Ứng Dụng Thẩm Mỹ Và Lâm Sàng (Cosmetic and Clinical Applications)

26 Modulating Affect and Mood with Botulinum Toxin Injections: Psychosocial Implications of Neuromodulators

depressive disorder. Plast Reconstr Surg
2015 Nov;136(5S):111S–119S.
Mitwalli H, Dolan C, Bacigalupi R.
Botulinum toxin for depression: Does
patient appearance matter? J Am Acad
Dermatol 2016 Jan:74(1):171–173.
Calzadilla, K, Marmur, M. Allergan Reports
Topline Phase II Data Supporting
Advancement of BOTOX®
(onabotulinumtoxinA) for the Treatment of
Major Depressive Disorder (MDD). PR
Newswire. 2017 Apr. Retrieved from

allergan-reports-topline-phase-ii-data-
supporting-advancement-of-botox-
onabotulinumtoxina-for-the-treatment-of-
major-depressive-disorder-mdd-300435486
.html.
Hennenlotter A, Dresel C, Castrop F, et al.
The link between facial feedback and
neural activity within central circuitries of
emotion – new insights from botulinum
toxin-induced denervation of frown
muscles. Cereb Cortex 2009;19:537–542.
Lewis MB. The positive and negative
psychological potential of botulinum-toxin
(Botox) injections. Abstract presented at:
British Psychological Society Harrogate,
North Yorkshire, England, United
Kingdom; Apr 9, 2013. Available from

abstracts?&ResultsType=Abstracts&
ResultSet_ID=9317&FormDisplayMode=
view&frmShowSelected=true&local
Action=details. Accessed February 5, 2017.
Izard, CE. Facial expressions and the
regulation of emotions. J Person Soc Psych
1990;58:487–498.
McIntosh DN. Facial feedback hypotheses:
Evidence, implications, and directions.
Motivation Emotion 1996;20:121–147.
Darwin, C.R. The Expression of Emotions in
Man and Animals. Oxford, England:
Oxford University Press, 1998:366.
Gellhorn E. The physiological basis of
neuromuscular relaxation. Arch Intern
Med 1958;102;392–399.
Strack R, Martin LL, Stepper S. Inhibiting
and facilitating conditions of facial
expressions: A non-obstrusive text of the
facial feedback hypothesis. J Pers Social
Psych 1988;54:768–777.
Alam M, Barrett KC, Hodapp RM, Arndt
KA. Botulinum toxin and the facial
feedback hypothesis: can looking better
make you feel happier? J Am Acad
Dermatol 2008;58(6):1061–1072.
Larsen RJ, Kasimatis M, Frey K. Facilitating
the furrowed brow: An unobstrusive test of
the facial feedback hypothesis applied to
unpleasant affect. Cognition Emotion
1992;6:321–338.
Ekman P. Facial expressions of emotion: An
old controversy and new findings. Phil
Trans R Soc Lond B 1992;335:63–69.
Gladwell M. The Naked Face. The New
Yorker (August 5, 2002), pp. 38–49.
Gladwell M. Blink (Chapter Six, Sections 2
and 3). New York: Little, Brown & Co.,
2005:197–214.
Ekman P, Levenson RW, Friesen WV.
Autonomic nervous system activity
distinguishes among emotions. Science
1983;221:1208–1210.
Winton WM. The role of facial response
in self-reports of emotion: A critique of
Laird. J Pers Soc Psych 1986;50:808–812.
McHugo GJ, Lanzetta JT, Sullivan DJ, et al.
Emotional reactions to a political leader’s
expressive displays. J Pers Soc Psych
1985;49:1513–1529.
Hatfield E, Cacioppo JT, Rapson RL.
Emotional Contagion. Cambridge:
Cambridge University Press, 1994.
Meltzoff AN, Moore MK. Newborn infants
imitate facial gestures. Child Develop
1983;54:702–709.
Stel M, Vonk R. Mimicry in social
interaction: benefits for mimickers,
mimickees, and their interaction. Br J
Psychol 2010;101:311–323.
Haughton VM, Turski PA, Meyerand B,
et al. The clinical applications of functional
MR imaging. Neuroimaging Clin N Am
1999;9:285–293.
Paulesu E, Connelly A, Frith CD, et al.
Functional MR imaging correlations with
positron emission tomography. Initial
experience using a cognitive activation
paradigm on verbal working memory.


Botulinum Toxins
Neuroimaging Clin N Am 1995;5:
207–225.
Enticott PG, Johnston PJ, Herring SE, et al.
Mirror neuron activation is associated with
facial emotion processing.
Neuropsychologia 2008;46:2851–2854.
Rives Bogart K, Matsumoto D. Facial
mimicry is not necessary to recognize
emotion: Facial expression recognition by
people with Moebius syndrome. Soc
Neurosci 2010;5:241–251.
Dienhardt K, Schiavo G. Endocytosis and
retrograde axonal traffic in motor neurons.
Biochem Soc Symp 2005;139–150.
Antonucci F, Rossi C, Gianfranceschi L,
et al. Long-distance retrograde effects of
botulinum neurotoxin A. J Neurosci
2008;28:3689–3696.
Tang-Liu DD, Aoki KR, Dolly JO, et al.
Intramuscular injection of 125I-botulinum
neurotoxin-complex versus
125I-botulinumfree neurotoxin: time
course of tissue distribution. Toxicon
2003;42:461–469.
Stel M, van den Heuvel C, Smeets RC.
Facial feedback mechanisms in autistic
spectrum disorders. J Autism Dev Disord
2008;38 1250–1258.
Oberman LM, Winkielman P,
Ramachandran VS. Slow echo: facial EMG
evidence for the delay of spontaneous, but
not voluntary, emotional mimicry in
children with autism spectrum disorders.
Dev Sci 2009;12:510–520.
Minio-Paluello I, Baron-Cohen S, Avenanti
A, et al. Absence of embodied empathy
during pain observation in Asperger
syndrome. Biol Psychiatry 2009;65:
55–62.
Fecteau S, Pascual-Leone A, Thoret H.
Psychopathy and the mirror neuron
system: preliminary findings from a
non-psychiatric sample. Psychiatry Res
2008;160:137–44.
Varcin KJ, Bailey PE, Henry JD. Empathic
deficits in schizophrenia: the potential role
of rapid facial mimicry. J Int Neuropsychol
Soc 2010;16:621–629.
Wang AT, Dapretto M, Hariri AR, et al.
Neural correlates of facial affect
processing in children and adolescents with
autism spectrum disorder. J Am Acad
Child Adolesc Psychiatry 2004;43:481–490.
Tardif C, Lain´e F, Rodriguez M, et al.
Slowing down presentation of facial
movements and vocal sounds enhances
facial expression recognition and induces
facial-vocal imitation in children with
autism. J Autism Dev Disord 2007;37:
1469–1484.
Zhao X, Leotta A, Kustanovich V, et al. A
unified genetic theory for sporadic and
inherited autism. Proc Natl Acad Sci USA
2007;104:12831–1286.
Wheelwright S, Auyeung B, Allison C, et al.
Defining the broader, medium and narrow
autism phenotype among parents using the
Autism Spectrum Quotient (AQ).
Molecular Autism 2010;1:10.
.molecularautism.com/content/1/1/10.
Accessed February 27, 2017.
Oberman LM, Winkielman P,
Ramachandran VS. Face to face: blocking
facial mimicry can selectively impair
recognition of emotional expressions. Soc
Neurosci 2007;2:167–178.
K¨uhn S, M¨uller BC, van der Leij A, et al.
Neural correlates of emotional synchrony.
Soc Cogn Affect Neurosci 2011;6(3):
368–374.
Cheng CM, Chartrand TL. Self-monitoring
without awareness: using mimicry as a
nonconscious affiliation strategy. J Pers Soc
Psychol 2003;85:1170–1179.
Stel M, van Dijk E, Olivier E. You want to
know the truth? Then don’t mimic! Psychol
Sci 2009;20: 693–699.
Zinchenko A, Kanske P, Obermeier C, et al.
Emotion and goal-directed behavior: ERP
evidence on cognitive and emotional
conflict. Soc Cogn Affect Neurosci
2015;10(11):1577–1587.



OnabotulinumtoxinA (Botox®) in Dermatology
Jason J. Emer, MD,1 Eileen Axibal, MD,2 Ellen S. Marmur, MD (FAAD),3 and Heidi Waldorf, MD3
1Cosmetic Dermatology and Body Contouring, Private Practice, Beverly Hills, CA
2Department of Dermatology, University of Colorado, Aurora, USA
3Mount Sinai School of Medicine, Department of Dermatology, New York, USA
Introduction
Since the approval of botulinum toxin for
medical use in the United States nearly
three decades ago, the use of neurotoxin has
become a standard of care for the treatment
of facial dynamic wrinkles. Of the various for-
mulations of botulinum toxin type A that are
available or in development, onabotulinum-
toxinA (Botox/Botox Cosmetic; Allergan,
Inc., Irvine, CA) is the most commonly used
and widely studied. It was approved by the
Food and Drug Administration (FDA) in
1989 for strabismus and blepharospasm and
started being used for off-label aesthetic pur-
poses in 1992 [1]. The FDA approved onabo-
tulinumtoxinA (BoNTA-ONA) for the treat-
ment of glabellar “frown” lines in 2002 [2] and
lateral canthal “crow’s feet” lines in 2013 [3].
In 2004, BoNTA-ONA was FDA approved for
the treatment of severe axillary hyperhidro-
sis inadequately managed by topical agents
in adult patients [4]. The toxin also contin-
ues to be widely used off-label to treat other
skin lines and for facial contouring, as well
as for palmoplantar and facial hyperhidro-
sis [5–8]. It is available worldwide and has
many non-dermatologic indications includ-
ing treatment of bladder dysfunction, chronic
headache, spasticity, cervical dystonia, bel-
pharospasm, and strabismus [4]. While the
use of botulinum toxins continue to expand
with new formulations and indications, this
chapter will focus specifically on onabo-
tulinumtoxinA and its FDA-approved uses in
dermatology.
Efficacy
Years of clinical trials and clinical use have
proven excellent efficacy BoNTA-ONA. In
2002 and 2003, two articles published by
Carruthers et al. reported on a total of 537
patients who enrolled in two separate phase
3 randomized, double-blinded, multi-center,
placebo-controlled studies of identical design
to evaluate the efficacy and safety of BoNTA-
ONA for temporary improvement in moder-
ate to severe glabellar lines [9, 10]. Of those
enrolled, 405 patients received BoNTA-ONA
and 132 patients received placebo. The total
dosage of BoNTA-ONA was 20 U, divided
equally into five injection points. Reduction
in glabellar line severity was superior in the
treatment group compared to the placebo
group at all study time points, both by investi-
gator and patient assessment. More recently,
three sequential phase 3 studies published in
2014 and 2015 further demonstrated the effi-
cacy and safety of onabotulinumtoxinA for its
newest cosmetic indication, crow’s feet lines
[11–13].
Two pivotal studies were conducted using
BoNTA-ONA for the treatment of primary
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
Figure .Vial types by units. Each vial of BoNTA-ONA contains either 50 U or 100 U. Potency is determined by
the amount of saline used for reconstitution.
axillary hyperhidrosis. Naumann and Lowe
randomized patients who received a single
treatment of 50 U per axilla or a placebo in
a ratio of 3 : 1 [14]. During the posttreatment
period dramatic improvements were noted
in the treatment group with respect to emo-
tional status, ability to participate in daily
and social activities, productivity at work,
and number of clothing changes per day.
The desired effects were rapid and long last-
ing (at least 16 weeks) with few reported
adverse events. Similar results were con-
firmed in a study by Lowe and Glaser who
treated patients with two differing BoNTA-
ONA dosages (50 U, 75 U, or placebo) [15].
Though off-label, studies have also validated
the efficacy of BoNTA-ONA in both palmar
[16–19] and plantar [20,21] hyperhidrosis.
Storage and Preparation
A vial of Botox® Cosmetic (BoNTA-ONA)
contains either 50 U Clostridium botulinum
type A neurotoxin complex, 0.25 mg human
albumin, and 0.45 mg sodium chloride; or
100 U Clostridium botulinum type A neuro-
toxin complex, 0.5 mg human albumin, and
0.9 mg sodium chloride in a sterile, vacuum-
dried form without a preservative [22]
(Figure 27.1). The initial recommendation to
freeze unopened vials (−5◦C or colder) has
been amended to allow storage in a refrigera-
tor (2–8◦C) for 24 or 36 months for the 50 U
and 100 U vials, respectively. The product
insert recommends dilution with 0.9% sterile
preservative-free saline; however, the use of
preserved isotonic saline reduces patient dis-
comfort without sacrificing efficacy and has
become standard of care [23] (Figure 27.2).
The manufacturers also recommend storage
of the reconstituted BoNTA-ONA in the
refrigerator,
toxin
administration
within
4–24 hours, and not freezing after recon-
stitution; however, studies have shown that
BoNTA-ONA retains its efficacy for at
least 4–6 weeks following reconstitution if
refrigerated at 4◦C [24, 25] and that there is
no difference in efficacy of injected Botox
after
2-weeks
of
refrigeration
(4◦C)
or
freezing (−20◦C) of a reconstituted vial com-
pared with freshly reconstituted Botox [26].
Despite initial concerns about toxin stability,
no reduction in efficacy has been found when
the vial contents are shaken and foamed
during reconstitution [27]. Reconstituted

