Purified botulinum toxin (BTX) was the first bacterial toxin used as a medicine. Since its introduction into clinical use, over 30 years ago, it has become a versatile drug in various fields of medicine. Its mechanism of inhibiting acetylcholine release at neuromuscular junctions following local injection is unique for the treatment of facial wrinkles. Other dose-dependent anti-neuroinflammatory effects and vascular modulating properties have extended its spectrum of applications.

2. JOURNAL CLUB PRESENTATION
Presented by:
Dr. Kamini Dadsena

3. CLINICAL USE OF
BOTULINUM TOXINS IN
ORAL AND
MAXILLOFACIAL
SURGERY
O.W. Majid ,
Department of Oral and Maxillofacial
Surgery, College of Dentistry, University
of Mosul, Mosul, Iraq
Int. J. Oral Maxillofac. Surg. 2010; 39: 197–207

4. OUTLINE
1. Introduction
2. History
3. Bacteriology
4. Structure and Toxicity
5. Mechanism of action
6. Preparations
7. Cosmetic use
8. Therapeutic use
9. Complications
10. References

5. INTRODUCTION
 Purified botulinum toxin (BTX) was the first bacterial toxin
used as a medicine. Since its introduction into clinical use,
over 30 years ago, it has become a versatile drug in various
fields of medicine.
 Its mechanism of inhibiting acetylcholine release at
neuromuscular junctions following local injection is unique for
the treatment of facial wrinkles.
 Other dose-dependent anti-neuroinflammatory effects and
vascular modulating properties have extended its spectrum of
applications.

6. HISTORY
 The idea of a possible therapeutic use for botulinum toxin (BTX)
was first developed by the German physician and poet Justinus
Kerner (1786–1862); he called it ‘sausage poison
 In 1897, Emile van Ermengem investigated an epidemic of botulism
in Ellezelles, Belgium, after the consumption of raw ham. He
isolated the bacteria from the ham and produced the disease in
laboratory animals by injecting the toxin produced by the
organism.
• Erbguth FJ, Naumann M. Historical aspects of botulinum toxin: Justinus Kerner (1786–1862) and the
‘‘sausage poison’’. Neurology 1999: 53: 1850–1853.
• Cherington M. Botulism: update and review. Semin Neurol 2004: 24: 155–163.

7. HISTORY
 Dembek ZF in 2007, BTX was developed as a biological weapon
by many countries in the twentieth century*.
 H. Vargas in 2000, Many countries stopped research related to
biological weaponry after signing the Biological and Toxin
Weapons Convention, purification of BTX for medical use
continued**.
 A therapeutic use for botulinum toxin type-A (BTX-A) was first
studied in primates by Scott et al in 1973***. In the late 1970s, the
toxin was introduced as a therapeutic agent for the treatment of
strabismus****.
• *Dembek ZF, Smith LA, Rusnak JM. Botulinum Toxin (chapter 16). In: Dembek ZF, ed: Medical Aspects of Biological
Warfare. Virginia: Office of TheSurgeon General 2007: 337–353.
• ** H. Vargas, L.T. Galatti, S.M. Parnes A pilot study evaluationing the treatment of postparotidectomy sialoceles
with botulinum toxin type A Arch Otolaryngol Head Neck Surg, 126 (2000), pp. 421–424
• *** A.B. Scott Botulinum toxin injection of eye muscles to correct strabismus Trans Am Ophthalmol Soc, 79 (1981),
pp. 734–770
• **** A.B. Scott, A. Rosenbaum, C.C. Collins Pharmacologic weakening of extraocular muscles Invest Ophthalmol,
12 (1973), pp. 924–927

8. HISTORY
 Niamtu in 2003, BTX was first used for treating facial wrinkles and
aging skin in 1988, but its widespread cosmetic use did not occur
until the mid-1990s*.
 There was much speculation about the storage, dilution, delivery
methods and treatment doses. In maxillofacial surgical practice,
Niamtu reported on the cosmetic use of BTX for facial rhytids and
dynamic lines in 1999 and 2000** , ***.
 During the mid- and late-1990s, BTX was used for lateral canthal
lines (crow's feet), platysmal banding, orbicularis oris injection,
masseter muscle injection and the treatment of
temporomandibular disorders (TMDs).
* J. Niamtu Botulinum Toxin A: A Review of 1,085 Oral and Maxillofacial Patient Treatments J Ora Maxillofac Surg, 61
(2003), pp. 317–324
** J. Niamtu Aesthetic uses of botulinum toxin A J Oral Maxillofac Surg, 57 (1999), pp. 1228–1233
*** J. Niamtu Cosmetic facial surgery Oral Maxillofac Surg Clin North Am, 12 (2000), p. 595

9. BACTERIOLOGY
 L.D.S. Smith in 1978, Clostridium species bacteria are
sporulating, obligate anaerobic, Gram-positive bacilli.
The spores of C. botulinum are ubiquitous, distributed
widely in soil and marine sediments worldwide and
often found in the intestinal tract of domestic grazing
animals * , **.
 J. Sobel etal in 2004, Under appropriate environmental
or laboratory conditions, spores can germinate into
vegetative cells that will produce toxin. C. botulinum
grows and produces neurotoxin in the anaerobic
conditions frequently encountered in the canning or
preservation of foods *** , ****.
• * L.D.S. Smith The occurrence of Clostridium botulinum and Clostridium tetani in the soil of the United States Health Lab Sci.,
15 (1978), pp. 74–80
• ** H. Sugiyama Clostridium botulinum neurotoxin Microbiol Rev., 44 (1980), pp. 419–448
• *** J. Sobel, N. Tucker, A. Sulka Foodborne botulism in the United States, 1900–2000 Emerg Infect Dis., 10 (2004), pp. 1606–1611
• *** J.K. Varma, G. KatsitadzenMoiscrafishvili. Signs and symptoms predictive of death in patients with foodborne botulism—
Republic of Georgia, 1980–2002 Clin Infect Dis., 39 (2004), pp. 357–362

