BOTULINUM TOXIN—PHYSIOLOGY AND APPLICATIONS IN
HEAD AND NECK DISORDERS
James Keir, MBChB
14 Stonelea Court, Meanwood, Leeds, Yorkshire LS7 2UH, United Kingdom.
E-mail: jameskeir@hotmail.com
Accepted 1 December 2004
Published online 16 May 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.20247
Abstract: This article is structured around a literature review
that was carried out using Ovid and Medline with the key words
‘‘botulinum,’’ ‘‘toxin,’’ and ‘‘ENT.’’ Botulinum toxin has been used
safely in humans for more than 20 years. The effects are tran-
sient, such that treatments are required to be repeated at
intervals. Its application to ENT provides a useful tool to treat
dystonia, autonomic dysfunction, facial nerve paresis, and hy-
perfunctional lines. It may also be of benefit in laryngeal re-
balancing and the treatment of headaches. Further research is
being carried out and new indications for treatment with
botulinum toxin may include sialorrhea and rhinorrhea. A 2005
Wiley Periodicals, Inc. Head Neck 27: 525 – 535, 2005
Keywords: Botulinum; toxin; ENT
A HISTORY OF BOTULINUM TOXIN
The use of botulinum toxin for aesthetic purposes
has become one of the most common cosmetic pro-
cedures performed today, and its use is a com-
monly discussed topic in the media.1 It was first
developed as therapeutic agent for the treatment
of disorders characterized by localized muscle
hyperactivity, especially around the eyes. Botu-
linum toxin is now widely used to treat many
conditions including most types of focal dystonia.2
Correspondence to: J. Keir
B 2005 Wiley Periodicals, Inc.
Botulinum Toxin
Its use in facial dystonias improves the disfigure-
ment and the discomfort and disability associated
with the condition.3
The word ‘‘botulism,’’ which is the clinical syn-
drome of botulinum toxin poisoning, comes from
the Greek word for sausage, botulus, because for a
long time it was used to refer to a particular ill-
ness caused by the ingestion of spoiled sausages.
Clostridium botulinum was first identified as a
causative agent in food poisoning in 1895 by
Professor Emile Pierre van Ermengem.4 He was
asked to investigate an episode of lethal food poi-
soning that arose because of the consumption of
uncooked ham at a wake. The symptoms demon-
strated were of autonomous dysfunction (dryness
of the mouth, nausea, paralytic ileus, postural
hypotension) and flaccid paralysis, all in the ab-
sence of fever. van Ermengem examined autopsy
specimens, the spoiled meat, and its effect when
fed to a series of animals.
It was discovered in 1919 by Professor Burke
of Stanford University that there were different
strains of the bacterium and that they produced
serologically different types of botulinum toxin.5
He proposed an alphabetical classification and
identified two serotypes, types A and B, in his ex-
periments. Further studies demonstrated another
HEAD & NECK June 2005 525
five serotypes so that, to date, seven serotypes of
botulinum neurotoxin have been identified and
named A to G.2
A crude form of botulinum toxin type A was
isolated in the 1920s, and later the first attempts
at purification were made.6,7 During World War
II, the US government assigned a number of
scientists at Fort Detrick in Maryland to develop
protection against such agents. It was isolated by
this group in crystalline form in 1946, and initial
insights into the mechanism of action came when
it was shown to block the release of acetylcholine
from motor nerve endings.8,9
Botulinum toxin was first tested in animals in
the 1960s and 1970s by Dr. Alan Scott, who was
an ophthalmologist seeking an alternative or
adjunct to surgery for strabismus. He had come
into contact with Dr. Edward Schantz, a toxicol-
ogist who had participated in the work at Fort
Detrick. Its safety was shown in humans in 1980,
when the selective weakening of specific extra-
ocular muscles with intramuscular injections of
FIGURE 1. (A) Neurospecific binding of the toxin to its receptor
botulinum toxin type A could correct gaze mis- on the presynaptic membrane takes place. The toxin – receptor
alignment in strabismus.10,11 complex is then internalized by endocytosis. (B) Acidification of
Botulinum toxin type B is now commer- the vesicle by proton pumping ATPase leads to membrane
cially available, with research into the other sub- translocation of the light chain into the cytoplasm. Heavy chain is
shown in black, and the light chain in grey.
types awaited.

