought it to the forefront [16, 18]. For
improving the jaw line contour and more
or less providing a visual effect of a “mini-
lift”, this procedure has been considered to
be helpful (Figure 15.5); however, results can
be highly variable and for that reason Levy
highlights the importance of proper patient
selection. The treatment is likely to cre-
ate a successful result when the patient has
retained the integrity of their skin elastic-
ity and their ligaments [16]. For this reason,
younger patients, as well as those patients
who have undergone a surgical neck lift are
ideal candidates. But a real lifting of the lower
face by means of injections of botulinum
toxin in a platysmal band and submandibu-
lar area as a substitute for a surgical neck lift
is impossible [10,17,19].
It was of course tempting to try, since “the
art of succeeding is the art of sometimes
being very daring”. But, although the art of
Figure .Position of injection points with 2U
onabotuliumtoxin per point for the so called
“Nefertiti lift”. Courtesy Dr. K. De Boulle, Belgium.
Figure .Example of a surgical cervicofacial
facelift to restore definition of the cervicofacial oval.
succeeding is “the art of sometimes being very
daring”, it is even more true to say “the art of
succeeding is the art of being sometimes very
daring, sometimes very careful”.
Only
the
classic
surgical
cervicofacial
facelift can tighten the skin and the platys-
mal
muscular-fascia system
and
restore
good definition of the cervicofacial oval by
resorbing the cutaneous-fatty surplus and
redetermining the platysma muscular edge
in a superoposterior tension vector [9,11,17]
(Figure 15.6).
When the different mechanisms of aging
and the different techniques are understood,
it becomes clear that these techniques are
complementary and not competitive. Surgery
addresses ptosis and cutaneous surplus, fill-
ing addresses depressions, loss of volume,
and the facial contours, lasers, and peel-
ings address signs of photodamage, and toxin
addresses the dynamic wrinkles. It is neces-
sary to know how to combine these tech-
niques since although they can all be used
alone, and in some rare cases may be com-
petitive, their evolution leans towards their
tremendous complementarities, and their
combination enables us to obtain results that
are increasingly complete and increasingly
convincing [3,12,20].
The first and the third characterizing
signs of the aging neck remain, that is, the

15 Neck Rejuvenation

appearance of platysmal bands and the loss of
definition of the mandibular edge.
Platysmal Bands
This is certainly the best indication at the
neck for botulinum toxin. As described ear-
lier, the platysma, a flat muscle, loses its
homogeneity with age and its fibers assem-
ble into clusters to form platysmal bands.
Between these bands, empty spaces or loosely
dense fibers are found, creating gaps in the
flat surface of the platysma. Understanding
these changes with aging is the basis for
understanding the treatment with botulinum
toxin and mastery of the technique [3,10,11].
Relaxation of the muscle fibers of the
platysma bands enables their reduction or
even disappearance, as they no longer con-
gregate in bands, barring the neck vertically,
but on the contrary, integrate with the relief
and the slope of the neck, softening the cervi-
cal line.
The indications are:
r Necks with mild sagging but with new
or marked bands, whether at rest or with
movement.
r Another excellent indication is as a com-
plement to a facelift.
In fact, with cervical cutaneous-fatty tissue
sagging – the first indication for a surgical
facelift – interventions targeting the platysma
bands may be incomplete even in the hands
of talented surgeons, and even if the result on
the cutaneous ptosis itself is excellent.
This is where the role for botulinum toxin
lies, in relaxing these bands and thereby
reducing them or even making them disap-
pear. This surgery–botulinum toxin combi-
nation is the demonstration of our adage
“Optimization
not
Opposition”
between
techniques [3,12,20].
The literature on treating platysmal bands
is quite divergent on techniques of injecting,
dosing per platysmal band, total dosing for
the neck, and patient outcome and overall sat-
isfaction [10,13,17,18,21–24].
Figure .Injecting botulinum toxin for platysmal
bands perpendicular to the skin and raising a bleb.
Courtesy Dr. K. De Boulle, Belgium.
The technique of treating the platysmal
bands is simple:
1. Visualize and mark the platysmal bands at
rest and in the dynamic state by a forced
cervical contraction.
2. In stages, inject a small dose of botulinum
toxin (e.g., 2 U of onabotulinumtoxin or
an equivalent of abobotulinumtoxin or
incobotulinumtoxin [15, 16, 19, 25, 26])
or every 2 cm along the length of these
cords, being careful to begin very high near
the bony mental or mandibular edge.
3. The injection must be strictly subcu-
taneous so that the diffusion occurs in
the muscle. To avoid deep diffusion, the
injection should under no circumstances
be submuscular. The best option is to raise
a bleb upon injection, as in an intradermal
test. If injecting by pinching the cord
between the thumb and index finger, be
careful not to inject between the two mus-
cular sheets folded as a sandwich (since
in this case, there will be five layers: skin–
muscle on the thumb side and submus-
cular space–muscle and skin on the index
finger side) (Figures 15.7 and 15.8).
4. The injection must cover the entire length
of the platysmal band, with an injection
every 2 cm [13,16,18,21].
5. Preferably relax all the platysmal bands,
because if only some bands or a part of
some bands are relaxed, the non-relaxed


Botulinum Toxins
Figure .Alternative injection technique: beware
of submuscular injection.
areas can become hypertonic and hyper-
active in a reflex manner, attempting to
compensate for the relaxed parts. This is
true for all muscles (the frontalis mus-
cle provides the best example: when only
the median part is relaxed, the lateral
part can become hypertonic, producing a
“Mephisto effect”) [3,7,11].
6. Refrain from using massive total doses
in the neck area (e.g., a total of 40–60 U
of onabotulinumtoxin or an equivalent
of abobotulinumtoxin or incobotulinum-
toxin) [13, 14, 19, 27]. Several recent pub-
lications have recommended a maximal
dose of 50 U for the global neck treatment
[15,16].
7. Be careful if injecting between the platys-
mal bands in the middle of the platysma.
Keep in mind what we described ear-
lier. There may be empty gaps at inter-
vals of muscular fibers, since the fibers
are clustered together to form the bands.
In this instance, the injection is bound
to occur deep in the submuscular spaces,
with all the adverse effects and dan-
gers that this can engender. In any case,
injecting between the cords has no ben-
efit, since the toxin is ineffective on the
other signs (cutaneous sagging of the neck
and horizontal cervical wrinkles) [4, 5, 8]
(Figure 15.9a, b).
8. The follow-up is generally uncomplicated,
with the odd bruising or ecchymosis [17].
Loss of Definition of the Mandibular Edge
This is the first sign of cervicofacial sagging.
The oval of the face is less well outlined due
to a mild ptosis at the mandibular edge that
comprises the horizontal branch of the lower
jaw and the angle of the jawbone. A hint
of jowls also begins to form. The mandibu-
lar edge is thus not as well covered by the
integument, which then covers its bony relief,
namely the muscular plane of the platysma
and the cutaneous fatty tissue, due to their
displacement by gravity [4,11,19].
A beneficial effect on the definition of the
mandibular edge can only be obtained in very
moderate cases, and it is essential to dis-
tinguish muscular looseness from sagging of
the integument. In the early stages, a result
(a)
(b)
Figure .(a) Unilateral platysmal band before treatment at max contraction. (b) Result 1 week after injection
of 12 U onabotulinum toxin in unilateral platysmal band. Courtesy Dr. K. De Boulle, Belgium.

15 Neck Rejuvenation

(a)
(b)
Figure .(a) Before treatment at rest. (b) After treatment with onabotulium toxin at rest. Courtesy Dr. K. De
Boulle, Belgium.
that is certainly an improvement may be
obtained, but it results from the relaxation of
the platysma muscle by the botulinum toxin
(Figure 15.10 and Figure 15.11).
In the moderate or marked forms, however,
a facelift effect can never be achieved, since
the cutaneous fatty tissue sagging dominates.
For cases of more advanced definition loss
and more sagging, this technique can only be
considered for individuals not ready nor eli-
gible for neck surgery, requesting an adjuvant
to previous neck surgery, or requesting mini-
mal or no downtime [10,17,24,27].
How can this beneficial effect be explained?
There are two possible explanations:
r The posterior and lateral fibers of the
platysma cover the mandibular edge and
are inserted higher up at the labial com-
missure, the skin of the mid-cheek, and
also entwine with the fibers of the risorius
muscle. The increased resting tone related
to aging therefore lowers these cutaneous
insertion areas and consequently results in
a depressant effect on the lower part of the
face. This depressant effect associated with
cutaneous sagging due to aging will also
lower the area relative to the mandibular
edge, leading to the loss of definition of the
oval at this level. Relaxation by botulinum
toxin will have the opposite effect: by lifting
these cutaneous insertion sites, the cuta-
neous area at the mandibular edge will
also rise and consequently this mandibular
edge will be better outlined through a bet-
ter application of the muscular-cutaneous
cover on the bony relief, providing a better
definition of the oval of the face [12,19].
r The second explanation also starts with
the principle of the increased resting tone
and consequent shortening of the verti-
cal muscle fibers. The muscular-cutaneous
cover, which is made up of the skin and
the platysma, integrates the natural curve
of this anatomical area of the upper neck,
that is, opposite and below the mandibular
edge. Shortening of the platysma tightens
it like the string on a bow, preventing this
muscle from applying itself to the relief of
the curve and submandibular space. There-
fore, by relaxing the platysma muscle at
this level, its fibers are lengthened, allowing
(a)
(b)
Figure .(a) Before treatment at max contraction. (b) After treatment with onabotulium toxin upon max
contraction. Courtesy Dr. K. De Boulle, Belgium.


Botulinum Toxins
Figure .The posterior and lateral fibers of the
platysma cover the mandibular edge and are
inserted higher up at the labial commissure.
better integration of the relief of the curve
and space of this submaxillary depression
(Figure 15.12).
The injections are made every 2 cm on
a line situated 1 cm below the horizontal
branch of the mandible. The injection must
be very superficial, subdermally, without ever
injecting through the platysma, to avoid deep
diffusion. Somewhere between three and six
injection points of a small dose of botulinum
toxin (e.g., 2 U of onabotulinumtoxin or
an
equivalent
of
abobotulinumtoxin
or
incobotulinumtoxin [21,25,26]) are generally
sufficient for each side. The platysma gener-
ally stops at the angle of the jaw, so there is no
need to inject behind this point.
Why is it often beneficial to combine the
relaxation of the depressor anguli oris with
that of the platysma? Because they have
certain synergistic actions. As discussed, the
fibers of the platysma are inserted midcheek
but also extend to the labial commissure and
entwine with the DAO fibers (Figure 15.14).
Thus, the platysma is a depressor for the infe-
rior part of the face, as well as for the angle of
the mouth in synergy with the DAO. There-
fore, it is better to relax all the muscles that
are responsible for a function, to avoid an
increased reactive tone in muscles that were
not or only partially relaxed.
Inject twice the dose of botulinum toxin per
point compared to the platysmal band injec-
tions (e.g., 4 U of onabotulinumtoxin or an
Figure .Injection point for m. depressor anguli
oris with botulinum toxin. Courtesy Dr. K. De Boulle,
Belgium.
equivalent of abobotulinumtoxin or incobo-
tulinumtoxin [21,25,26]):
r subcutaneously and superficial to the
DAO, avoiding excess depth, so as not to
pass through the DAO risking to address
the depressor labii inferioris
r 1 cm above the mandibular edge, avoiding
going too high and then risking diffusion
towards the orbicularis labii muscle
r 2 cm behind its anterior edge, that is, 2 cm
behind the line of the labial commissure,
so as not to risk diffusion medially, beyond
the anterior edge of the DAO, towards
the depressor labii inferioris muscle (Fig-
ure 15.13).
Patient Selection
Although there are no clear guidelines on
proper patient selection to ensure a success-
ful outcome with neurotoxin injection to the
neck, most experts in the field agree on a few
key principles [15,16,28,29]:
r Treatment should be considered only for
patients with satisfactory skin elasticity of
the neck. Therefore, younger patients tend
to see more improvement with the treat-
ment.
r Patients with minimal drooping of sub-
mental fat see more marked improvements
(Figure 15.15).
r Patients should have retained laxity in the
platysma muscle. To assess this feature, the

15 Neck Rejuvenation

Figure .Dissection by L. Belhaouari and F.
Lauwers., Department of Anatomy Toulouse
University, France. Source: Reproduced from Ref. [3]
courtesy L. Belhaouari; © 2013.
patient is asked to contract the platysma
muscle; an ideal candidate will have loss of
the mandibular border with platysma con-
traction [15].
Preventing Complications and Side Effects
The follow-up is uncomplicated, and ecchy-
mosis is very rare. Side effects are minimal
and are related to the motor function of the
platysma muscle with exertion, particularly
during forced inspiration. The resulting dis-
comfort can be avoided by being cautious in
initial treatment and thus reducing on the
total quantity of toxin injected. Complica-
tions to the neck are essentially the risks of
diffusion in deeper layers. Diffusion beneath
the platysma muscle may be related either to
the mere fact of injecting too deeply, or to a
too high total dose. [13–16,24].
Overdose
The total must not exceed 40–60 U of
onabotulinumtoxin
or
an
equivalent
of
abobotulinum or incobotulinumtoxin for an
entire neck [13–16, 21, 30]. We have learned
that the first indication for botulinum toxin
in the neck is the relaxation of platysmal
bands, and to a lesser degree the beginning
of loss of definition of the mandibular edge.
There is therefore, at least to our knowledge,
no need to strive to treat confirmed cervical
sagging
(the
“Botulinum
Toxin
Facelift”
does not exist), or horizontal “accordion”
wrinkles on the neck. Doing so would be
completely useless, and would risk increasing
the injected doses and inflicting the risk of
overdose.
Injecting too Deeply
This is obviously a technical error. We should
recall the two items described earlier. First,
between the platysma bands in the middle of
the platysma muscle, there may be open gaps
of muscular fibers since the fibers are clus-
tered together to form the bands. An injec-
tion at this level does not meet the muscu-
lar barrier and is mandatorily deep in the
submuscular spaces. Second, if injecting the
platysma bands from laterally by pinching
between the thumb and index finger, be care-
ful not to inject between the two muscu-
lar sheets folded as a sandwich (since in this
case, there will be five layers: skin–muscle
on the thumb side and submuscular space–
muscle and skin on the index finger side). The
Figure .Source: Reprinted courtesy L.
Belhaouari from Ref. [1]; © 2006, L.
Belhaouari.