10. BACTERIOLOGY
 W. Huang etal in 2000 and P.T. Ting in 2004 reported Seven
different strains of Clostridium have been described
(designated A, B, C (1 and 2), D, E, F and G), and each
produces a distinct neurotoxin identified by the corresponding
letter of the bacterial strain producing it, so, there are 7 distinct
neurotoxins (BTX-A, -B, -C, -D, -E, -F, -G)
 W. Huang in 2000 and T.C. Flynn in 2006 Humans can be
affected by the toxins of 5 strains (A, B, E, F and G) and are not
affected by the toxins of strains C and D .
 J.L. Middlebrook in 1997 reported All 7 toxins may
potentially cause botulism in humans given a high enough
exposure.
• T.C. Flynn Update on botulinum toxin Semin Cutan Med Surg, 25 (2006), pp. 115–121
• W. Huang, J.A. Foster, A.S. RogachefskybPharmacology of botulinum toxin J Am Acad Dermatol, 43 (2 Pt 1) (2000), pp. 249–259
• P.T. Ting, A. Freiman The story of Clostridium botulinum: From food poisoning to BOTOX Clin Med, 4 (2004), pp. 258–261
• J.L. Halpern, L.A. Smith, K.B. Seamon, K.A. Groover, W.H. HabigSequence homology between tetanus and botulinum toxins detected by an antipeptide
antibody Infect Immun., 57 (1989), pp. 18–22
• C.L. Hatheway Clostridium botulinum and other clostridia that produce botulinum neurotoxins A.H.W. Hauschild, K.L. Dodds (Eds.), Clostridium
botulinum—Ecology and Control in Foods, Marcel Dekker, Inc, New York, NY (1992), pp. 3–10
• D.R. Franz Botulinum toxins F.R. Sidell, E.T. Takafuji, D.R. Franz (Eds.), Textbook of Military Medicine, Part I: Warfare, Weaponry, and the asualty—
Medical Aspects of Chemical and Biological Warfare, Department of the Army, Office of The Surgeon General, Borden Institute, Washington, DC (1997),

11. BACTERIOLOGY
 J.L. Halpern in 1989 reported that There is some serum
cross-reactivity among the serotypes because they share some
sequence homology with one another as well as with tetanus
toxin.
 C.L. Hatheway in 1992 reported All 7 neurotoxins are
structurally similar but immunologically distinct.
• J.L. Halpern, L.A. Smith, K.B. Seamon, K.A. Groover, W.H. Habig Sequence homology between tetanus and botulinum toxins
detected by an antipeptide antibody Infect Immun., 57 (1989), pp. 18–22
• C.L. Hatheway Clostridium botulinum and other clostridia that produce botulinum neurotoxins A.H.W. Hauschild, K.L. Dodds
(Eds.), Clostridium botulinum—Ecology and Control in Foods, Marcel Dekker, Inc, New York, NY (1992), pp. 3–10

12. STRUCTURE AND TOXICITY
 W. Huang in 2000 Toxins produced by clostridial bacteria
are high-molecular-weight protein complexes that include
3 key proteins:
i. A 150-kda toxin,
ii. A non-toxin hemagglutinin protein, and
iii. A non-toxin non-hemagglutinin protein.
 The 150-kDa toxin is composed of a 100-kDa heavy chain
and a 50-kDa light chain. Disulfide and noncovalent bonds
link the heavy and light chains, and both chains are
required for neurotoxicity.
W. Huang, J.A. Foster, A.S. Rogachefsky Pharmacology of botulinum toxin J Am Acad Dermatol, 43 (2 Pt 1) (2000), pp.
249–259

13. STRUCTURE AND TOXICITY
 B.A. Herrero in 1967 based on animal studies, estimated human
LD50 is approximately 0.09–0.15 μg by intravenous administration,
D.R. Franz in 1993 reported 0.7–0.9 μg by inhalation and 70 μg by
oral administration.
 A.B. Scott in 1988 Based on findings from primate studies, human
LD50 for intramuscular BTX injection is estimated at 2500–3000 U
for a 70-kg adult (35–40 U/kg).
 A. Carruthers in 2001 reported that BTX is the most toxic material
known. It is 4 times more lethal in mice than tetanus toxin, 1 × 1010
more lethal than curare, and 100 × 1010 more lethal than sodium
cyanide.
• A. Carruthers, J. Carruthers Botulinum toxin type A: History and current cosmetic use in the upper face Semin Cutan Med Surg, 20 (2001),
pp. 71–84
• D.R. Franz, etal Efficacy of prophylactic and therapeutic administration of antitoxin for inhalation botulism B.R. DasGupta (Ed.), Botulinum
and Tetanus Neurotoxins: Neurotransmission and Biomedical Aspects, Plenum Press, New York, NY (1993), pp. 473–476
• A.E. Ecklung, etal Experimental botulism in monkeys—Aclinical pathological study Exp Mol Pathol., 6 (1967), pp. 84–95
• E.J. Schantz, etal Properties and use of botulinum toxin and other microbial neurotoxins in medicine Microbiol Rev., 56 (1992), pp. 80–99
• A.B. Scott etal Systemic toxicity of botulinum toxin by intramuscular injection in the monkey Mov Disord., 3 (1988), pp. 333–335

14. MECHANISM OF ACTION
 M.F. Brin in 2000, BTX is a protease that causes temporary chemical
denervation of skeletal muscle by blocking the Ca+2-mediated
release of acetylcholine from nerve endings of alpha and gamma
motor neurons (myoneural junction), producing a transient dose-
dependent weakening of the muscle activity rendering it
nonfunctional without systemic effects.
 A. Blitzer in 2001, This inhibition of muscular contraction is believed
to be followed by the sprouting of new axon terminals, which results
in synaptic regeneration and the reestablishment of neuromuscular
transmission.
• M.F. Brin Botulinum toxin therapy: basic science and overview of other therapeutic applications A. Blitzer (Ed.),
Management of facial lines and wrinkles, Lippincott, Williams and Wilkins, Philadelphia (2000 p), pp. 279–302
• A. Blitzer, L. Sulica Botulinum toxin: basic science and clinical uses in otolaryngology Laryngoscope, 111 (2001), pp. 218–226

15. MECHANISM OF ACTION
 J. O’day in 2001 The area of flaccidity produced may be larger than
the area of muscle denervated. Weakening of surrounding
muscles not injected may also occur because of toxin diffusion.
 C.M. Shaari in 1991 reported based on Animal studies that BTX-A
diffuses across fascial planes to surrounding muscles.
 N.S. Sadick in 2004 reported Clinical effect occurs within
approximately 3–7 after administration, followed by 1–2 weeks of
maximum effect and full nerve recovery within 3–6 months
(approximately 3 months).
• C.M. Shaari Quantifying the spread of botulinum toxin through muscle fascia Laryngoscope, 101 (1991), pp. 960–
963
• J. O’day Use of botulinum toxin in neuro-ophthalmology Curr Opin Opthalmol, 12 (2001), pp. 419–422
• N.S. Sadick, S.L. Matarasso Comparison of botulinum toxins A and B in the treatment of facial rhytides Dermatol
Clin, 22 (2004), pp. 221–226