PHARMACOLOGY AND MECHANISM OF ACTION translocation is triggered by acidification of the

Botulinum neurotoxins are primarily inactive,
polypeptide di chains of 150 kDa that are re-
leased during bacterial lysis and are cleaved by
tissue proteases into heavy (100 kDa) and light
(50 kDa) chains with different roles in nerve cell
intoxication. After lysis, this generates an active
di-chain neurotoxin composed of a heavy chain
and a light chain bridged by an interchain
disulfide bond.12 They are bound with nontoxic
proteins to form a complex giving a total
molecular weight of approximately 900 kDa for
type A and 700 kDa for type B.13
The intoxication occurs in four distinct steps
(which are shown in Figure 1): cell binding, inter-
nalization by means of endocytosis, membrane
translocation, and catalyzation of the hydrolysis
of peptides.
In types A and B, the heavy chain is re-
sponsible for selective binding of the neurotoxin
to receptors on the surface of the presynaptic
membrane of cholinergic nerve cells. This is fol-
lowed by internalization inside vesicles by means
of endocytosis and membrane translocation of
the light chain into the nerve cell cytoplasm. The
vesicle lumen by a proton pumping ATPase,
which leads to conformational change of the toxin.
In its acid conformation, the toxin inserts into the
lipid bilayer, and translocation of the light chain
is promoted. The light chain is set free by
reduction of the interchain disulfide bond and
acts as a zinc-dependent metalloproteinase in-
side the cell to prevent the release of vesicle-
bound acetylcholine.12,14 The neurotoxins are
able to prevent release by disrupting peptides
necessary for docking and ultimately exocytosis
of the acetylcholine-containing vesicle. In type
A, the light chain cleaves SNAP-25, a 25-kDa
synaptosomal-associated protein, whereas the
light chain of type B cleaves vesicle-associated
membrane protein (VAMP).15,16
Little is known of the intracellular events af-
ter type B use. However, the clinical effects of
type A subside because of collateral sprouting
of new nerve terminals occurring with time. With
time, the original functional endplate is re-
established, and the sprouts regress.17
These differences in mechanism of action may
explain variations in clinical performance. Type B

526 Botulinum Toxin HEAD & NECK June 2005

studies have shown that doses many times
greater than that of type A are required to treat
those with the same indications. There are also
differences in the complication profile.18 – 23
BOTULINUM TOXIN PRODUCTS
Botulinum toxin type A is commercially available
as either Botox or Dysport, both of which are sold
in a lyophilized form that must be reconstituted
with physiologic saline. Botox, which is manufac-
tured by Allergan Inc. (Irvine, CA), is available
internationally in 100 U per vial. It is shipped on
dry ice and should be stored in a freezer at 5jC.
Dysport is manufactured by Ipsen Limited (Berk-
shire, UK) and is primarily used in Europe,
because it is not licensed in the United States.
It is distributed in 500-U vials and needs to be
stored at 2 to 8jC. Type B toxin is sold as Neu-
robloc (or Myobloc in the United States), which is
a premanufactured aqueous solution. It is dis-
tributed in 2500, 5000, or 10,000 U and is licensed
in the Unites States and several European
countries in the treatment of cervical dystonia.
For all the preceding products, doses are
determined by in vitro mouse assays in units of
biologic activity (U). One unit is defined as the
amount of neurotoxin complex protein that is
lethal in 50% of female, Swiss-Webster mice after
an intraperitoneal injection (mouse LD50). How-
ever, differences in serotype, formulation, and
the way lethality tests are performed between
manufacturers means results in units that vary
greatly in their potency between the products.
