Spasticity

Chemodenervation and Neurolysis

Chemodenervation, which interrupts neuronal signaling and is achieved with the use of BTX, or neurolysis, which destroys nerve tissue, is typically used to treat spasticity of focal origin and is often used before, after, or in combination with other therapeutic modalities, such as physical therapy or serial casting.35 The agent is injected directly into the muscle (motor point block) or nerve (nerve block), preferably as close as possible to the motor end plates.36,37,38

A key to the success of chemodenervation or neurolysis for the treatment of spasticity is patient selection.39 In particular, if the injection of the targeted muscle or nerve would lead to a weakening that would decrease the current level of functioning, i.e., would reduce tone that is compensating for muscle weakness, the patient is not typically a candidate. Chemodenervation and neurolysis are also not effective in treating fixed contracture or other joint deformities.40

Before the advent of the use of BTX in the treatment of spasticity, alcohol or phenol was often used.41 Today, however, alcohol is rarely used for the treatment of spasticity, and phenol is typically reserved for use in those cases that require the injection of large muscles or a large number of muscles. Phenol and BTX may also be combined to achieve maximum effect in specifically targeted muscles.40

Botulinum toxin
BTX type A (BOTOX®) affects the neuromuscular junction through binding, internalization, and inhibition of acetylcholine release. It must enter the nerve endings to exert its chemodenervating effect. Once inside the cholinergic nerve terminal cell, BTX-A inhibits the docking and fusion of acetylcholine vesicles at the presynaptic membrane.42,43

BTX type-A does not have FDA approval for the treatment of spasticity. However, it has been well studied in the treatment of spasticity from all causes, particularly in cerebral palsy and post-stroke spasticity.44-51 Clinical effects are usually seen within 24 to 72 hours. The maximum weakening effect is almost always seen at 2 weeks after injection. Duration of effect is usually 12 weeks but may be longer (sometimes up to 16 weeks or more) with adjunctive therapies such as stretching, casting, or other physical therapies. Gradually, muscle function returns by the regeneration or sprouting, which occurs when the blocked nerves form new neuromuscular junctions. BTX-A is dose dependent and reversible secondary to the regeneration process. Once begun, treatment with BTX-A is continually evaluated. Follow-up is crucial to gauge the response to BTX-A therapy and to fine tune muscle selection and the dosage.49

The principal adverse effect is excess weakness in the injected muscle. Spread beyond the injected muscle does occur, although care in placing the injection in the muscle belly minimizes this possibility. BTX-A should be used with extreme caution in people with neuromuscular diseases such as myasthenia gravis or amyotrophic lateral sclerosis or in those taking aminoglycoside antibiotics. Although antibody formation appears to be rare with the use of BTX-A in the treatment of spasticity,52 it is recommended, when possible, to wait at least 3 months between injections and to use the minimum effective dose.

BTX-B or Myobloc® has not been adequately evaluated in the treatment of spasticity to recommend its use in this patient population. The only randomized controlled trial that has assessed the use of BTX-B in spasticity found that 10,000 units of did not reduce muscle tone, and dry mouth was a common adverse event in the patients treated with BTX-B.49

Phenol
Phenol causes nonselective tissue destruction in the injected area, including coagulation of nerves and muscle necrosis. As mentioned, phenol is typically used when treating large muscles, such as those of the anterior thigh.53,54 The duration of effect of phenol can be quite variable, from less than 1 month to more than 2 years.

There are several potential adverse events attributed to the use of phenol, such as dysesthesias. Nonselective tissue destruction to muscles or nerves may cause temporary or permanent pain in the muscle near the injection site.