27 OnabotulinumtoxinA (Botox®) in Dermatology

Figure .Reconstitution solutions.
Left, 0.9% sterile preservative-free
saline; right, preserved isotonic saline.
product should be clear, colorless, and free
of particulate matter. A publication in 2012
by Liu et al. suggested that a single vial
of botulinum toxin type A can be safely
administered to multiple patients, assum-
ing standard safe injection techniques are
followed [28]. This proposition was based a
survey of physician members of the Ameri-
can Society of Dermatologic Surgery, which
found that most physicians routinely store
botulinum toxin for a period of >1 week and
use each vial for more than one patient, and
not a single case of infection was observed.
Treatment
The onset of BoNTA-ONA has been shown
to be rapid within 1–2 days [29]. In two clin-
ical trials, the degree of response by both
investigator and patient assessment was sim-
ilar at day 7 and day 30, with peak effect
seen on day 30 [9, 10]. Results from two
large studies demonstrated that duration of
BoNTA-ONA effect in minimizing glabellar
and lateral canthal lines was frequently ≥4
months [30, 31]. The clinical effect is deter-
mined by both the number of units of toxin
injected as well as the concentration [32–
34]. Most practitioners use between 1 and
3 ml of saline to reconstitute for aesthetic
use; A 5 U/0.1 ml preparation is prepared by
2 ml of preservative-free saline into the 100 U
vial [35, 36]. Consensus recommendations
and package insert validate 100 U/2.5 ml =
4 U/0.1 ml as the most versatile concentra-
tion [37]. In a dose-dilution study in which a
total dose of 30 U BoNTA-ONA was recon-
stituted in 1, 3, 5, or 10 ml saline, no differ-
ences in safety or efficacy were seen between
groups in treating glabellar rhytides [33].
Dosage can be increased to correlate with the
size of the treated muscle. Results of a 2009
study by Kane et al. demonstrated the effi-
cacy of dosing Dysport based on gender and
muscle-mass [38]; while not directly stud-
ied, these results could reasonably be applied
to Botox. In general, higher concentrations
mean low injection volumes, less pain and
edema, and more precise placement of prod-
uct [32]. Delivery of the same number of units
in a lower concentration requires a higher
volume and therefore has the potential for
increased pain and a larger field of effect.
This can be utilized to an advantage or may
lead to unpredictable side effects nearby or
far from injection placement. Dosing units
vary by treatment location, as outlined in
Table 27.1. The other variable in treatment is
needle/syringe type. Some physicians prefer
to use a 32-guage needle (A; TSK SteriJect,
TSK Laboratory, Tochigi-Ken, Japan) rather


Botulinum Toxins
Table .Typical starting dosages of onabotulinumtoxinA for various target regions.
Target region
Total starting dosage in unitsa
Glabellar compex
20–40 (5–7 sites)
Forehead
10–30 (4–8 sites)
Crow’s feet
8–20 per side (1–4 sites)
Vertical lip lines
4–6 (4 sites)
Mouth corners
2–8 per side (1 site)
Bunny lines
2–6 (1–3 sites)
Dimpled chin
2–10 (1–2 sites)
Platysmal bands
10–15 per band (2–10 sites)
Axillary hyperhidrosis
50–100 per axilla (1–2 cm/site; multiple sites)
Palmar hyperhidrosis
50–100 per palm (1–2 cm/site; multiple sites)
Plantar hyperhidrosis
50–100 per sole (1–2 cm/site; multiple sites)
a Units are unique to this product.
than the more common 30/31-gauge needles
(B; BD Precision Glide, Becton Dickinson &
Co, Franklin Lakes, NJ) to help reduce side
effects such as pain during injection. Also, an
array of syringe types is available for injection
and can be chosen based on personal prefer-
ence (Figure 27.3).
Glabella
The first FDA approved cosmetic indication
for botulinum toxin was for treatment of
glabellar frown lines using a total dose of
20 s. The glabellar complex includes the
procerus, corrugator supercilii, depressor
Figure .Syringes and needles. Some physicians prefer to use a 32-guage needle (a) TSK SteriJect, TSK
Laboratory, Tochigi-Ken, Japan, rather than the more common 30-gauge needle (b) BD Precision Glide, Becton
Dickinson & Co, Franklin Lakes, NJ, to help reduce side effects such as pain during injection. Also, an array of
syringe types is available for injection and can be chosen based on personal preference. (c) Injekt-F Tuberkulin
Low Waste Syringe, B. Braun Medical, Bethlehem, PA;. (d) BD Leur-Lok Tip Syring, Becton Dickinson & Co,
Franklin Lakes, NJ; (e) BD Tuberculin Slip Tip Syringe, Becton Dickinson & Co, Franklin Lakes, NJ; (f) BD
SafetyGlide Insulin Syringe, Becton Dickinson & Co, Franklin Lakes, NJ.

27 OnabotulinumtoxinA (Botox®) in Dermatology

supercilii, and interdigitation of the medial
fibers of the orbicularis oculi and frontalis
muscles. The procerus is the primary muscle
responsible for the horizontal lines of the
glabella and the others contribute to the
formation of the vertical lines. Numerous
injection techniques have been described
with
early
injection
incorporating
elec-
tromyographic guidance to locate the muscle
accurately
[34,
39].
Most
clinical
trials
have dictated starting doses of 20–25 U of
BoNTA-ONA split equally into five injection
sites for treatment of the glabellar complex.
Additional or fewer injection points may
be indicated in certain circumstances such
as in men for maintenance of a horizontal
brow (two additional) or when products have
the ability to diffuse more easily (two fewer)
[40–42]. Gender is particularly important
and should be taken into consideration as
the female brow is typically more arched and
the male brow is classically more horizontal
(Figure 27.4 and Figure 27.5). Women may
require a lower starting dosage than men; in
general, men have more muscle mass and
thicker, sebaceous skin which may require
starting dosages approximately twice that
which is used for women [43–45]. Practi-
tioners should evaluate the patient’s facial
expression at rest and during movement
prior to any dosing to assess any asymmetries
of positioning, ptosis, and muscular mass.
Figure .Female forehead anatomy. Typical
rhytides of the frontalis muscle are evident during
forehead elevation with an arched appearance of the
eyebrows. Notice the frontalis is one large muscle
with broad insertions, rather than two discreet
muscles with specific insertions.
Orbicularis Oculi
The more recent FDA approved cosmetic
indication for BoNTA-ONA (2013) is treat-
ment of the lateral canthal lines, or crow’s
feet, using a total dose of 24 s (12(on each
side, with 4 o at each of three injection
sites). Lateral canthal lines are caused by
contraction of the orbicularis oculi muscles.
These are sphincter-like muscles encircle the
eyes and aid in eye closure; they are broad,
thin, and superficial, and wrinkles in this
region develop from a combination of muscle
activity (eye closing and facial expressions)
and photoaging. Typically, sites are injected
superficially along the lateral orbital rim with
2–5 U of BoNTA-ONA each. To minimize
toxin diffusion and paralysis of neighboring
muscles (zygomaticus minor, zygomaticus
major, and levator labii superioris muscle),
typical aliquots are distributed approximately
1 cm apart and lateral to the outer can-
thus. The usual number of injections is
two to five per side and precise location of
these points depend on pretreatment analy-
sis, which takes into account the activity of
the muscle and orbital line patterns observed.
Figure .Male forehead anatomy. Male forehead
rhytides are typically large and broad as compared to
females, given an increased distance between the
eyebrows and the frontal hair line. Notice the skin is
more glabrous, due to increase sebaceous activity.
Also, here is a good example of the frontalis muscle
as two discrete muscle bellies with insertions more
prominent over the eyebrows and with sparing of
part of mid-upper forehead. Further, the male
eyebrows are more horizontal and less arched as
compared to females.


