April 2006 DentaIUpdate l65

DraISurgery
PreetpaI Singh hogaI
A Peview of the Current Uses
of 8otox for Dentally-Pelated
Procedures
Abstract: 8otox is the most widely used abbreviation for botulinum toxin type A (8tA). This drug has received wide coverage in the press
and media for its cosmetic advantages, especially in the facial region. The clinician may be aware of the many courses becoming available
and aimed at dentists to start using it in the cosmetic context. This paper intends to provide a basic understanding of the many functional
uses of the drug in the orofacial region that may be relevant to everyday practice.
CIinicaI ReIevance: Awareness of the current medical, as opposed to purely cosmetic, uses of botulinum toxin in the orofacial region is
desirable and this paper should inform clinicians and their patients with respect to this increasingly popular drug.
Dent Update 2006, 33: 165-168
8otox is the commonly used and abbreviated
name for botulinum toxin type A (8tA). There
has been much press and media coverage
lately with respect to its cosmetic uses in
the facial region. However, there is little
awareness of the non-cosmetic medical
uses of 8tA in the orofacial region, and the
many clinically proven uses of 8tA. Clinicians
may find that patients are becoming more
inquisitive about its nature and may seek
advice from their dentist as to its suitability.
This may be owing to the fact that more
dentists are offering this treatment in the
cosmetic context. Prom a medicolegal point
of view, it is important that dentists wishing
to use 8tA are appropriately indemnified.
Protection societies may provide cover at
an increased subscription as this is classed
as a high-risk procedure. Nevertheless, it
will be necessary to confirm the extent of
involvement and provide evidence of training
undertaken in order to use the drug safely.
This paper highlights the pharmacology of
the drug and current uses in the orofacial
region which may be relevant to the clinician
from a non-cosmetic point of view.
PharmacoIogy
8otox (Alleton) is the USA trade
name of a botulinum type A neurotoxin
complex produced by the bacterium
Clostt|J|um ootul|num. |n the UK, another
trade name is Dysport (lsen). This anaerobic
spore-forming bacterium has eight serotypes,
producing distinct exotoxins. 8otulinum
toxin is one of the most toxic substances
known. Types A and 8 exotoxins are the
most commonly used, therapeutically. The
highly concentrated type 8 toxin, Neurobloc
(VeJeus) is a newer preparation indicated
PreetpaI Singh hogaI, 8DS, MPDS,
PCS(Lng), Senior House Officer in Oral
and Maxillofacial Surgery, AIison Hutton,
8ChD, MPDS PCS(Ldin), Senior House
Officer in Oral and Maxillofacial Surgery,
Andrew Monaghan, PDS, PPCS(Maxfac),
Consultant in Oral and Maxillofacial
Surgery, 8irmingham Children's Hospital.
for specialist use only and for those who
have developed antibodies to type A. we will
consider Dysport, ie type A.
FormuIation
The Dysport powder must be
reconstituted in saline before use (Pigure l).
Lach vial of Dysport contains:
500 units of Clostt|J|um ootul|num type
A toxin-haemagglutinin complex (l unit is
defined as the median lethal intraperitoneal
dose in mice).
AIison Hutton
Andrew Monaghan
Figure 1. Presentation/formulation of Dysport.
DraISurgery
l66 DentaIUpdate April 2006
Albumin solution 20% l25 mcg.
Lactose 2.5 mg.
The recommended dosage
depends on the number of units in|ected and
varies according to the area being in|ected
and the desired outcome. Dysport is supplied
in 500 unit vials and is less potent than 8otox,
which is supplied in l00 unit vials. Hence,
caution is required depending on which
preparation is used.
Method of action
The toxin inhibits the release of
acetylcholine at the neuromuscular |unction.
Considering the contraction of a skeletal
muscle fibre, we can see how 8tA causes
muscle paralysis, it interrupts a key step in
the contraction process (Pigure 2):
The action potential arrives at the motor
nerve terminal by a wave of depolarization.
Calcium channels open in the nerve
terminal due to the depolarization of the
plasma membrane.
Calcium flows into the nerve terminal
along a concentration gradient.
