Mechanism of action:

Botulinum toxin is a protein, produced by the bacterium Clostridium botulinum. To understand its effect, let's review how our muscles work. The brain sends messages to the muscles to make them contract and move. These messages first go to the spinal cord. From there, they are carried by peripheral nerves to the muscles. A chemical called acetylcholine transmits this message from the nerve to the muscle. Sometimes an abnormality in the brain or spinal cord can lead to excessive or uncoordinated messages to the muscles. Then, these muscles go into spasm or assume twisting postures, many times causing pain. Botulinum toxin prevents the release of acetylcholine from nerve endings to muscles, thereby blocking the abnormal order from the brain. This reduces muscle spasms, abnormal postures, as well as associated pain.

When ingested in large quantities, like in food poisoning, it can be fatal by paralyzing all muscles in the body. However, the amount used as medicine is very small.

This bacterium produces 7 types of botulinum toxin. Only Type A and Type B are commercially available. In the US, type A is marketed as Botox®, and type B as Myobloc®. The art in the botulinum toxin injections lies in the selection of correct muscles and determining the appropriate dose that reduces the spasms in the muscle without completely paralyzing it. Sometimes an EMG machine is used to guide the injections. The effect of botulinum toxin starts in 2-14 days, and usually lasts for about 3 months. It needs to be re-injected periodically to continue the effect.

Indications:

It is used for conditions that lead to abnormal muscle contractions. It does not cure these disorders, but relieves the symptoms.

The FDA approved indications for Botox® are cervical dystonia in adults (a condition with abnormal head position and neck pain), strabismus (crossed eyes), blepharospasm (involuntary forceful closure of eyelids), and hemifacial spasm in patients 12 years of age and above. Botox Cosmetic® has recently been approved to use for frown lines in the forehead. Myobloc® is approved for cervical dystonia.

However, over the years, botulinum toxin has been used successfully for many other conditions as an "off-label" use. These conditions include spasticity (from stroke, multiple sclerosis, cerebral palsy, or head trauma), dystonia (involuntary twisting postures) of the arms or legs, tremors, headaches, or even drooling. One should take into consideration that botulinum toxin treatment is rather expensive. "Off-label" uses are not always covered by insurance companies or Medicare.

Side effects and risks:

Like with any other injection, there can be pain, small amount of bleeding, or risk for infection.

Side effects specific for Botulinum toxin depend on the site of injection. If too much is injected in the neck, it can lead to difficulty holding the head upright or swallowing disorder. Injection around the eye can lead to double vision, droopy eyelids, or dry eyes. Injection in the arm may lead to weakness in the handgrip. These side effects are transient. Sometimes, it can also give rise to flu-like symptoms.

One of the major benefits of botulinum toxin therapy is that it is local. A pill can go to many parts of the body and brain, and can lead to generalized side effects such as sleepiness, dizziness, or upset stomach. However, although the vast majority of botulinum toxin remains in the muscle that is injected, there is a small chance that it can affect other muscles or organs in the body. Therefore, one should exercise extreme caution if it is considered in patients who are in poor general condition, or have underlying problems in the muscles or nerves.

Additional resources:

• Botulinum Treatment Clinic: UI Hospitals and Clinics, Department of Neurology