Botulinum Toxins
injections thus must be very superficial, sub-
dermally, without ever passing through the
platysma.
What are the Risks of Deep Diffusion?
[10–14,16,18,21,24,27,30,31]
r Posture and static cervical support defect
from weakening of the muscle tone, par-
ticularly in the case of diffusion towards
the sternocleidomastoid. This can lead to
neck tightness and difficulties in bending
the neck.
r On the other hand, the platysma is con-
tributing to bending the head forward. Too
aggressive relaxation might result in the
inability to bring the head forward.
r Smile discomfort.
r Risks of dysphagia, salivary insufficiency,
from diffusion to the infra-hyoid muscles.
r Difficulty swallowing.
r Respiratory function disorders.
Serious Adverse Events are Extremely Rare
Rare cases of dysphagia, swallowing diffi-
culties, speech disorders, false alimentary
routes or respiratory disorders resulting in
potentially fatal inhalation pneumonia have
been described. These cases were reported
in medical treatments, therefore at high
therapeutic doses after injection in points
other than the platysmal cervical muscula-
ture, in patients presenting with excessive
muscular weakness. It is therefore not a risk
in aesthetic indications and at doses used in
cosmetic treatment. As such, we should not
provide cosmetic treatment to patients with
any suspicion or history of this type of disease
[16,31].
Conclusion
There are multiple techniques for addressing
the signs of cervicofacial aging, and the devel-
opment of techniques increasingly clearly
favors the mildest treatments, keeping in
mind their efficacy and their safety. A sub-
tle mix of these factors will direct our indica-
tions for treatment. For the neck, botulinum
toxin currently has benefits, but does not
have the level of efficacy that can be seen
in other areas in the face. It is nevertheless
fantastic to treat platysmal bands and early
loss of the mandibular edge without having
to resort to more invasive surgical proce-
dures, and to complement these surgical pro-
cedures, which remain the first indication for
sagging and ptosis of the neck integument.
Our art is to be audacious while remaining
cautious, to maintain our credibility and the
trust of our patients.
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Kane M. The functional anatomy of the
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Fagien S, Raspaldo H. Facial rejuvenation
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556.



Correction of Facial Asymmetry
Scott Rickert, MD (FACS),1 Lesley F. Childs, MD,2 and Andrew Blitzer, MD (DDS, FACS)3
1Attending Physician, Assistant Professor of Otolaryngology, Pediatrics, and Plastic Surgery, NYU Langone Medical Center, New York, USA
2Attending Physician, Assistant Professor of Laryngology, Neurolaryngology, and Professional Voice, UT Southwestern, Dallas, TX
3Director, NY Center for Voice and Swallowing Disorders; Senior Attending Physician, St. Luke’s/Roosevelt Hospital; Professor of Clinical
Otolaryngology, Columbia University College of Physicians and Surgeons, New York, USA
Introduction
The facial nerve is the most commonly
paralyzed nerve in the human body [1]. This
impairment can be significant, as the seventh
cranial nerve is not only responsible for facial
expression, but also eye protection, lacrima-
tion, oral competence, salivation, taste, and
sensation. The constancy of facial expression
is universal and cross-cultural. Without the
ability to make meaningful facial expression,
individuals can become socially isolated
and emotionally unwell. The list of possible
etiologies for facial nerve paralysis is exten-
sive and most commonly include trauma,
Bell’s palsy, and iatrogenic and idiopathic
causes [1].
Assessment
Several different methods exist for assess-
ment of facial nerve impairment. None of
the current instruments have been shown to
sufficiently and reliably assess all the differ-
ent types of facial asymmetry, including facial
paralysis, focal partial facial weakness, and
synkinesis. Thus, in assessing facial asymme-
try, one must use the appropriate instruments
for the condition of the patient.
The House–Brackmann system is the most
widely used [2] (Table 16.1).
While the House–Brackmann scale is use-
ful for gross quantifications of facial function,
it does not reliably assess synkinesis or partial
facial function well.
The Facial Clinimetric Evaluation (FaCE)
scale is a 15-item instrument used to assess
facial impairment and disability. It has been
deemed a reliable and valid instrument
for most facial asymmetries, but does not
address synkinesis adequately.
The Synkinesis Assessment Questionnaire
(SAQ) [3] is a nine-item instrument found
to be valid and reliable for the assessment of
synkinesis but does not adequately address
more global facial asymmetries (Figure 16.1).
Question 9 is not used in the scoring of
SAQ.
Treatment
In caring for patients with facial nerve weak-
ness, protection of the eye is of the utmost
importance. Specifically, the goal is to pro-
tect the cornea from irreversible complica-
tions that could lead to blindness. Lubrication
strategies such as ophthalmic drops, oph-
thalmic ointment, taping the eyelid at night,
and the use of a moisture chamber help to
prevent ocular complications.
There are many surgical procedures that
are used to address the asymmetric face. The
Botulinum Toxins: Cosmetic and Clinical Applications, First Edition. Edited by Joel L. Cohen and David M. Ozog.
© 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.
Companion Website:


Botulinum Toxins
Table .The House–Brackmann system.
Grade
Description
Characteristics
I
Normal
Normal facial function in all nerve branches
II
Slight
Gross: Slight weakness on close inspection, slight synkinesis
At rest: Normal tone & symmetry
Motion:
Forehead: Good to moderate movement
Eye: Complete closure with minimum effort
Mouth: Slight asymmetry
III
Moderate
Gross: Obvious but not disfiguring facial asymmetry. Synkinesis is noticeable
but not severe. May have hemi-facial spasm or contracture
At rest: Normal tone & symmetry
Motion:
Forehead: Slight to moderate movement
Eye: Complete closure with effort
Mouth: Slight weakness with maximum effort
IV
Moderately
severe
Gross: Asymmetry is disfiguring and/or obvious facial weakness
At rest: Normal tone & symmetry
Motion:
Forehead: No movement
Eye: Incomplete eye closure
Mouth: Asymmetrical with maximum effort
V
Severe
Gross: Only slight, barely noticeable, movement
At rest: Asymmetrical facial appearance
Motion:
Forehead: No movement
Eye: Incomplete closure
Mouth: Slight movement
VI
Total
No facial function
procedures generally are aimed at creating a
balanced face at rest and in motion. At rest,
upper eyelid gold weight placement and/or
lower eyelid canthoplasty can help to address
the asymmetric orbital region, and prevent
drying of the cornea. Static facial slings as well
as a standard rhytidectomy can help to pro-
vide static correction of lower and midface
gross asymmetries at rest.
More dynamic solutions can help provide
correction at rest and with motion. Muscle
transposition using the temporalis or mas-
seter muscle is one example of a dynamic
sling. Nerve grafting and neurorrhaphy via
end-to-end
nerve
anastomosis
(typically
great auricular or hypoglossal), jump graft-
ing (typically as hypoglossal with sural or
great auricular), interposition grafting, or
cross-facial grafting can provide long-term
nerve innervation to areas lacking current
innervation.
The recent advent and use of botulinum
toxin as well as cosmetic fillers has provided
a promising avenue for nonsurgical treatment
of facial asymmetry, both major and minor.
With the vast variety of presentations of
facial asymmetry, it is important to formulate
a solution that is specific to the patient. The
goal of creating a balanced face at rest and
in motion must always be the essence of
the treatment. This can be through a single
modality treatment or a combination of
surgical and/or nonsurgical treatments. An
example of combination therapy can be
shown in rehabilitation after acoustic neu-
roma resection with disturbance of the facial
nerve function at surgery. The combination
of a hypoglossal-facial nerve anastomosis

16 Correction of Facial Asymmetry

Synkinesis Assessment Questionnaire (SAQ)
Date:
Please answer the following questions regarding facial function, on a scale from 1 to 5,
according to the following scale:
1 = seldom or not at all
2 = occasionally, or very mildly
3 = sometimes, or mildly
4 = most of the time or moderately
5 = all the time or severely
1
When I smile, my eye closes
2
When I speak, my eye closes
3
When I whistle or pucker my lips, my eye closes
4
When I smile, my neck tightens
5
When I close my eyes, my face gets tight
6
When I close my eyes, the corner of my mouth moves
7
When I close my eyes, my neck tightens
8
When I eat, my eye waters
9
When I smile, my lower lips are matched in position
10
When I move my face, my chin develops a dimpled area
Total Synkinesis Score: Sum of Scores 1 to 9/45 × 100
Question
Score
Figure .The Synkinesis Assessment Questionnaire.
with botulinum toxin injections for synki-
nesis optimized the facial symmetry at rest
and in motion [4].
Synkinesis
Botulinum toxin has proven to be most use-
ful in those patients who develop aberrant
regeneration of fibers after facial nerve injury.
Synkinesis, which is the presence of unin-
tentional motion in one area of the face
produced during intentional movement in
another area of the face, represents one of
the most troubling sequelae of facial nerve
paralysis. Synkinetic movements are not only
socially debilitating, but also can be quite
painful, with simultaneous spasm of multi-
ple muscle groups. Commonly, synkinesis is
oculo-oral, involving involuntary oral com-
missure movement with voluntary eye clo-
sure, or vice versa. Surgical intervention for
synkinesis is extremely challenging due to
the aberrant reinnervation, and yields mixed
results at best.
The etiology of synkinesis is thought to
be multifactorial, with evidence supporting
the role of aberrant axonal regeneration as
well as central involvement of facial nucleus
hyperexcitability. Two types of synkinesis
are typically described [5]. First is a syner-
gistic synkinesis where movement on the
affected side is similar to but more excessive
than that on the unaffected side. Secondly
is a paradoxical synkinesis, in which the
secondary facial movement is in a direction
antagonistic to normal facial movement [5].
Bajaj-Luthra et al. [6] quantitatively analyzed
the patterns of synkinetic facial movements
on both the affected and unaffected sides.
One of the major focuses of facial movement
revolves around an area known as the modi-
olus, where several facial muscles converge
just lateral to the buccal angle and form
a three-dimensional fibromuscular mass.
Patients with oculo-oral synkinesis were
noted to have increased modiolar motion
during eye closure relative to controls. This
motion was noted to be asymmetry with
increased intensity in both the horizontal and
vertical plane [6].
As mentioned earlier, most facial grad-
ing systems focus on facial impairment and
disability (House–Brackmann system, FaCE


