Therapeutic uses of botulinum toxin

Botox now has a wide range of non-cosmetic uses, write Caroline Dodson and Mr Tim Whittlestone.

Squint caused by congenital cranial nerve palsy can be corrected (Photograph: SPL)
Squint caused by congenital cranial nerve palsy can be corrected (Photograph: SPL)

Botulinum neurotoxin inhibits the synaptic release of acetylcholine. However, unlike other neurotoxins, the effects of botulinum toxin remain localised.1

In recent years these features have been exploited and botox used to treat conditions associated with striated and smooth muscle spasm.

Strabismus
In adults with a concomitant squint from childhood, botox is injected, via electromyography, into the relevant extra-ocular muscle.2 The blockade of alpha-motor neurone transmission relaxes the muscle, giving the impression of an aligned gaze.3

Although this is arguably a cosmetic use, botox can restore function. For example, in a cranial nerve VI palsy that paralyses the lateral rectus, injection into the medial rectus essentially matches the paralysis and prevents it pulling the eye out of alignment.

Focal dystonias
Botox is now the first-line treatment of cervical dystonia, with 75 per cent of patients experiencing considerable improvement in their pain and disability.2

It is also an established, although less successful, treatment for some 'occupational' focal dystonias such as writer's or musician's cramp.

Perhaps less expectedly, botox is used for some speech abnormalities, most commonly spasmodic dysphonia. Injection under indirect laryngoscopy or electromyography into the thyroarytenoid muscle weakens the spasm4 and up to 90 per cent of patients report a total or almost total return to a normal voice.3

Spasticity
Botox has also been used to treat more widespread dystonia. It has been shown to improve function and range of movement in patients with limb spasticity following stroke or head injury.4

Similarly, it is hoped that early intervention in children with cerebral palsy will prevent the progressive contraction deformities and muscle hypertrophy.

Genitourinary uses
Botox can be used to relieve both urinary retention and urge incontinence. In the former, the hypertonic external urethral sphincter (for example in MS) is injected transperineally.3

In urge incontinence, botox is injected into the smooth muscle of the bladder to both enlarge its functional capacity and prevent reflex micturition through inhibition of parasympathetic and gamma-neurone innervation.

Vaginismus can be relieved by injecting botox into the muscles of the anterior vaginal wall. It inhibits both alpha-motor neurone transmission to the striated musculature and gamma- neurone transmission governing the reflex contraction.

Gastrointestinal uses
In achalasia, the endoscopic injection of botox into the cardiac sphincter inhibits the excitatory vagal input (mediated by acetylcholine) but leaves the relaxatory input (mediated by NO and vasoactive intestinal peptide) unaffected.5 Treatment alleviates symptoms in 70 per cent of patients.3

In chronic anal fissures, botox injection into the internal sphincter can reduce pain, bleeding and constipation without the risk of permanent incontinence associated with traditional surgical sphincterotomy.4

Hypersecretory disorders
The most common non-muscular use of botox is in palmar, axillary and facial hyperhidrosis, exploiting its inhibition of the sympathetic innervation of sweat glands. Interestingly, effects appear to last significantly longer (6-24 months) than in other uses.3

In hypersalivation, botox injections into parotid and submandibular glands inhibit the parasympathetic secretory stimulation.6

Adverse effects
Botox appears to have few adverse effects, with influenza-like symptoms being the most common (although still rare).

A degree of atrophy of the target muscle can occur, although it recovers on reinnervation, but the most significant risks come from unintended involvement of neighbouring muscles. In cervical dystonia, diffusion into the muscles of the oropharynx can cause dysphagia.

The future
Potential uses of botox currently being researched include the treatment of low back pain, intractable hiccups and vocal tics associated with Tourette's syndrome.3 It may also have a role in appetite suppression through the slowing of gastric emptying.4

  • Ms Dodson is a fourth year medical student at Bristol University and Mr Tim Whittlestone is consultant urologist at the Bristol Royal Infirmary

References

1. Pellizzari R, Rossetto O, Schiavo G, Montecucc C. Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses. Philos Trans R Soc Lond B Biol Sci 1999; 354: 259-68.

2. Munchau A, Bhatia K. Uses of botulinum toxin in medicine today. BMJ 2000; 320: 161-5.

3. Bentsianov B, Zalvan C, Blitzer A. Noncosmetic uses of botox. Clin Dermatol 2004; 22: 82-8.

4. Verheyden J, Blitzer A. Other Noncosmetic uses of botox. Dis Mon 2002; 48: 5, 357-66.

5. Mandal A, Robinson R. Indications and efficacy of botulinum toxin in disorders of the gastrointestinal tract. Eur J Gastroenterol Hepatol 2001; 13: 603-9.

6. Laskawi R, Ellies M. The role of botulinum toxin in the management of head and neck cancer patients. Curr Opin Otolaryngol Head Neck Surg 2007; 15: 112-6.

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