16. PREPARATIONS
BTX-A
 Botox
 Dysport
 Xeomin
 Prosigne and
 PurTox
BTX-B
 Myoblocs
 NeuroBlocs

17. BTX-A
 Botox (Allergan Inc, USA): BTX-A was first used in humans in 1968
to treat strabismus by A.B. Scott.
 It is specifically approved for the therapeutic treatment of
strabismus, blepharospasm, cervical dystonia and axillary
hyperhidrosis.
 Each vial of Botox contains 5 ng (100 U) of air-dried toxin. Each vial
contains 500 μg of albumin and 900 μg of sodium chloride.
• A.B. Scott, A. Rosenbaum, C.C. Collins Pharmacologic weakening of extraocular muscles Invest Ophthalmol, 12 (1973), pp. 924–927
• J. Carruthers, etal The evolution of botulinum neurotoxin type A for cosmetic applications J Cosmet Laser Ther, 9 (2007), pp. 186–193
• J.A. Carruthers etal 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, 46 (2002), pp. 840–849
• S.J. Carruthers etal Consensus recommendations on the use of botulinum toxin type A in facial aesthetics Plast Reconstr Surg, 114 (6
Suppl) (2004), pp. 1S–22S
• S. Fagien, etalPatient-reported outcomes with botulinum toxin type A treatment of glabellar rhytids: A double-blind, randomized,
placebo-controlled study Dermatol Surg, 33 (1 Spec No.) (2007), pp. S2–S9
• M. Hallett One man's poison—Clinical applications of botulinum toxin N Engl J Med, 341 (1999), pp. 118–120
• N.J. Lowe etal Botulinum A exotoxin for glabellar folds: A double-blind, placebo-controlled study with an electromyographic injection
technique J Am Acad Dermatol, 35 (1996), pp. 569–572
• P. Lowe, etal Comparison of two formulations of botulinum toxin type A for the treatment of glabellar lines: A double-blind, randomized
study J Am Acad Dermatol, 55 (2006), pp. 975–980
• P.L. Lowe, etal A comparison of two botulinum type A toxin preparations for the treatment of glabellar lines: Double-blind, randomized,
pilot study Dermatol Surg, 31 (2005), pp. 1651–1654

18. BTX-A
 Dysport (Ipsen Limited, UK) is another BTX-A product approved
for cosmetic use.
 Each vial contains 12.5 ng (500 U) of air-dried toxin, 125 μg of
albumin, and 2.5 mg of lactose. Dysport comes from a different
type A strain of bacteria than Botox and doses are not equivalent.
Direct comparisons of Botox and Dysport in animal studies
suggest that the equivalence doses are 1 U Botox to 2.5–5 U
Dysport.
S.L. Matarasso Comparison of botulinum toxin types A and B: A bilateral and double-blind randomized evaluation in the
treatment of canthal rhytides Dermatol Surg, 29 (2003), pp. 7–13

19. BTX-A
 Xeomin (NT-201; Merz Pharmaceuticals GmBH, Germany) F.
Mancini in 2003, packaged as a freeze-dried powder, is a purified
BTX-A that is free of the accessory complexing proteins
(hemagglutinin and nonhemagglutinin) found in the other BTX-A
products.
 Jost in 2007 reported that xeomin is less immunogenic than
other BTX-A products.
 S.R. Freeman in 2008 found that it useful when large amounts of
toxin are required for extended periods.
F. Mancini, etal Double-blind, placebo-controlled study to evaluate the efficacy and safety of botulinum toxin type A in the
treatment of drooling in parkinsonism Mov Disord, 18 (2003), pp. 685–688
Jost Wh etal Botulinum neurotoxin type A free of complexing proteins (XEOMIN) in focal dystonia Drugs, 67 (2007),
pp. 669–683
S.R. Freeman, J.L. Cohen New Neurotoxins on the Horizon Aesthetic Surg J, 28 (2008), pp. 325–330

20. BTX-A
 K. Wohlfarth etal in 2007 and Dressler D etal in 2008 found that
Botox and Xeomin have similar dose-dependent paralytic effects
and minimal diffusion effects on surrounding musculature and . It
has been suggested that conversion of Botox and Xeomin doses
can be performed in a 1:1 ratio allowing exchange of both BTX
drugs in a therapeutic setting.
• Dressler D, Mander GJ, Fink K. Equivalent potency of Xeomin and BOTOX. Abstracts Toxins 2008/Toxicon 51: 10.
• K. Wohlfarth, etal Neurophysiological double-blind trial of a botulinum neurotoxin type a free of complexing proteins Clin
Neuropharmacol, 30 (2007), pp. 86–94

21. BTX-A
 Prosigne (Lanzhou Biological Products Institute, China) X. Tang in
2000, it has been available for clinical use there since October
1993.
 C.R. Rieder in 2007, Preliminary studies suggest that Prosigne may
have therapeutic actions comparable with Botox for some
therapeutic purposes.
 PurTox (Mentor Corp, Santa Barbara, CA, USA) S.R. Freeman in
2008 is a purified BTX-A that is undergoing trials to approve its
efficacy in some therapeutic uses.
• C.R. Rieder, etal A double-blind, randomized, crossover study of prosigne versus botox in patients with blepharospasm and
hemifacial spasm Clin Neuropharmacol, 30 (2007), pp. 39–42
• X. Tang, X. Wan Comparison of Botox with a Chinese type A botulinum toxin Chin Med J (Engl), 113 (2000), pp. 794–
798
• S.R. Freeman, J.L. Cohen New Neurotoxins on the Horizon Aesthetic Surg J, 28 (2008), pp. 325–330

22. BTX-B
 Myobloc (Solstice Pharmaceuticals, South San Francisco, CA, USA)
A.L. Ramirez in 2002 has shown efficacy in clinical trials for the
treatment of various movement disorders since 1995 and was
approved by the FDA for the treatment of cervical dystonia and
hemifacial spasm in 2001163.
 M.F. Lew in 2000, T. Alster and L. Baumann in 2003 ,its efficacy in the
treatment of lateral canthal, glabellar and forehead rhytides. It
appears to offer versatility in cosmetic neuroblockade by exhibiting
action in patients resistant to BTX-A products
• A.L. Ramirez etal Botulinum toxin type B (MyoBloc) in the management of hyperkinetic facial lines Otolaryngol Head Neck Surg, 126 (2002), pp. 459–
467
• T. Alster, etal Botulinum toxin type B for dynamic glabellar rhytides refractory to botulinum toxin type A Dermatol Surg, 29 (2003), pp. 516–518
• L. Baumann, etal A double-blinded, randomized, placebo-controlled pilot study of the safety and efficacy of Myobloc (botulinum toxin type B)-
purified neurotoxin complex for the treatment of crow's feet: A double-blinded, placebo- controlled trial Dermatol Surg, 29 (2003), pp. 508–515
• M.F. Lew, etal The safety and efficacy of botulinum toxin type B in the treatment of patients with cervical dystonia: Summary of three controlled
clinical trials Neurology, 55 (12 Suppl 5) (2000), pp. S29–S35
• N.J. Lowe, etal Botulinum toxins types A and B for brow furrows: Preliminary experiences with type B toxin dosing J Cosmet Laser Ther, 4 (2002), pp.
15–18
• S.L. Matarasso Comparison of botulinum toxin types A and B: A bilateral and double-blind randomized evaluation in the treatment of canthal
rhytides Dermatol Surg, 29 (2003), pp. 7–13
• N. Sadick Prospective open-label study of botulinum toxin type B (Myobloc) at doses of 2,400 and 3,000 U for the treatment of glabellar wrinkles
Dermatol Surg, 29 (2003), pp. 501–507
• N.S. Sadick Botulinum toxin type B for glabellar wrinkles: A prospective open-label response study Dermatol Surg, 28 (2002), pp. 817–821
• N.S. Sadick etal Comparison of botulinum toxins A and B in the treatment of facial rhytides Dermatol Clin, 22 (2004), pp. 221–226