Botulinum Toxins
scale), but do not reliably assess synkine-
sis as part of facial impairment. The recent
advent of a validated SAQ [3], the patient-
graded nine-item questionnaire focused on
assessment of facial synkinesis, has allowed
for more consistent and reliable evaluation of
patients with synkinesis.
Several
different
nonsurgical
therapies
have been used to treat synkinesis. One of
the earliest reported physiotherapy programs
with consistent positive results for synkinesis
rehabilitation has been mime therapy. This
technique was originally developed in the
Netherlands as a collaboration between
clinicians and mime actors [7]. Today, the
most common therapeutic modalities for the
treatment of facial synkinesis include facial
neuromuscular retraining and botulinum
toxin administration, which can augment the
retraining.
When initially evaluating a patient with
synkinesis, it is crucial to note atypical fea-
tures of synkinesis such as facial weakness,
facial numbness, a decreased corneal reflex
or any other cranial nerve abnormalities. In
these clinical scenarios, a space-occupying
lesion should be excluded with an imaging
study, typically magnetic resonance imaging
and/or angiography. If such a lesion is iden-
tified, neurosurgical consultation and further
workup is warranted.
When botulinum toxin is used to help treat
synkinesis, the goal is to weaken the abnor-
mally stimulated facial musculature to allow
for more symmetrical movement as well as
postures at rest. The upper and lower face
is treated at the same initial setting. Optimal
dosing is decided on an individuated basis
based upon the patient’s active and passive
facial symmetry. A thorough understanding
of facial anatomy is crucial for a proper treat-
ment technique. The zygomaticus muscles,
levator angli oris, depressor angli oris, riso-
rius, and the platysma are the most often
injected muscles under electromyographic
control [8].
The zygomaticus major muscle arises from
the zygomatic bone in front of the zygo-
maticotemporal suture. The muscle descends
obliquely and inserts into the angle of the
mouth. This muscle draws the angle of the
mouth backward and upward, as in laughing.
The zygomaticus minor originates from the
malar bone and inserts into the outer portion
of the upper lip. It draws the upper lip back-
ward, upward, and outward.
The levator angli oris arises from the
canine fossa, just below the infraorbital fora-
men. These fibers insert into the angle of the
mouth. The depressor angli oris arise from
the oblique line of the mandible and insert
into the angle of the mouth. The action of
this muscle depresses the angle of the mouth,
acting antagonistically to the action of the
levator.
The risorius arises in the fascia over the
masseter and passes horizontally forward,
superficial to the platysma. It then inserts into
the skin at the angle of the mouth. Its action
retracts the angle of the mouth.
The platysma is a broad sheet arising from
the fascia covering the upper parts of the pec-
toralis major and deltoid. The fibers cross the
clavicle and proceed obliquely upward and
medially along the side of the neck. The ante-
rior fibers interlace, below and behind the
symphysis menti, with the fibers of the mus-
cle of the opposite side; the posterior fibers
cross the mandible, some being inserted into
the bone below the oblique line, others into
the skin and subcutaneous tissue of the lower
part of the face, many of these fibers blending
with the muscles about the angle and lower
part of the mouth. The platysma retracts and
depresses the angle of the mouth [9].
Botulinum toxin is typically effective for
3–4 months after the injection. Patients
receive follow-up treatment and injections
as needed, typically on a 3- to 4-month
schedule. To minimize side effects and ade-
quately gauge response, additional or ‘touch-
up’ treatments are typically deferred until the
patient’s following visit when a higher total
dose can be used [5].
Asymmetry of Smile
Asymmetry of facial features can be balanced
using strategically well placed injections

16 Correction of Facial Asymmetry

of botulinum toxin. An asymmetrical smile,
where the musculature on one side contracts
at a different force than the other side, has
a significant and overlooked impact on the
patient’s quality of life. Subtle differences are
frequently noticed in the overall appearance
of an unbalanced face. Similarly a ‘gummy’
smile, with too much lip retraction can make
patients self-conscious as well. The elevators
of the upper lip include the levator labii supe-
rioris, the levator labii superioris alaeque
nasi, the zygomaticus major and minor,
the levator anguli oris, and the risorius. The
depressors of the lower lip include the depres-
sor labii inferioris, mentalis, and platysma.
Depending on the asymmetry, botulinum
toxin injections to individual muscles can
help balance the smile and decrease excess
pull of the upper or lower lip. These injections
are all carried out under electromyographic
control [5] to minimize complications of poor
injection placement.
Furthermore, if there appears to be a hol-
lowing or flattening effect of the smile unable
to be corrected by balancing injections on
the opposing side, directed filling injections
(calcium hydroxylapatite, fat) can be used to
balance the asymmetry as well.
Asymmetry of Eyelids
Asymmetry of the eyelids or ‘drooping’ eye-
lids can be addressed with nonsurgically
with small doses of botulinum toxin. Care-
ful injection in the lower lid lateral to
the mid-pupillary line helps to prevent the
excess activity of the orbicularis oculi caus-
ing ‘drooping’ eyelids. This allows the lower
lid to ‘tighten’ and correct minor asymme-
tries. When the ‘drooping’ is excessive, com-
bination therapy of lower blepharoplasty with
adjunctive botulinum toxin has been shown
to be an effective treatment. It is important to
perform a snap test of the lower eyelid prior
to any intervention and ensure there is ade-
quate tone of the eyelid. If the tone is inad-
equate, intervention may lead to blepharitis
and/or epiphora.
Masseter Hypertrophy/
Reshaping of Face
Masseteric hypertrophy is commonly caused
by bruxism, temporomandibular joint disor-
ders, or a misaligned jaw and presents with
local mandibular discomfort and a boxy facial
appearance. Initial treatments of masseteric
hypertrophy were surgical, but botulinum
toxin is a very effective way to systematically
decrease the hypertrophy. But chemically
deinnervating the muscle under electromyo-
graphic control [8], over time the muscle
begins to decrease in size – relieving local
discomfort and correcting facial appearance.
Unless the underlying cause of the hypertro-
phy muscle is fully addressed, repeated treat-
ments of botulinum toxin are necessary to
prevent further hypertrophy.
Paresis of the Face
Patients with unilateral facial weakness fre-
quently note frustration in their inability to
have a balanced face. Many physicians are
reluctant to treat them symptomatically as
they frequently recover their nerve function
and the timeline for potential recovery is not
always consistent. Although these patients
are a “moving target” as they potentially
recover, injections in the healthy (nonparetic)
side of the face to balance the face are very
effective and provide a great deal of relief to
the patient while they wait for their recov-
ery. It is recommended that the injections
are not too aggressive but they should bal-
ance the asymmetry as seen on exam. The
advantage of botulinum toxin is its effective
time frame of 3–4 months – if there had been
some interval recovery in the 3- to 4-month
time frame, the facial balancing injections can
be adjusted accordingly to continue to have
a balanced, symmetric face. In conjunction
with botulinum toxin injections, local filling
materials (calcium hydroxyapatite, or poly-
lactic acid) can help balance the face. Par-
ticular areas of need include the naso-labial
crease on the more functional side as well as


Botulinum Toxins
minor corrections in symmetry of the mouth
and eyebrows.
Disorders of Lipodystrophy
Disorders of lipodystrophy include congen-
ital and acquired disorder of lipodystrophy.
Currently, the predominant cause of lipodys-
trophy is associated with the use of highly
active antiretroviral therapy (HAART) in the
treatment of HIV. It typically presents with
loss of fat from the face and can give an
appearance of sunken eyes and prominent
cheekbones. While changing the HAART
regimen has been shown to improve symp-
toms in some patients [10], most need treat-
ment for their change in facial appear-
ance. Local filling materials such as calcium
hydroxylapatite, or poly-L-lactic acid can be
used to help careful address of the area of
wasting. It is important to attempt to create
adequate facial symmetry while individualiz-
ing each patient’s treatment.
Complications of Facial Botulinum
Toxin Injections
Several complications can arise from facial
musculature administration of botulinum
toxin. As always, it is important to have
an experienced medical professional who
has an excellent grasp of facial anatomy to
obtain the best results from administration of
botulinum toxin. Since the toxin is typically
effective for 3–4 months, any complications
will last a similar amount of time but will dis-
sipate as the toxin does.
Injection of botulinum toxin below the
orbital rim can lead to diffusion of the toxin
into the levator muscle of the upper lid lead-
ing to upper lid ptosis. It is possible to help
stimulate Muller’s muscle with a sympath-
omimetic eye drop such as Apraclonidine
0.5% or 1.0% drops (1 drop tid) while waiting
for the toxin to dissipate.
Excessive toxin in the musculature around
the eye may result in muscular weakness and
a decreased blink. If untreated, an exposure
keratitis may develop over time. Treatment of
exposure keratitis is typically frequent use of
ophthalmic artificial tear solution, ointment,
and/or a temporary patch over the eye for
protection.
Injection of botulinum toxin in the lower
face superficially may lead to local diffusion
into the nasolabial fold and cause a local
flattening of the fold. If this effect is strong
enough, it may lead to an asymmetric smile.
This is correctable over time by using smaller
doses on future visits and/or balancing the
facial asymmetry by injecting toxin into the
unaffected side. Also, one can inject filling
materials such as hydroxyapatite crystals or
fat to correct localized facial asymmetry and
remedy contour variations that may result
from injection of botulinum toxin [8].
Excessive toxin in the perioral region may
result in lip weakness or oral incompetence.
This would manifest itself as intermittent
drooling or escape of food and drink dur-
ing meals. Injection deep to the platysma in
the anterior neck may result in dysphagia
or hoarseness. Dietary modification may be
needed in cases of severe dysphagia.
There have been reported cases of immune
resistance to botulinum toxin (either A or B).
This can be tested in individuals by injecting
a small dose in the glabellar region and seeing
if it effectively smooths the horizontal rhytids
in the area. If there is no noted effect from the
initial injection, one should try the other type
of botulinum toxin (A or B). Frequently those
with some immune resistance to one type of
botulinum toxin do not have resistance to the
other type.
Case Presentations
The two cases presented below illustrate
some of the challenges of each case and the
need to individualize treatment, whether it is
single modality or combination treatment.
Case 1
A 66-year-old woman presents after a hem-
orrhagic midbrain cerebrovascular accident

16 Correction of Facial Asymmetry

(a)
(b)
(c)
Figure .(a) Preoperative photograph; (b) planned intervention overlaying photograph (black x, botulinum
toxin injection sites); (c) 2-month postoperative photograph.
with right facial paralysis. To treat her appro-
priately she underwent a combined treatment
of surgical and nonsurgical interventions.
She first underwent static reconstruction
with a gold weight to the right upper eyelid,
a right sided static sling, and a right sided
browlift. She also underwent a hypoglossal-
facial nerve anastomosis. This was followed
botulinum toxin injections to the left face
(left frontalis, left levator anguli oris, left
zygomaticus, and left depressor anguli oris)
to create symmetry to the face (Figure 16.2).
Case 2
A 50-year-old woman presents after blunt
trauma to the left face with left facial nerve
paralysis. To treat her appropriately she
underwent a combined treatment of surgical
and
nonsurgical
interventions.
She
first
underwent surgical reconstruction of the
facial nerve with a sural nerve interposition
graft. This was followed by injection of
botulinum toxin into the three grossly asym-
metric muscles – right risorius, right levator
anguli oris, and right zygomaticus. A small
amount of local filling material (calcium
hydroxapatite) is also used to equilibrate the
asymmetric nasolabial folds (Figure 16.3).
Conclusion
Correction of facial asymmetry is a com-
plicated issue and depends greatly on the
(a)
(b)
(c)
Figure .(a) Preoperative photograph; (b) planned intervention overlaying photograph (black x, botulinum
toxin injection site; blue areas. area of placement of filling material); (c) 6-month postoperative photograph
after further botulinum toxin injection/filler.


Botulinum Toxins
condition of the individual patient. Each
patient must be thoroughly evaluated and
include aspects of facial symmetry, weakness,
wasting, synkinesis, and potential recovery.
Each patient’s treatment should be indi-
vidualized as monotherapy or combination
therapy (surgical and/or nonsurgical) and
handled
by
professionals
with
excellent
knowledge of facial anatomy. Above all the
goal in cases of facial asymmetry is to create a
balanced, symmetric face at both rest and in
motion.
References
Clark JM, Shockley WW. Management and
reanimation of the paralyzed face. facial
plastic and reconstructive surgery. In Papel
ID (Ed.) Facial Plastic and Reconstructive
Surgery (pp 660–685). New York, NY:
Thieme Medical Publishers, Inc., 2002.
House JW, Brackman DE. Facial nerve
grading system. Otolaryngol Head Neck
Surg. 1985;93:146–147.
Mehta RP, WernickRobinson M, Hadlock
TA. Validation of the Synkinesis
Assessment Questionnaire. Laryngoscope
2007 May;117(5):923–926.
Laskawi R. Combination of
hypoglossal-facial nerve anastomosis and
botulinum toxin injections to optimize
mimic rehabilitation after removal of
acoustic neurinomas. Plast Reconstr Surg
1997 April;99(4):1006–1011.
Neely JG, Cheung JY, Wood M, et al.
Computerized quantitative dynamic
analysis of facial motion in the paralyzed
and synkinetic face. Am J Otol 1992 Mar;
13(2):97–107.
Bajaj-Luthra A, VanSwearingen J,
Thornton RH, et al. Quantitation of
patterns of facial movement in patients
with ocular to oral synkinesis. Plast
Reconstr Surg 1998 May;101(6):1473–
1480.
Beurskens CH, Heymans PG. Positive
effects of mime therapy on sequelae of
facial paralysis: stiffness, lip mobility, and
social and physical aspects of facial
disability. Otol Neurotol 2003 Jul;24(4):
677–681.
Blitzer A, Brin MF. Management of
hemifacial spasm and facial synkinesis with
local injections of botulinum toxin. Oper
Tech Otolaryngol-Head Neck Surg 2004
June;15(2):103–106.
Gray H. Anatomy of the Human Body, 20th
edn. New York, Bartelby.com, 2000.
Peterson S, Martins CR, Cofrancesco J Jr.
Lipodystrophy in the patient with HIV:
social, psychological, and treatment
considerations. Aesthet Surg J 2008
Jul–Aug;28(4):443–451.