There is an increase of calcium causing
the synaptic vesicles to fuse with the plasma
membrane and empty acetylcholine into the
cleft.
Acetylcholine diffuses across the synaptic
cleft and combines with acetylcholine
receptor sites on the motor end plate.
This increases the conductance of sodium
and potassium and results in depolarization
of the end plate.
Llectrical conductance continues.
Muscles in|ected become weak
within 2-20 days.
2
Pecovery of the nerve
and transmission of action potentials will
gradually recover as new nerve terminals
form. This process takes 6-8 weeks.
3
|f an accidental overdose occurs
there is an antitoxin available which will
neutralize the toxin if given within a few
hours. |t will not be effective if given later, as
the toxin will have already been taken up by
the nerve terminals.
3
Indications
DentaI
8ruxism
Masseteric hypertrophy
Temporomandibular |oint (TM1) dislocation
Temporomandibular |oint dysfunction
syndrome
Sialorrhoea (excessive saliva production)
Prey's syndrome
Chronic facial pain
Hemifacial spasm
Some other uses
Cosmetic
Neuromuscular disorders
Ophthalmologic disorders
Dystonia (abnormal involuntary posturing or
twisting)
|ntractable hiccups
Urinary retention
Contra-indications
Pregnancy and breast-feeding mothers
(because teratogenicity has not been
excluded).
Diseases affecting neuromuscular
transmission, eg myasthenia gravis.
3
CompIications
Pain on in|ection, a topical anaesthetic
cream may therefore be required (LMLA,
).
Post-in|ection bruising (reduced by
keeping in|ections superficial).
Local spread, causing unwanted paralysis
of nearby muscles.
Dysphagia
Nasal speech
Plu-like symptoms
Asthenia (weakness) and urinary
incontinence (associated with higher dose
and possibly due to systemic spread)
Development of tolerance
2,3
Side-effects may not be apparent
for up to a week later and will depend on the
area in|ected.
Some conditions treated using
otox
Masseteric hypertrophy
Muscular hypertrophy commonly
affects the muscles of mastication, notably
the masseters, although sometimes the
temporal muscles may be affected. |t may be
unilateral or bilateral. |t is a benign condition
characterized by painless swelling centred
over the angle of the mandible. Occasionally,
it is misdiagnosed as parotitis or malignant
neoplasm but, more commonly, patients seek
advice for cosmetic reasons.
2
The condition
is most common in the second and third
decades and there is no sex predeliction.
The aetiology is obscure but commonly
involves a work hypertrophy attributable to
clenching. 8ruxism, constant gum chewing
and mastication of hard foods can lead to
an enlargement on one or both sides. There
Figure 2. Close-up of a motor nerve terminal.
l
April 2006 DentaIUpdate l67
DraISurgery
may be intra-oral signs, such as wear facets,
and TM1 problems may also be evident.
Palpation may reveal muscles that are normal
in tone but, when asked to clench, they
become bony hard, corresponding to the
anatomic configuration of the masseters.
This increases the rectangular shape of the
face and may lead to a 'winged' appearance
of the mandible
4
(Pigure 3). Computerized
tomography or MP| may be useful when
a confident diagnosis of masseteric
hypertrophy is not possible.
5
Treatment of masseteric
hypertrophy is generally not required
unless there are cosmetic concerns. Surgical
reduction used to be achieved by removing
the medial bulk of the muscle by an extra-
oral, or more commonly, intra-oral approach.
However, a medical approach that negates
the requirement for an in-patient stay
and general anaesthetic is preferable. 8tA
provides a simple effective alternative in
many cases. Once prepared, it is in|ected
percutaneously into the muscle, after initial
in|ection of local anaesthetic. 8y virtue of its
mode of action, this effectively produces a
functional denervation of the muscle that
subsequently atrophies. The effects can last
from 6-l8 months and repeat in|ections may
then be required. Lven if hypertrophy returns,
it is likely that the relief from spasm, pain and
psychological disturbance in the short term
is beneficial.
Recurrent disIocation of the 7M1
The primary treatment of a
mandibular dislocation is reduction by
manual manipulation. This may sometimes
require sedation or general anaesthesia.