This leads to marked differences in dosing. Doses
of Dysport can therefore be three to six times
higher than the doses of Botox typically used to
treat the same condition.24,25
ADMINISTERING BOTULINUM TOXIN
When administering the toxin, the physician
should evaluate the patients with a thorough
history and examination. A discussion of the
nature of the problem and the expected effect
should take place with informed consent ob-
tained. If a cosmetic change is anticipated, pho-
tographs of the patient’s face at rest and activity
should be taken. The skin should be prepared
and marked at the site for injection, which should
be recorded on a diagram in the patient’s medi-
cal records. A topical anaesthetic such as eutec-
tic mixture of local anesthetics (EMLA) cream
may be used to decrease the discomfort of the
Botulinum Toxin
procedure. The toxin is drawn up in syringe and
injected with a 30-gauge needle at an angle of
30 degrees. Anatomy is essential in choosing the
site for injection, although some clinicians favor
the use of the electromyographic (EMG) needle.
This is connected to the EMG machine and
ground and reference leads placed on the face or
supraclavicular area. If the needle is in the ac-
tive part of the muscle and the patient now
accentuates the specific facial expression that
produces the unwanted line, a burst of activity
will be heard on the speaker of the EMG. A dis-
tant signal (ie, one in which there is a low fre-
quency, dull sound) should provoke the needle
being moved until the signal is maximal and the
toxin then injected. After the injections, the pa-
tient should be asked not to massage the in-
jected area for several hours to avoid diffusion to
adjacent muscles.26
The clinical effect of botulinum toxin is dose
related. This allows treatment to be modified
according to the requirements of individual pa-
tients. The dose required to produce a given
degree of denervation is related to the mass of the
targeted muscle. There is no way to determine
in advance the dose of botulinum toxin required
for therapeutic effect in a patient never treated
before. The dose used also obviously is deter-
mined by the particular clinical application it is
used for. The range of effective doses between
patients for a given disorder may differ by several
orders of magnitude.27
Improvement in symptoms usually occurs
within 3 to 5 days, with clinical efficacy generally
seen within the first 7 to 10 days. The effect of
botulinum toxin begins to wear off 10 to 12 weeks
after injection.28
COMPLICATIONS AND ADVERSE REACTIONS
Contraindications to the use of botulinum toxin
include pregnancy or active breastfeeding, and it
is relative contraindicated in pre-existing neu-
romuscular conditions. Some medications, such
as aminoglycosides, penicillamine, quinine, and
calcium channel blockers, can potentiate their
effect by interfering with neuromuscular trans-
mission and should not be used concomitantly
with the treatment.29
The therapeutic use of botulinum toxin gen-
erally has been safe and well tolerated. Formation
of antibodies may occur if the neurotoxins elicit an
immune response. Although this is not a safety
concern, it may lead to a nonresponse of subse-
HEAD & NECK June 2005 527
quent botulinum toxin injection by blocking the
therapeutic effects. Neutralizing antibodies de-
veloped against one serotype have not been re-
ported to block the biologic activity of another
serotype.30 Prevalence of resistance is <5%31 and
is associated with dose and frequency of treat-
ments. To minimize the chance of resistance, the
smallest effective dose is used, and the interval
between treatments is extended for as long as pos-
sible to minimize exposure.32 This research, how-
ever, was based on old preparations that had an
increased protein load compared with the newer
toxin, which has reportedly less antigenicity.