Complications and Diffusion
Matteo C. LoPiccolo, MD,1 Farhaad R. Riyaz, MD,1 and David M. Ozog, MD (FAAD, FACMS)2
1Henry Ford Health System, Department of Dermatology, Detroit, USA
2Chair, Department of Dermatology; C.S. Livingood Chair in Dermatology; Director of Cosmetic Dermatology, Henry Ford Hospital, Detroit, MI, USA
Introduction
Major or persistent unwanted effects from
cosmetic
botulinum
toxin
injection
are
extremely rare. This is due to the relatively
short duration of action and natural reversal
of the toxin effect. However, the practitioner
who administers botulinum toxin for both
on-label and off-label indications must still
be extremely familiar with potential side
effects and discuss them with his or her
patient prior to treatment [1].
In general, complications can be cate-
gorized as those caused by an unintended
direct pharmacologic effect of the toxin (a
true side effect), those caused by improper
technique when administering the toxin
(such as improper placement or amount of
the medication), and effects secondary to
spread of the field effects of the toxin; termed
“diffusion” by many clinicians. Injection-
related and minor adverse events, major and
systemic reactions, and lastly site-specific
complications
from
injection
of
onabo-
tulinumtoxinA (Botox®, Allergan, Irvine,
CA), abobotulinumtoxinA (Dysport®, Medi-
cis, Scottsdale, AZ), incobotulinumtoxinA
(Xeomin®, Merz Pharma, Raleigh, NC) and
rimabotulinumtoxinB (Myobloc®, Solstice,
San Francisco, CA) will be discussed.
It is important to document any complica-
tions that arise after toxin injection for future
dose and placement location adjustment,
whether the patient or healthcare provider
notices the undesired result. This strategy can
improve patient satisfaction and over time
will refine your injection technique.
Diffusion
Diffusion will be addressed comprehensively
in a separate chapter, but due to its impli-
cation in many adverse events caused by
botulinum toxin, it is briefly explained here.
Many clinicians have adapted the term dif-
fusion to describe the field of muscular and
eccrine gland effects exerted by an injec-
tion of botulinum toxin. Field effect spread
occurs both horizontally to adjacent struc-
tures, and vertically to tissues superficial and
deep to the original placement of toxin. The
degree of diffusion seen with the injection of
botulinum toxin may be influenced by sev-
eral factors. Dilution of toxin and volume of
injection may affect the area of toxin effects.
While one study failed to show a difference
in safety or efficacy with larger volume dilu-
tions [2], other investigators observed up to
a 50% greater area of effect on forehead lines
with a fivefold greater dilution of toxin [3].
Higher dilutions have also been shown to lead
to a greater incidence of adverse effects (such
as eyebrow ptosis when treating glabellar
Botulinum Toxins: Cosmetic and Clinical Applications, First Edition. Edited by Joel L. Cohen and David M. Ozog.
© 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.
Companion Website:


Botulinum Toxins
rhytides), suggesting an increased diffusion of
toxin with increased dilutions [4]. A recent
study of abobotulinumtoxin effects on sweat
glands suggests that the type of skin, location
of injection, and increased activity of sweat
glands all appeared to influence the field of
effect [5]. Depth or volume of injection did
not affect field size. Some authors suggest that
manual manipulation of the treatment area
may increase the extent of toxin diffusion [6].
Lastly, the scope of field effects cannot
be directly generalized across all types of
botulinum toxins. While there appears to be
no difference in diffusion between onabo-
tulinumtoxinA and abobotulinumtoxinA at a
dose ratio of 1 : 2.5 U [7], a greater degree
of diffusion with abobotulinumtoxin has been
observed with 1 : 3, 1 : 4, and greater dosing
ratios [8–11]. Additionally, botulinum toxin
B has been shown to have a larger radius of
effect compared to onabotulinumtoxinA in
treating forehead wrinkles [12].
Complications and Adverse
Reactions
Common Minor and Injection Site Reactions
The most common adverse events reported
with the use of both botulinum toxin A
(BoNTA) and botulinum toxin B (BoNTB)
are injection-related, local, and self-limited.
Localized pain, erythema, swelling, ten-
derness, bleeding, and bruising can be
experienced at the injection site, with resolu-
tion occurring in minutes to days following
the procedure (Figure 17.1). The degree of
these effects varies with site and number
of injections. Pain can be minimized with
intrafollicular orifice injection technique, use
of bacteriostatic saline for toxin preparation,
smaller gauged needles, and pretreatment
with topical anesthetic or cryoanalgesia
[13, 14]. Avoidance of nonsteroidal anti-
inflammatory drugs, vitamin E, and aspirin
10–14 days prior to injection may decrease
the extent of bruising [14]. For patients that
are particularly susceptible to bruising, ice
can be used before treatment as a vasocon-
strictor. If bleeding occurs from an injection
site, immediate pressure should be applied
before continuing with the treatment. If
bruising occurs, it can be treated with
595 nm pulsed dye laser with 10 mm spot,
10 ms pulse duration and 7 J/cm2 [47].
Brief, self-limited headaches are also com-
mon following injections of the facial muscles
[6, 15–17]. In one series, approximately 1%
of 320 patients receiving BoNTA) injections
experienced severe, debilitating headaches
[18]. These are thought to be a result of imme-
diate muscle spasm from injection prior to
paralysis from toxin [39]. It may be helpful
to avoid touching the needle to the deeper
periosteal structures, keeping the injections
more superficial just above or into the supe-
rior aspect of the muscle. Other minor
reactions rarely reported include nasopha-
ryngitis, skin tightness, respiratory illness,
and flu-like symptoms.
Local injection site infections are exceed-
ingly rare despite various reconstitution pro-
tocols and millions of injections annually.
Reactivation of herpes simplex virus infec-
tion has rarely occurred, and herpes zoster
virus reactivation after injection of botulinum
toxin type A has also been reported [46].
(b)
(a)
Figure .(a) Injection site erythema and (b) hematoma formation immediately following onabotulinumtoxin
injection. Photograph courtesy of D. Hexsel, MD.

17 Complications and Diffusion

Fever, chest pain, chills, anxiety, dysgeusia,
tinnitus, and peripheral edema have also been
observed, although currently no evidence
exists that these reported effects are conclu-
sively linked to botulinum toxin [15, 16, 19].
Additionally, rimabotulinumtoxinB is associ-
ated with dry mouth, throat, and eyes, even
in instances of injection at distant anatomic
areas [19,20].
Severe and Systemic Complications
As mentioned earlier, the therapeutic and
cosmetic use of BoNTA and BoNTB has
been generally safe and well tolerated, and
most adverse effects are local and self-limited
[6]. Systemic effects, while rare, have also
been reported. Generalized muscle weakness
known as asthenia, diplopia, blurred vision,
ptosis, dysphagia, dysphonia, dysarthria, uri-
nary incontinence, and dyspnea have been
reported following the administration of both
BoNTA and BoNTB [15,16,19].
Hypersensitivity reactions including urti-
caria, soft-tissue edema, and anaphylaxis
leading to death (at a dose of 100 U onabo-
tulinumtoxinA for cervical dystonia) have
been reported with the use of onabotulinum
toxin [48]. In the case of death from anaphy-
laxis, lidocaine was used as a dilutent, and
thus the causative agent cannot be conclu-
sively identified. In patients with pre-existing
cardiovascular disease being treated for non-
cosmetic purposes, death from arrhythmia
and myocardial infarction have occurred
[49]. In addition, new onset and recurrent
seizures, syncope, and acute angle closure
glaucoma have also been reported follow-
ing onabotulinumtoxinA administration, al-
though a direct causal relationship cannot
be determined. Importantly, these severe
and life threatening events have not been
observed with the dermatologic use of up to
100 U at a time [15].
A variety of neuromuscular adverse events
have ensued with the use of botulinum toxin
as well. These symptoms may begin within
days following the procedure and may persist
up to 6 months. After the injection of 1400 U
of abobotulinum toxin for axillary and palmar
hyperhidrosis, a case of “botulism-like syn-
drome” followed in which generalized mus-
cle weakness, distant EMG muscle jitters,
decreased cardiovascular reflex following
deep breathing, diffuse asthenia, diplopia,
mild bilateral ptosis, as well as decreased
lacrimation, salivation, and sweating arose
[21]. Generalized muscle weakness subse-
quent to injection of 250 U of abobotulinum
toxin for cervical dystonia has also been
reported [22, 23]. In both cases, large doses
were used and generalized diffusion likely
caused the reported effects. Pre-existing
neuromuscular disorders including myasthe-
nia gravis, amyotrophic lateral sclerosis, and
Lambert–Eaton syndrome may increase the
risk of developing botulism-like syndrome,
and are thus contraindications to the use
of botulinum toxin [17]. Should a patient
experience botulism-like syndrome, intra-
venous anti-toxin should be administered as
soon as toxicity is suspected. Multiple anti-
toxins are available and dosing varies among
preparations [24]. These treatments are not
commercially available; they are reportedly
kept frozen in discreet nationwide stockpile
locations and must be approved for release
by federal health officials.
Severe dysphagia has followed abobo-
tulinumtoxinA administration for cervical
dystonia. Aspiration may result from severe
dysphagia and is a particular risk when
treating patients in whom swallowing or
respiratory function is already compromised
[16]. This adverse outcome can persist for
several weeks and may require the use of
a feeding tube to maintain adequate nutri-
tion and hydration. The adverse systemic
effects seen with rimabotulinumtoxinB are
similar to those seen with BoNTA, including
botulism-like syndrome, severe respiratory
compromise, and dysphagia [19].
Site Specific Complications
Forehead
Before injecting the forehead with botulinum
toxin, it is best to examine the frontalis
muscle in its full range of motion and map
out any desired injection sites. This will help


Botulinum Toxins
avoid improper placement of the toxin and
associated adverse outcomes.
The most substantial complication en-
countered when treating the frontalis mus-
cle for forehead lines is brow ptosis. This
outcome is not only aesthetically unfavor-
able, but may produce a visual impairment
that is temporarily debilitating to the patient.
This commonly results from placement of
the toxin too close to the eyebrow or when
diffusion of the toxin occurs to the infe-
rior portion of the frontalis. Thus, injections
should be placed at least 2 cm above the
brow or orbital rim and simultaneous paral-
ysis of the brow depressors should be consid-
ered to minimize this risk [25]. Patient selec-
tion is also important in the avoidance of this
effect; younger patients are preferred can-
didates for the treatment of upper forehead
lines. Following injection of the frontalis,
older patients and men may develop a redun-
dant pocket of skin beneath the brow, termed
pseudoptosis. If ptosis occurs, chemodener-
vation of the glabellar complex may reduce
depressive forces and elevate the medial brow
by 1–2 mm [25]. If the glabellar complex has
already been treated with toxin, 1–2 U of
onabotulinum toxin in the lateral orbicularis
oculi may also elevate the lateral brow (Fig-
ure 17.2).
Care must also be taken that a “cockeyed”
brow is not created when treating forehead
lines. This occurs when the lateral fibers of
the frontalis are not adequately paralyzed in
relation to the medial aspect of the mus-
cle, leading to cephalad movement of the lat-
eral portion of the brow. This effect may be
seen unilaterally or symmetrically, where it
is termed the “Nicholson” brow for its simi-
larity to actor Jack Nicholson’s naturally ele-
vated lateral brow. This is best avoided by
ensuring that the lateral forehead injections
are placed lateral to the iris. If it occurs, a
small amount of toxin (1–3 U onabotulinum)
may be injected into the lateral fibers of the
frontalis to lower the brow to an even posi-
tion. This should be injected 2 cm above
the brow as the original medial injections
should have been. Larger amounts of toxin
may overcorrect the defect, leading to an
overly depressed or “hooded” lateral brow,
which may partially cover the eye [25].
Glabella
The
most
concerning
complication
of
BoNTA and BoNTB injection of the glabellar
complex is upper eyelid ptosis, which in early
studies occurred in 0.8% to 9.0% of injections
(Figure 17.3) [4, 25–29]. The current rate of
this complication is much lower than 1%,
due to both lower amounts of toxin used in
these areas and more superficial injection
techniques. This occurs because of diffusion
of the toxin through the orbital septum
leading to paralysis of the upper eyelid lev-
ator palebrae superioris and superior tarsal
(b)
(a)
Figure .(a) Right eyelid ptosis following onabotulinumtoxin injection of the right frontalis muscle.
(b) Partial resolution following 2 U onabotulinumtoxin to the lateral orbicularis oculi.