Botulinum Toxins
Duration of effect in this area is usually less
than the upper face and is dose-dependent
with higher dosages yielding longer-lasting
results. For patients who desire more open
eyes (increased scleral show), lower eye lat-
eral rounding, or improvement of infraorb-
tial rhytides, a small aliquot of toxin can
be injected into the inferior orbicularis oculi
below the midpupillary line [46,47].
Hyperhidrosis
BoNTA-ONA currently remains the only
neurotoxin that is specifically approved by
the FDA for the treatment of primary axil-
lary hyperhidrosis, using 50 in each axilla.
The Minor test, an iodine starch test, can
be done immediately prior to treatment to
allow for delineation of affected areas [48]
(Figure 27.6). If utilizing the Minor test, is rec-
ommended that patients discontinue all anti-
hyperhidrotic therapeutic agents – including
antiperspirants – 5 days prior to improve the
test’s accuracy [49]. Approximately 50 U of
BoNTA-ONA are needed for the treatment
of one axillae [50], with 20 injections dis-
tributed evenly, spaced 1–2 cm apart, in the
hyperhidrotic area. In patients with more sur-
face area of involvement, however, additional
units are often given so that the total dose per
axilla may actually be 60–100 units. Mark-
ing the area of involvement with a surgical
Figure .Palmar hyperhidrosis. Clammy hands
with palmar glistening in a patient with severe
hyperhidrosis.
Figure .Iodine starch test. Iodine starch test is
used as an aid for identifying localized areas of
sweating in order to concentrate toxin injection for
increased clinical efficacy and patient satisfaction.
pen in a grid pattern can help ensure proper
distribution of the product. Injections should
stay superficial and should be injected next to,
not directly on, skin markings to decrease the
risk of skin tattooing. Increasing the accuracy
of injection placement improves clinical effi-
cacy and patient satisfaction [51]. Although
not FDA approved, use of BoNTA-ONA is
also common in palmar and plantar hyper-
hidrosis and is covered in depth in Chapter 23
of this textbook (Figure 27.7).
Safety and Complications
Similar to other BoNTA products, BoNTA-
ONA is generally well tolerated. In 2005, Cote
et al. reviewed all therapeutic and cosmetic,
serious and nonserious, adverse events from
BoNTA-ONA
administration
that
were
reported to the FDA from December 1989 to
May 2003 (serious) and December 2001 to
November 2002 (nonserious) [52]. Of 36 seri-
ous adverse events, 30 were included in the
FDA-approved label as possible complica-
tions and the remaining six were considered
unrelated to the treatment. No deaths were
reported among cosmetic users. The most
commonly reported non-serious side effects
were lack of effect, injection site reaction,
and ptosis. A meta-analysis of the number

27 OnabotulinumtoxinA (Botox®) in Dermatology

and
frequency
of
adverse
events
from
BoNTA-ONA in 36 studies involving 2309
subjects revealed no severe adverse events
[53]. Complications such as pain, bruising,
and swelling are mainly dependent on the
location (knowledge of target anatomy and
avoidance of visible veins) and technique
(speed, needle gauge, pressure, and/or ice)
of injection, as the periocular, perioral, and
lid margins consist or thin, friable skin which
is highly vascular with many superficial
vessels prone to injury. Most of the available
evidence suggests that hematoma and ecchy-
moses at injection sites occur in less than 1%
of injections [54]. Common adverse effects of
neurotoxin therapy in cosmetic indications
are listed in Table 27.2.
Headache and blepharoptosis have shown
to be the most significant treatment-related
adverse effects related to glabellar treat-
ment, with headache more likely to be due
to injection procedure than the drug itself
given that headache occurs with equal fre-
quency in those treated with BoNTA-ONA
and placebo [9, 10]. Overall, headaches from
BoNTA-ONA injection are mild and require
no specific therapy, although a small subset
of patients have been reported to develop
more severe, debilitating headaches – likely
due to micro-trauma from the needle being
inserted too deep into the forehead and thus
“tapping” periosteum – which are fortunately
benign and spontaneously remit within days
to weeks with or without treatment (anal-
gesic) [55]. Unintended paralysis of neighbor-
ing muscles, or ptosis, is the most significant
complication that can occur with cosmetic
neurotoxin treatment. Local spread of toxin
occurs by diffusion even up to 3 cm in diame-
ter from the injection point [56]. The package
insert of BoNTA-ONA reports blepharopto-
sis occurring in 3% of 405 subjects, whereas
an early trial that included injectors with less
experience reported blepharoptosis in 5.4%
of patients [9, 22]. To limit the incidence
of unwanted adjacent muscle paralysis, it is
helpful to grasp the specific glabellar mus-
cles prior to each injection to localize delivery
and apply digital pressure during injection.
Table .Common adverse effects of neurotoxin
therapy in cosmetic indications.
Upper face
Common:
Bruising/Ecchymosis
Swelling
Ptosis (eyebrow, eyelid)
Asymmetry
Rare:
Interference with eye lid function/physiology
Lower lid retraction / scleral show
Effect on upper lip movement
Atrophy
Globe perforation
Lower face
Common:
Bruising/Ecchymosis
Swelling
Asymmetry
Rare:
Increase or loss of dental show on smiling
Effect on oral muscle strength
Inability to raise or lower lips / irregular lip
movement
Difficulty swallowing
Neck weakness
Dry mouth
Drooling
Palmoplantar
Muscular weakness interfering with fine motor
function
It is also important to place corrugator injec-
tions at least 1 cm above the bony orbital
rim, place orbicularis oculi muscle injections
at least 1–2 cm from the lateral orbital rim,
and place frontalis injections at least 1–2 cm
above the upper line of the eyebrow. Of
note, at the time of writing of this chapter the
use of botulinum toxin in the frontalis mus-
cle is considered off-label yet is commonly
performed. In certain situations, it is helpful
to consider lower dilutions that give higher


Botulinum Toxins
localized concentrations and lower injection
volumes to help reduce spread or unwanted
diffusion. Increased clinician experience can
minimize rates of ptosis.
Adverse events associated with treatment
of axillary hyperhidrosis with BoNTA-ONA
are uncommon. Minimal pain and mild sub-
jective compensatory hyperhidrosis in non-
axillary regions in 5% of patients have been
described [14]. In the off-label treatment of
palmoplantar hyperhidrosis, the most signif-
icant complication is the possibility of tem-
porary hand weakness because of diffusion of
toxin to the intrinsic hand muscles. This may
occur in as many as two-thirds of patients
reflecting as minor weakening of finger grip
strength that can last for 3–5 weeks [57,
58]. Superficial placement in the high dermis
may help reduce muscle effects and increase
patient comfort.
To minimize patient discomfort during
injections for hyperhidrosis, pretreatment
and posttreatment application of ice or
ethyl chloride spray, topical anesthetic under
occlusion, nerve blocks, and/or frequent
changing of the needle tip (as the needle tip
may dull after multiple punctures) can be
used [59–61]. Vibratory massage devices are
also commonly employed to relieve injection
pain; the ability of a non-noxious stimulus
to suppress discomfort is thought to work
through the gate control theory of pain, in
which the benign stimulus closes the “gates”
to the painful input and prevents the adverse
sensation from traveling to the central ner-
vous system [62].
Patient Satisfaction
Numerous studies have demonstrated sus-
tainably high patient-satisfaction rates with
cosmetic BoNTA-ONA treatments [63,64]. A
2015 report by Trinidade de Almeida et al.
found that long-term, continuous treatment
with onabotulinumtoxinA for a mean of 9.1
years was associated with very high patient
satisfaction [65]. Several clinical trials in
treating upper facial lines have demonstrated
significant improvements from baseline and
versus placebo in patient self-assessment
scores in which the patients rate the degree
to which their facial lines bother them, make
them look older than they would like, prevent
them from having a smooth facial appear-
ance, and/or make them look tried, stressed,
or angry when that is not how they feel [66].
High satisfaction rates with BoNTA-ONA
treatment results have helped to build inter-
est and create new indications in the nonin-
vasive aesthetic market.
Conclusion
The trend in the use of neurotoxin prod-
ucts for facial aesthetics is towards utiliz-
ing the lowest dosage possible for “natu-
ral” yet smooth, youthful appearances. For
best results, practitioners must have detailed
knowledge of the facial anatomy, neurotoxin
product characteristics, and must be able to
individualize assessments for success. Clini-
cal trials and real-time experience will delin-
eate major differences between the available
neurotoxins and their most practical uses in
facial aesthetics, as well as other uses such as
hyperhidrosis. As the most extensively stud-
ied and longest used neurotoxin worldwide,
onabotulinumtoxinA can provide safe, effec-
tive, and reproducible results – and we expect
to see additional FDA approvals for other cos-
metic regions (including the forehead) in the
future.
References
Carruthers JD, Carruthers JA. Treatment of
glabellar frown lines with C. botulinum-A
exotoxin. J Dermatol Surg Oncol 1992;
18(1):17–21.
FDA. BOTOX Cosmetic Approval Letter.
2002.
FDA. FDA approves Botox Cosmetic to
improve the appearance of crow’s feet lines.

27 OnabotulinumtoxinA (Botox®) in Dermatology

September 2013;
NewsEvents/Newsroom/
PressAnnouncements/ucm367662.htm.
Accessed February 27, 2017.
Botox [Prescribing information]. BOTOX
(onabotulinumtoxinA) for injection, for
intramuscular use, intradetrusor, or
intradermal use. Irving, CA: Allergan; 2016.
Carruthers J, Carruthers A. The evolution
of botulinum neurotoxin type A for
cosmetic applications. J Cosmet Laser Ther
2007;9(3):186–192.
Said S, Meshkinpour A, Carruthers A,
Carruthers J. Botulinum toxin A: its
expanding role in dermatology and
esthetics. Am J Clin Dermatol 2003;4(9):
609–616.
Glaser DA, Hebert AA, Pariser DM, Solish
N. Facial hyperhidrosis: best practice
recommendations and special
considerations. Cutis 2007;79(5 Suppl):
29–32.
Gregoriou S, Rigopoulos D, Makris M,
et al. Effects of botulinum toxin-a therapy
for palmar hyperhidrosis in plantar sweat
production. Dermatol Surg 2010;36(4):
496–498.
Carruthers JA, Lowe NJ, Menter MA, et al.
A multicenter, double-blind, randomized,
placebo-controlled study of the efficacy and
safety of botulinum toxin type A in the
treatment of glabellar lines. J Am Acad
Dermatol 2002;46(6):840–849.
Carruthers JD, Lowe NJ, Menter MA,
Gibson J, Eadie N, Group BGLIS.
Double-blind, placebo-controlled study of
the safety and efficacy of botulinum toxin
type A for patients with glabellar lines. Plast
Reconstr Surg 2003;112(4):1089–1098.
Carruthers A, Bruce S, de Coninck A, et al.
Efficacy and safety of onabotulinumtoxinA
for the treatment of crows feet lines: a
multicenter, randomized, controlled trial.
Dermatol Surg 2014;40(11):1181–1190.
Moers-Carpi M, Carruthers J, Fagien S,
et al. Efficacy and safety of
onabotulinumtoxinA for treating crow’s
feet lines alone or in combination with
glabellar lines: a multicenter, randomized,
controlled trial. Dermatol Surg 2015;41(1):
102–112.
Carruthers J, Rivkin A, Donofrio L, et al. A
multicenter, randomized, double-blind,
placebo-controlled study to evaluate the
efficacy and safety of repeated
onabotulinumtoxinA treatments in
subjects with crow’s feet lines and glabellar
lines. Dermatol Surg 2015;41(6):
702–711.
Naumann M, Lowe NJ. Botulinum toxin
type A in treatment of bilateral primary
axillary hyperhidrosis: randomised, parallel
group, double blind, placebo controlled
trial. BMJ 2001;323(7313):596–599.
Lowe NJ, Glaser DA, Eadie N, et al.
Botulinum toxin type A in the treatment of
primary axillary hyperhidrosis: a 52-week
multicenter double-blind, randomized,
placebo-controlled study of efficacy and
safety. J Am Acad Dermatol 2007;56(4):
604–611.
P´erez-Bernal AM, Avalos-Peralta P,
Moreno-Ram´ırez D, Camacho F.
Treatment of palmar hyperhidrosis with
botulinum toxin type A: 44 months of
experience. J Cosmet Dermatol 2005;4(3):
163–166.
Lowe NJ, Yamauchi PS, Lask GP, et al.
Efficacy and safety of botulinum toxin type
a in the treatment of palmar hyperhidrosis:
a double-blind, randomized,
placebo-controlled study. Dermatol Surg
2002;28(9):822–827.
Simonetta Moreau M, Cauhepe C, Magues
JP, Senard JM. A double-blind,
randomized, comparative study of Dysport
vs. Botox in primary palmar hyperhidrosis.
Br J Dermatol 2003;149(5):1041–1045.
Solomon BA, Hayman R. Botulinum toxin
type A therapy for palmar and digital
hyperhidrosis. J Am Acad Dermatol
2000;42(6):1026–1029.
Vadoud-Seyedi J. Treatment of plantar
hyperhidrosis with botulinum toxin type A.
Int J Dermatol 2004;43(12):969–971.
Vlahovic TC, Dunn SP, Blau JC, Gauthier
C. Injectable botulinum toxin as a
treatment for plantar hyperhidrosis: a case