Botulinum toxin may diffuse to nearby or
adjacent muscle, leading to adverse effects such
as ptosis or drooling after facial injections.33 It
may also affect muscles distant from the site of
injection; a recent report documented three cases
of generalized muscular weakness associated
with its use.34 Long-term use of botulinum toxin
causes reversible denervation atrophy in the
muscles injected.35 Further research has demon-
strated diminished size of type IIB fibers in
muscles distant from the injection site36 and
abnormalities on EMG.37,38
Generalized reactions that have idiosyncrati-
cally occurred include nausea, fatigue, malaise,
flu-like symptoms, and rashes at sites distant
from the injection. Single-fiber electromyographic
weakness and changes in neuromuscular trans-
mission have been found in muscles distant to the
injection site. This is possibly due to a small
amount of toxin diffusing into the circulation.39,40
Untoward sequelae that may occur at any in-
jection site include pain, edema, erythema, ecchy-
mosis, headache, and short-term hyperesthesia.41
In the 23 years that botulinum toxin has been
used in humans, there have been no reported
deaths from an overdose. The estimated lethal
dose for a 70-kg human, based on primates, is
approximately 2800 U (40 U/kg).42
CLINICAL USES FOR BOTULINUM TOXIN
IN OTORHINOLARYNGOLOGY
In otorhinolaryngology, the use of botulinum
toxin is rapidly expanding. This includes the
treatment of autonomic dysfunction; spasmodic
dysphonia, vocal tics, stuttering and voice tremor,
oromandibular and cervical dystonia, and bleph-
arospasm; hemifacial spasm and facial nerve
paresis; cricopharyngeal dysfunction, laryngeal
rebalancing, and tension headache, as well as
use in cosmetic applications.
528 Botulinum Toxin
Autonomic Dysfunction. Frey’s syndrome and
hyperhydrosis (gustatory sweating and flushing
on the cheek) is a well-described complication
of parotid gland surgery. It was first reported in
1757 by Duphenix in a case secondary to trauma
but is most commonly seen after parotid gland
surgery. It has also been described after radical
neck dissection43 or submaxillary gland sur-
gery and may also occur after infection. The
incidence of Frey’s syndrome after parotidectomy
has been reported to be as high as 100% when a
Minor’s starch test was used for diagnosis.44
However, many of these are asymptomatic, with
only 30% being severely embarrassed by sweating
after parotidectomy.43
The cause of the syndrome is thought to be
misdirected regeneration of damaged axons.45
When the skin is raised during parotidectomy,
the postganglionic sympathetic fibers to the
sweat glands in the flap are severed. Postgan-
glionic parasympathetic fibers from the auriculo-
temporal branch of the mandibular nerve supply-
ing the parotid gland are also severed when the
salivary gland is removed. This allows cross-
innervation of the sweat glands by branches of
the auriculotemporal nerve and consequently
gustatory stimulation.46
Botulinum toxin, in addition to acting on
muscle, has an effect on cholinergic autonomic
nerve terminals.47 Both the parasympathetic
nerves stimulating salivary gland secretion and
the sympathetic fibers that cause sweating are
cholinergic autonomic fibers. Hence, the regener-
ation of axons may be misdirected, and botulinum
toxin inhibits both salivation and sweating.
Drobik and Laskawi48 first proposed treat-
ment of Frey’s syndrome with botulinum toxin
injection in 1994 and presented a case with
12 months’ follow-up in the following year. The
methods described include identification of the
area for injection using Minor’s starch test. This
involves the application of a solution containing
iodine, ricine oil, and alcohol painted onto the
affected cheek.49 The identified area is then
marked and divided into small squares of approx-
imately 4 cm2. In each square, 2.5 U of botulinum
toxin type A (Botox) are injected intracutane-
ously. Patient self-assessment and a repeated
Minor’s test after treatment demonstrate excel-
lent results.50 Indeed, intracutaneous injections
in the area of sweating seem to have the potential
to be curative in the treatment of Frey’s syn-
drome, perhaps through sweat gland atrophy
from chronic denervation. Some patients may re-
HEAD & NECK June 2005
quire more than one treatment, but the extent of
sweating decreases with each successive set of
injections until it is no longer troublesome.51 – 53
Experience with intracutaneous injection in cases
of Frey’s syndrome among some clinicians sug-
gest it is a technically difficult procedure that
may be unnecessary. Furthermore, its proposed
immediate subcutaneous injection may allow a
greater diffusion of drug and has lasting clinical
effects in treating gustatory sweating.