17 Complications and Diffusion

Figure .Left eyelid ptosis following
onabotulinumtoxin to the glabella. Photograph
courtesy of A. Carruthers, MD.
muscle [6]. It is more commonly caused when
injecting the lateral corrugator just above the
pupil in some patients. This effect may be
avoided by keeping the injection medial to
the mid pupillary line. As this portion of the
corrugator inserts directly into the dermis,
injections of only 1–2 mm deep are sufficient
for desired treatment effect, and are unlikely
to cause spread to the deeper structures in
the orbit.
In the rare instance that lid ptosis develops,
it begins between 2 and 10 days following
injection, and may persist for 2–4 weeks. The
degree of ptosis may be mild upon awakening
but becomes progressively more pronounced
throughout the day, eventually causing visual
impairment. Such events are more common
in older individuals, as the orbital septum
may be thin or absent. It has also been
reported in patients with a history of surgery
in this area including brow lifts. Any prior
surgery in this area may change predictable
patterns of diffusion. Patients with a baseline
ptosis or redundant eyelid skin may depend
on frontalis action to fully open the eye and
should be identified prior to treatment. Cau-
tion is warranted when considering glabellar
injection for these patients.
A patient complaining of “heavy eyebrows”
is likely experiencing eyebrow ptosis. This
is another commonly reported complication.
Interestingly, the incidence of brow ptosis
has been shown to decrease with successive
treatments of the glabella [28, 29]. Injections
should be placed at least 1 cm above the
orbital rim for corrugator treatment and 2 cm
above the rim for frontalis treatment. Small
volumes should be used to minimize diffu-
sion. It is also important to avoid injecting
toxin into the eyebrow lateral to the inner
canthus, as this may also increase the likeli-
hood of ptosis. Additionally, patients should
be instructed to avoid manipulation of the
injected area and to actively contract the
glabellar complex [6].
Patients who choose to apply ice to the
treated area to minimize potential bruis-
ing should do so by holding pressure in
an upward direction rather than massaging
the area, which promotes diffusion. Alpha-
adrenergic agonist eye drops including apra-
clonidine 0.5% and phenylepherine 2.5% may
be used to treat eyelid ptosis should it occur.
These agents cause contraction of the adren-
ergic Muller’s muscle of the upper eyelid,
leading to 1–2 mm of elevation of the lash
margin [25]. Drops should be applied at three
times daily for symptomatic improvement
until the ptosis resolves, which is usually in 1–
6 weeks [30]. Bruising may occur from injec-
tions in this region, but much less commonly
than bruising in the peri-orbital area. Rarely,
lid swelling, forehead rigidity, and forehead
muscle spasms occur from administration of
botulinum toxin into the glabella [4, 26, 28,
31–33]. Diagonal lines along the nasal side-
wall (bunny lines) may also develop, which
can easily be treated with 3–5 U of (onabo-
tulinum) toxin in the medial aspect of the
proximal nasal sidewall.
Compared to injections of botulinum toxin
into other facial sites, headaches may be more
common with injections into the glabella.
Unlike the previously mentioned 1% over-
all rate of postinjection headache, 11% of
botulinum patients and 20% of placebo
patients reported headache in the Botox
Glabellar Lines II Study Group [34].
Periorbital Lines
Several untoward affects may occur when
administering BoNTA for cosmetic improve-
ment of periocular rhytides. This region is
the most likely to develop bruising follow-
ing injection, as numerous superficial veins in
the area are susceptible to injury [25, 33, 35].


Botulinum Toxins
The injections in this area should be kept
superficial similar to a bleb from a PPD injec-
tion, thus avoiding deeper structures which
may not be visible to the naked eye. Adequate
lighting is key, and vein imaging may be con-
sidered to decrease the risk of vessel puncture
[50].
Treatment of crow’s feet lines may also lead
to excessive skin folding atop the zygomatic
arch. While itself aesthetically unpleasing,
this may also lead to an exacerbation of zygo-
maticus lines as the redundant skin gravi-
tates downward. Pre-assessment of skin laxity
prior to injecting this area is key, and patients
with considerable scleral show, excessive skin
beneath the eye, or a slow snap test of the
lower eyelid may be more likely to have an
unfavorable result. Festooning, or bagginess
of the infraorbial skin, has been reported after
treatment of this area perhaps due to inhi-
bition of the lymphatic muscle pump [51].
Bruising may be avoided by minimizing the
number of injection sites, and injecting the
toxin in a series of superficial blebs [25]. Icing
the area pre- and postinjection will also con-
strict vessels and minimize bruising. If an
early bruise is visible, the application of direct
pressure and treatment with a 595-nm vascu-
lar laser may be used to minimize spread and
expedite resolution [36]. In instances where
the patient has a history of significant bruis-
ing or cannot tolerate any bruise, for exam-
ple due to an upcoming social commitment, a
small bleb of lidocaine with epinephrine may
be placed at the site 10 minutes prior to injec-
tion to induce vasoconstriction.
Diffusion of toxin is also of concern in this
periorbit. Diffusion inferiorly to the zygo-
maticus major may interfere with lip upturn-
ing and lead to an asymmetric smile and
flaccid cheek. Likewise, diffusion inferior-
medially to the orbicularis oculi may cause a
lower ectropion. Lastly, medial diffusion may
lead to paralysis of the lateral rectus mus-
cle, producing a temporary but debilitating
diplopia [25]. The above complications are
best eluded by placement of injections no
less than 1 cm beyond the orbital margin,
staying superficial as the zygomaticus muscle
lies deep to the orbicularis oculi, and avoid-
ing the inferior margin of the zygoma. If
diplopia occurs, patching of the affected eye
can provide symptomatic relief and is needed
for 7–10 weeks following symptom onset
[37]. Other options include prismatic lenses
or intentional paralysis of the contralateral
medial rectus. An ophthalmology referral
should be considered.
In addition to the adverse effects discussed
above, the use of botulinum toxin B for peri-
ocular rhytides has been reported to cause
mild to severe dry mouth and dry eyes. The
average onset is roughly 12 days from injec-
tion, with symptoms persisting for nearly a
month [38].
Upper and Lower Lip
While lip rhytides respond well to botulinum
toxin treatment, clinicians should be cautious
with its use in this area. Incompetence of
the oral sphincter, flaccidity of the cheek,
asymmetry of the smile and difficulty with
speech may easily result from over dosage and
diffusion of toxin, and overtreatment of the
orbicularis oris muscle (Figure 17.4). Patients
should be warned regarding these potential
issues. Injections should be placed superfi-
cially and in a symmetrical pattern. Some
authors recommend using a large-volume
dilution to assure uniformity in toxin spread
[25]. Treatment should be initiated at a low
dose ( 0.5–1 U abobotulinum toxin per injec-
tion site, to a maximum of 4 sites), which may
Figure .Asymmetric lower lip following perioral
onabotulinumtoxin injection. Photograph courtesy
of A. Carruthers, MD.

17 Complications and Diffusion

then be titrated up to the desired effect dur-
ing subsequent sessions if necessary. Despite
these techniques, some individuals find dif-
ficulty in whistling and forming “s” and “p”
sounds for days-to-weeks following the injec-
tion. Singers, musicians, and others who rely
on fine perioral muscle dexterity should be
counseled on these effects and are not good
candidates for this procedure. Lastly, flatten-
ing of the upper vermillion may occur, which
is easily corrected with the addition of dermal
filler [25].
Cheek and Chin
Treatment of the depressor anguli oris (DAO)
to elevate the corners of the mouth may
be complicated by diffusion of toxin to the
obicularis oris, leading to an incompetent
oral sphincter or flaccid cheek. Injections of
the DAO should be made at the angle of
the jaw posterior to the nasolabial fold and
small doses should be used to best prevent
these effects [25]. The depressor labii infe-
rioris (DLI) may also be affected, leading to
an asymmetric smile (Figure 17.5). When this
occurs, 2 U of (onabotulinum) toxin may
be injected into the opposite DLI to restore
symmetry.
The mentalis is also commonly treated to
alleviate chin clefts, folds, and lines. One
must avoid injecting directly into the men-
tal fold in these cases, as this may easily pro-
duce an incompetent mouth or asymmetric
Figure .Asymmetric smile following 2 U of
onabotulinumtoxin to the depressor anguli oris, with
inadvertent toxin affects to the left depressor labii
inferioris.
smile. Injections that are placed too laterally
or superficially also can cause this issue [39].
Dosing should rarely exceed 6 U of onabo-
tulinum toxin in this area [25,40].
Platysmal Bands and Horizontal Neck Lines
The platysma may be treated with botulinum
toxin to alleviate prominent vertical bands
and horizontal neck lines [24]. Initially it was
felt that large doses of toxin were needed
for successful chemodenervation of this rel-
atively large muscle: some authors reported
the use of up to 200 U per session [41]. Such
high doses of botulinum toxin in this area may
have significant, potentially life-threatening
adverse effects. The spread of toxin A or B
to the deep muscles of deglutition in the lar-
ynx can lead to dysphagia [24]. Neck weak-
ness may develop as a function of direct injec-
tion of the sternocleidomastoid, trapezius, or
splenius capitus muscles, diffusion of toxin
to the strap muscles, or a combination of
these effects [42]. Uncommonly, respiratory
distress and death have been reported follow-
ing botulinum toxin injection in the neck [15,
16,19,25]. It has been found that lower doses
are equally effective as the initially reported
high doses, with a lower incidence of side
effects. Superficial injection and the use of
smaller doses of toxin (starting with 6–8 U of
onabotulinum per platysmal band, and titrat-
ing upward to effect) are advised to decrease
the risk of these complications [25,40].
Less common sequelae from injecting in
this area include edema, erythema, ecchymo-
sis, muscle soreness, and neck discomfort.
Bruising was the most common side effect in
one series of BoNTA use, occurring in less
than 20% of the patients. Less than 10% of
patients reported transient, mild neck dis-
comfort occurring 2–5 days after the treat-
ment [24].
Hyperhidrosis
Treatment of palmar hyperhidrosis with
50–100 U of onabotulinum (and respec-
tive equivalents of abobotulinumtoxinA and
rimabotulinumtoxinB) has been associated
with decreased handgrip strength and finger


Botulinum Toxins
power [10, 43]. This likely occurs secondary
to diffusion of the toxin to the underlying
musculature. This effect is transient, with
subjective grip strength and finger power
reductions lasting approximately two weeks.
A small study comparing onabotulinum to
abobotulinum in a 1 : 4 dosing ratio for pal-
mar hyperhidosis suggests that this effect
may be more frequently experienced with
the latter preparation [10]. No direct com-
parison has been made at alternate dosing
ratios, however. Dry mouth and dry throat are
adverse events experienced with botulinum
toxin B for palmar hyperhidrosis, but not
routinely with BoNTA [20]. Some clinicians
regard injection with botulinum toxin B in the
palm to be more painful to their patients than
injection with BoNTA, although a recent
study found the injection of rimabotulinum-
toxinB to be as painful as placebo [20].
Superficial placement of toxin may help
prevent these effects when treating the palm.
Treatment should be limited to one hand per
session due to these risks-bilateral loss of
grip strength may cause significant disability
[25]. In patients who have experienced this
effect, decreasing the injected dose placed
directly above the thenar eminence should
be considered during subsequent treatments
[43]. Other common adverse reactions seen
with injection of BoNTA and BoNTB into the
palms include self-limited and localized tin-
gling, pain, and numbness [44].
Patients treated for axillary hyperhidro-
sis have experienced localized itching with a
mean duration of two to three weeks, and
compensatory sweating in other areas lasting
up to 12 weeks [43,45]. Compensatory sweat-
ing is comparatively less severe than the pre-
ceding condition as it generally does not deter
patients from seeking future treatments.
In summary, adverse effects from botu-
linum toxins are infrequent and can be
minimized with careful injection technique
and knowledge of the local anatomy. Fortu-
nately, most events are transitory in nature
and can be easily managed by the astute
clinician.
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

