Botulinum toxin (BoNT), often referred to as a “miracle poison,” is one of the deadliest biological substances known to man.1 BoNT is a neurotoxin produced by Clostridium botulinum.

A rod-shaped anaerobic bacterium, 
C. botulinum is commonly found in the soil. The bacterium has been known to cause botulism — a rare but serious, and sometimes fatal, paralytic illness. While the danger of this BoNT is very real, it has found its way into modern medicine as a treatment for a wide array of conditions ranging from strabismus to muscle spasms to hyperhidrosis.


Background 


BoNT was identified for therapeutic use more than a century ago.2 The toxin’s first effects on neuromuscular transition were discovered in the 1940s. In the late 1960s, ophthalmologists began experimenting with chemodenervation in monkeys. The 1980s saw the first human use of the toxin to treat two ophthalmic conditions, strabismus and blepharospasm. 


In 2002, the FDA approved BoNT as a wrinkle-reducing agent, licensed and marketed under the tradename Botox.2 In 2004, the FDA approved Botox for the treatment of primary hyperhidrosis.2 By 2007 the use of Botox to diminish facial wrinkles was the most common cosmetic procedure performed in the United States.2

Science


BoNT acts by binding to receptor sites on the cholinergic nerve terminals. This action results in a decrease in the release of acetylcholine, causing a neuromuscular blockade.3 The chemodenervation experiments in the 1960s were initially conducted using Rhesus monkeys with strabismus. By injecting a tiny amount of BoNT into the horizontal rectus muscles in the stronger eye, the toxin caused minor muscular paralysis and strengthened the use of the other eye.

Subsequent human experiments showed that injecting BoNT into the extraocular muscles of 42 strabismus patients had a uniformly beneficial effect that lasted up to 411 days without systemic or local complications.4

 

Botox is also used in the treatment of muscle spasms. The muscle-weakening effect produced by BoNT lessens the spams and can last for 60 to 70 days.5 Two large Cochrane systematic reviews of 16 randomized, placebo-controlled trials overwhelmingly supported both the safety and the efficacy of Botox for the relaxation of persistent cervical muscle contraction.6

Botox represents the only true semi-ablative therapy for the treatment of primary hyperhidrosis. This condition — which typically involves the palms, soles and axillae — causes excessive, drenching perspiration. Affecting an estimated 2% to 3% of the population in the United States, hyperhidrosis has, to date, had no other satisfactory or effective treatment.7

In one randomized, placebo-controlled, double blinded study, 145 patients with severe hyperhidrosis (rates of axillary sweat production >50 mg per minute) were given an injection of BoNT type A (BoNT/A) into the axilla.8 Two weeks after the initial injections, the mean (+/- SD) rates of sweat production were 24±27 mg per minute in the axillae treated with BoNT/A and 144±113 mg per minute in the axillae treated with placebo.8

Botox is also widely used for the treatment and management of migraine headaches. In a double-blind, controlled study, 123 patients known to have frequent, severe migraines were monitored after receiving injections of either BoNT/A or an inert liquid for three months.9 At the trial’s end, patients who received the active toxin showed a greater than 50% reduction in both the frequency and severity of migraine episodes.9

Another common but debilitating condition that responds well to Botox therapy is temporomandibular joint syndrome (TMJ). According to the National Institutes of Health, 10 million people in the United States suffer from TMJ, a condition that was responsible for 17 million lost working days in 2001.10 In a literature review, researchers found sufficient evidence for the safety and efficacy of Botox treatment in TMJ.6 



Safety concerns


Botox therapy is generally safe when administered by a trained health-care professional. Pain and excessive muscle weakness (in the injected area) are the most commonly noted side effects. 



How supplied, dose


BoNT is injected into the designated area with a fine-gauge needle. Total dose is determined largely by muscle mass at the injection site. The injections are administered directly into the targeted muscle through hollow Teflon-coated needles. Cases requiring localization of a very small muscle are usually guided by electromyography.11 



Summary


BoNT now plays a significant role in the management of a wide variety of medical conditions, and the list of possible new indications is rapidly expanding. Unfortunately, cost may be a significant barrier since many insurance plans do not cover BoNT treatment.


References


1. Erbguth FJ. Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin. Mov Disord. 2004;19 Suppl 8:S2-S6.


2. Münchau A, Bhatia KP. Uses of botulinum toxin injection in medicine today. BMJ 2000;320:161. Available at www.bmj.com
/content/320/7228/161.


3. Drugs, Diseases & Procedures: Botulinum Toxin page. Medscape Reference web ite. Available at emedicine.medscape
.com/article/325451-overview#aw2aab6b4. 


4. Scott AB, Miller JM, Shieh KR. Treating strabismus by injecting the agonist muscle with bupivacaine and the antagonist with botulinum toxin. Trans Am Ophthalmol Soc. 2009;107:104-109.


5. Bihari, K. Safety, effectiveness, and duration of effect of BOTOX after switching from Dysport for blepharospasm, cervical 
dystonia, and hemifacial spasm dystonia, and hemifacial spasm. Curr Med Res Opin. 2005;21:433-438.


6. Persaud R, Garas G, Silva S, et al. An evidence-based review of botulinum toxin (BOTOX) applications in non-cosmetic head and neck conditions. JRSM Short Rep. 2013;4:10.


7. PubMed Health website. Hyperhidrosis page. Available at www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004518.


8. Heckmann M, Ceballos-Baumann AO, Plewig G, et al. Botulinum toxin A for axillary hyperhidrosis (excessive sweating). N Engl J Med. 2001;344:488-493. Available at www.nejm.org/doi
/full/10.1056/NEJM200102153440704.


9 Silberstein S, Mathew N, Saper J, Jenkins S. Botulinum toxin type A as a migraine preventive treatment. For the BOTOX migraine clinical research group. Headache. 2000;40:445-450.


10. National Institutes of Health website: National Institute of Dental and Craniofacial research: TMJ Disorders page. Available at www.nidcr.nih.gov/OralHealth/Topics/TMJ/TMJDisorders.htm. 


11. Nigam PK, Nigam A. Botulinum toxin. Indian J Dermatol. 2010,55:8-14.


All electronic records accessed on July 15, 2013.