Spasmodic Dysphonia and Voice Tremor. ‘‘Spas-
modic dysphonia’’ and ‘‘laryngeal dystonia’’ are
clinical terms used to describe an action-induced,
laryngeal motion disorder. Patients with dystonia
may have primary (idiopathic) or secondary (eg,
neurologic) disease. Dystonia may be generalized,
multifocal, or focal. Spasmodic dysphonia is a
form of focal dystonia in which the action is that
of speaking. It was first described in 1871 by
Traube55 using the term ‘‘spastic dysphonia’’
when describing a patient with nervous hoarse-
ness. In 1899, Gowers56 described functional
laryngeal spasm in which the vocal cords were
brought together too forcibly in speech. Aronson
formally distinguished between two types of
spasmodic dysphonia: an adductor type caused
by irregular hyperabduction of the vocal cords
and an abductor type caused by intermittent
abduction of the vocal cords. Some patients dis-
play a combination of mixed adductor and abduc-
tor dysphonia. The first injection of botulinum
toxin into the human larynx took place in 1984,
with significant relief of symptoms.57
Patients with the adductor type exhibit a
choked, strained strangled voice quality with
abrupt initiation and termination of voice, result-
ing in short breaks in phonation. The voice is
generally reduced in loudness and is monotone.
Voice tremor is frequently observed, as are a slow
speech rate and decreased smoothness of speech,
which reduces intelligibility.58
Patients with the abductor type have a
breathy, effortful voice quality, with abrupt ter-
mination of voicing resulting in aphonic, whis-
pered segments of speech. The voice is reduced
in loudness, and vocal tremor related to inter-
mittent spasm or hypertonia of the posterior
cricoarytenoid muscles is frequently observed.
Vocal tremor is a common feature of neuro-
logic disorders and is a sign of neurologic dis-
turbance. Some disorders may demonstrate voice
tremor in combination with dysarthric speech (eg,
Parkinson’s disease). It is present in 25% to 65%
Botulinum Toxin
of patients with spasmodic dysphonia. Its treat-
ment is essentially the same with injection of
botulinum toxin into thyroarytenoid muscles
and in some cases into the cricothyroid or thyro-
hyoid muscles.59
In a series of patients with primary laryngeal
involvement, 16% had spread of dystonia to
another part of the body.60
All patients considered for treatment should
have a full history and head and neck examina-
tion. Fiberoptic laryngoscopy is performed in
all patients to observe glottal function with
particular reference to disruptions, spasms,
breathy breaks, and tremor while the patient
speaks with connected speech segments. Diagno-
sis may be aided by video recording and analyzing
with slow speed and stop action. Additional
speciality examinations include acoustic and
aerodynamic measurements to evaluate for trem-
or, fundamental frequency, pitch and amplitude
pertubation, harshness, fluency breaks, breath-
iness during sustained phonation and speech, and
percutaneous EMG to evaluate tremor and areas
of hyperactivity.
For the treatment of adductor dystonia, the
injection of botulinum toxin into the thyroaryte-
noid complex is achieved with an EMG needle.
The patient is placed in the supine position with a
pillow underneath the upper back and the neck
extended. The thyroid and cricoid cartilages are
palpated, and the midline of the cricothyroid
membrane is identified. The needle is placed into
the thyroarytenoid vocalis complex by impaling
the muscle through the cricothyroid membrane.
The needle is advanced at an approximately
30-degree angle up and 30-degree angle laterally.