23. BTX-B
 S.L. Matarasso in 2003, Myobloc is preconstituted in vials containing
25 ng (2500 U)/0.5 cc, 50 ng (5000 U)/1.0 cc and 100 ng (10,000
U)/2.0 cc of product in solution with 0.05% albumin.
 S.R. Freeman in 2008, Treatment of patients with cervical dystonia
with Botox and Myobloc led to attempts at equivalency doses in
many cosmetic studies (1 U Botox equals approximately 50–100 U
Myobloc)
• S.L. Matarasso Comparison of botulinum toxin types A and B: A bilateral and double-blind randomized evaluation in the
treatment of canthal rhytides Dermatol Surg, 29 (2003), pp. 7–13
• S.R. Freeman, J.L. Cohen New Neurotoxins on the Horizon Aesthetic Surg J, 28 (2008), pp. 325–330

24. BTX-B
 T.C. Flynn in 2003 & 2004, N.J. Lowe in 2002, S.L. Matarasso in 2003
and A.L. Ramirez in 2002 reported based on Studies comparing the
cosmetic efficacies of BTX-A and BTX-B that the latter causes more pain
during injection, has shorter action and probably a less predictable
diffusion pattern.
 S.R. Freeman in 2008 reported that BTX-B could be useful in situations
in which rapid onset is desirable or in which there are concerns about
antibody production to BTX-A.
• T.C. Flynn Myobloc Dermatol Clin, 22 (2004), pp. 207–211
• T.C. Flynn, R.E. Clark Botulinum toxin type B (MYOBLOC) versus botulinum toxin type A (BOTOX) frontalis study: rate of onset
and radius of diffusion Dermatol Surg, 29 (2003), pp. 519–522
• N.J. Lowe, P.S. Yamauchi, G.P. Lask, R. Patnaik, D. Moore Botulinum toxins types A and B for brow furrows: Preliminary
experiences with type B toxin dosing J Cosmet Laser Ther, 4 (2002), pp. 15–18
• S.L. Matarasso Comparison of botulinum toxin types A and B: A bilateral and double-blind randomized evaluation in the
treatment of canthal rhytides Dermatol Surg, 29 (2003), pp. 7–13
• A.L. Ramirez, J. Reeck, C.S. Maas Botulinum toxin type B (MyoBloc) in the management of hyperkinetic facial lines
Otolaryngol Head Neck Surg, 126 (2002), pp. 459–467
• S.R. Freeman, J.L. Cohen New Neurotoxins on the Horizon Aesthetic Surg J, 28 (2008), pp. 325–330

25. COSMETIC USES
 Intramuscular injection of BTX to reduce facial wrinkles is the most
common cosmetic procedure performed in many countries. In
conjunction with fillers, BTXs allow the practitioner to sculpt the face
through alterations in the dynamics of the facial muscles. The limited
on-label uses of these drugs for hyperkinetic forehead wrinkles and
brow furrows belie its range of cosmetic applications.

26. FACIAL WRINKLES
 J. Niamtu in 1999 S. Fagien in 2001 and J.E. Frampton in 2003 The
cosmetic potential of BTX-A was first explored in the mid 1980s in
the treatment of hyperfunctional facial lines. Since then, BTX-A has
been used to temporarily treat glabellar lines and other
hyperfunctional facial lines such as horizontal forehead lines, lateral
canthal lines ‘crow's feet’, platysma bands and perioral lines.
S. Fagien, F.S. Brandt Primary and adjunctive use of botulinum toxin type A (Botox) in facial aesthetic surgery: beyond the glabella
Clin Plast Surg, 28 (2001), pp. 127–148
J.E. Frampton, S.E. Easthope Botulinum toxin A (Botox cosmetic): a review of its use in the treatment of glabellar frown lines Am J
Clin Dermatol, 4 (2003), pp. 709–725
J. Niamtu Aesthetic uses of botulinum toxin A J Oral Maxillofac Surg, 57 (1999), pp. 1228–1233

27. FACIAL WRINKLES
 J. Carruthers in 1992, Multiple injection techniques have been
described. Some authors describe a method based on brow
position.
 J. Niamtu in 1999, 2000 and 2003 describe a method based on needle
angulation and measurement and All injections are now made
perpendicular to the skin surface and are tailored to the specific
anatomy, but they must be 10 mm away from the bony orbit
because the apparent diffusion of BTA is approximately 10 mm.
• J. Carruthers, A. Carruthers Treatment of glabellar frown lines with C. botulinum-A exotoxin J Dermatol Surg Oncol, 18
(1992), pp. 17–21
• J. Niamtu Aesthetic uses of botulinum toxin A J Oral Maxillofac Surg, 57 (1999), pp. 1228–1233
• J. Niamtu Botulinum Toxin A: A Review of 1,085 Oral and Maxillofacial Patient Treatments J Oral Maxillofac Surg, 61 (2003), pp.
317–324
• J. Niamtu Cosmetic facial surgery Oral Maxillofac Surg Clin North Am, 12 (2000), p. 595

28. MASSETERIC & TEMPORALIS MUSCLE
HYPERTROPHY
 M. Metai in1994, B.A. Rijsdijk in 1998 and B. Bentsianov, etal in 2004
The early results of treatment with intramasseter injections of BTX
have been encouraging and satisfying to patients, but the effect
has not been well quantified.
 A.M. Isaac in 2000, Temporalis muscle hypertrophy is less common
but has been managed successfully using BTX injection; there were
no appreciable side effects
• B. Bentsianov, etal Botulinum toxin treatment of temporomandibular disorders, masseteric hypertrophy, and cosmetic masseter reduction
Oper Tech Otolaryngol Head Neck Surg, 15 (2004), pp. 110–113
• M. Metai Morphological and functional-changes in masseter after administration of botulinum toxin for treatment of masseteric hypertrophy
J Dent Res, 75 (1996 May), p. 1164 A.P. Moore, etal The Medical Management of Masseteric Hypertrophy With Botulinum Toxin Type A Br J
Oral Maxillofac Surg, 32 (1994), pp. 26–28
• B.A. Rijsdijk Botulinum toxin Type A treatment of cosmetically disturbing masseteric hypertrophy (DUT) Ned Tijdschr Geneeskd, 142 (1998),
pp. 529–532
• A.M. Isaac Unilateral temporalis muscle hypertrophy managed with botulinum toxin type A Br J Oral Maxillofac Surg, 38 (2000), pp. 571–572