Botulinum Toxins
study. J Am Podiatr Med Assoc 2008;98(2):
156–159.
Botox [Prescribibg information]. BOTOX®
Cosmetic (onabotulinumtoxinA) for
injection, for intramuscular use. Irving,
CA: Allergan; 2016.
Alam M, Dover JS, Arndt KA. Pain
associated with injection of botulinum A
exotoxin reconstituted using isotonic
sodium chloride with and without
preservative: a double-blind, randomized
controlled trial. Arch Dermatol 2002;
138(4):510–514.
Hexsel DM, De Almeida AT, Rutowitsch M,
et al. Multicenter, double-blind study of the
efficacy of injections with botulinum toxin
type A reconstituted up to six consecutive
weeks before application. Dermatol Surg
2003;29(5):523–529; discussion 529.
Garcia A, Fulton JE. Cosmetic denervation
of the muscles of facial expression with
botulinum toxin. A dose-response study.
Dermatol Surg 1996;22(1):39–43.
Yang GC, Chiu RJ, Gillman GS.
Questioning the need to use Botox within 4
hours of reconstitution: a study of fresh vs
2-week-old Botox. Arch Facial Plast Surg
2008;10(4):273–279.
Trindade De Almeida AR, Kadunc BV, Di
Chiacchio N, Neto DR. Foam during
reconstitution does not affect the potency
of botulinum toxin type A. Dermatol Surg
2003;29(5):530–531; discussion 532.
Liu A, Carruthers A, Cohen JL, et al.
Recommendations and current practices
for the reconstitution and storage of
botulinum toxin type A. J Am Acad
Dermatol 2012;67(3):373–378.
Beer KR, Boyd C, Patel RK, Bowen B, James
SP, Brin MF. Rapid onset of response and
patient-reported outcomes after
onabotulinumtoxinA treatment of
moderate-to-severe glabellar lines. J Drugs
Dermatol 2011;10(1):39–44.
Baumann L, Dayan S, Connolly S, et al.
Duration of clinical efficacy of
onabotulinumtoxinA in crow’s feet lines:
results from two multicenter, randomized,
controlled trials. Dermatol Surg 2016;42(5):
598–607.
Glogau R, Kane M, Beddingfield F, et al.
OnabotulinumtoxinA: a meta-analysis of
duration of effect in the treatment of
glabellar lines. Dermatol Surg 2012;
38(11):1794–1803.
Borodic GE, Ferrante R, Pearce LB, Smith
K. Histologic assessment of dose-related
diffusion and muscle fiber response after
therapeutic botulinum A toxin injections.
Mov Disord 1994;9(1):31–39.
Shaari CM, George E, Wu BL, et al.
Quantifying the spread of botulinum toxin
through muscle fascia. Laryngoscope
1991;101(9):960–964.
Shaari CM, Sanders I. Quantifying how
location and dose of botulinum toxin
injections affect muscle paralysis. Muscle
Nerve 1993;16(9):964–969.
Klein AW. Dilution and storage of
botulinum toxin. Dermatol Surg 1998;
24(11):1179–1180.
Klein AW, Kreyden OP. Storage and
dilution of botulinum toxin. Curr Probl
Dermatol 2002;30:126–130.
Carruthers J, Fagien S, Matarasso SL,
Group BC. Consensus recommendations
on the use of botulinum toxin type a in
facial aesthetics. Plast Reconstr Surg
2004;114(6 Suppl):1S–22S.
Kane MA, Brandt F, Rohrich RJ, et al.
Evaluation of variable-dose treatment with
a new U.S. Botulinum Toxin Type A
(Dysport) for correction of moderate to
severe glabellar lines: results from a phase
III, randomized, double-blind,
placebo-controlled study. Plast Reconstr
Surg 2009;124(5):1619–1629.
Lowe NJ, Maxwell A, Harper H. Botulinum
A exotoxin for glabellar folds: a
double-blind, placebo-controlled study
with an electromyographic injection
technique. J Am Acad Dermatol 1996;
35(4):569–572.
Sadick NS. The cosmetic use of botulinum
toxin type B in the upper face. Clin
Dermatol 2004;22(1):29–33.

27 OnabotulinumtoxinA (Botox®) in Dermatology

Rzany B, Ascher B, Fratila A, et al. Efficacy
and safety of 3- and 5-injection patterns (30
and 50 U) of botulinum toxin A (Dysport)
for the treatment of wrinkles in the glabella
and the central forehead region. Arch
Dermatol 2006;142(3):320–326.
Carruthers A. Botulinum toxin type A:
history and current cosmetic use in the
upper face. Dis Mon 2002;48(5):299–322.
Monheit G, Carruthers A, Brandt F, Rand
R. A randomized, double-blind,
placebo-controlled study of botulinum
toxin type A for the treatment of glabellar
lines: determination of optimal dose.
Dermatol Surg 2007;33(1 Spec No.):
S51–S59.
Carruthers A, Carruthers J, Said S.
Dose-ranging study of botulinum toxin
type A in the treatment of glabellar rhytids
in females. Dermatol Surg 2005;31(4):
414–422; discussion 422.
Flynn TC. Botox in men. Dermatol Ther
2007;20(6):407–413.
Flynn TC, Carruthers JA. Botulinum-A
toxin treatment of the lower eyelid
improves infraorbital rhytides and widens
the eye. Dermatol Surg 2001;27(8):
703–708.
Flynn TC, Carruthers JA, Clark RE.
Botulinum A toxin (BOTOX) in the lower
eyelid: dose-finding study. Dermatol Surg
2003;29(9):943–950; discussion 950–941.
Swinehart JM. Treatment of axillary
hyperhidrosis: combination of the
starch-iodine test with the tumescent
liposuction technique. Dermatol Surg
2000;26(4):392–396.
Grunfeld A, Murray CA, Solish N.
Botulinum toxin for hyperhidrosis: a
review. Am J Clin Dermatol 2009;10(2):
87–102.
Heckmann M, Ceballos-Baumann AO,
Plewig G, Group HS. Botulinum toxin A for
axillary hyperhidrosis (excessive sweating).
N Engl J Med 2001;344(7):488–493.
Hexsel D, Rodrigues TC, Soirefmann M,
Zechmeister-Prado D. Recommendations
for performing and evaluating the results of
the minor test according to a sweating
intensity visual scale. Dermatol Surg
2010;36(1):120–122.
Cot´e TR, Mohan AK, Polder JA, et al.
Botulinum toxin type A injections: adverse
events reported to the US Food and Drug
Administration in therapeutic and
cosmetic cases. J Am Acad Dermatol
2005;53(3):407–415.
Naumann M, Jankovic J. Safety of
botulinum toxin type A: a systematic
review and meta-analysis. Curr Med Res
Opin 2004;20(7):981–990.
Wollina U, Konrad H. Managing adverse
events associated with botulinum toxin
type A: a focus on cosmetic procedures.
Am J Clin Dermatol 2005;6(3):141–150.
Alam M, Arndt KA, Dover JS. Severe,
intractable headache after injection with
botulinum A exotoxin: report of 5 cases.
J Am Acad Dermatol 2002;46(1):62–65.
Huang W, Foster JA, Rogachefsky AS.
Pharmacology of botulinum toxin. J Am
Acad Dermatol 2000;43(2 Pt 1):249–259.
Klein AW. Complications with the use of
botulinum toxin. Dermatol Clin 2004;
22(2):197–205, vii.
Klein AW. Contraindications and
complications with the use of botulinum
toxin. Clin Dermatol 2004;22(1):66–75.
Richards RN. Ethyl chloride spray for
sensory relief for botulinum toxin
injections of the hands and feet. J Cutan
Med Surg 2009;13(5):253–256.
Smith KC, Comite SL, Storwick GS. Ice
minimizes discomfort associated with
injection of botulinum toxin type A for the
treatment of palmar and plantar
hyperhidrosis. Dermatol Surg 2007;33(1
Spec No.):S88–S91.
Campanati A, Lagalla G, Penna L, et al.
Local neural block at the wrist for
treatment of palmar hyperhidrosis with
botulinum toxin: technical improvements.
J Am Acad Dermatol 2004;51(3):345–348.
Kuwahara H, Ogawa R. Using a vibration
device to ease pain during facial needling
and injection. Eplasty 2016;16:e9.


Botulinum Toxins
Rivers JK, Bertucci V, McGillivray W, et al.
Subject satisfaction with
onabotulinumtoxinA treatment of glabellar
and lateral canthal lines using a new
patient-reported outcome measure.
Dermatol Surg 2015;41(8):950–959.
Chang BL, Wilson AJ, Taglienti AJ, et al.
Patient perceived benefit in facial aesthetic
procedures: FACE-Q as a tool to study
botulinum toxin injection outcomes.
Aesthet Surg J 2016;36(7):810–820.
Trindade de Almeida A, Carruthers J, Cox
SE, et al. Patient satisfaction and safety
with aesthetic onabotulinumtoxinA after at
least 5 years: a retrospective cross-sectional
analysis of 4,402 glabellar treatments.
Dermatol Surg 2015;41(Suppl 1):
S19–S28.
Carruthers A, Carruthers J.
Patient-reported outcomes with botulinum
neurotoxin type A. J Cosmet Laser Ther
2007;9(Suppl 1):32–37.