Combination Therapy of Botulinum Toxin with other Nonsurgical
Procedures
Amy Forman Taub, MD1,2 and Lauren Fine, MD (FAAD)3,4
1Director, Founder, Advanced Dermatology, LLC, Lincolnshire, USA
2Assistant Clinical Professor/Northwestern University Medical School, Chicago, USA
3Associate Dermatologist & Cosmetic Fellow, Advanced Dermatology, LLC, Chicago, USA
4Associate Dermatologist, Chicago Cosmetic Surgery and Dermatology, Chicago, USA
Introduction
Most aesthetic practitioners combine treat-
ments to achieve the best results for their
patients. These combinations are myriad and
difficult to study. In the medical world, it
is rare for more than one drug to be stud-
ied concurrently, unless they have been com-
bined into one drug (or are both made by the
same company). In dermatology, the ingre-
dients are often combined into one drug to
increase compliance, reduce cost, and make
it possible for the drug to be approved. In
the aesthetic world things are no different.
While there are many patients who only have
one type of laser treatment, filler or toxin, it
has become common for two or more to be
performed simultaneously. Since botulinum
toxin (BoNT) is the most commonly per-
formed aesthetic treatment, it stands to rea-
son that it would also be the most com-
monly combined with other treatments. One
study combined BoNT with five different
hyaluronic acid (HA) fillers into 13 areas of
facial zones and resulted in 92.6% patient sat-
isfaction 6 months after therapy [1]. Although
it is intuitive that combining therapies will
achieve better results, many investigators
have attempted to understand and quantify
these benefits. Herein we attempt to present
the data on these combinations and try to put
them into clinical perspective.
Fillers and Botulinum Toxin
Aging of the face is a complex, multifac-
torial process that results in rougher skin
texture, increased laxity, decreased elasticity,
dyschromia, telengiectasias, and the develop-
ment of fine lines and wrinkles. Volume loss
and muscle hyperactivity are also contribut-
ing factors to the aging process, resulting in
concavities, and static and dynamic rhytides.
Since dermal fillers restore volume while
BoNT reduces muscle movement, combining
therapies is an appealing option for rejuvena-
tion of the aging face. Not all studies included
in this chapter were performed with the same
form of BoNT. It will be referred to through-
out this chapter as BoNT, unless specifically
referred to by their generic names (onabo-
tulinum, abobotulinum or incobotulinum).
In one of the first studies examining the
combined use of BoNT and soft tissue
augmentation, Faigen and Brandt [2] found
that patients who had BoNT injected 1 week
prior to filler in deep glabellar furrows or lips
experienced
increased
longevity
of
the
hyaluronic acid. Two hypotheses for the
Botulinum Toxins: Cosmetic and Clinical Applications, First Edition. Edited by Joel L. Cohen and David M. Ozog.
© 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.
Companion Website:


Botulinum Toxins
cause of this increased longevity were sug-
gested: (i) BoNT causes a reduction in the
dynamic muscular component of wrinkle
formation preventing attenuation of the
material via repetitive muscular activity,
and/or (ii) by inhibiting repetitive move-
ment, the milieu for creating new collagen
surrounding the implanted material was
improved [3].
In another study focused on the glabel-
lar area, 16 patients with severe glabellar
rhytids at rest treated with both BoNT and
a hyaluronic acid filler responded better than
those treated with BoNT alone [4]. 94% of
subjects injected with combination therapy
had mild rhytides after therapy, whereas 0%
of subjects treated with BoNT monotherapy
achieved no or mild rhytides (Table 18.1).
In a prospective randomized single-blinded
study of 38 patients with moderate to severe
glabellar rhytides, BoNT plus HA filler com-
bination treatment improved outcomes both
at rest and on maximum frown compared
to HA filler alone [5]. Furthermore, the
Table .Combination treatments with toxins and fillers.
Authors
Study
design/Methods
Evaluation schedule
Clinical results
Comments
Carruthers,
Carruthers, &
Maberley 2003
[4]
Retrospective study
of 16 subjects
treated with
BoNT-A & Hylan B
versus BTZ-A
alone for glabellar
rhytids; Responses
assessed clinically
and
photographically
Before (Baseline) &
After BoNT-A/
Hylan B treatment
photographs
After BoNT-A
alone none (0%)
had achieved no or
mild rhytids. After
BoNT-A & Hylan B
only 1 of 16 (6%)
had moderate
glabellar rhytids
with the remainder
(94%) being mild.
Carruthers &
Carruthers 2003
[5]
Prospective,
randomized study
of 38 subjects
receiving BoNT-A
& Restylane or
Restylane alone for
glabellar rhytids;
Responses assessed
clinically and
photographically
Baseline and every
2 weeks for
32 weeks
Combined group
showed better
response at rest
and maximum
frown; response
maintained for
significantly longer
(32 vs.18 wks). At
week 16 response
rates 95% vs. 83%
(combination vs.
BoNT-A alone)
Study limitations-
no BoNT-A only
arm.
Patel, Talmor, &
Nolan 2004 [7]
Prospective,
randomized study
of 65 subjects
receiving BoNT-A
(22), Zyderm (20),
or both (23) for
glabellar rhytids;
responses assessed
using patient
satisfaction scores
and independent
physician
evaluation
Baseline, 1 week,
1 month, and
3 months
At all
posttreatment
visits combination
group had greater
improvement in
wrinkle severity
than either group
alone (79% vs 56%
& 50% at 1month)

18 Combination Therapy of Botulinum Toxin with other Nonsurgical Procedures

(a)
(b)
Figure .(a) Before treatment; (b) 3 weeks after one syringe HA to vertical glabellar furrows and 45 units of
BoNT to glabella. Source: Courtesy of Amy Forman Taub, MD.
combination treatment nearly doubled the
median duration of response compared with
treatment with HA filler alone (32 weeks
versus 18 weeks). Of note, this study did
not include a BoNT only arm, so the effect
of BoNT alone compared with combination
treatment cannot be assessed (Table 18.1).
In yet another split-face randomized control
trial of 20 patients, half received BoNT in
the glabella and the other half received BoNT
and hyaluronic acid filler; 24 weeks after
treatment, glabellar rhytides showed more
improvement on the combination side than
in the toxin only side [6]. Patel et al. found
similar results [7]; 65 patients with moderate
to severe glabellar rhytides received BoNT,
collagen, or a combination of the two. After
1 month, subjects in the combination group
demonstrated significantly greater improve-
ment in furrows (79% versus 56% in BoNT
alone and 50% in the filler group alone;
p < 0.05). Furthermore, the clinical effects
were longer-lasting and patient satisfaction
was higher in the subjects receiving both
BoNT and collagen (Table 18.1).
The glabellar folds appear to be the most
common area of the face to be treated
with a combination of BoNT and filler (Fig-
ure 18.1). Monotherapy with BoNT alone
is very effective in younger patients with
primarily dynamic rhytids. With increasing
photodamage and laxity, glabellar lines can
become “etched” at rest and BoNT alone
may be insufficient for full correction. If the
number “1 or 11” vertical rhytid is obvious
in the glabella without contraction, combi-
nation treatment (filling the vertical depres-
sions 1–2 weeks after relaxing the muscles
with BoNT) is usually necessary for full cor-
rection [8, 9]. In one experienced injector’s
experience [8, 10], about 15% of patients
treated with the aforementioned protocol


Botulinum Toxins
require maintenance with BoNT only and
do not require further filling for 1–2 years.
Pretreatment with BoNT allows for assess-
ment of residual static rhytides after the toxin
takes effect. According to the consensus rec-
ommendations put forth by the Facial Aes-
thetics Consensus Group (FACG) in 2008,
BoNT is used in combination with filler in
the glabellar area about 25 percent of the
time [9]. In 73% of faculty combining treat-
ments and staging treatments were reported
in new patients, first injecting with BoNT and
then with filler.
Although there is clear and ample evi-
dence that combination of HA and BoNT in
the glabellar area results in superior correc-
tion and longevity, extreme caution should
be taken with filler injection in this area due
to potential complications such as vascular
occlusion leading to skin and tissue necro-
sis. These rare but serious complications can
occur from inaccurate needle placement or
applying too much pressure during injection
[11–14]. Material should flow easily through
the needle during injection of the glabella.
Robust fillers (increased particle size or con-
centration used mainly for deep volume
restoration), permanent or semi-permanent
fillers should not be used here to avoid
this complication. Injections should be rela-
tively superficial. Hyaluronic acid fillers only
are recommended in the glabella because
hyaluronidase can be administered at the first
sign of occlusion (blanching, pain or a sense
of significant pressure on the part of the
patient) and may alleviate the blockage and
prevent ischemic necrosis of tissue. Injection
of filler into the glabella is not FDA approved.
Shaping of the brow is another area par-
ticularly well suited for combination therapy
with BoNT and filler. It is useful to view
the brow region as a three-dimensional area.
Brow ptosis is a common manifestation of
the aging face and can inadvertently con-
vey fatigue or disinterest. BoNT alone in the
glabella of younger women will raise the brow
approximately 1–2 mm [15]. Placement of
BoNT in the lateral brow depressor will help
lift the lateral brow, restoring a more defined
arch [16]. Injection of filler into the lateral
brow fat pad at the superior orbital rim will
further augment the lateral brow lift and will
anteriorly project the lateral brow contour,
resulting in a more youthful brow. According
to the FACG, BoNT is used alone to shape
the brow area about 50% of the time [9]. Over
90% of this expert faculty group use filler in
a subset of patients to replace volume in this
area.
In
the
crow’s
feet
area
a
combined
approach has also been studied. In an open-
label, nonrandomized pilot study by Beer,
et al. [17], 20 subjects with mild to moderate
temporal volume loss as well as glabellar
and/or periorbital rhytids were
studied.
They received a combination of BoNT in
the glabellar or periocular area as well as
hyaluronic acid filler in the glabellar or tem-
poral area. Although improvement declined
at 3–9 months depending on whether toxin
or filler were used, 64% of patients who had
previously used toxin alone stated the results
were superior with the combination. While
all FACG faculty members continue to treat
this area with BoNT, 80% of faculty members
now use it in combination with filler to
enhance malar volume [9]. Subcutaneous
injection of filler inferior and lateral to the
lateral canthus can augment a flat zygoma;
combining BoNT to the crow’s feet area
simultaneously can further lift and reshape
the upper cheek, ultimately achieving a
more youthful zygoma [16]. Compared to
the perioral region, filler in the cheek area
lasts significantly longer since there is much
less movement [17, 18]. When smile lines
around the eyes extend medially to the malar
cheek, BoNT alone should be avoided due
to risk of affecting the infraorbital nerve and
asymmetric smile, as well as lower lid ptosis.
For the treatment of more medial malar
smile lines all FACG faculty members use
primarily hyaluronic acid fillers alone; fewer
than 20% report occasional combination
treatment in this area. The midportion of the
obicularis oculi is a difficult area to treat. A

18 Combination Therapy of Botulinum Toxin with other Nonsurgical Procedures

small dosage of BoNT can be used to soften
the palpebral part of the orbicularis oculi at
the mid-pupillary line providing a prior snap
test reveals good elasticity of the muscle. This
can result in a more open eye, with the shape
of the eye changing slightly from almond to
round. This change in shape should always
be discussed with the patient first. This is
sometimes the first area that women in their
twenties and early thirties notice rhytids.
These rhytids cannot currently be corrected
with available fillers due to the area being
too superficial to get a natural looking result
and the risk of Tyndall effect. Using toxin
here for full relaxation of the muscle would
lead to ectropion; however, use of filler in
the tear trough may improve some infraor-
bital rhytides via stretch, analogous to the
improvement in zygomatic cheek rhytides
from cheek augmentation.
Another application of BoNT and filler
combination is reshaping of the nasal dorsum
and tip. The contour of the nasal tip can be
affected by loss of volume as well as surgi-
cal depression or previous injury. Filler injec-
tion can result in elevation of the bridge of
the nose and recontour of the tip. Injection of
filler at the base of the columella can elevate
the nasal tip. Small amounts of of BoNT to
each side of the nasal spine area (levator labii
superioris) and each lower nasalis (depressor
septi nasi) can further improve the aesthetics
of the nasal tip [9,19]. Care must be taken in
this area, as well as in the glabellar area, due to
reports of blindness after filler injections [20].
Although not limited to these areas alone, the
highest risk of blindness is from the glabella,
nose, and nasolabial fold.
The lower face is another area amenable
to combination therapy. A helpful approach
in treatment of this area is to view the area
as a whole rather than as isolated regions
[9]. While photodamage, textural changes,
and loss of elasticity contribute to aging in
this area, it is volume loss in the melomen-
tal folds and lips and the muscular contrac-
tion of the orbicularis oris that make this
area so well suited for combination therapy.
Repetitive contraction of the orbicularis oris
is responsible for radiating perioral rhytides.
The combined injection of BoNT into the
depressor anguli oris, mentalis, and platysma
removes the muscular depressor action of
the lower face, thereby elevating the lateral
oral commissures to a more relaxed, neutral
position [21]. BoNT injection of the men-
talis also ameliorates dimpling of the chin.
The simultaneous addition soft tissue filler to
buttress the mouth corners and prejowl sul-
cus will result in a more youthful appearance
than with BoNT alone. The addition of vol-
ume to the prejowl sulcus softens the percep-
tion of jowls and gives the face a more oval
and less rectangular orientation (Figure 18.2).
Treating in multiple sessions on different
days can be advantageous to reassess needs.
To address vertical lip rhytides, injection of
4–8 U of onabotulinumtoxin in the upper lip
(a)
(b)
Figure .(a) Melomental folds mouth frown and puckered chin prior to BoNT to depressor anguli oris and
chin hyaluronic acid filler to melomental folds and chin. (b) Postcombined treatment with BoNT and filler.
Source: Courtesy of Amy Forman Taub, MD.