6

Pressure is applied by exerting a downward
force on the posterior teeth or retromolar
area and guiding the TM1 back over the
articular eminence into the glenoid fossa.
However, repeated TM1 dislocation will
require preventive measures.
6
This may occur
in patients who have had a cerebrovascular
accident or dyskinesia/dystonia, where the
patients have abnormal involuntary, often
forceful, posturing or twisting (including
involuntary |aw opening). Currently, the
options may include in|ection of sclerosant
around the TM1 to create fibrosis to limit
mandibular movement, or eminectomy
(surgical refashioning of the articular
eminence to limit the condylar path).
8tA provides a non-surgical
approach to preventing recurrent dislocation.
|n effect, the percutaneous in|ection of toxin
into the muscles that causes dislocation
will result in their atrophy and weakening.
The most common muscles in|ected are the
lateral pterygoids and the effects can last
for 3 months or longer, whereafter repeat
in|ections may be necessary. This technique
has the advantage that no permanent
changes to TM1 function or muscles are
induced and the effects are reversible.
3
The lateral pterygoid, along with
other muscles, may be in|ected accurately
with the aid of electromyographic guidance.
A hollow Teflon-coated needle electrode
is attached to the LMG apparatus which
displays muscle activity (action potentials)
as visual and sound output. After local
anaesthesia, the needle electrode is passed
percutaneously through the cheek in the
preauricular region below the anterior
zygomatic process, about l cm in front
of the condylar process, with the mouth
slightly open. The position within the lateral
pterygoid muscle is confirmed by asking
the patient to open his/her mouth against
the resistance of the hand and eliciting a
specific response from the LMG machine. The
needle is aspirated to prevent intravascular
placement and toxin is in|ected into the
muscle.
3,6
Chronic faciaI pain
Chronic facial pain (also known
as myofascial pain, TMPDS) is a common
multicausal, functional disorder presenting to
the general dental practitioner, oral surgery
and maxillofacial departments on a regular
basis.
7
Current treatments may include the
use of conservative physiotherapy exercises,
occlusal or splint therapy and drug treatment
with antidepressants or muscle relaxants.
Often, the patients have had multiple failed
treatments.
7,8
Chronic hyperactivity of the
muscles of mastication and resulting
hypermobility of the condyle is commonly
associated with chronic facial pain and
headache. The local in|ection of 8tA has
been reported to be an effective treatment
in these cases. The muscles most often
targeted are the masseter, temporalis medial
and lateral pterygoids. |n one study, an
improvement in painful symptoms could
be expected in up to 90% of patients who
did not respond to conservative methods.
8

Hence, the use of 8tA may be a useful aid in
the management of this difficult condition.
DrooIing
Drooling can be caused by
several conditions such as cerebral palsy,
neuro-degenerative disease, stroke and
head and neck carcinoma, which result
in the inability to hold saliva in the oral
cavity and co-ordinate a swallow.
9
Lxcessive
Figure 3. Lxample of a patient with masseteric hypertrophy.
DraISurgery
l68 DentaIUpdate April 2006
drooling can cause perioral maceration,
chapping and infection, anti-social odour,
embarrassment and discomfort for
the patient and their families. Affected
individuals may need to wear a bib or
frequently change their clothes.
l0
Treatment options include,
behavioural management, removable
appliances to encourage lip and tongue
movement, scopolamine patches, other
drugs with anticholinergic properties and
surgical re-routing of submandibular gland
ducts. A more recent method of control is
the in|ection of botulinum toxin into the
salivary glands themselves.
when in|ected into the
gland, 8tA will reduce the amount of
saliva produced. This occurs because the
stimulation of cholinergic receptors is
inhibited, therefore reducing the amount of
saliva secreted. Ultrasound may be used to
ensure correct placement of the toxin.
Despite a reduction in salivary
flow, patients will maintain a basal rate of
secretion. Therefore, adverse effects of a dry
mouth, such as increased dental caries and
intra-oral infections, are avoided.