Index
a
abobotulinumtoxinA
(Dysport®/Azzalure®)
5, 65–77, 137
action halo measurement
114–16
chest
271
comparisons with other
BoNTA formulations
44, 66, 68, 69
dimpled chin
270
face lifting
270–271
forehead
73, 153, 154–7,
158, 267
gingival smile
269
glabellar lines
125, 133,
134, 135, 136, 137, 265
hyperhidrosis
227–8, 303,
304, 306, 307, 307–8,
308, 309, 310
Marionette lines
270
microinjections in upper
face
265
nasal wrinkles
269
neck
205, 206, 207, 208,
271
patient selection
122
perioral
192, 193, 195, 196,
197, 269–270
periorbital
267
reconstitution
110, 112,
113, 136
topical applications
321
accessory proteins
37–8, 66
“accordion wrinkles”
203,
209
action halo
110
measurement
114–15,
116–17
additives, effects on migration
and action halo
116–17
adjunctive therapy see
combination therapy
adrenaline see epinephrine
adverse events see
complications
aesthetics and cosmetics
5–6
BoNTA
70, 71–5, 85–90,
135
ethnicity and
277–81
BoNTB
56–8
brow muscles and
20
ethnicity and
277–81
face muscles
25
history
3
natural look
263–73
neuromodulators and their
aesthetic targets
346–8
newer agents
98–106
affect and mood, modulating
345–56
African Americans and black
people
275, 276, 277,
278, 279
aging
199–202
ethnicity and
275, 276,
277, 279, 280, 281
forehead
150–1
neck
199–202, 203–4
orbital aperture
34
perioral area, severity scales
193
skin
13–14, 199
aldehydes, axillary
hyperhidrosis
288
allergic and hypersensitivity
reactions
135, 223
alpha motor neurons
42
aluminium chloride
287–8
anaesthesia see intravenous
regional anesthesia;
nerve block; vibratory
anesthesia
analgesic, BoNTA as
329–32
anatomy
13–36
brow
18–21, 22, 148, 166,
167, 361
forehead
148–50, 361
glabellar
137–8
lower leg
185–6
masseter muscle
178
neck
199–202
periocular area
166–9
ANT-1207 (from Anterios)
106, 319, 326
anticholinergics in
hyperhidrosis
systemic
288, 303
topical
288
antigenicity see
immunogenicity
antiperspirants
287–8,
302–3
antiretroviral drug-related
lipodystrophy
218
apocrine glands
286
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:


Index
apoeccrine glands
286
“apple dumpling (dimpled)
chin”
194–5, 270–1
arteries, facial
17
arthritic joint pain
331
Asians
276, 277, 278
contouring
276, 280
assessment (pretreatment) see
pretreatment
preparation
asymmetry (facial)
213–20
correction
213–20, 268–9
forehead lines and
154
atrial fibrillation
339
atrophy, neck
199, 201
autistic children
353
axillary hyperhidrosis
106,
117, 228, 285–98, 303,
322–3, 333, 357–8, 362,
364
axonal transport, retrograde
43
Azzalure
5, 65, 66, 263
b
beauty enhancement
263–73
benign familial pemphigus
(Hailey–Hailey disease)
291, 334
Bier’s block see intravenous
regional anesthesia
biological weapons
2
bite force in masseter strength
quantification
184–5
black people incl. African
Americans
275, 276,
277, 278, 279
blepharoplasty
165, 217, 254,
264
blepharoptosis see ptosis
blepharospasm
98, 174
blood supply (vasculature),
facial
17
BoCouture see
incobotulinumtoxinA
bones, craniofacial
33–4
BoNTA and BoNTB see type A
(neuro)toxin; type B
(neuro)toxin
Botox®
see
onabotulinumtoxinA
Botox Cosmetic®
see
onabotulinumtoxinA
Botulax
98, 103
botulism
1, 2, 3
clinical
43
botulism-like syndrome
223
brain, BoNTA migration to
352–3
breast cancer and
reconstruction with
implants
332
breast-feeding and lactation
124, 135, 159
broadband light therapy
238–41
brow (eyebrow)
18–21,
165–76
anatomy
18–21, 22, 148,
166, 167, 361
contour/shape
changing (contouring/
shaping)
173, 236,
268
ethnicity and
276, 278
depressors
18, 20, 137–8
elevators
18, 20
females vs. male
19, 361
lateral lift/elevation
73–4,
127
ptosis see ptosis
tattoos
264
BTX-A and BTX-B see type A
(neuro)toxin; type B
(neuro)toxin
buccinator
29, 201
bullous dermatosis, linear IgA
(LABD)
339
“bunny lines” (nasal wrinkles)
24, 25, 174–5, 225, 269,
348
c
calcitonin gene-related
peptides (CGRPs)
42,
329, 330, 331, 336
calf contouring
185–9, 281
cancer
breast
332
skin
253–8, 338
“canine smile”
28
canthal angle, lateral ethnicity
and
276, 278, 279
canthal lines
lateral see crow’s feet
medial
277
capsaicin
329, 332–3
carbon dioxide (CO2) laser
322
hyperhidrosis
289
resurfacing
241
carotid arteries, external and
internal
17
Carruthers, Dr. Jean
3
cautions see contraindications
central-fan pattern (lateral
canthus)
172
cervical dystonia
42, 55
BoNTA
79, 159, 223
BoNTB
58
cervical wrinkles, horizontal
202–3, 206
CGRPs (calcitonin gene-
related peptides)
42,
329, 330, 331, 336
cheek
complications affecting
227
fat compartments
15,
15–16
chemabrasion (manual)
245
chemical peels
2445
chemodenervation see
denervation
children
autism
353
granulosis rubra nasi
334
palmar hyperhidrosis
307
parotid duct injury
338
chin
128
complications affecting
227
dimpling
194–5, 270–1
ChinaTox
98, 105
chromhidrosis
309–10

Index

clinical (medical/therapeutic)
applications
7, 135,
285–315, 329–68
historical perspectives
3–5
skin
276, 277, 278, 329–43
cancer
253–8, 338
Clostridium botulinum
2, 3,
37
serotypes see serotypes
cold-induced analgesia see
cryoanalgesia; ice
color (skin)
275–83
combination/adjunctive
therapy
7, 233–51
face lifting
270–271
glabellar lines
233–6,
271
lower face
237–8, 270
neck and chest
271
periorbital lines
267
commissures, oral
75, 195–6
compensatory hyperhidrosis
303, 310, 335
complexing proteins, BoNTAs
and freedom from
79–80, 122, 133, 134–5
implications
81–4
complications (and adverse
events/side effects)
142, 218, 221–31,
362–4
beauty enhancement
266,
269, 270
BoNTA
59, 60, 142,
160–1, 362–4
lower face contouring
184–5
lower leg contouring
187–9
neck rejuvenation
209
BoNTB
60, 223
minor common
222–3
PurTox®
101–2
reconstitution and
111
severe and systemic
135,
223
site-specific
223–8
forehead
159–61, 223
computed tomography (CT),
masseter hypertrophy
measurement
181
connective tissue growth
factors and
hypertrophic scars
260
consensus conferences
71,
122
consent
122, 140, 152, 154
contouring and (re)shaping
brow
173, 236, 267–268
brow see brow
ethnicity and
280
lower face
74–5, 177–85,
189
lower leg
185–9, 281
in masseter hypertrophy
217, 280
contraindications/cautions/
avoidance
BoNTA
123–4, 135,
159–61
drugs (other than toxins)
159, 222
forehead
159–61
periocular area
165
lower lid treatment
267
corrugator supercilli
20, 53,
138, 277, 338
BoNTA vs BoNTB injection
57, 58
cosmeceuticals
244–5
cosmetics see aesthetics and
cosmetics
craniofacial hyperhidrosis
308
craniofacial shape and
ethnicity
177
craniofacial skeleton
33–4
Croma Pharma and Hugel’s
Botulax
98, 103
crow’s feet (lateral canthal/
orbicular lines; LCLs)
5, 22, 59, 60, 70, 74, 89,
98–9, 106, 117, 126,
126–7, 167–8, 171–2,
173, 267, 279–80, 317,
319, 323, 324, 361
BoNTAs
89, 359, 361
ethnicity and
279–80
newer formulations
98–9, 319, 322, 323,
324, 326
combination (nonsurgical)
therapy
236, 239, 242,
247
complications
226
cryoanalgesia (cold-induced
analgesia) in palmar
hyperhidrosis
304,
305
see also ice
CTGF (connective tissue
growth factors) and
hypertrophic scars
260
d
Daeroong Pharmaceutical
Company
97–8
Darier’s disease
334–5
darker skin
275–83
daxibotulinumtoxinA
for injection (RT002)
106
for topical use (RT001)
105–6, 319–20, 324–6,
326
deep crumpling lines
203
denervation
(chemodenervation)
72
darker skin
278, 280
in facial reconstruction
273
in lateral eyebrow lift
74
temporary (and recovery
from)
3, 4, 41
depression
338, 348–9
depressor(s)
brow
18, 20, 137–8
lip
18, 27, 29–31
depressor anguli oris (DAO)
16, 27, 29–31, 201, 216,
270
complications involving
227