29. THERAPEUTIC USES
 B. Freund, etal in 2000, D.D. Truong in2006, BTX has evolved from a
poison to a versatile clinical tool in conditions resulting from
muscular hyperfunction, includes focal dystonias, vocal tics and
stuttering, cricopharyngeal achalasia, various manifestations of
tremor, hemifacial spasm, temporomandibular joint dysfunction,
bruxism, masticatory myalgias, sialorrhea, hyperhidrosis and
headache.
 K.A. Stefan in 2004, BTX used in dental implantology for the
prophylactic reduction of masseter and temporalis muscle strength
after implantation in immediate load protocols.
• B. Freund, etal Botulinum toxin: new treatment for temporomandibular disorders Br J Oral and Maxillofac Surg, 38 (2000), pp.
466–471
• D.D. Truong, W.H. Jost Botulinum toxin: Clinical use (Review) Parkinsonism and Related Disorders, 12 (2006), pp. 331–355
• K.A. Stefan, etal The therapeutic use of botulinum toxin in cervical and maxillofacial conditions: an evidence-based review Oral Surg Oral Med
Oral Pathol Oral Radiol Endod, 104 (2007), pp. e1–e11

30. TEMPOROMANDIBULAR JOINT (TMJ)
 B. Freund, etal in 1999, B.J. Freund, etal in2002, The injection of BTX-A
into the masseter and temporalis muscles of patients with TMD
reduced subjective pain and tenderness
 P.C. Song, etal in 2007, This was attributed to the presumed action of
BTX on nociceptors and P.L. Durham etal in 2004, the inhibitory effect
of specific protein-receptor binding within the intracellular
compartment on the release of neuropeptides and inflammatory
molecules, such as calcitonin gene-related peptide, substance P, and
glutamate
 S. Arnaud, etal in 2006, Most patients with restricted mouth opening
experienced some degree of improvement in the maximal range of
vertical motion after BTX therapy. Muscular relaxation, reduction of
inflammation in the muscle and the TMJ, and the guarding response
to pain may contribute to this finding
• B. Freund, etal The Use of Botulinum Toxin for the Treatment of Temporomandibular Disorders: Preliminary Findings J Oral Maxillofac Surg, 57 (1999), pp. 916–920
• B.J. Freund, etal Relief of tension-type headache symptoms in subjects with temporomandibular disorders treated with botulinum toxin-A
Headache, 42 (2002), pp. 1033–1037
• P.C. Song, etal The emerging role of botulinum toxin in the treatment of temporomandibular disorders Oral Dis, 13 (2007), pp. 253–260
• P.L. Durham etal Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for
migraine therapy Headache, 44 (2004), pp. 35–42
• S. Arnaud, etal Nonsurgical management of traumatic injuries of the parotid gland and duct using type A botulinum toxin Plast Reconstr Surg, 117

31. TEMPOROMANDIBULAR JOINT (TMJ)
 M.F. Brin, etal in1987, B. Daelen etal in1997 and M. Bakke, etal in
2005, BTX injection into the lateral pterygoid muscle has reduced
the clicking associated with TMD. Clicking was permanently
eliminated in some cases with a small but distinctive positional
improvement in the disc–condyle relationship.
 C.B. Ivanhoe, etal in 1997 and Several studies have described the
treatment of bruxism with BTX. Some authors have found that BTX-
A injection into the flexor muscles of the mandible produced
subjective and objective reductions in the power of muscular
voluntary contraction in most subjects.
 B. Freund in 2003, Intramuscular injection of BTX as an adjunct to
arthrocentesis of the TMJ gave encouraging results regarding
duration of improvement. 78
M. Bakke, etal Treatment of severe temporomandibular joint clicking with botulinum toxin in the lateral pterygoid muscle in two cases of anterior disc displacement Oral
Surg Oral Med Oral Pathol Oral Radiol Endod, 100 (2005), pp. 693–700
M.F. Brin, etal Localized injections of botulinum toxin for the treatment of focal dystonias and hemifacial spasm Mov Disord, 2 (1987), pp. 237–254
B. Daelen etal Treatment of recurrent dislocation of the temporomandibular joint with type A botulinum toxin Int J Oral Maxillofac Surg, 26 (1997), pp.
458–460
C.B. Ivanhoe, etal Bruxism after brain injury: successful treatment with botulinum toxin- A Arch Phys Med Rehabil, 78 (1997), pp. 1272–1273
B. Freund, M. Schwartz Intramuscular injection of botulinum toxin as an adjunct to arthrocentesis of the temporomandibular joint: preliminary
observations Br J Oral Maxillofac Surg, 41 (2003), pp. 351–352

32. TEMPOROMANDIBULAR JOINT (TMJ)
 D.M. Pérez etal in 2004, BTX-A was first used to treat surgical failures
and then used as initial treatment. Treating only the lateral pterygoid
muscle appears to be sufficient to prevent temporarily recurrent
dislocation
 B. Daelen etal in1997 and D.M. Pérez etal in 2004, BTX injection
therapy is also an option in patients who suffer recurrent dislocation
of the TMJ as a result of impaired muscle coordination secondary to
oromandibular dystonia, neuroleptically induced early and late
dyskinesias, epilepsy and brain-stem syndromes.
D.M. Pérez, P.G. Espiga Recurrent Temporomandibular Joint Dislocation Treated With Botulinum Toxin: Report of 3 Cases J Oral Maxillofac Surg, 62 (2004), pp. 244–246
B. Daelen etal Treatment of recurrent dislocation of the temporomandibular joint with type A botulinum toxin Int J Oral Maxillofac Surg, 26 (1997), pp.
458–460

33. SALIVARY SECRETORY DISORDERS
 K.O. Bushara in 1997 and R. Giess in 2000 Topical injection of BTX-A
as a minimally invasive option for the treatment of drooling has
been used for many years in neurological diseases.
 P. Capaccio etalin 2008 Its greatest limitation in this indication is its
transient effectiveness (3–4 months), requiring multiple and
expensive administrations.
 M. Ellies in 2000 and 2003 The therapeutic effect is based on the
inhibitory action of the toxin at the cholinergic receptors of the
salivary gland cells, shown in animal experiments.
• K.O. Bushara Sialorrhea in amyotrophic lateral sclerosis: a hypothesis of a new treatment-botulinum toxin A injections of the parotid glandsMed Hypotheses, 48
(1997), pp. 337–339
• R. Giess, M. Naumann, E. Werner Injections of botulinum toxin A into the salivary glands improve sialorrhoea in amyotrophic lateral sclerosis J
Neurol Neurosurg Psychiatry, 69 (2000), pp. 121–123
• P. Capaccio etal Botulinum toxin therapy: a tempting tool in the management of salivary secretory disorders Am J Otol – Head and Neck
Medicine and Surgery, 29 (2008), pp. 333–338
• M. Ellies, R. Laskawi, S. Rohrbach-Volland, C. Arglebe Up-todate report of botulinum toxin therapy in patients with drooling caused by different
etiologies J Oral Maxillofac Surg, 61 (2003), pp. 454–457
• M. Ellies, R. Laskawi, G. Tormahlen The effect of local injection of botulinum toxin A on the parotid gland of the rat: An immunohistochemical
and morphometric study J Oral Maxillofac Surg, 58 (2000), pp. 1251–1256

