SOURCE: NEJM
One Man's Poison -- Clinical Applications of Botulinum Toxin
Botulinum toxin is one of the deadliest poisons known, causing death by
muscle paralysis. As a poison, it is most commonly encountered as a source
of food poisoning, and there are shivers around the world when it surfaces
as a possible biologic weapon. Botulinum toxin is produced by the bacterium
Clostridium botulinum. It is a polypeptide consisting of a light chain and a
heavy chain bridged by a single disulfide bond. There are seven
serologically distinct but structurally similar types of botulinum toxin: A,
B, C, D, E, F, and G.
Alan Scott first had the idea that small doses of botulinum toxin injected
directly into overactive muscles might be used to treat patients with
strabismus. After the successful treatment of these patients, investigators
began using focal injections of botulinum toxin for other conditions
involving overactive contraction of muscle. There were early excellent
results in patients with blepharospasm and hemifacial spasm, and the Food
and Drug Administration (FDA) approved the use of botulinum toxin A for
these three conditions in 1989. Since its introduction into the U.S. market,
botulinum toxin has been approved for use in more than 60 countries.
Although there have been no further FDA-approved indications, botulinum
toxin has been used in many other clinical situations characterized by
excessive muscle contraction; in other countries, it has been approved for
treatment of cervical dystonia and spasticity of the lower limbs in children
with cerebral palsy.
In addition to blepharospasm, other types of focal dystonia, such as
cervical dystonia (spasmodic torticollis), spasmodic dysphonia, and focal
dystonia of the limbs, including writer's cramp and musician's cramp, are
treated with botulinum toxin A. In each instance, the toxin is injected
into the endplate zone of the hyperactive muscle. Multiple sites of
injection are often needed. The toxin also ameliorates spasticity and has
proved useful for the treatment of spasms such as those that occur in
multiple sclerosis and after stroke or spinal cord injury. In patients with
these conditions, the toxin reduces muscle tone, improves the range of
motion, and makes possible improved hygiene by making it easier to cleanse
areas of the body. It is also effective for the spastic hypertonia of the
calf muscles that causes toe walking in children with cerebral palsy.
Similarly, the ear clicking in patients with essential palatal tremor
(myoclonus) can be reduced by injection of botulinum toxin into the tensor
veli palatini muscle.
Detrusor-sphincter dyssynergia, which occurs in patients with spinal cord
injuries, can be improved with injection of botulinum toxin into the
internal urethral sphincter. Focal injection into the lower esophageal
sphincter can improve dysphagia in patients with achalasia. Endoscopic
injection of botulinum toxin into the papilla of Vater provides short-term
relief in half the patients with symptoms of biliary disease without
evidence of biliary obstruction. The clinical response can predict whether
these patients will gain long-term benefit from endoscopic sphincterotomy.
In this issue of the Journal, Brisinda et al. confirm the previously
suggested usefulness of injections of botulinum toxin A for the treatment of
chronic anal fissure. Moreover, they show that botulinum toxin is superior
to topical nitroglycerin, another effective nonsurgical treatment. In most
circumstances, it is necessary to inject the toxin approximately every three
months, since the underlying disorder is not cured and the effects of the
toxin fade over this period. For patients with chronic anal fissure,
however, the paralysis of the internal anal sphincter allows healing to
occur, and the injections do not need to be repeated. Botulinum toxin has
also been injected into the external anal sphincter for the treatment of
nonrelaxing puborectalis syndrome, a cause of constipation.
There are several dermatologic indications for botulinum-toxin therapy.
Facial wrinkles are maintained by the contraction of small muscle fibers in
the face, and such wrinkles can be eliminated with small injections of the
toxin. Glabellar furrows of the forehead (frown lines) and lateral canthal
rhytids (crow's feet) are the most responsive to treatment. Botulinum toxin
can also block activation of cholinergically innervated sweat glands and has
proved useful in patients with severe axillary or palmar hyperhidrosis.
There is early evidence that botulinum toxin is useful for some types of
headache, including tension headache and migraine, when injected into the
pericranial muscles that may be overcontracting.
--
Judith Richards, London, Ontario, Canada
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