Index
depressor anguli oris (DAO)
(Continued)
marionette lines and
29,
270
mouth frown and
195–6
neck rejuvenation and
201, 208
synkinesis and
216
depressor labii inferioris (DLI)
17, 27, 30–1, 201
chin dimpling and
194,
195
complications involving
227
mouth frown and
195,
196
neck rejuvenation and
201, 208
depressor nasi septi
25–6
depressor supercilii
138
dermal–epidermal junction
and wrinkles
14
dermatochalasis
150, 153,
159
dermatology see skin
diffusion
110, 114–17, 155,
209–10, 221–2
BoNTA
70, 71, 155, 156,
158
forehead
155, 156
BoNTBs
56, 83
definition
110
risks of deep diffusion
209–10
in neck rejuvenation
205, 209–10
in periorbital treatment
226
see also migration
digital ischemia
336
dilution
109–10, 135–6
definition
109–10
forehead patients
156
glabellar patients
134,
135
types of diluents
FDA-approved
111
injection pain and
112–13
volume of (volume of
reconstitution)
113,
134, 135
dimpling of chin
194–5,
270–1
dissociation,
incobotulinumtoxinA
81
“Doctor Spock brow”
18, 73,
160
dosing (for facial rhytides)
136
BoNTA
71, 265–71, 360
chest
271
forehead
153, 160–1,
267–8
glabella
136–7, 265
hyperhidrosis
290
lower face contouring
182, 183, 185
neck
205, 206, 207, 208,
271
periocular/periorbital
171, 172, 173, 174,
266–7
perioral wrinkles
269–270
BoNTB
58
hyperhidrosis
290–1
excessive see overdose
drugs (pharmaceuticals other
than botulinum toxin)
contraindicated/cautions
with
159, 222
hyperhidrosis
302–3
axillary
287–8
interactions
135
neuromuscular junction
124
duration of action/effects
141
incobotulinumtoxinA
81–2
DWP-450 (Nabota)Nabota
98, 103
dynamic expression lines, neck
14, 203
dyshidrotic Eczema
333
dysphagia
223
Dysport®
see
abobotulinumtoxinA
e
eccrine glands
286, 299, 300
hidrocystomas
335
non-botulinum treatment
288, 289, 303
eczema, dyshidrotic
333
ejaculation, premature
339
electrical muscle stimulation
245–6
elevators
brow
18, 20
lip
18, 26–9, 31
gummy smile and
196
emotion (facial)
emotional contagion
349–50, 351
facial display
350, 352, 353
indicators
346–8
endoscopic sympathectomy in
hyperhidrosis
289–90, 303, 309
epicanthal (superior palpebral)
fold, lack in Asians
276
epicondylitis, lateral
331
epidermal–dermal junction
and wrinkles
14
epidermolysis bullosa simplex
(EBS)-Weber–
Cockayne (WC) type
334–5
epinephrine (adrenaline)
as additive
116–17
sweating and sweat glands
and
286, 299
erbium dual mode laser
resurfacing
242
ethnicity and race
craniofacial shape and
177
skin color and
275–83
European studies
abobotulinumtoxinA
67,
71
incobotulinumtoxinA
98–9
onabotulinumtoxinA
86

Index

evaluation (pretreatment) see
pretreatment
preparation
examination see pretreatment
preparation
exocytosis of
neurotransmitters
37,
39, 41, 42
experimentation on humans
2–3
expression (facial)
345, 346,
348, 349, 350–3
emotion see emotion
mood affected by
338, 353
musculature (MFE)
17–32,
346–8
attenuation of action
348
neuropsychiatric
disorders and
349
relaxation with BoNTA
348
negative, reducing/
attenuation
338, 353
extensor digitorum brevis
(EDB)
82, 85
eye
ethnicity and shapes of
276
region around see
periorbital/periocular
region
eyebrow see brow
eyelids
127, 166–7
anatomy
166–7
asymmetric/drooping
217
dermatochalasis
150, 153,
159
evaluation
125, 166–7
ptosis see ptosis
treatment
127
wrinkles/lines
127, 267
see also entries under
blepharo-
f
face
anatomy see anatomy
asymmetry see asymmetry
contouring/shaping see
contouring and shaping
emotional display
350,
352, 353
expression see expression
fat compartments
14–16
feedback hypothesis
338,
349–52, 353
flushing (persistent)
335–6
hyperhidrosis
308
lifting
271
lines and wrinkles see
rhytides
in masseter hypertrophy,
reshaping
217
mimicry hypothesis
349–50, 352, 353
nerve supply
16–17
reconstructive surgery
253–8, 337
rejuvenation/sculpting
191
adjunctive therapy
6
rhytides/wrinkles/lines see
rhytides
scars see scars
skeleton
33–4
vasculature
17
see also lower face; midface;
upper face
Facial Clinimetric Evaluation
(FaCE) scale is
213
facial nerve
16–17, 150
aberrant regeneration after
injury
215
weakness (paresis) and
paralysis
213–20
failure of treatment
142
antibodies and
83–4, 142,
185, 189
fat compartments, facial
14–16
FDA see Food and Drug
Administration
female forehead and brow
anatomy
19, 361
fibroblasts and pathogenic
scars
259–60, 337
fillers
233–8
5-fluorouracil, keloids
259
flushing, persistent facial
335–6
Food and Drug Administration
(FDA)
2, 5, 44, 53
BoNTA
53, 65, 121, 122,
124, 317, 329, 357
forehead
147–64
aging and
150–1
anatomy
148–50, 361
complications
159–61,
223–4
fat compartments
14–15
wound healing of surgical
scars
254
wrinkles/lines
72–3,
125–6, 147–64, 267–9
administration of toxin
158–9
BoNTA
72–3, 89–90,
114, 115, 125–6,
147–64, 278
BoNTB
56, 115
contraindications
159–61
dose selection
154–7
horizontal
149, 150, 151,
153, 157, 267–9
key points of technique
159
patient approaches
141–4
formulations
5
beauty enhancement
263
BoNTA see type A
(neuro)toxin
BoNTB
5, 55
topical
319
frequency of glabellar
treatment
142
Frey’s syndrome
308–9
frontal bone
20, 22, 23
frontalis muscle
16, 19–20,
59, 126, 149, 153,
267–8, 363
frown
glabellar frown lines see
glabellar lines
mouth see mouth


Index
“frozen” look
152, 160, 263,
265, 268
“full denture smile”
28
full-fan pattern (lateral
canthus)
172
future directions (incl. newer
toxins and BoNTA)
7,
97–107
dermatology
329–43
hyperhidrosis
310
neuropsychiatry
345, 353
topical BoNTA
326
g
Galderma’s “liquid” toxin
105
gastrocnemius
185, 186,
187
ethnicity and
281
gender and forehead and brow
anatomy
19, 361
gingival (gummy) smile
28,
196–7, 217, 269
glabellar administration for
forehead patients
157
too broad or high
160
glabellar lines/wrinkles/
rhytids
71–2, 124–5,
133–45, 265–6, 360–1
anatomical considerations
137–8
BoNTA
(abobotulinumtoxinA)
67, 68, 69–70, 71–2,
85–9, 124–5, 133–45,
265–6, 359, 360–1, 363
BoNTB
56, 57, 58, 59
combination therapy
233–6, 271
complications of treatment
224–5
headaches
225, 336, 363
newer toxins
98, 99, 100,
102
“golf ball (dimpled) chin”
194–5, 270–1
gravimetric testing of
hyperhidrosis
286,
301–2
gummy smile
28, 196–7, 217,
269
gustatory sweating
308–9
h
Hailey–Hailey disease
291,
334
hairline, receding
148,
158
halo of action see action halo
hands
ischemic digits
336
palmar hyperhidrosis
116,
227–8, 290, 293, 304–7,
335, 362
headaches
363
in glabellar treatment
225,
336, 363
migraine
42, 331–2
healing, wound see wound
healing
heat treatment, hyperhidrosis
289
heavy chains
4, 39–40, 54,
55, 65, 79
hematoma
126, 222
Hengli/Prosigne
182, 264,
317
herpes simplex virus
222
herpes zoster
222, 330
hidrocystomas, eccrine
335
highly active antiretroviral
drug (HAART)-related
lipodystrophy
218
histamine and pruritus
332
histology
skin color and
276
wrinkles
13–14
history
1–3
neck rejuvenation
199
history-taking
122–3
HIV see human
immunodeficiency
virus
horizontal (transverse)
wrinkles
cervical
202–3, 206
forehead
149, 150, 151,
153, 157, 267–9
House–Brackmann scale
213, 214
Hugel’s Botulax
98, 103
human experimentation
2–3
human immunodeficiency
virus (HIV)
HAART-associated
lipodystrophy
218
TAT
319
hyaluronic acid (HA) fillers
233, 234–5, 236, 238,
267
hyaluronidase
117, 236
hyperhidrosis
106, 227–8,
285–315, 333–9, 362
axillary
106, 117, 228,
285–98, 303, 322–3,
333, 357–8, 362, 364
compensatory
303, 310,
335
complications of treatment
227–8
dermatologic conditions and
333–9
diagnosis/measurement
287–8, 301–2
focal (general aspects)
285, 289–90
primary
286, 300, 302
unilateral
310
generalized
285, 299–300,
301
palmar
116, 227–8, 290,
293, 304–7, 335, 362
plantar
288, 307–8, 362,
364
quality of life
286, 287,
300–1
severity
287, 300
treatments
287–93,
302–10
hyperkinetic/hyperfunctional
facial lines
5, 6, 19,
58, 74, 147, 151
hypersensitivity and allergic
reactions
135, 223
hypertrophic
osteoarthropathy,
primary
336–7

Index

hypertrophic scars
258–60,
337
hypertrophy
benign prostatic (benign
prostatic enlargement)
338–9
calf
185, 186, 187, 189
electrical stimulation-
induced
245–6
masseter see masseter
hypoglossal–facial nerve
anastomosis
214–15
hypohidrosis and anhidrosis
action halo measured by
extent of
114–15
forehead
156
palmar
304
progressive segmental
310
i
ice and pressure (with
injections)
palmar hyperhidrosis
306
plantar hyperhidrosis
307–8
imaging, masseter
hypertrophy
measurement
181
immunogenicity/antigenicity
(antibodies to toxin;
immune resistance)
43–4, 83–4, 134–5, 218
BoNTA
43–4, 55, 67, 68,
83–4, 189
immunoglobulin A bullous
dermatosis, linear
(LABD)
339
inactive neurotoxin in
incobotulinumtoxinA
80–4
incobotulinumtoxinA
(BoCouture/Xeomin®/
XU)
5, 65, 79–95, 97,
98–101, 137
action halo measurement
114–16
aesthetic applications
85–90
chest
271
comparisons with other type
A formulations
44,
66, 68, 69
potency
84–5
complexing proteins and
freedom from them
79–84
face lifting
270–271
forehead
153, 154–5, 157,
267
gingival smile
269
glabellar lines
125, 133,
134, 135, 136–7, 137,
265
hyperhidrosis
303
inactive
80–4
manufacture and
production
79–80
Marionette lines
270
nasal wrinkles
269
neck
205, 206, 207, 208,
209, 271
patient selection
122
periocular/periorbital area
169, 172, 267
perioral area
193, 194, 195,
196, 197, 269–270
reconstitution
110–11,
136
indications
abobotulinumtoxinA
44
lower face
75
upper face
71
FDA-approved
44
infections, injection
site-related
222
informed consent
122, 140,
152, 154
injection (administration)
140
hyperhidrosis
axillary
291–2
facial
308, 309
palmar
304–7
plantar
307–8
pain from, diluent type and
112–13
repeated see repeated
treatments
syringes and needles for see
syringes and needles
techniques and points (sites)
265–71
beauty enhancement
265–71
complications
222–3
forehead
153, 157–8,
267–9
glabellar
140, 265–6
hyperhidrosis, see
subheading above
lower face contouring
179–80
lower leg contouring
186
periocular/periorbital
172–5, 266–7
perioral
192–3, 195–6,
269–70
too deep, in neck
rejuvenation
209–210
innervation see nerve supply
intense pulsed light (IPL)
238–41, 259
International Board
Botulinum Toxin
71
intervals between glabellar
treatments
142
intravenous regional
anesthesia (IVRA;
Bier’s block)
palmar hyperhidrosis
305
plantar hyperhidrosis
307
iontophoresis
322
in hyperhidrosis
288,
303
ischemic digits
336
itching (pruritus)
332–3
j
jaw
128–9
see also mandible
joint pain, arthritic
331
jowel fat compartment
16
k
keloidal scars
258–60
keratosis follicularis
334–5


