Botulinum toxin is a neurotoxic protein produced by Clostridium botulinum bacteria. It is the most lethal substance known but also has therapeutic uses. Commercially available botulinum toxins are types A and B. It is widely used cosmetically for wrinkles and therapeutically for conditions like TMJ disorders, sialorrhea, and muscle spasms. Its mechanism of action involves blocking acetylcholine release at neuromuscular junctions, causing temporary muscle paralysis. Common complications include pain, weakness, and dry mouth. Contraindications include pregnancy, myasthenia gravis, and drug interactions.

1. Clinical Use of Botulinum Toxins
in Oral and Maxillofacial Surgery
Sanchit Goyal
PG Trainee

2. Contents
• Introduction
• History
• Bacteriology
• Structure and Toxicity
• Mechanism of Action
• Preparations
• Cosmetic Uses
• Therapeutic Uses
• Complications
• Contraindications

3. Introduction
• Botulinum toxin (BTX) is a neurotoxic protein
produced by the bacterim Clostridium
botulinum and related species.
• Infection with the bacterium may result in a
potentially fatal disease called botulism.
• Human median lethal dose(LD50) of 1.3-
2.1ng/kg IV or IM and 10-13 ng/kg when
inhaled

4. • Commercially available BTX are Type A and B.
• Widely used in cosmetic applications for the
treatment of facial wrinkles, TMJ disorders,
sialorrhea, headache and neuropathic facial
pain, muscle movement disorders and facial
nerve palsy.

5. Commercial Available Brands

6. History
• Idea of therapeutic use was first developed by
Justinus Kerner; called it ‘sausage poison’.
• In 1870, Muller coined the term botulism.
• 1897, Emile Van Ermengem isolated the
bacteria from the ham and produced the
disease in lab animals.
• BTX was developed as a biological weapon in
20th century by many countries.

7. • Therapeutic use of BTX-A was studied in
primates by Scott et al in 1973.
• In late 1970s toxin was introduced as a
therapeutic agent for treatment of strabismus.
• In 1988, used for treating wrinkles and aging
skin.
• Niamtu reported on the 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 TMDs.

8. Bacteriology
• Clostridium species bacteria are sporulating,
obligate anaerobic, Gram-positive bacilli.
• 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.
• Under appropriate environmental or laboratory
conditions, spores can germinate into
vegetative cells that will produce toxin.

9. • C. botulinum grows and produces neurotoxin
in the anaerobic conditions frequently
encountered in the canning or preservation of
foods.
• Seven different strains of Clostridium have
been described (A, B, C (1 and 2), D, E, F and
G).
• Humans can be affected by the toxins of 5
strains (A, B, E, F and G)

10. Structure and Toxicity
• Toxins produced by clostridial bacteria are high-
molecular-weight protein complexes that
include 3 key proteins: a 150- kDa toxin, a non-
toxin hemagglutinin protein, and a non-toxin
non-hemagglutinin protein.
• Disulfide and noncovalent bonds link the heavy
and light chains, and both chains are required
for neurotoxicity.

11. • BTX is the most toxic material known
• It is 4 times more lethal in mice than tetanus
toxin, 1 X1010 more lethal than curare, and
100 X 1010 more lethal than sodium cyanide.
• 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).

12. Mechanism of Action
• 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.
• 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.

13. • The area of flaccidity produced may be larger
than the area of muscle denervated as a result of
postulated paralysis of gamma motor neurones,
so the output of the muscle spindles is reduced
leading to reduced muscular contraction at
adjacent sites within the injected muscle.
• Weakening of surrounding muscles not injected
may also occur because of toxin diffusion.
• Animal studies have demonstrated that BTX
diffuses across fascial planes to surrounding
muscles

14. • Clinical effect occurs within approximately 3–7
days (typically seen after 1–3 days) after
administration, followed by 1– 2 weeks of
maximum effect, which then levels off to a
moderate plateau until full nerve recovery
within 3–6 months (typically at approximately
3 months).