34. SALIVARY SECRETORY DISORDERS
 BTX has found application for sialorrhea in Parkinson's disease by G.
Lagalla, etal in 2006, amyotrophic lateral sclerosis by R. Giess, etal in 2000,
cerebral palsy and carcinoma of the upper digestive tract by M. Porta,
etal in 2001.
 C. Drobik in 1995, Capaccio etal in 2008 BTX has also been used
successfully to treat auriculotemporal (Frey's) syndrome P. Drummond in
2002, it reduces the skin area affected by gustatory sweating by
inhibiting the sweat glands abnormally re-innervated by the cholinergic
pathway.
 M. Ellies in 2003 BTX-A also has advantages in temporarily drooling
states because its effect is only temporary. P. Capaccio etal in 2008 In
patients with recurrent and chronic parotitis, BTX injection resulted in a
reduction in the number of episodes of parotid swelling.
G. Lagalla, etal Botulinum toxin type A for drooling in Parkinson's disease: a double-blind, randomized, placebo-controlled study Mov Disord, 21 (2006), pp. 121–125
R. Giess, etal Injections of botulinum toxin A into the salivary glands improve sialorrhoea in amyotrophic lateral sclerosis J Neurol Neurosurg Psychiatry, 69
(2000), pp. 121–123
M. Porta, etal Treatment of sialorrhea with ultrasound guided botulinum toxin type A injections in patients with neurological disorders J Neurol Neurosurg
Psychiatry, 70 (2001), pp. 538–540
P. Capaccio etal Botulinum toxin therapy: a tempting tool in the management of salivary secretory disorders Am J Otol – Head and Neck Medicine and
Surgery, 29 (2008), pp. 333–338
Drobik, R. Laskawi Frey's syndrome: treatment with botulinum toxin Acta Otolaryngol Stockh, 115 (1995), pp. 459–461
P. Drummond Mechanism of gustatory flushing in Frey's syndrome Clin Auton Res, 12 (2002), pp. 144–146

35. FACIAL PAIN
(OTHER THAN MYOFASCIAL ORIGIN)
 studies have been conducted B.J. Freund in 2000 G.E. Borodic in 2002
on the use of BTX-A in pain conditions such as tension headache,
myofascial pain, migraine, trigeminal neuralgia, bruxism and
hemifacial contracture after seventh cranial nerve injury.
 G. Borodic in 2002 BTX-A was found promising in postoperative
wound pain including reconstructive facial and oral surgery,
traditional and endoscopic sinus surgery, TMJ surgery and blowout
fracture repair. Chronic facial pain following post-dental procedures
was associated with a poor results.
G.E. Borodic, , M.A. Acquadro The Use of Botulinum Toxin for the Treatment of Chronic Facial Pain J Pain, 3 (2002), pp. 21–27
B.J. Freund M. Schwartz Treatment of chronic cervical-associated headache with botulinum toxin A: A pilot study Headache, 40 (2000), pp. 231–
236
G. Borodic, M. Acquadro Management of facial pain with botulinum toxin in a tertiary pain clinic
Naunyn Schmiedebergs Arch Phannacol, 365 (Suppl 2) (2002), p. R14

36. FACIAL NERVE PALSY (FNP)
 S.A. Sadiq in 1998 and M.F. Ellis etal 2001, BTX injection, through an
orbital route or a skin crease, provides a good means of inducing a
protective ptosis by temporarily paralyzing the levator palpebrae
superioris
 G.C. Gusek-Schneider, etal in 1998 This intentionally induced ptosis
may be useful in intensive care patients to prevent desiccation of
the cornea.
 R.J. Hofmann in 2000 and F.J. Montoya in 2002 An aberrant
connection of the salivary sceromotor fibres to the fibres of the
lacrimal gland may develop after a facial palsy, causing a
hyperlacrimation whenever the patient salivates (crocodile tears).
Injection of BTX into the lacrimal gland is a successful treatment for
hyperlacrimation in these cases .
M.F. Ellis, M. Daniell An evaluation of the safety and efficacy of botulinum toxin type A (BOTOX) when used to produce a protective ptosis Clin Exp Ophthalmol, 29
(2001), pp. 394–399
S.A. Sadiq, R.N. Downes A clinical algorithm for the management of facial nerve palsy from an oculoplastic perspective Eye, 12 (Pt 2) (1998), pp. 219–
223
G.C. Gusek-Schneider, etal Protective ptosis by botulinum A toxin injection in corneal affectations Klin Monatsbl Augenheilkd, 213 (1998), pp. 15–22
R.J. Hofmann Treatment of Frey's syndrome (gustatory sweating) and ‘crocodile tears’ (gustatory epiphora) with purified botulinum toxin Ophthalmic
Plast Reconstr Surg, 16 (2000), pp. 289–291
F.J. Montoya, etal Treatment of gustatory hyperlacrimation (crocodile tears) with injection of botulinum toxin into the lacrimal gland Eye, 16 (2002), pp.
705–709

37. FACIAL NERVE PALSY (FNP)
 M.W. Armstrong in 1996, N.W. Bulstrode and R.P. Clark, in 2005, In
patients with facial asymmetry, chemo-denervation of the normal
side with BTX has been reported to be an effective disguising tool.
In this setting, BTX reduces the relative hyperkinesis of the
contralateral side to the paralysis, resulting in a more symmetrical
function of the face.
M.W. Armstrong, etal Treatment of facial synkinesis and facial asymmetry with botulinum toxin type A following facial nerve palsy Clin
Otolaryngol Allied Sci, 21 (1996), pp. 15–20
N.W. Bulstrode, D.H. Harrison The phenomenon of the late recovered Bell's palsy: treatment options to improve facial symmetry
Plast Reconstr Surg, 115 (2005), pp. 1466–1471
R.P. Clark, C.E. Berris Botulinum toxin: a treatment for facial asymmetry caused by facial nerve paralysis Plast Reconstr Surg, 115
(2005), pp. 573–574

