Pediatric Movement Disorders - Treatments

Botulinum and Other Toxins

Botulinum toxin is a synthetic form of the toxin produced by the bacterium clostridium botulinum. This toxin, in its natural state, occasionally causes severe food poisoning from improperly canned foods and may cause weakness in infants exposed to honey.

When a small amount of the purified form of the toxin is injected directly into muscle, side effects of generalized weakness and gastrointestinal disturbance are avoided; only the targeted muscle becomes weak. This has been used as a very successful therapy for improving muscle stiffness in children with spasticity or dystonia. The use of botulinum toxin injections has led to a revolution in therapy for many children with movement disorders. Botulinum toxin is used in combination with physical therapy and, in some cases, along with serial casting. This combination approach helps to loosen muscles for correct positioning. Botulinum toxin may also be used to predict the effect of surgery on the muscles. The effects of botulinum toxin are temporary and full muscle strength usually returns within 3 to 6 months; therefore, if an undesired result occurs, there is no permanent effect. Unfortunately, this also means that to achieve desired results, most children need injections every 3 to 6 months. These injections are moderately uncomfortable and sometimes require sedation or, in some cases, anesthesia.

The exact mechanism of the beneficial effect of botulinum toxin remains under debate. The toxin operates by impairing the ability of nerves to release the transmitter acetylcholine onto muscle; thereby, it weakens the muscle contraction. However, the toxin has this same effect on the intrinsic muscle fibers that are used to sense muscle stretch. Therefore, the possibility has been raised that part of its effect in spasticity is due to a decrease in the signals sent from the muscle stretch receptors back to the spinal cord.

There are currently two available forms of botulinum toxin: botulinum toxin type A (BOTOX®, Dysport®[in Europe]), and botulinum toxin type B (Myobloc™). Both types of toxin work in the same way, but each has its own range of side effects and duration of effect. The toxin is injected directly into the affected muscles, often at several locations. When more than one muscle is involved, multiple injections are needed. The total dose given to a child cannot exceed certain safety limits. Often it is necessary to use EMG to identify muscle activity and correct location. It may also be helpful to electrically stimulate the muscle to ensure that the toxin injection targets the correct muscle.

There are no known severe side effects of botulinum toxin therapy. Most commonly, when it is first attempted in a child, the dosage is only approximate so that there is either insufficient effect or excessive weakness. It is possible to have pain, bleeding, or infection at the injection site; an allergic reaction is also possible. It is theoretically possible that an injection directly into a vein could cause more diffuse weakness and gastrointestinal problems, but standard injection techniques prevent this occurrence.

If the initial botulinum toxin injection is helpful, the child returns for further injections when the effects have worn off. This interval must be at least three months. The dosage may need to be adjusted or different muscles targeted in order to maximize the effects. After an injection, the full effect may require 2 to 3 weeks to be seen. Often the physician examines the child 2 to 4 weeks after the injection to determine its effects and plan future injections. If the effects are not as desired, they usually wear off completely within 3 to 6 months.

Long-term treatment with botulinum toxin can lead to the development of antibodies in some patients. Antibodies are proteins produced by the immune system to fight foreign invaders. Antibodies bind to and inactivate BTX, rendering it useless for spasticity reduction. Once a person forms antibodies to a particular type of BTX (A or B), further injections with that type are ineffective. Antibodies against BTX-A have been found in about 5% of patients who receive it regularly in high doses, as in treatment for cervical dystonia. The incidence of antibodies to type B in cervical dystonia patients is also in this range or higher. The incidence of antibodies to either type in the spasticity population is unknown, but antibody resistance has been reported in spasticity patients. A patient who has developed antibody resistance to one type may obtain benefit by switching to the other type.

Phenol and alcohol injections have also been used to weaken muscles. The duration of effect can be quite variable, from one month to six months or more and the injections are often considerably more painful than those of botulinum toxin. These injections are significantly less expensive but usually require anesthesia due to considerable pain from the procedure.