Mechanism of action
Botulinum toxin is a product of Clostridium botulinum, and ingestion of the organism or its spores results in botulism. Botulinum toxin blocks pre-synaptic release of acetylcholine from the nerve terminal. Seven immunologically distinct toxins (types A–G) have been purified. Local intramuscular injection of botulinum toxin A (Botox) was approved to treat strabismus and blepharospasm associated with dystonia. When injected, the agent spreads through muscle and fascia approximately 30 mm, binding presynaptic cholinergic nerve terminals and resulting in a chemical denervation. 23
Botulinum toxin injection is off-label for treatment of spasticity, but it may be an appropriate option for selected patients with severe localized spasms. Injection effectively reduces muscle tone and spasms in patients with severe spasticity due to stroke, traumatic brain injury, and other causes.77–80
Botulinum toxin injection is promising therapy for the treatment of spasticity in children with cerebral palsy.82,83 Its judicious use can delay surgery until children reach a more suitable age.
In a randomized, crossover, double-blind study, Snow and colleagues81 studied botulinum toxin A in 9 wheelchair- or bed-bound patients with advanced multiple sclerosis (MS). Muscle tone, frequency of spasms, and hygiene and self-care scores were used to assess efficacy. Botulinum toxin injection significantly reduced spasticity and improved ease of nursing care, with no adverse effects.
Physicians who inject it should be trained in the use of Botox, with attention to relevant topical anatomy and kinesiology. Onset of focal muscle fiber paralysis begins in 24 to 72 hours, with a maximal effect seen at 5 to 14 days. The paralysis is transient, lasting 12 to 16 weeks.
To produce optimal effects, it may be necessary to localize specific muscles with electromyographic guidance.
Injection site reactions can occur and antibodies may develop to specific immunologic strains, limiting efficacy.
Because the delivery of toxin is not entirely contained, the paralysis of muscles may not be exact. Excessive weakness (ultimately reversible) may result.23
Reviewed and revised May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.
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