Botulinum Toxins
(a)
(b)
(c)
(d)
Figure .Cumulative effects of treatments on one woman’s face. (a) Pretreatment; (b) after
incobotulinumtoxinA; (c) after incobotulinumtoxinA + CaHA; and (d) after incobotulinumtoxinA + CaHA HA.
Source: Fink 2014 [22]. Reproduced with permission of Matrix Medical Communications.
and 3–8 units in the lower lip can be used
along with HA filler to enhance volume and
help shape the vermillion border. Lastly, an
important use of BoNT in the lower face is to
treat asymmetric smiles. There may be differ-
ent timing strategies for accomplishing this
combination. Some may do on the same day,
but it would be important then to inject the
filler first and complete any manual massage
before injecting BoNT. Once injected, toxin
should not be manipulated as it may be spread
to more distant areas and cause inadvertent
effects.
A
multiple
treatment
program
with
incobotulinumtoxin,
calcium
hydroxylap-
atite (CaHA) (Radiesse® Merz Pharmaceu-
ticals GmbH, Frankfurt, Germany), and HA
(Belotero®, Merz Pharmaceuticals GmbH,
Frankfurt, Germany) was undertaken for
10 women to determine if their apparent
age was reduced. The photographs were
rated by each of 50 na¨ıve judges based on
age, health and attractiveness. The apparent
age of all 10 women was statistically sig-
nificantly improved in a stepwise fashion
over the four-step treatment protocol [22]
(Figure 18.3).
In late 2009, injectable poly-L-lactic acid
(Sculptra®, Valeant) was approved by the US
Food and Drug Administration (FDA) for the
correction of shallow to deep nasolabial fold
contour deficiencies and other facial wrin-
kles. Currently, there are no clinical trials
examining the combination of BoNT with
poly-L-lactic acid. In our experience, com-
bining procedures has yielded similar results
as compared with combined BoNT and HA
filler (Figure 18.4). although there are no for-
mal studies looking at this combination.
Current aesthetic thinking leads one to
analyze the face as a complex 3-dimensional
object: not only at rest but also in motion. It
is a mistake to think of eradication of lines
and creases as the end goal of aesthetic treat-
ments. It appears that in selected areas of the
face, a combination approach leads to a bet-
ter and more lasting result for our patients.
Neutralizing the rhytidogenic and/or depres-
sor action of selected facial muscles while
simultaneously or sequentially restoring lost
volume are currently the primary tools the
aesthetic surgeon has to create a balance
that looks natural and harmonious in the
aging face. Recent consensus recommenda-
tions confirm this vision [23].
Broadband Light Sources/
Nonablative Light-based
Treatment and BoNT
Pulsed light (IPL) is a nonablative light-
based technology used to effectively treat
the dyschromia and telengiectasis associ-
ated with photoaging. Previous studies have

18 Combination Therapy of Botulinum Toxin with other Nonsurgical Procedures

(a)
(b)
Figure .(a) Before treatment; (b) 6 weeks after one vial Sculptra® injections to cheeks, nasolabial folds, and
melomental folds, and 4 U BoNT in vertical upper lip lines (as well as glabella and forehead). Source: Courtesy of
Amy Forman Taub, MD.
shown that IPL alone can improve the appear-
ance of facial rhytides [24–28]. The ratio-
nale behind combination broadband light
therapy and BoNT chemodenervation is to
more effectively and permanently treat facial
rhytides commonly treated by either modal-
ity alone. There was also concern regarding
energy-based devices potentially inactiving
toxin when used in combination.
In 2004, Carruthers & Carruthers pub-
lished the first prospective, randomized study
of 30 patients comparing IPL treatment alone
or in combination with BoNT for facial aging
[29]. All subjects received full-face broad-
band light treatment; subjects assigned to
the combination group also received 15 units
of BoNT to the crow’s feet of each side of
the face. Compared with the IPL-only group,
patents receiving both BoNT and IPL demon-
strated improvements in crow’s feet rhytides
at rest and on maximum smile, as well
as a slight improvement in the appearance
of telengiectasias, lentigines, apparent pore
size, and skin texture. Their responses were
assessed both clinically and photographically.
These results suggest that both treatments
may act synergistically to produce opti-
mal facial rejuvenation [29, 30] (Table 18.2).
Khoury et al. examined the effects of full-
face IPL combined with intradermal injection
of BoNT of the cheeks [31]. Patients in this
study were treated with IPL plus eight 0.1-ml
intradermal injections of onabotulinumtoxin
in one cheek (8 U total) and eight injections
of saline in the contralateral cheek. A sig-
nificantly higher number of patients showed
improvements in small wrinkles and fine lines
with IPL plus toxin than IPL plus saline (93%
vs 29% at week 4). A greater improvement in
erythema was also noted on the combination
side. Other factors such as hyperpigmenta-
tion, apparent pore size, texture, and overall


Botulinum Toxins
Table .Combinations of broad-band light or non-ablative laser with BoNT.
Authors
Study
design/Methods
Evaluation
schedule
Clinical results
Comments
Khoury, Saluja,
Goldman 2008 [31]
Prospective,
randomized,
double-blind, split
face study of 14
females all
receiving standard
IPL treatment
along with BoNT
injections to one
cheek & saline in
the other cheek;
responses assessed
photographically.
Baseline,
1 week, 4 weeks,
8 weeks
A significantly
higher
proportion of
subjects showed
improvement in
small wrinkles
and fine lines
with IPL +BoNT
than IPL+saline
(93% versus
29%) at week 4.
BoNT-A & IPL side
also achieved a
greater degree of
improvement in
erythema. Other
efficacy measures
(hyperpigmenta-
tion, pore size, skin
texture) showed
comparable
improvements with
both regimens.
Carruthers &
Carruthers 2004
[29]
Prospective
randomized study
of 30 women with
crow’s feet rhytids
treated with
BoNT-A &
Broadband Light
(BBL) versus BBL
alone; responses
assessed clinically
and
photographically.
Baseline, 3 wks,
6 wks, 9 wks,
12 wks, 18 wks,
26 wks
BoNT-A/IPL
group
experienced
better response
to treatment,
both at rest and
on maximum
smile; combined
group also had
slightly
improved
response in
associated
lentigines,
telangicatasia,
pore size, facial
skin texture.
Skin biopsies
showed an increase
in dermal collagen
in each group.
While BBL alone
produced
remarkable
improvements in
telangictasias,
lentigines, and skin
texture, the
BoNT-A
co-treatment
increased these
results by 15%.
Semchyshyn &
Kilmer 2005 [32]
19 subjects
received BoNT-A
injections to either
glabellar or crow’s
feet areas. One side
of the treated area
was treated with
either VBeam
Laser,
SmoothBeam laser,
CoolGlide laser, or
an IPL or RF device
within 10 min of
BoNT-A injections;
responses assessed
photographically.
Baseline and
2–3 weeks
posttreatment
No evidence of
decrease in
efficacy of
BoNT-A
denervation
observed when
glabellar or
perioral areas
were treated
with VBeam
Laser,
SmoothBeam
laser, CoolGlide
laser, or an IPL
or RF device
within 10 min of
BoNT-A
injection.
First and only study
to explore effects of
combining
BoNT-A and
various
non-ablative lasers
and RF.

18 Combination Therapy of Botulinum Toxin with other Nonsurgical Procedures

appearance were also measured, and showed
no difference between the arms (Table 18.2).
The idea that you would put an area “at rest”
while you are “fixing it” is similar to a bone
mending a fracture [29]. It is intuitive and one
that patients understand when you explain
it. These two studies, although small, sug-
gest that there is a real scientific construct to
this principle, but these results may be short-
lived. According to the graphs presented in
the Caruthers’s paper, at 26 weeks the broad-
band light alone group seemed to have bet-
ter resting results for rhytides (71% moderate
and 29% mild) versus the combination group
(92% moderate and 8% mild), with the suc-
cess rate of 21% in rhytides at 26 weeks in
IPL alone group and 0% improvement in the
combo group [29]. In Khoury et al’s stud-
ies, the effect remained statistically signifi-
cant into the eighth week when the study
ended [31]. At the very least, one could use
BoNT combination to get faster results with
fine rhytides while the patient has to wait
for the collagen production resulting from
the heated fibroblasts takes place. The patient
perception of better results in the early phases
of treatment with nonablative photorejuve-
nation may encourage them to complete their
series of treatments as well as continue any
adjunctive skin care. It would be interesting to
perform a study on patients who completed a
series of nonablative treatments and had half
of them continue their BoNT throughout one
year then let it wash out versus those who dis-
continued it after the first treatment.
Semchyshyn & Kilmer evaluated whether
the use of IPL immediately after BoNT injec-
tions had any effect on the efficacy of the
chemodenervation [32]). Subjects received
BoNT immediately prior (within 10 min-
utes) to laser rejuvenation. Pretreatment and
2-week posttreatment photos were com-
pared, and no signs of decreased BoNT effi-
cacy were demonstrated. Of note, this study
also included subjects treated with BoNT
and pulsed dye laser, long pulsed infrared
laser, Nd:YAG 1064 long pulsed laser and
monopolar radiofrequency device and found
similar results (Table 18.2). More recently a
retrospective study looking at combining
microfocused ultrasound with BoNT and
fillers affirmed the safety of the combina-
tions [33].
To date, this is the only published work
exploring BoNT in combination with these
latter devices, their purpose being to demon-
strate that energy based systems when
applied immediately after BoNT does not
inactivate the toxin nor increase side effects
of either device. When combining energy
based treatment and BoNT injections it is
still probably better to treat with the energy
based device first because the puncture
wound and slight bit of dried blood may
cause an area of increased absorption in the
skin and hence an injury that could lead to
a complication. One of the authors (AFT)
typically waits 30 minutes after an energy
based device treatment to allow the skin to
cool, prior to injecting BoNT.
BoNT and Laser Resurfacing
Since the mid-1990s, laser resurfacing of the
skin has revolutionized cosmetic dermatol-
ogy. Ablative lasers such as the carbon diox-
ide and erbium:YAG laser selectively target
water as the chromophore, precisely vapor-
izing the epidermis and superficial dermis,
leading to profound wound healing and der-
mal remodeling. Besides improving skin tex-
ture and dyschromia, resurfacing addresses
static rhytides by stimulating new colla-
gen formation. Since BoNT treats dynamic
rhytides, a combination of the two yields a
global reduction of all rhytides. Combining
BoNT denervation with laser resurfacing also
prevents disruption of newly deposited der-
mal collagen due to a reduction of dynamic
muscle activity [34].
There are numerous anecdotal reports of
the benefits of combination therapy. Fagien
reported “enhanced” laser results, partic-
ularly in the crow’s feet region, in patients
pretreated with abobotulinumtoxin before
resurfacing [34,35]. He theorized that BoNT
pretreatment may improve the smoothing of