The laryngologist listens for the muscle interfer-
ence pattern on the EMG. Patients are instructed
not to cough or swallow while the needle is in the
airway. If there is difficulty tolerating the
procedure, 0.3 cm3 of 1% lidocaine may be injected
into the airway through the cricothyroid mem-
brane. In the treatment of abductor dystonia, the
same preparation is used, although in this case,
the needle is placed posterior to the posterior edge
of the thyroid lamina. The needle is advanced
through the inferior constrictor muscle to the
cricoid cartilage and then moved under EMG
guidance to the optimum position. The patient is
asked to sniff to yield maximum abduction; 2.5 U/
0.1 cm3 is used per thyroarytenoid muscle in each
case, and repeated treatments are usually re-
quired. One side at a time is injected, and further
doses may be into the same muscle or contralat-
HEAD & NECK June 2005 529
eral muscle, depending on response. Side effects
of this treatment include breathy hypophonia and
clinically insignificant aspiration. In the abductor
patient, treatment is associated with greater risk,
including mild to severe stridor caused by
paralysis of the posterior cricoarytenoid muscle.
There have been anecdotal reports requiring
tracheostomies. Results of treatment of adductor
spasmodic dysphonia with botulinum toxin in-
jection are excellent, with an average benefit of
90% of normal function achieved. Treatment
of the abductor type leads to an average benefit
of 66.7% of normal voice.61
Vocal Tics and Stuttering. The success of botu-
linum toxin in the treatment of spasmodic dys-
phonia has led to its use in other conditions in
which there is inappropriate or excessive muscu-
lar contraction in the larynx. Stuttering blocks,
similar to dystonic spasms, are action-induced,
task-specific movement abnormalities. They may
involve respiratory, phonatory, and/or articula-
tory mechanisms of speech. When the glottis is
affected, treatment with botulinum toxin may
result in an increased fluency by both subjective
and objective measures.62 The effectiveness of
behavioral therapy has meant it is not used as a
long-term treatment.
Botulinum toxin has been used successfully in
controlling vocal tics of Gilles de la Tourette
syndrome, including coprolalia.63 – 65 Its success
in this context suggests an effect on the central
nervous system, possible mediated through affer-
ent pathways.
Oromandibular Dystonia. Oromandibular dysto-
nia is classified according to the clinical effects
of the predominant muscular forces. It may,
therefore, be jaw opening, jaw closing, jaw devia-
tion, or tongue protrusion dystonia or a combi-
nation of these. Some of these will be less
amenable to treatment because of difficulties in
compromising function during treatment. For
example, tongue muscle treatment may lead to
dysarthria and dysphagia.66 Injection of the di-
gastric muscles in jaw opening may cause swal-
lowing to be affected by diffusion of toxin to
intrinsic tongue muscles, and it may be necessary
to manage this complication with the insertion of
a nasogastric tube. These problems have led to a
limitation of what may be achieved intraorally
with this treatment. The types of oromandibular
dystonia treated most successfully are limited to
530 Botulinum Toxin
involvement of the masseter, temporalis, and ex-
ternal pterygoid muscles.
Its use in this condition has led to its appli-
cation in the treatment of temporomandibular
disorders. These are described as a group of con-
ditions affecting the temporomandibular joint,
masticatory muscles, and associated structures.
It often is seen as pain and dysfunction specific
to the jaw.67,68
Botulinum toxin has also been used in the
treatment of the tensor veli palatine muscle to
relieve the clicking tinnitus of palatal myoclo-
nus.69,70 Localizing the muscle may be difficult,
because mouth opening may suppress the my-
oclonus. EMG is particularly useful in placing
the injection.71
Cervical Dystonia. Cervical dystonia or torticollis
is a common form of focal dystonia.72 The use of
botulinum toxin was first described by Tsui in
1986, and since that time, its injection into the
various neck muscles has become the first-line
therapeutic approach.73
The treatment of cervical dystonia, as in other
cases, relies on a thorough knowledge of anat-
omy. This may include the sternocleidomastoid,
the trapezius, semispinalis capitis, the splenius
capitis, the levator scapulae, and all of the lesser
paraspinal muscles. Botulinum toxin type A
(Botox) is injected into the affected muscles
using total doses of 100 U per neck.73 It must be
remembered that weakening one muscle will
lead to the unopposed pull of its antagonist, and
this may lead to a change in direction of the
neck deviation.