16. Preparation

17. Preinjection Check List
• Emergency drugs.
• An established injection protocol that includes the
specific locations and appropriate doses for the
condition to be treated.
• All injection sites should have been evaluated
properly.
• The practitioner must be aware of all medications
and supplements that are taken by the patient to
minimize any effect on the potency of the BTX.
• Medical conditions; vital signs, such as blood
pressure, should be noted before injecting.
• Informed consent signed by the patient

18. Uses
1. Cosmetic
- Facial Wrinkles
- Maseteric and Temporalis Hypertrophy
- Correction of Gummy Smile
2. Therapeutic
- TMJ disorders
- Salivary Secretory Disorders
- Facial Pain
- Nerve Palsies
- Muscle Movement Disorders
- Perioperative use of BTX

19. Cosmetic Uses
1. Facial Wrinkles
• Wrinkles appears as a
result of the pulling of the
skin by the underlying
musculature.
• BTX reduces the mimetic
effects of wrinkles and
folds, and should
therefore be applied in
areas of dynamic motion,
such as the glabella,
frontal region, and peri-
orbital lines

20. Glabellar Wrinkles

21. Frontal Wrinkles

22. Peri-Orbital Lines (Crow’s Feet)

23. Injection Techniques

24. Masseter Hypertrophy
• Masseteric hypertrophy usually results from
anatomical asymmetry of the jaw, clenching,
excessive chewing of gum or congenital
malformations.
• May by unilateral or bilateral

26. Temporalis Hypertrophy
• Less common
• Can be managed successfully using BTX
• With no appreciable side effects.

27. Proposed locations of botox injection for the temporalis and
masseter muscles

28. Correction of Gummy Smile
• The exposure of more than 3 mm of the gum
during the smile is known as gingival or
gummy smile (GS).
• GS represents an aesthetic disorder and
therefore various correction methods are
proposed, including gingivoplasty, orthodontic
treatment, orthognathic surgery, and bone
resection.

29. • BTX a simple, fast, and effective method for the
aesthetic correction of GS.
• Various causes have been described for GS,
including lip length, clinical crown length,and
mainly altered passive eruption or vertical
maxillary excess.
• Behavior of perioral muscles critically influences
the structure of the smile and, patients with GS
had at least 20% greater facial muscular capacity
to raise the upper lip when smiling (Peck et al
1992)

30. Muscles Responsible for Gummy Smile

31. Classification Of Gummy Smile Based On Area Of Gingival Exposure
Type of GS Clinical appearance Main muscles involved
Anterior Major gum exposure (>3 mm)
in area
Between canine teeth
LLSAN
Posterior Major gum exposure (>3 mm)
posterior to
Canines, with normal
exposure (<3 mm)
In anterior region
Zm and zmi
Mixed Excessive gum exposure in
both areas
(Anterior and posterior)
Llsan, zm, and zmi
(Combination of >2)
Asymmetric Excessive or more apparent
gum exposure
On one side only
Llsan and/or zm/zmi
ipsilateral
Rosemarie Mazzuco et al 2010 J American Academy of Dermatology

32. Anterior Gummy Smile Posterior Gummy Smile

33. Mixed Gummy Smile Asymmetric Gummy Smile

34. Therapeutic Uses

35. Salivary Secretory Disorders
• Xerostomia is one of the first manifestations of
botulism.
• Topical injection of BTX-A as a minimally invasive
option for the treatment of drooling has been
used for many years in neurological diseases.
• Greatest limitation in this indication is its transient
effectiveness (3–4 months), requiring multiple
and expensive administrations.
• The therapeutic effect is based on the inhibitory
action of the toxin at the cholinergic receptors of
the salivary gland cells.

36. • Treatment is mostly focused on the parotid gland
and to a lesser extent on the submandibular
gland. The sublingual gland is seldom injected.
• Parkinson’s disease, amyotrophic lateral sclerosis
cerebral palsy, and carcinoma of the upper
digestive tract.
• Posttraumatic and iatrogenic salivary sialoceles
and Cysts or salivary fistulas after sialadenectomy
or oropharyngeal cancer surgery.
• Frey’s Syndrome

37. Areas of BOTOX injection in Major
Salivary Glands
10-20 U
10-15 U

38. TMJ Disorders
• BTX is used for treatment of TMJ and masticatory
muscle pain, reduced jaw opening capacity,
recurrent TMJ dislocations and masticatory
hyperactivity.
• TMDs may be divided into
– Myofascial
– Arthrogenic
• Joint noise, pain and restricted range of motion
are most frequent symptoms.
• The source of chronic myofascial pain is not clear.