9
Frey's syndrome
Gustatory sweating occurs
during meals and comprises sweating
and flushing of the skin, most commonly
occurring in the forehead, parotid and
submandibular regions. This usually
occurs after parotid gland surgery, radical
neck dissection and submandibular
surgery. Although the condition is
asymptomatic, many patients are
embarrassed by sweating. when the
skin is raised during parotidectomy, for
example, the sympathetic nerve fibres to
the sweat glands in the flap are severed.
Parasympathetic fibres that feed the gland,
from the auriculotemporal nerve branch
of the mandibular nerve, are also severed
when the gland is excised. Upon healing,
there may be abnormal crossed over
regeneration of nerve axons resulting in
parasympathetic innervation of the sweat
glands. Therefore, on eating, these fibres will
now cause sweating of the skin.
Treatment methods have
included trials of different flap designs
to reduce postoperative complications,
resection of the auriculotemporal nerve
during parotidectomy, and topical use of
aluminium chloride in alcohol solution (only
temporary relief ). The use of 8tA has proved
the most effective alternative to these
techniques and is the most widely used. |t is
in|ected intracutaneously into the affected
area. The use of an iodine solution painted
over the skin, with subsequent application
of potato starch, may be carried out
beforehand. The patient may then be given
a sour sweet to chew to elicit sweating.
This will cause small black spots to occur
at the gland openings. Thus the affected
areas can be pinpointed for in|ection
with botulinum.
ll
The method of action is
similar to that for drooling.
Aesthetic/cosmetic uses
The most common facial areas
treated are the glabella (procerus and
corrugator muscles), forehead (frontalis
muscle) and eyes (orbicularis occuli). Small
amounts of 8tA are in|ected into these
ma|or muscles at specific points. Other
muscles that may be treated include: upper
lip elevators (to reduce gingival exposure
in high lip line), nasalis (nose), risorius and/
or zygomaticus ma|or (nasogenial furrow),
orbicularis oris (wrinkles around the lips),
depressor anguli oris (pulls the angle of
the mouth down), mentalis (accounting
for the half moon-shaped transverse line
on the chin) and platysma (age-related
changes in the neck).
l2
A working knowledge of the
facial anatomy is essential to avoid effects
such as unwanted paralysis of facial
muscles, whereby the patient will have to
wait several months for normal function to
resume.
l3,l4
ConcIusion
Despite public awareness of
8otox only as a cosmetic treatment, there
are various medical and dental conditions
which may benefit from its administration.
|t could be anticipated that additional
indications will arise. However, correct
training in the use of 8otox is essential.
References
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8utterworth 1. lunJomentol Pt|nc|les
onJ Ptoct|ce ol Anoesthes|o. London,
UK: Martin Dunitz Ltd, 2002.
2. Moore AP, wood GD. The medical
management of masseteric
hypertrophy with botulinum toxin
type A. 8t 1 Otol Vox|lloloc 5ut l994,
32: 26-28.
3. Daelen 8, Thornwirth v, Koch A.
Treatment of recurrent dislocation of
the temporomandibular |oint with
type A botulinum toxin. lnt 1 Otol
Vox|lloloc 5ut l997, 26: 458-460.
4. Smyth AG. 8otulinum toxin treatment
of bilateral masseteric hypertrophy. 8t
1 Otol Vox|lloloc 5ut l994, 32: 29-33.
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botulinum toxin: case report. 1 Otol
Vox|lloloc 5ut l999, 57: l0l7-l0l9.
6. Moore AP, wood GD. Medical
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temporomandibular |oint dislocation
using botulinum toxin A.
8t 0ent 1 l997, 183: 4l5-4l7.
7. |srael HA, Desmond ward 1, Horrell 8,
Scrivani S1. Oral and maxillofacial
surgery in patients with chronic
orofacial pain. 1 Otol Vox|lloloc 5ut
2003, 61: 662-667.
8. von Lindern 11, Niederhagen 8,
8erge S, Appel T. Type A botulinum
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2003, 61: 774-778.
9. Lllies M, Laskawi P, Pohrbach-volland
S, Arglebe C. Up to date report of
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l0. Kilpatrick NM, 1ohnson H, Peddihough
D. Sialorrhea: a multidisciplinary
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l2. Matilde M, Sposito M. New indications
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