Botulinum Toxins
newly resurfaced skin long enough to affect
“more permanent eradication of wrinkles”
[2, 34, 35]. West & Alster first reported on
the effects of BoNT injections on movement-
associated rhytids after CO2 laser resurfacing
[37]. Compared to a control group of patients
receiving
laser
resurfacing
alone,
those
receiving BoNT immediately following laser
resurfacing were found to have greater and
longer lasting improvement of the forehead,
glabellar, and canthal rhytides (Table 18.3).
Carruthers & Carruthers treated four female
patients
asymmetrically
with
BoNT-A
before CO2 laser resurfacing and found that
patients were more satisfied overall with
the pretreated side, however the degree of
improvement and satisfaction was not quan-
tified (Table 18.3). Furthermore, the recur-
rent crow’s feet tended to be coarser, thicker,
and more obvious in the non-pretreated side
[37, 38]. Regular postoperative injections
given every 6–12 months may prolong the
effects of resurfacing [37–39].
Zimbler
and
colleagues
went
on
to
examine the effect of BoNT injection one-
week prior to laser resurfacing with either
CO2 or erbium dual-mode laser [41]. In
a prospective, randomized split-face trial
of 10 patients, the pre-injected sites were
found to have statistically significant greater
improvement over the untreated sites. The
results were clinically most significant in the
crow’s feet area (Table 18.3). For optimal
results, the authors recommended contin-
ued
maintenance with BoNT
injections
post –resurfacing. Lask et al. performed a
split-face study on periorbital rhytides; one
side received Er:YAG laser resurfacing with
BoNT versus the contralateral side with
Er: YAG resurfacing and saline injection
[42]. At 12-week follow-up, the side treated
with
combination
therapy
demonstrated
significantly greater improvement in the
appearance of periorbital rhytides, texture,
pigmentation, and other features of peri-
orbital skin aging than the control side
(Table 18.3).
As is the case with soft-tissue augmenta-
tion, BoNT should be given 1–3 weeks prior
to resurfacing, thereby allowing the toxin to
prevent muscle activity at the time of resur-
facing [37, 39, 40]. By treating dynamic mus-
cles prior to resurfacing, they will have less
influence on the deposition and organization
of newly remodeled collagen and elastic fibers
and ultimately helps the remodeled dermis
heal with a smoother surface topography
[29,41].
In recent years, fractional ablative and non-
ablative resurfacing for skin rejuvenation has
gained popularity due to fewer risks and
reduced downtime compared to traditional
resurfacing. The only published literature on
this combination is a case report. Beer and
Waibel reported on the synergism of BoNT
and fractional resurfacing of rhytides in the
cheek area in a single patient [43]. One day
prior to laser treatment with a 1,540-nm
fractional nonablative laser four injections
of 1 U abobotulinum toxin into each cheek.
Three treatments were conducted at 3-week
intervals. Significant improvement of the
radiating rhytides was noted after each treat-
ment (Figure 18.5). Since this was not a split-
face study, it is unclear what contribution
was made by either component, although
the accompanying photo demonstrates more
improvement in cheek rhytides than would
be expected with three nonablative resurfac-
ing treatments, even with the highest energy
settings.
Although there have been no large clini-
cal double-blind studies performed compar-
ing combination of laser resurfacing with and
without BoNT, these cited studies point to an
improvement in results of laser resurfacing
with preceding BoNT, with the most proven
effects observed in the periorbital area. In
this author’s experience, similar results using
BoNT and other ablative resurfacing modal-
ities such as the 2790 nm YSGG laser
have been obtained (Figure 18.6). Although
it seems intuitive that putting the skin to
rest while it is creating new collagen would
enhance and prolong the result, it would be
beneficial to have more double-blind placebo
controlled studies as well as clarification of
the underlying molecular mechanisms.

18 Combination Therapy of Botulinum Toxin with other Nonsurgical Procedures

Table .Combination of BoNT with laser resurfacing.
Authors
Study design/Methods
Evaluation schedule
Clinical results
Comments
West & Alster
1999 [37]
40 patients who had
received full face CO2
laser resurfacing were
randomized to receive
BoNT-A injections to
glabella, forehead, or
lateral canthal regions
or no additional
treatment; responses
assessed clinically &
photographically
Baseline and at 3, 6,
& 9m
Enhanced and
prolonged
correction of
movement-
associated rhytids
of the glabella,
forehead, and
lateral canthal
region in the BoNT
group vs
non-BoNT treated
pts.
Zimbler et al.
2001 [41]
Prospective,
randomized, blinded,
split-face study of 10
female subjects
comparing BoNT-A
pretreatment (crows
feet, forehead lines,
glabellar frown lines)
and laser resurfacing
(CO2 or erbium
dual-mode laser)
versus laser
resurfacing alone;
Responses assessed
clinically and
photographically
Baseline, 6 weeks,
3mo, 6mo
Sites pretreated
with BoNT showed
statistically
significant
improvement over
the nontreated side,
with crows feet
region showing the
greatest
improvement.
For optimum
results,
continued Botox
maintenance
post-procedure
is
recommended.
No difference
between
resurfacing
modalities
Yamauchi, Lask,
Lowe 2004 [42]
Prospective,
randomized,
placebo-controlled
study comparing
efficacy and safety of
BoNT-A and
periorbital Er:YAG
resurfacing versus
resurfacing alone in
33 subjects; responses
assessed clinically and
photographically
Baseline, 1 wk,
2 wks, 4 wks,
8 wks, 12 wks.
BoNT-treated side
improved
significantly more
than placebo side
in diminishing
periorbital rhytids,
textural,
pigmentation, and
other features of
periorbital aging.
Beer & Waibel
2007 [43]
Case report of
fractional resurfacing
of cheeks combined
with BoNT-A to each
cheek one day prior to
first resurfacing
session
3 treatment
sessions, 3 weeks
apart
Significant
improvement of
cheek rhytids noted
after first laser
treatment;
improvement
increased after
second resurfacing
session and was
enhanced slightly
after the third.
Specifically
looks at cheek
rhytids.
Limitations –
case report, no
control


Botulinum Toxins
(a)
(b)
Figure .Left cheek (a) prior to and (b) following BoNT and fractional resurfacing. Source: Beer 2007 [43].
BoNT and Other Modalities –
Chemical Peels, Chemabrasion,
Cosmeceuticals
Chemical peels, topical medications, and
various
cosmeceuticals
are
additional
options available for the aesthetic patient
to improve their aging face. These are also
frequently used in combination with BoNT,
although again there are few controlled
studies. In a multicenter clinical study led
by Dr. Jody Comstock, 2,697 patients who
were also undergoing various procedures
such as abobotulinumtoxin, dermal fillers,
nonablative and ablative laser treatments,
(a)
(b)
Figure .(a) Before treatment. (b) 2 weeks after full face Erbium:YSGG and 53 U of BoNT to glabella, forehead,
and lateral brow depressors. Source: Courtesy of Amy Forman Taub, MD.

18 Combination Therapy of Botulinum Toxin with other Nonsurgical Procedures

microdermabrasion, and chemical peels also
applied a four-step tretinoin/hydroquinone
treatment system for a mean of 4 weeks pre-
treatment and 6 weeks posttreatment [44].
Patient’s demographics were typical of the
antiaging market (95% females aged 35–65).
Among the 239 patients that received BoNT
and
the
topical
regimen,
improvements
of at least 1 grade in sallowness, tactile
roughness,
hyperpigmentation,
and
fine
periocular lines were observed in > 80% of
patients. More than 30% of patients in the
BoNT group experienced at least a 2-grade
improvement in hyperpigmentation, tactile
roughness, and periocular fine lines. They
concluded that the complementary use of a
tretinoin/hydroquinone based system may
result in additional improvements in various
signs of facial aging versus other treatments
alone. A major limitation of this study is
that both treatment options were not tested
alone.
Marina Landau examined the combination
of chemical peels with BoNT in three patients
clinically and photographically [45]. All three
patients experienced a significant improve-
ment, however these results were not specif-
ically quantified and they were not compared
to either treatment alone. Landau speculates
that the combination treatments create a syn-
ergistic rejuvenating effect that is likely more
significant than either therapy alone.
Kadunc and colleagues looked at the effect
of BoNT pretreatment of the orbicularis oris
muscle for upper perioral vertical wrinkles
with manual chemabrasion in 12 patients
[46]. The BoNT was injected unilaterally
at the vermillion border 1 week prior to
chemabrasion
(35%
trichloroacetic
acid
followed by dermasanding). Two blinded
observers at baseline, 30 days, 90 days,
180 days, and 3 years assessed wrinkle
severity by using a four-point Facial Wrinkle
Severity Scale (FWSS). From day 90 to year
3, the BoNT injected sides showed smaller
grades in the FWSS than control sides (p <
0.05). Few other studies looking at BoNT
combination therapy have been able to
successfully
demonstrate
the
potential
long-term benefits of combined therapy.
BoNT and Monopolar
Radiofrequency
Monopolar Radiofrequency (MRF) employs
radiofrequency energy via capacitive cou-
pling to provide volumetric tissue heating
of the deep dermis and subcutaneous tis-
sues while simultaneously cooling the epider-
mis (47–49). The result is dermal remodel-
ing which takes place over a 3- to 6-month
period. It is used as a lifting, tightening, and
contouring procedure for treatment of the
face, neck, brow, eyelid, and body areas. In
the forehead and periocular area, both MRF
and BoNT are used for brow elevation and
reduction of periocular rhytides. Dr. Stephen
Bosniak was one of the first aesthetic physi-
cians who noted that pretreatment of the
brow depressors with BoNT 2 weeks before
MRF aids in relaxation of the muscles that
depress the brow [50]. By eliminating the
downward pull of the brow depressors, unop-
posed collagen remodeling can occur [50].
Although the final result may not be appreci-
ated for 4–6 months, at the conclusion of the
MRF procedure some degree of brow eleva-
tion should be apparent. In the lateral canthal
area, pretreatment of the orbicularis oculi
sphincter with BoNT will allow greater tem-
poral lifting with MRF [8,50]. Unfortunately,
there are no quantitative studies to prove
the synergy between these two procedures,
just the anecdotal observations of numerous
practitioners in the aesthetic arena.
BoNT and Muscle Stimulation (MS)
A device utilizing repetitive high-amplitude
electrical stimulation of the muscles of
the face and neck can be used to increase
muscular volume. The goal is to induce
muscular hypertrophy that will lead to a
lift and firming of the brow, cheeks, jaw-
line, and neck and is based on the “body
building of the face” protocol described
by Mulholland [52]. While proven to yield
substantial 3-demensional improvements in
facial volume by patients and physicians, this
procedure remains relatively obscure in the


Botulinum Toxins
(a)
(b)
Figure .(a) Before treatment. (b) One year after 47 Pan GTM lift treatments and 3 weeks after BoNT to
glabella, forehead, and crow’s feet. Source: Courtesy of Amy Forman Taub, MD.
cosmetic market due to lack of marketing
and promotion, and difficulty of training
and implementation. However, one of the
authors has used this procedure successfully
for 14 years in their practice. This author
completed a study of 17 adult women aged
50–56 years undergoing the 20 treatments
over 10 weeks and monthly treatments
thereafter followed up to 12 months. Most
these subjects also had BoNT in the upper
one-third of the face [51]. While the improve-
ments in lift for the jowls, cheek, eye, and
neck area from MS could be measured, the
improvement in the brow area could not be
assessed due to the confounding variable of
the BoNT treatment. Since the MS therapy
would enhance the movement of the frontalis
muscle as well as the periocular muscles,
this could both enhance lift and result in
rhytidogenesis. However, in our experience,
consistent indefinite high-voltage treatments
in combination with BoNT in the upper
one-third of the face results in an enhanced
cosmetic
result
over
that
of
myofacial
stimulation alone (Figure 18.7, Figure 18.8,
and Figure 18.9). One theory is that BoNT
injected into facial muscles that are antag-
onistic to facial elevators effectively “frees”
the facial elevator muscles, allowing more
complete hypertrophy to occur during the
MS process. However, one could as easily
argue that for the upper one-third of the
face these two modalities are antagonistic
more than synergistic, since stimulation of
muscle could increase dynamic rhytides.
Muscle stimulation enhances facial appear-
ance through the increased volume that
the “hypertrophied” facial elevator muscles
occupy.
Conclusions
The
combination
of
BoNT
and
other
aesthetic
procedures:
fillers,
lasers
and
light sources, and tissue tightening, along

18 Combination Therapy of Botulinum Toxin with other Nonsurgical Procedures

(a)
(b)
Figure .(a) Before treatment. (b) 2 years after 34 Pan G lift treatments and 3 weeks after 54 U BoNT to
glabella and crow’s feet and six syringes of juved`ermUltraTM to nasolabial and melomental folds. Source:
Courtesy of Amy Forman Taub, MD.
(a)
(b)
Figure .(a) Before treatment. (b) 5 months after 20 Pan GTM lift treatments and 60 U of BoNT in glabella,
forehead, and crow’s feet. Source: Courtesy of Amy Forman Taub, MD.


Botulinum Toxins
with chemical peels, cosmeceuticals, and
microcurrent is a fact of life in almost all
aesthetic clinics today. In our fast-paced life
many patients desire reducing the number
of visits required, leading to multiple proce-
dures being performed at one visit [53, 54].
Three major factors have put most aesthetic
providers at ease with providing concurrent
treatments: (i) the burgeoning number of
aesthetic tools; (ii) better understanding of
the complexities of aging changes neces-
sitating
multiple
different
interventions;
and (iii) studies demonstrating the safety of
doing multiple procedures [54]. At the very
least, the combination of BoNT with other
rejuvenation procedures is additive in terms
of combination therapy [22] (Figure 18.3).
There is much literature, albeit mostly small
studies some of which are not placebo con-
trolled, which indicate that there is a very real
synergism between BoNT and fillers as well
as intense pulsed light and possibly ablative
and non-ablative lasers [55]. The best evi-
dence exists for both efficacy and longevity
for the BoNT and filler combination in
the glabellar area, With newer technology
that enables us to more easily study the
3-dimensional static and active components
of the human face, we will no doubt discover
new relationships between wound healing,
metabolism and other molecular activities in
the skin and facial muscle movement, leading
to a deeper understanding of the scientific
underpinnings of combination therapy.
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