39. • Injection into the masseter and temporalis
muscles with TMD reduced subjective pain and
tenderness with objective and subjective
weakening of the masticatory muscles.
• This is due to action of BTX on nociceptors and
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

40. • Patients with reduced mouth opening
experienced improvement in mouth opening
after BTX therapy.
• Muscular relaxation, reduction of
inflammation in the muscle and the TMJ.
• BTX injection into the lateral pterygoid muscle
has reduced the clicking associated with TMD.
• BTX injection into the flexor muscles of the
mandible produced subjective and objective
reductions in the power of muscular
contractions.

41. BTX for Prevention of Post-Traumatic
TMJ Ankylosis
Jiewen Dai et al. Journal of Medical Hypothesis and Ideas 2015

42. Facial Pain ( Other Than Myofacial
Pain)
• Use of BTX in pain conditions such as tension
headache, myofacial pain, migraine, trigminal
neuralgia, bruxism and hemifacial contracture.
• Postoperative wound pain can be managed with
BTX but post-dental procedures is asssociated
with a poor results.

43. Facial Nerve Palsy
• 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
• Useful in intensive care patients to prevent
desiccation of the cornea.
• BTX-A is commonly used to relieve the
symptoms of synkinesis with marked
improvement

44. • In patients with facial asymmetry, chemo-
denervation of the normal side with BTX.
• BTX reduces the relative hyperkinesis of the
contralateral side to the paralysis, resulting in
a more symmetrical function of the face.

45. Other nerve palsies
• Third nerve palsy – commonly due to trauma.
• BTX injection to the lateral rectus muscle for
treatment of third-nerve palsy. BTX injection
decreases the likelihood of contracture of the
lateral rectus muscle, thereby allowing return of
medial rectus muscle function.
• The abducens nerve can be injured during a
severe orbital trauma. In such cases, BTX injection
of the medial rectus muscle has been studied
with variable improvements

46. Frey’s Syndrome
• Frey’s Syndrome (gustatory sweating)
has been drescribed as a secretory
alteration of the eccrine sweat glands
located in the facial area due to an
inappropriate response to cholinergic
stimulus from the auriculotemporal
nerve fibers. It is most frequently
encountered as a complication of
parotidectomy.
• Clinically it results in sweating and
flushing of facial skin during
salivation.

47. Perioperative Use of BTX
• The presence of postoperative involuntary
movements may be detrimental to healing.
• BTX weakens the muscle and in so doing may
improve postoperative recovery and healing.
Wound healing improves if the muscles
involved are injected with BTX prior to surgery.
• Patients undergoing eyelid reconstructive
surgery had successful wound healing after
adjunct treatment with BTX.

48. • BTX 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.
• BTX has also been beneficial during the initial
osseointegration phase for dental implants.

49. Potential Therapeutic Uses

50. Topical Formulations
• For treatment of focal hyperhidrosis of the
palms, soles, axillae and facial areas.

51. Keloid and Hypertrophic Scar
• BTX-A can improve the appearance of
hypertrophic scar and inhibit its growth.
• Evidence supporting this potential use arise
from BTX’s ability to prevent excessive muscle
contraction of the skin near keloid tissue, and
its reported influence on cellular apoptosis
and cellular proliferation

52. Complications
• Immunogenicity
• Allergy
• Local complication
– Pain
– Oedema
– Erythema
– Ecchymosis
– Short-term hypoesthesia
• Other reported adverse effects are :
Headache, blepharoptosis and perioral
muscular palsy.

53. • In therapeutic applications, complications are;
 Pain
 Erythema
 Ecchymosis
 Dry eyes
 Mouth droop
 Ptosis and lid oedema
 Facial muscle weakness
 Asymmetry of facial expression
 Xerostomia
 Transient dysphagia
 Restricted mouth opening
 Nasal regurgitation
 Infection
 Blurred vision
 Salivary duct calculi

54. - Neutralizing antibodies to BTX-A can lead to
loss of treatment effect.
- Clinical resistance to BTX-A has been estimated
as high as 7%.
- BTX-B is an alternative therapeutic agent.

55. Contraindications
• Contraindications are generally few.
• Pregnancy and breast feeding
• Disorders of the neuromuscular junction
(myasthenia gravis, amyotrophic lateralizing
sclerosis, myopathies)
• Drug interactions (aminoglycoside antibiotics,
quinidine, calcium channel blockers, magnesium
sulfate, succinylcholine, and polymyxin).
• Other reported contraindications are Eaton–
Lambert syndrome and hypersensitivity to BTX or
one of its ingredients

56. THANK YOU