Index
Kerner, Dr. Justinus
“W`uurst”
1
l
lactation and breast-feeding
124, 135, 159
lagophthalmos
165, 170
Langer’s lines
254
laser use
322
hyperhidrosis
289
for resurfacing
241–5
vertical lip lines
192
lateral canthal angle (palpebral
fissure inclination) and
ethnicity
276, 278,
279
lateral canthal lines see crow’s
feet
lateral epicondylitis
331
lateral eyebrow lift/elevation
73–4, 127
Latin Americans
275, 276
LD50 (median lethal dose)
44, 45, 68–9, 154
leg (lower), contouring
185–9, 281
lethal dose, median (LD50)
44, 45, 68–9, 154
levator anguli oris
27, 29, 216
gummy smile and
196
levator labii superioris, gummy
smile and
196–7
levator labii superioris alaeque
nasi
27, 28
gummy smile and
196–7
levator palpebral superioris
23, 24, 72, 74
lidocaine, hyperhidrosis
291
light-based therapies
238–41
light chains
4, 39, 40, 41, 42,
55, 79
linear immunoglobulin A
bullous dermatosis
(LABD)
339
lines of aging see rhytides
lines of Langer
254
lip
26–32, 192–4
complications of treatment
226–7
depressors
18, 27, 29–31
elevators see elevators
lines
127, 192–4, 226–7
ethnicity and
280
vermillion border
127,
227, 245, 280
lipodystrophy disorders
185,
218
liquid formulations of BoNTB
55–6
lower face
beauty enhancement
269–71
combination therapy
237–8, 270
complications
218, 363
contouring
74–5, 177–85,
189
ethnicity and
280
lower leg contouring
185–9,
281
m
magnetic resonance imaging
(MRI), masseter
hypertrophy
measurement
181
malar fat compartments
15
male forehead anatomy
19,
361
mandible
anatomy
33–4, 178
contouring
177–8
ethnicity and
280, 281
masseter injections and
their effects on
184
in neck rejuvenation, loss of
definition of edge
206–8, 209
see also jaw
marionette folds/lines
29–30, 270
mask-like appearance
267
masseter muscle
25, 128–9,
178, 217
hypertrophy
6, 84, 128–9,
178, 184, 185, 189,
217
ethnicity and
276, 280
mastectomy, reconstruction
after
332
mastication (and muscles of
mastication)
29, 33,
178, 184
masseter treatment and
129, 184
maxilla
33
mechanism (mode) of action
38–43, 134, 332
historical perspectives
3–4
neuropsychiatric disorders
349
sensory
42–3
wound healing
337
medical applications see
clinical applications
Meditoxin/Neuronox
98,
103–5, 264, 317, 337
melanin
276
melanosomes
275–6
men’s (male) forehead and
brow anatomy
19, 361
mental crease/fold
194–5
complications
194–5, 227
see also chin
mentalis
27, 31, 270
chin dimpling and
194–5,
270
complications involving
227
marionette lines and
270
“Mephisto brow”
18, 73, 160,
206
Merz Aesthetics scale
89,
152
Mexicans and skin color
276
microwave treatment,
hyperhidrosis
289
midface
beauty enhancement
268–71
expression musculature
26–32
migraine
42, 331–2
migration/spread
110,
114–17
BoNTA
82–3, 114, 115
to brain
352–3

Index

incobotulinumtoxinA
82–3, 114, 115
forehead
155
mime therapy in synkinesis
216
mimicry, facial
349–50, 352,
353
minimal skin excision in
hyperhidrosis
289
Minor’s (starch–iodine) test
287, 301, 303, 307, 308,
309
MiraDry
289
mirror neurons
349, 352
mode of action see mechanism
of action
Moebius syndrome
352
Mohs micrographic surgery
255, 338
“Mona Lisa smile”
28
monopolar radiofrequency
energy
245
mood and affect, modulating
345–56
motor neurons
41, 42, 43
mouth
angle of
128
downturned corners (mouth
frown)
195–6
ethnicity and
280
gummy smile treatment
and movements of
269
see also oral commissures;
perioral region
Mu(e)ller’s muscle
73, 74,
218, 225
multiple treatments see
repeated treatments
muscles
electrical stimulation
245–6
facial expression see
expression
forehead
149, 153
hypertrophy see
hypertrophy
masticatory see mastication
neck
200–2
Myobloc[O] see type B
(neuro)toxin
n
Nabota (DW-450)
98, 103
nasal bones
33, 138
nasal flare
24
nasal wrinkles (“bunny lines”)
24, 25, 174–5, 225, 269,
348
nasalis
24, 25, 175, 269
nasolabial fat compartments
15
natural look
263–73
NDSTM
platform delivery
technology
319
neck
129, 199–211, 271
aging
199–202, 203–4
anatomy
199–202
needles see syringes and
needles
“Nefertiti neck lift”
33, 204
nerve blocks
palmar hyperhidrosis
305,
307
plantar hyperhidrosis
307
nerve supply/innervation
face
16–17
forehead
149–50
sympathetic
299
NeuroBloc®
see type B
(neuro)toxin
neuromodulators,
psychosocial
implications
345–56
neuromuscular junction
3, 4,
41, 42, 66, 81
adverse events affecting
223
pharmaceutical agents
(other than BoNT)
interacting at
124
pre-existing disorders
135
Neuronox
98, 103–5, 264,
317, 337
neuropeptides
42
pain and
329, 330, 332
pruritus and
332
psoriasis and
334
neuropsychiatric disorders
338, 345–56
neurotransmitters
3, 4, 39,
40, 43, 45
exocytosis
37, 39, 41, 42
sweating and
299
newer toxins and applications
see future directions
“Nicholson brow”
18, 24
nose, see entries under nasal
o
onabotulinumtoxinA (Botox®/
BotoxCosmetic®/BU/
Vistabel®/Vistabex)
5, 65, 136–7, 357–68
action halo measurement
114–16
chest
271
comparisons with other
formulations
44, 68,
69, 98–101
potency
84–5
dimpled chin
270
epinephrine added to, in
axillary hyperhidrosis
117
face lifting
270–271
forehead
73, 153, 154–7,
158, 159, 160, 267–8
gingival smile
269
glabellar frownlines
85–8,
125, 133, 134, 135,
136–7, 265
hyperhidrosis
303, 304,
307, 308, 309, 310
axillary
227–8, 290, 291,
292, 293, 357–8, 362
keloids
258
lower face contouring
179
Marionette lines
270
microinjections in upper
face
265
nasal wrinkles
269
neck
205, 206, 207, 208,
209, 271
patient selection
122
periocular/periorbital area
168–9, 267, 270


Index
onabotulinumtoxinA
(Continued)
crow’s feet
89, 127, 359,
361
eyelids
127
perioral area
193, 194, 195,
196, 197
reconstitution
110,
111–12, 113, 136, 358
storage and preparation
358–9
surgical wounds
254,
255–8
onset of action/response
141
incobotulinumtoxinA
81–2
ophthalmic nerve
149–50
oral commissures
75, 195–6
see also mouth; perioral
region
orbicularis oculi
5, 16, 19, 20,
22–3, 138, 361–2
divisions/portions/segments
22–3, 167
forehead treatment and
224
glabellar treatment and
140
periocular area treatment
and
167, 168, 170–1,
173, 174, 361–2
orbicularis oris
5, 16, 17, 25,
26, 27, 28, 29, 31, 192,
237, 280
gummy smiles and
196
orbit
aging
34
fat compartments
15
injections below
72, 218
orbicularis oculi orbital
portion
22, 167, 173
see also periorbital/
periocular region
osteoarthropathy, primary
hypertrophic
336–7
overdose
218
forehead
160
lower face
74
neck
209
periocular
218
perioral
191, 192, 193, 195,
218
p
pachydermoperiostosis
pachydermia
336–7
pain
alleviation
329–32
injection
diluent type and
112–13
hyperhidrosis treatment
291
periocular
173
perception
42–3
palmar hyperhidrosis
116,
227–8, 290, 293, 304–7,
335, 362
palpebral fissure inclination
(lateral canthal angle)
and ethnicity
276,
278, 279
palpebral fold, superior, lack in
Asians
276
palpebral portion/segment of
orbicularis oculi
22,
74
parotid (gland and duct)
Frey’s syndrome and
335
skin cancer involving
338
patient
pretreatment preparation
and assessment see
pretreatment
preparation/
assessment/evaluation
satisfaction with
onabotulinumtoxinA
use
364
selection see selection
“peach pit (dimpled) chin”
194–5, 270–1
pectoralis major
271
pediatrics see children
pemphigus, benign familial
(Hailey–Hailey disease)
291, 334
penile retraction
339
peptide transporters for
topical BoNTA
applications
319–23
axillary hyperhidrosis
293,
322
periocular region see
periorbital/periocular
region
perioral region
127–8,
191–8, 269–270
lines
191–3, 270
overdose
191, 192, 193,
195, 218
periorbital/periocular region
165–76, 266–7
excessive toxin dose
218
lines, BoNTA
89–90,
165–76, 225–6, 266–7,
361–2
complications
225–6
ethnicity and
278–9
see also crow’s feet
perspiration see sweating
pharmacology
44–5
BoNTB
53–5
see also drugs
photodamage and photoaging
light-based therapies
238
neck wrinkles
202
photographs
140
masseter hypertrophy, serial
181–2, 183
physical examination see
pretreatment
preparation/
assessment/evaluation
physiotherapy in synkinesis
216
pigmentation disorders
336
pigmented skin
275–83
piloleiomyomas, multiple
cutaneous
331
plantar hyperhidrosis
288,
307–8, 362, 364
platysma
27, 32–3, 200–1,
205–6
aging
201
bands
75, 90, 129, 201,
202, 204–6