38. OTHER NERVE PALSIES
 H.S. Metz in 1988, N. Saad, in 1992 and M.R. Talebnejad, etal in
2008, There are few reports (level 4 evidence) of BTX injection to
the lateral rectus muscle for treatment of third-nerve palsy.
 M.L. Mazow in 1999 BTX injection decreases the likelihood of
contracture of the lateral rectus muscle, thereby allowing return of
medial rectus muscle function
 N.L. Rowe, L.I. Williams in Maxillofacial injuries (2nd edition), The
abducens nerve can be injured during a severe orbital trauma.
• H.S. Metz, M. Mazow Botulinum toxin treatment of acute sixth and third nerve palsy Graefes Arch Clin Exp Ophthalmol, 226 (1988), pp. 141–144
• N. Saad, J. Lee The role of botulinum toxin in third nerve palsy Aust N Z J Ophthalmol, 20 (1992), pp. 121–127
• M.R. Talebnejad, etal The role of Botulinum toxin in management of acute traumatic third-nerve palsy J AAPOS, 12 (2008), pp. 510–
513
• M.L. Mazow Third cranial nerve palsy: Diagnosis and management strategies A.L. Rosenbaum, A.P. Santiago (Eds.), Clinical
Strabismus Management: Principles and Surgical Technique, W.B. Saunders, Philadelphia (PA) (1999), pp. 251–258
• N.L. Rowe, L.I. Williams Fracture of the zygomatic complex and orbit L.I. Williams (Ed.), Rowe and Williams’ Maxillofacial injuries (2nd
edition), Vol. 1, Churchill Livingstone (1994), p. 515

39. MUSCLE MOVEMENT DISORDERS
 BTX has been used since 1977 as a therapeutic agent in the
treatment of numerous neuromuscular disorders.
 A Blitzer, etal in 1997 Matarasso, etal in 1999, M.A. Kane in1999 R.
Laskawi,etal in 2002, A specific type in this category is hyperkinesia
of the platysma. In the literature, data on successful treatment of the
platysma with BTX are nearly always related to its use for aesthetic
indications. BTX also provides a favorable therapeutic option
• A Blitzer, etal The management of hyperfunctional facial lines with botulinum toxin: A collaborative study of 210 injection sites in 162
patients Arch Otolaryngol Head Neck Surg, 123 (1997), pp. 389–392
• F.S. Brandt, B. Bellman Cosmetic use of botulinum toxin Aexotoxin for the aging neck Dermatol Surg, 24 (1998), pp. 1232–1234
• M.A. Kane Nonsurgical treatment of platysmal bands with injection of botulinum toxin A Plast Reconstr Surg, 103 (1999), pp. 656–663
• Matarasso, etal Botulinum A exotoxin for the management of platysma bands Plast Reconstr Surg, 103 (1999), pp. 645–652
• R. Laskawi,etal, SurgicalnNonsurgical Treatment Options in Patients With Movement Disorders of the Platysma J Oral Maxillofac Surg,
60 (2002), pp. 157–162

40. MUSCLE MOVEMENT
DISORDERS
J. Jankovic, etal in 1987 reported that BTX-A injections are considered a safe and
efficient local treatment for focal dystonia and muscle spasms 105
condition Author
Oromandibular dystonia 1. Blitzeretal etal Ann Otol Rhinol Laryngol, 98 (1989), pp. 93–97
2. N. Hermanowicz, etalLaryngoscope, 101 (1991), pp. 1216–1218
3. E.K. Tan etalNeurology, 53 (1999), pp. 2102–2107
Cervical dystonia
(spasmodic torticollis)
1. A. Brashear etal Neurology, 53 (1999), pp. 1439–1446
2. M.F. Brin, etal Neurology, 53 (1999), pp. 1431–1438
3. C.L. Comella, etal Neurology, 65 (2005), pp. 1423–1429
4. R. Stell etal BMJ, 297 (1988), p. 616
Hemifacial spasm 1. M.F. Brin, etal Mov Disord, 2 (1987), pp. 237–254
2. Y.C. Park etal J Korean Med Sci, 8 (1993), pp. 334–340
3. E.K. Tan etal J Neurol Sci, 219 (1–2) (2004), pp. 151–155
4. D.M. Yoshimura etal Muscle Nerve, 15 (1992), pp. 1045–1049
Tardive dyskinesia 1. E. Stip etal Br J Psychiatry, 161 (1992), pp. 867–868
2. D.D. Truong, etal J Clin Psychopharmacol, 10 (1990), pp. 438–439
3. J. Yasufuku-etal J Neurol Neurosurg Psychiatry, 58 (1995), pp. 511–512
Tardive tongue
protrusion dystona
1. P.D. Charles etalSouth Med J, 90 (1997), pp. 522–525
2. S.A. Schneider, etal Neurology, 67 (2006), pp. 940–943

41. PERIOPERATIVE USE OF BOTULINUM
TOXINS
 Adler C. in 2008 reported that In maxillofacial surgery,
patients undergoing eyelid reconstructive surgery had
successful wound healing after adjunct treatment with
BTX.
 G. Lger in 2006 BTX was better than placebo in the
wound healing of facial lacerations requiring surgery.
 G. Mckellar etal in 1992 reported that BTA has been
used to immobilize muscles after jaw fractures to reduce
the displacing forces on the fracture ends and obtain
good immobilization especially if rigid internal fixation is
not available or feasible.
• Adler C. Perioperative Use Of Botulinum Toxins. Abstracts Toxins 2008; Toxicon 51: 44
• G. Lger, etal Botulinum toxin to improve facial wound healing: a prospective, blinded, placebo-controlled study Mayo Clin Proc, 81 (2006), pp. 1023–1028
• G. Mckellar, etalThe use of botulinum-toxin in the treatment of oromandibular dystonias and fractures of the mandibular condyle Aust N Z J Med, 22 (1992),
p. 428

42. PERIOPERATIVE USE OF BOTULINUM
TOXINS
 K.A. Stefan etal in 2007 reported that BTX has also
been beneficial during the initial osseointegration phase
for dental implants.
 This indication is mostly experimental, but some authors
have found it to be safe and effective in the prophylactic
reduction of masseter and temporalis muscle strength
after implantation in immediate loading protocols.
(Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 104 (2007), pp. e1–e11)

43. COMPLICATIONS
 The most important side effects reported for cosmetic
use of BTX include immunogenicity, allergy and local
complications.
 Neutralizing antibodies to BTX-A toxins can lead to loss
of treatment effect.
 M.F. Brin etal in 1999 reported clinical resistance to
BTX-A has been estimated as high as 7%.
 A. Brashear and M.F. Brin etal in 1999 investigated
BTX-B as an alternative therapeutic agent.
M.F. Brin, etal Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia Neurology, 53 (1999), pp.
1431–1438
A. Brashear, etal Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia Neurology, 53
(1999), pp. 1439–1446

44. COMPLICATIONS
 J.C. Cather etal in 2002 and J. Niamtu in 2003
reported Adverse effects such as pain, oedema,
erythema, ecchymosis and short-term hypoesthesia may
occur after injection of BTX-A.
 J. Niamtu, S.Z. Said in 2003 and R.S. Stern in 2004
reported other adverse events like headache,
blepharoptosis and perioral muscular palsy.
J.C. Cather, etal Update on botulinum toxin for facial aesthetics Dermatol Clin, 20 (2002), pp. 749–761
J. Niamtu Botulinum Toxin A: A Review of 1,085 Oral and Maxillofacial Patient Treatments J Oral Maxillofac Surg, 61 (2003), pp. 317–324
S.Z. Said, etal Botulinum toxin A: its expanding role in dermatology and esthetics Am J Clin Dermatol, 4 (2003), pp. 609–616
R.S. Stern Clinical practice. Treatment of photoaging N Engl J Med, 350 (2004), pp. 1526–1534

