Injectable neuromuscular blockade in the treatment of spasticity and movement disorders.
Neuromuscular blockade via injection of alcohol, phenol, or botulinum toxin reduces the tone of overactive muscles in order to restore the appropriate balance between agonists and antagonists. Such a restoration allows improved stretch and increased resting length and can reduce the likelihood of contracture. Alcohol or phenol, injected onto the motor nerve, denatures proteins and promotes axonal degeneration. The onset of action is within hours, whereas the duration of action is variable, ranging from 2 weeks to 6 months and beyond. The advantages of alcohol or phenol chemodenervation lie in their low cost and lack of antigenicity. The disadvantages include the technical difficulty of the injections and significant risk for pain as a result of treatment. Botulinum toxins, purified forms of Clostridium botulinum exotoxins, are injected directly into muscle, where they cleave one or more vesicle fusion proteins, thus blocking release of acetylcholine at the neuromuscular junction. Three commercial products--two of serotype A and one of B--are available. Each differs in its unit potency, side effects, and duration of action. On average, botulinum toxin has a clinical onset of action approximately 12 to 72 hours after injection, with a peak effect at 1 to 3 weeks. Effects then plateau for 1 to 2 months, with patients often requiring reinjection approximately every 3 months. Side effects may include local discomfort at the site of the injection and excessive weakness of the injected or nearby muscles, although more distant effects may occur. Antibody formation is a significant clinical concern and eventually obviates treatment benefit in approximately 5% of patients. Switching serotypes may be effective, at least temporarily. Consensus dosing guidelines have been developed and are presented within. Numerous studies have suggested that botulinum toxin has a role in the care of children with spasticity or dystonia related to cerebral palsy, and may improve equinus, gait, upper extremity use, comfort, and care. Evidence of functional improvement remains equivocal in the severely impaired child; however, there is evidence for improvement in less impaired children. The optimal candidate for injectable neuromuscular blockade is one who has a limited number of muscles that need treatment, who does not have fixed contracture, and who retains selective motor control. The ultimate goal of treatment for the hypertonic child is to maximize function, comfort, and independence. Hypertonia is only one aspect of the upper motoneuron syndrome, which includes both positive and negative symptoms. The treatment program, in which chemodenervation is only one tool, requires a multidisciplinary evaluation and individualized plan to address the whole patient.
D018726:Anti-Dyskinesia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001905:Botulinum Toxins / Q000009:adverse effects / Q000627:therapeutic use*; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D020820:Dyskinesias / Q000188:drug therapy*; D000431:Ethanol / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007273:Injections, Intramuscular; D009069:Movement Disorders / Q000188:drug therapy*; D009128:Muscle Spasticity / Q000188:drug therapy*; D018482:Muscle, Skeletal / Q000503:physiopathology; D019800:Phenol / Q000009:adverse effects / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic
D018726:Anti-Dyskinesia Agents; D002492:Central Nervous System Depressants; D019800:Phenol; D000431:Ethanol; D001905:Botulinum Toxins