Most patients report subjective improvement
in the pain caused by muscle spasm. The most
common adverse events are dysphagia, neck
muscle weakness, and voice changes.74
Blepharospasm. Blepharospasm is the involun-
tary eye closure produced by spasmodic contrac-
tions of the orbicularis oculi.75 It is termed
‘‘essential blepharospasm’’ when only the orbital
and periorbital muscles are involved. However in
most patients with blepharospasm, other facial,
pharyngeal, laryngeal, oromandibular, and cer-
vical muscles are affected. Idiopathic cervicocra-
nial dystonia characterized by blepharospasm
and by oromandibular involuntary movements is
referred to as Meige’s syndrome.
In blepharospasm, the lateral and medial
parts of the eyelid are injected subcutaneously
HEAD & NECK June 2005
with botulinum toxin. One study describes the
use of botulinum A toxin with an initial dosage of
12.5 U per eyelid in two separate injections, a
total of four injections or 25 U per eye. 76
Published reports document that in approxi-
mately two thirds of patients, the condition was
improved, with many regaining nearly normal
function.76 – 78 In addition to the reduction of
spasms, patients also report a decrease in asso-
ciated sensory complaints such as foreign body
sensations in the eyes and photophobia.
Treatment is directed to minimize the chance
of ptosis, diplopia, midface weakness, and epi-
phora. This is achieved by injecting no closer to
the eye than the orbital margin to minimize in-
traorbital diffusion, avoiding the medial lower lid
to spare the lacrimal pumping apparatus, and
injecting no lower than the malar eminence to
prevent midface effects.27
Hemifacial Spasm. Hemifacial spasm is charac-
terized by initially progressive, involuntary, ir-
regular, clonic or tonic movements of muscles
innervated by the seventh cranial nerve unilat-
erally. It often initially affects the orbicularis
oculi muscle, followed by gradual spread to other
parts of the face.
This disorder arises when the nerve is com-
pressed at the root exit zone by an ectopic
anatomic or pathologic structure, resulting in
emphatic transmission.79 – 82 The most common
cause of hemifacial spasm is compression by an
atherosclerotic aberrant or intracranial artery
as first described by Cambell and Keedy in 1974.83
Microvascular decompression of the facial
nerve root through a retrosigmoid craniotomy
has proven to be very successful in controlling this
disorder,84 so that botulinum toxin remains a
nonsurgical alternative. The facial muscles for
injection are identified with a thorough knowl-
edge of anatomy and the aid of EMG. These may
include orbicularis oculi, orbicularis oris, the zy-
gomatic muscles, frontalis, corrugator, paranasal
region, mentalis, submental area, and platysma.
Doses of botulinum toxin type A (Botox) used
vary, but one publication gives an average of
approximately 30 U per muscle in this appli-
cation.85 The treatment gives excellent results,
with 95% of patients having a marked to moder-
ate improvement, and it may be used to manage
the condition in the long term by repeated
injection.85 – 88 Temporary facial weakness is the
most common side effect, followed by lid weakness
and ptosis.85
Botulinum Toxin
The principal disadvantages of this method
are the necessity for chronic treatment, the po-
tential for ophthalmic complications similar to
those of blepharospasm, and facial asymmetry
secondary to muscle weakening.88
Facial Nerve Paresis. During the acute phase of
facial nerve paresis, botulinum toxin may be used
to effect a therapeutic ptosis for corneal protec-
tion.89 In the recovery phase, facial nerve paresis
may be accompanied by synkinesis. When this is
troublesome, as in the case of involuntary eyelid
closure, botulinum toxin may be useful.90
Botulinum toxin has also been used to improve
the facial symmetry of patients with facial
paralysis by decreasing the excessive pull of the
contralateral facial muscles during emotional
expression. Injections of 2.5 to 5 U into each of
the contralateral zygomaticus major, levators labii
superioris, and anguli oris or risorius muscles
leads to increased symmetry of the smile of
moderate or marked benefit in most cases.91
Cricopharyngeal Dysfunction. The cricopharyn-
geus muscle is the major component of the upper
esophageal sphincter. The ring-shaped structure
maintains a constant basal tone and luminal
occlusion at rest but allows rapid relaxation and
contraction on swallowing. Dysfunction of this
muscle is a well-known cause of dysphagia that is
most effectively treated in persistent cases by
cricopharyngeal myotomy. In unclear cases or
where there are temporary problems, botulinum
toxin may be used.