45. COMPLICATIONS
IN THERAPEUTIC APPLICATIONS
In therapeutic applications, complications were mostly local and relatively mild,
such as pain, erythema, ecchymosis of the region injected, dry eyes, mouth droop,
ptosis and lid edema, facial muscle weakness, asymmetry of facial expression
during dynamic facial movements, xerostomia, transient dysphagia, restricted
mouth opening, nasal regurgitation and nasal speech, headache, blurred vision,
dizziness, upset stomach, infection, neck weakness, voice changes, difficulties in
chewing and breathing risk of aspiration, recurrent jaw dislocation, dysarthria,
salivary duct calculi and local injuries of the carotid arteries or branches of the
facial nerve
A. Blitzer in 1989, M.F. Brin in 1995, G.E. Borodic in 2002, C.L. Comella in 2005
• A. Blitzer, M.F. Brin, P.E. Greene, S. FahnBotulinum toxin injection for the treatment of oromandibular dystoniaAnn Otol Rhinol Laryngol, 98 (1989), pp. 93–97
• G.E. Borodic, M.A. Acquadro The Use of Botulinum Toxin for the Treatment of Chronic Facial Pain J Pain, 3 (2002), pp. 21–27
• M.F. Brin, A. Blitzer, S. Herman Orofaciomandibular and lingual dystonia A.P. Moore (Ed.), Handbook of Botulinim Toxin Treatment, Blackwell Scientific,
Oxford, England (1995), pp. 151–163
• M.F. Brin, A. Blitzer, S. Herman Oromandibular dystonia: Treatment of 96 patients with botulinum toxin J. Jankovic, M. Hallett (Eds.), Therapy With Botulinum
Toxin., Marcel Dekker, New York, NY (1994), pp. 429–435
• M.F. Brin, S. Fahn, C. Moskowitz Localized injections of botulinum toxin for the treatment of focal dystonias and hemifacial spasm Mov Disord, 2 (1987), pp.
237–254
• C.L. Comella, J. Jankovic, K.M. Shannon, J. Tsui, M. Swenson, S. Leurgans Comparison of botulinum toxin serotypes A and B for the treatment of cervical
dystonia Neurology, 65 (2005), pp. 1423–1429

46. COMPLICATIONS
 A. Blitzer in 1989 reorted that Systemic side effects are rarely
reported, generally not dose related, and can include transient
weakness, fatigue, nausea and pruritis.
 B. Bentsianov in 2004 reported that Flu-like syndromes have
been reported, but they are generally of brief duration.
 M.F. Lew in 1997, A. Brashear, M.F. Brin in 1999 and D.
Dressler in 2003 reported some adverse effects such as
xerostomia and dysphagia are more frequently seen after
treatment with BTX-B than BTX-A.
• A. Blitzer, M.F. Brin, P.E. Greene, S. FahnBotulinum toxin injection for the treatment of oromandibular dystoniaAnn Otol Rhinol Laryngol, 98 (1989), pp. 93–
97
• B. Bentsianov etal Botulinum toxin treatment of temporomandibular disorders, masseteric hypertrophy, and cosmetic masseter reduction Oper Tech
Otolaryngol Head Neck Surg, 15 (2004), pp. 110–113
• Brashear, etal Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia Neurology, 53 (1999), pp. 1439–1446
• M.F. Brin, etal Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia Neurology, 53 (1999), pp. 1431–1438
• D. Dressler, R. Benecke Autonomic side effects of botulinum toxin type B treatment of cervical dystonia and hyperhidrosis Eur Neurol., 49 (2003), pp. 34–
38M.F. Lew, etal Botulinum toxin type B: A double-blind, placebo-controlled, safety and efficacy study in cervical dystonia Neurology, 49 (1997), pp. 701–
707

47. CONTRAINDICATIONS
Allergan lists Botox contraindications as (Botox Package Insert. Irvine, CA,
Allergan, Inc.)
1. Pregnancy and breastfeeding,
2. Disorders of the neuromuscular junction (myasthenia gravis,
amyotrophic lateralizing sclerosis, myopathies)
3. Theoretical drug interactions (aminoglycoside antibiotics,
quinidine, calcium channel blockers, magnesium sulfate,
succinylcholine, and polymyxin).
W. Huang etal in 2001 (J Am Acad Dermatol, 43 (2 Pt 1) (2000), pp. 249–259)
1. Eaton–lambert syndrome
2. Hypersensitivity to BTX or one of its ingredients.

48. POTENTIAL THERAPEUTIC USES
TOPICAL FORMULATIONS
• De Almeida AT Dermatol Surg 2007: 33(1 Spec No.):S37–S43
• Moreau MS Br J Dermatol 2003: 149: 1041–1045.
• Talarico-Filho S etal Dermatol Surg 2007: 33(1 Spec No.):S44–S50
• Glogau RG in 2007 Dermatol Surg 2007: 33(1 Spec No.):S76–S80.
• Moreau MS etal in 2003, De Almeida AT etal and,
Talarico-Filho S etal in 2007, Because intradermal BTX
injection has been successful in treating focal hyperhidrosis of
the palms, soles, axillae and facial areas. investigators have
considered the potential for a topical formulation.
• Glogau RG in 2007 Topical BTX has been used for axillary
hyperhidrosis with promising results

49. KELOID AND HYPERTROPHIC SCAR
 Clinical observations of A. David etal in 2002, G. Lger
etal in 2006 and X. Zhibo etal in 2008 indicate that BTX-
A can improve the appearance of hypertrophic scar and
inhibit its growth.
 A. Carruthers etal in 2001 reported the evidence
supporting this potential use arise from BTX's ability to
prevent excessive muscle contraction of the skin near
keloid tissue.
 X. Zhibo etal in 2008 and C.-C. Yao etal in 2006
reported its influence on cellular apoptosis and cellular
proliferation.
• A. David, etal Botulinum toxin to minimize facial scarring Facial Plast Surg, 18 (2002), pp. 35–39
• G. Lger, etal Botulinum toxin to improve facial wound healing: a prospective, blinded, placebo-controlled study Mayo Clin Proc, 81 (2006), pp. 1023–1028
• X. Zhibo, etal Potential therapeutical effects of botulinum toxin type A in keloid management Medical Hypotheses, 71 (2008), p. 623
• A. Carruthers, etal Botulinum toxin type A: History and current cosmetic use in the upper face Semin Cutan Med Surg, 20 (2001), pp. 71–84
• X. Zhibo, etal Botulinum toxin type A affects cell cycle distribution of fibroblasts derived from hypertrophic scar J Plast Reconstr Aesthet Surg, 61 (2008), pp.
1128–1129
• C.-C. Yao, etal Novel action of botulinum toxin on the stromal and epithelial components of the prostate gland J Urol, 175 (2006), pp. 1158–1163