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Botulism toxin (BTX) is produced during the growth and autolysis of the strictly anaerobic, spore-forming, Grampositive rod Clostridium botulinum. BTX can be differentiated serologically into 8 types. Recently, botulinum toxin type A (BTX A) has been recognized as an agent that can be used in the treatment of focal dystonias, including blepharospasm, oromandibular dystonias, and spasmodic torticollis.
BTX A acts as a presynaptic neurotoxin that blocks neuromuscular transmission by binding to receptor sites on motor or sympathetic nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. This inhibition occurs as the neurotoxin cleaves SNAP-25, a protein integral to the successful docking and release of acetylcholine from vesicles located within nerve endings. When BTX A is injected intramuscularly in therapeutic doses, it produces partial chemical denervation of the muscle, resulting in a localized reduction in muscle activity. This causes dose-dependent weakness or paralysis in skeletal muscle. The effect of BTX A can last from 3 to 6 months, and local paralysis is reversed chiefly by neural sprouting with reinnervation of the muscle. In addition, when injected intradermally, BTX A produces temporary chemical denervation of the sweat glands, resulting in local reduction of sweating.
The Food and Drug Administration (FDA) first approved BTX for use in focal dystonia in 1989. Following completion of clinical trials, the FDA approved BTX A use in treating cervical dystonias, primary axillary hyperhidrosis, blepharospasm, and strabismus. These clinical problems have been challenging to clinicians and generally treated surgically with poor results. BTX has been widely adapted for these applications because it provides a minimally invasive approach to treating these challenging clinical problems. One of the most popular and successful applications of BTX has been in the treatment of hyperkinetic facial lines.
BTX A is produced by Allergan and is supplied in 100-unit vials. One unit of BTX corresponds to the calculated median intraperitoneal lethal dose (LD50) in mice. Unopened BTX must be stored in a refrigerator (2º to 8ºC), and preservative-free normal saline is used for reconstitution. In general, 1 to 8 mL of saline is added to 1 vial, producing a concentration of 10 to 1.25 units per 0.1 mL. Once reconstituted, the effectiveness of BTX begins to diminish after 4 hours. Therefore, immediate administration of BTX is recommended. The recommended doses range from 5 units to 25 units per muscle. The cumulative dose of BTX treatment in a 30-day period should not exceed 200 units.1