The cricopharyngeus, as stated, is activated
at rest, which permits the use of EMG guidance
in percutaneous injection.92,93 An alternative is
by directly injecting the muscle at endoscopy
with the patient under general anaesthesia.94
Patients demonstrate a 70% to 100% improve-
ment when undertaking this treatment.92,95,96
Some cricopharyngeal spasm is caused or aggra-
vated by reflux of gastric acid, which must be
treated before relaxing the sphincter. Heartburn
has been reported as a complication of this
procedure.95
Cricopharyngeal spasm may rarely prevent
the successful use of tracheoesophageal speech
after laryngectomy, and botulinum toxin has been
used in its treatment.97 – 99
Laryngeal Rebalancing. Rontal and Rontal100
coined the term ‘‘laryngeal rebalancing’’ to refer
HEAD & NECK June 2005 531
to the chemodenervation of the interarytenoid
muscle and the ipsilateral thyroarytenoid and
lateral cricoarytenoid muscle in the treatment
of anteromedial cricoarytenoid dislocation. This
term may be appropriately applied to an array
of uses. Botulinum toxin has been used to weaken
adductors as an adjunct to the treatment of
vocal fold granuloma,101,102 posterior glottic
synechiae,103 and dysphonia plica ventricu-
laris.104 The underlying principle is manipula-
tion of the neural input to the larynx to improve
healing or resolution of existing disease. It has
been proposed that botulinum toxin be used to
lateralize the vocal folds to maintain the air-
way in cases of bilateral paralysis, but, as yet,
it has only been reported in an animal model.105
Tension Headache. Binder first noted that pa-
tients receiving botulinum toxin for cosmetic
reasons reported an improvement or cessation
of migraine symptoms. This was confirmed in
a double-blind, controlled trial.106 This treat-
ment has also been promising in the treatment
of chronic treatment of chronic tension head-
ache.107,108
Cosmetic Applications. Hyperfunctional facial
lines that run perpendicular to underling mus-
cle forces are caused by skin pleating with muscle
contraction. Weakening the underlying mus-
cle with botulinum toxin reduces or eliminates
these lines, which has been shown in a placebo-
controlled, double-blind study.109 It is effective in
improvement of lines of the forehead, glabella,
lateral orbits, and the nasolabial region.110,111
Botulinum toxin has also been used to reduce
platysmal bands and adjust brow position.112 – 114
With glabellar hyperkinetic lines as an exam-
ple of technique, 10 U of botulinum toxin type A
(Botox) may be injected into each corrugator
muscle either with or without EMG guidance.
This treatment gives excellent results, and 75% of
patients are satisfied with the improvement in
their appearance.115
Future Research Areas. Further research in the
use of botulinum toxin in the treatment of
sialorrhea is awaited; however, there are no
current documented studies of its use in humans
at present. There is also potential for the treat-
ment of rhinorrhea, with work currently under-
way on a suitable delivery vehicle for the toxin.54
532 Botulinum Toxin
CONCLUSION
Botulinum toxin has been used safely in humans
for more than 20 years. The effects are transient,
such that treatments are required to be repeated
at intervals. Its application to ENT provides a
useful tool to treat dystonia, autonomic dysfunc-
tion, facial nerve paresis, and hyperfunctional
lines. It may also be of benefit in laryngeal
rebalancing and the treatment of headaches.
Further research is being carried out, and new
indications for treatment with botulinum toxin
may include sialorrhea and rhinorrhea.
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