Index

complications of
treatment
227
function
201
poisoning, sausage
1–2
poly-L-lactic acid
218,
238
posttreatment care
141
potency (and its assessment)
44, 45, 56
BoNTAs
84–5
pregnancy
124, 135, 159
premature ejaculation
339
preparation of patient
139–42
preseptal portion/segment of
orbicularis oculi
22–3, 167, 174
pretarsal portion/segment of
orbicularis oculi
20,
22–3, 127, 165, 167,
170, 172, 174
pretreatment preparation/
assessment/evaluation
(incl. examination)
122–3
beauty enhancement
264–5
facial nerve impairment
213
in synkinesis
216
forehead treatment
151–4
glabellar treatment
139–40
lower face contouring
178
periocular treatment
169–72
procerus
20, 21, 124, 138,
361
injection
57, 58, 72, 86,
140, 277, 337, 338
Prosigne/Hengli
182, 264,
317
prostatic enlargement, benign
338–9
pruritus
332–3
psoriasis, inverse
333–4
psychosocial implications of
neuromodulators
345–56
ptosis, eyelid (blepharoptosis)/
eyebrow
166, 236,
278
treatment-related
67, 73,
125, 142, 160, 166, 224,
224–5, 225, 265, 278,
308, 363
pulsed light, intense (IPL)
238–41, 259
PurTox®
97, 101–3, 106
q
quality of life (QoL) with
hyperhidrosis
286,
287, 300–1
r
race see ethnicity
radiofrequency energy
245
Raynaud’s phenomenon
336
reconstitution
109, 110–13,
135–6, 263–4
definition
109
reconstitution
110,
111–12, 113, 136,
358–9
reconstructive facial surgery
253–8, 337
rejuvenation, facial see face
repeated (multiple) treatments
glabellar lines
141–2
lower face
268–269
contouring
182–4
midface
269
reshaping see contouring
retrograde axonal transport
43
Revance Therapeutics’ topical
neurotoxin (RT001)
105–6, 319–20, 324–6,
326
rhytides/wrinkles/lines (face)
13–14, 357–68
action halo measured by
reduction in
114
BoNTA
85–90, 367–8
upper face
71–4, 89–90,
277–8, 363, 364
BoNTB
56–8
defining
13
hyperfunctional/
hyperkinetic
5, 6, 19,
58, 74, 147, 151
nasal (“bunny lines”)
24,
25, 174–5, 225, 269,
348
neck
199, 202–3, 271
newer agents
98–106
perioral
191–3, 270
lip see lip
upper face
BoNTA
71–4, 89–90,
277–8, 363, 364
ethnicity and
277–9
forehead see forehead
glabellar see glabellar lines
periorbital/periocular see
periorbital/periocular
region
rimabotulinumtoxinB see type
B (neuro)toxin
risorius
29, 201–2, 216
Ross syndrome
310
RT001 (daxibotulinumtoxinA
for topical use)
105–6, 319–20, 324–6,
326
RT002 (daxibotulinumtoxinA
for injection)
106
s
safety
142
onabotulinumtoxinA
362–4
stored solutions
112
see also complications
sagging in neck
199, 202,
203, 205, 206
satisfaction (patient) with
onabotulinumtoxinA
use
364
sausage poisoning
1–2
scars
hypertrophic
258–60, 337
keloidal
258–60
reconstructive surgery-
related
253–6
Scott, Dr. Alan
2


Index
selection (patient)
121–31
forehead treatment
151–4
neck treatment
208–9
periocular treatment
169–72
selection of patient see patient
sensory innervation of
forehead
149–50
sensory mechanisms of action
42–3
serotypes, C. botulinum
2, 3, 37, 38, 55, 56, 60,
133
immunogenicity and
43
shaping see contouring
Siax (Neuronox)
98, 103–5,
264, 317, 337
side effects see complications
skeleton, craniofacial
33–4
skin
anatomy in aging vs youthful
skin
13–14
color
275–83
disorders (dermatology)
329–43, 357–68
BoNTA
329–43, 357–68
cancer
253–8, 338
forehead
148–9
minimal excision in
hyperhidrosis
289
neck
199–203
toxin delivery through see
transcutaneous/
transepidermal delivery
smiling
asymmetry
216–17
gummy/gingival smile
28,
196–7, 217, 269
muscles and
25, 26, 27, 28,
30, 31
types of smile
28
SNAP-25 (synaptosomal
associated protein-25)
4, 37, 40, 41, 55, 65,
321, 352
SNARE complex
40, 41, 42,
43, 55
soft tissue fillers (for
augmentation)
233–8
sole (plantar surface),
hyperhidrosis
288,
307–8, 362, 364
soleus
185, 186, 187
solutions
stored see storage
vigorous mixing
112
see also reconstitution
Speywood units
66
sphincteric muscle, orbicularis
oris as
31
“Spock brow”
18, 73, 160
spread see diffusion; migration
stability, incobotulinumtoxinA
81
starch–iodine (Minor’s) test
287, 301, 303, 307, 308,
309
sterility, stored solutions
112
storage (of solutions)
136,
263–4
effectiveness of stored
solutions
111–12
onabotulinumtoxinA
358–9
safety and sterility
112
vigorous mixing of stored
solutions
112
stratum corneum
317, 318,
321–2
structure
botulinum toxin
37–41
facial, ethnicity and
276
Subcision®
266, 270
subcutaneous fat, neck
199
substance P
42, 329, 330,
332, 333, 336
superficial
musculoaponeurotic
system (SMAS)
16,
32, 149
surgery
dermatologic
329–43
focal, in hyperhidrosis
288–9, 303
wound healing of surgical
sites
253–8, 337
SV2 (synaptic vesicle 2)
39
swallowing difficulties
223
sweat glands
286
sweating (perspiration)
285,
299
abnormal see hyperhidrosis;
hypohidrosis
action halo measured by
extent of reduction in
114–15
anatomy and physiology/
pathophysiology
286,
299
symmetry (importance and
its assessment)
123,
265
chin
128
forehead/brow
125–6
lips
128
see also asymmetry
sympathetic nervous system
299
endoscopic sympathectomy
in hyperhidrosis
289–90, 303, 309
synaptic vesicle 2 (SV2)
39
synaptobrevin (VAMP;
vesicle-associated
membrane protein)
4,
40, 55
synaptosomal associated
protein-25 (SNAP-25)
4, 37, 40, 41, 55, 65,
321, 352
synkinesis
213, 215–16
assessment (incl. Synkinesis
Assessment
Questionnaire)
213,
215
syringes and needles
359–61
forehead patients
158
glabellar patients
136
hyperhidrosis
axillary
291–2
palmar
305, 306, 307
plantar
307
systemic adverse effects
223
in glabellar treatment
135
systemic agents in
hyperhidrosis
288,
303

Index

t
TAT (trans-activator of
transcription)
319
tattoos, brow
264
temperature and
incobotulinumtoxinA
stability
81
temporal-cheek fat
compartments
14–15, 15–16
temporal lift
127
temporalis
25
tennis elbow
331
TGF-β1 (transforming growth
factor beta 1) and
keloids
259–60
therapeutic applications see
clinical applications
thoracoscopic (endoscopic
thoracic)
sympathectomy in
hyperhidrosis
289–90, 303, 309
tinnitus
339
topical treatment and agents
317–28
axillary hyperhidrosis
287–8, 322–3
daxibotulinumtoxinA
Topical Gel (RT001)
105–6, 319–20, 324–6,
326
touch-up treatment
123, 265
beauty enhancement
265
forehead
154, 160
glabellar lines
140, 266
nasal wrinkles
269
neck and chest
271
perioral
198
trans-activator of transcription
(TAT)
319
transcutaneous/
transepidermal delivery
317–26
axillary hyperhidrosis
292,
322–3
transforming growth factor
beta 1 (TGF-β1) and
keloids
259–60
transient receptor potential
vanilloid receptor 1
(TRPV1-receptors)
42–3, 329, 333, 336
transporter peptides see
peptide transporters
transverse wrinkles see
horizontal wrinkles
treat-to-goal approach
152
trigeminal nerve, ophthalmic
division
149–50
TRPV1 (transient receptor
potential vanilloid)
receptors
42–3, 329,
333
“turkey neck”
199, 201, 202
type A (neuro)toxin (BTX-A;
BoNTA; BTA)
65–95,
121–64, 317–43
beauty enhancement
263–73
complexing proteins see
complexing proteins
consensus conferences
71,
122
dermatology
329–43,
357–68
diffusion and migration see
diffusion; migration
ethnicity and aesthetics and
277–81
FDA and
53, 65, 121, 122,
124, 317, 329, 357
forehead rhytides
72–3,
89–90, 125–6, 147–64,
278
formulations
5
comparisons between
various types
44, 68,
69
comparisons with type B
via action halo
measurement
115–16
see also specific
formulations/types
glabellar lines
67, 68,
69–70, 71–2, 85–9,
124–5, 133–45, 265–6,
359, 360–1, 363
hyperhidrosis
227–8,
290–3, 304, 304–5, 307,
308, 309, 310
immunogenicity
43–4, 55,
67, 68, 83–4, 189
lower face contouring
74–5, 177–85, 189
mechanism of action
134
patient selection
121–31
perioral area
191–8,
269–70
potency
84–5
properties/mechanism of
action/clinical effects
3–4, 5
psychosocial implications of
neuromodulators and
345–56
scars
of facial reconstructive
surgery
254, 254–5
keloidal and hypertrophic
258–60
topical
105–6, 317–28
type B (neuro)toxin (BoNT
type B; BoNTB;
rimabotulinumtoxinB;
Myobloc®;
NeuroBloc®)
5,
53–77
action halo measurement
compared with type A
115–16
adverse events/
complications
60,
223
aesthetic practices
56–8
formulations
5, 55–6
hyperhidrosis
227–8,
290–1, 310
properties/mechanism of
action/clinical effects
3–4, 53–77
reconstitution
111, 358–9
reconstructive surgery scars
255
treatment considerations
58
type E (neuro)toxin
41


Index
u
ulcer, healing
337
upper face
aesthetics
beauty enhancement
265–9
ethnicity and
277–80
expression musculature
18–24
lines see rhytides
upper-fan pattern (lateral
canthus)
172
v
VAMP (vesicle-associated
membrane protein;
synaptobrevin)
4, 40,
55
van Ermengem; Emile Pierre
2
vanilloid receptor 1 (VR1)
329
vasculature, facial
17
vasoactive intestinal peptide
(VIP)
332
veins, facial
17
vermillion border
127, 227,
245, 280
vertical lip lines
192–4, 280
vesicle-associated membrane
protein (VAMP;
synaptobrevin)
4, 40,
55
vibratory anesthesia and
massage devices (in
hyperhidrosis)
364
palmar hyperhidrosis
305–6
plantar hyperhidrosis
307
video-assisted thoracoscopic
sympathectomy in
hyperhidrosis
289–90
VIP (vasoactive intestinal
peptide)
332
Vistabel®
see
onabotulinumtoxinA
Vistabex®
see
onabotulinumtoxinA
vitiligo
336
volume of dilution or
reconstitution
113,
134, 135
w
warfare
2
Weber–Cockayne (WC)-type
epidermolysis bullosa
simplex
334–5
women’s (female) forehead
and brow anatomy
19, 361
wound healing
337
surgical site
253–8,
337
wrinkles see rhytides
x
Xeomin®
see
incobotulinumtoxinA
z
zygoma
33
zygomatic nerve
16–17
zygomaticus
15, 26, 27, 28,
29, 168, 171
gummy smile and
196
injections and
126,
169, 216, 219, 226,
267