Spasticity

Chemodenervation and Neurolysis

Chemodenervation and neurolysis interrupt neuronal signaling and are typically used to treat spasticity of focal origin. One or the other, or both, are often used before, after, or in combination with other therapeutic modalities, such as physical therapy or serial casting.35

Chemodenervation refers to a blockade of neuronal signaling, while neurolysis refers to destruction of nerve tissue. In the context of spasticity treatment, chemodenervation is accomplished with botulinum toxin (BoNT), injected directly into the affected muscle, preferably as close as possible to the motor end plates. Neurolysis is accomplished with either phenol or ethyl alcohol, injected either onto a motor nerve (nerve block) or into the muscle near the motor end plates (motor point block).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 BoNT 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 those cases that require the injection of large muscles or a large number of muscles. Phenol and BoNT may also be combined to achieve maximum effect in specifically targeted muscles.40

Botulinum toxin
BONT 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, BoNT inhibits the docking and fusion of acetylcholine vesicles at the presynaptic membrane.42,43

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. The effects of BoNT-A are dose dependent and reversible. Gradually, muscle function returns by the sprouting of new nerve terminals, followed by the restoration of function of the original terminal and atrophy of the newly sprouted ones. Once begun, treatment with BoNT-A is continually evaluated. Follow-up is crucial to gauge the response to therapy and to fine tune muscle selection and the dosage.49

BoNT-A as Botox® (onabotulinumtoxinA) is FDA-approved for the treatment of upper-limb spasticity in adults. It has also been well studied for the treatment of spasticity of the lower limbs, and in children with cerebral palsy.44-51 Two other forms of BoNT-A are available commercially, including Dysport® (abobotulinumtoxinA) and Xeomin®.

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. BoNT 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 BoNT-A in the treatment of spasticity,52 it is recommended to wait at least 3 months between injections and to use the minimum effective dose.

BoNT-B as Myobloc® (rimabotulinumtoxin B) 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 BoNT-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 BoNT-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.