Botulinum Neurotoxin Injections

The introduction of botulinum neurotoxin as a therapeutic tool in the late 1980s revolutionized the treatment of dystonia.

Botulinum neurotoxin injections provided a new, localized method to significantly relieve symptoms for many people. Botulinum neurotoxin, a biological product, is injected into specific muscles where it acts to relax the muscles and reduce excessive muscle contractions.

Botulinum neurotoxin is derived from the bacterium Clostridium botulinum. It is a nerve "blocker" that binds to the nerves that lead to the muscle and prevents the release of acetylcholine, a neurotransmitter that activates muscle contractions. If the message is blocked, muscle spasms are significantly reduced or eliminated.

Forms of botulinum neurotoxin

Two forms of botulinum neurotoxin are available for patients. These are botulinum neurotoxin type A (trade names Botox, Dysport, and Xeomin) and botulinum neurotoxin type B (trade names Myobloc and Neurobloc).

Other 'serotypes' of botulinum neurotoxin are under investigation as potential therapeutic agents. These include (in addition to types A and B) types C, D, E, F, and G. Each one has different properties and actions. No two are exactly alike. At present, type F is the only additional form that has shown some promise as a viable treatment for humans.

Although the overall effect is similar, the specific mechanism by which each serotype achieves this effect is different. For example, both type A and type B block the neurotransmitter acetylcholine, but they do so by breaking up different proteins within the nerve cell.

Botulinum neurotoxin type A is commercially available in the United States as Botox from Allergan, Inc, Dysport from Ipsen, Ltd, and Xeomin from Merz. Botulinum type B is available from Solstice Neurosciences/US WorldMeds as Myobloc in the United States, and as Neurobloc abroad.

Botulinum neurotoxin type A is approved by the US Food and Drug Administration (FDA) or the treatment of blepharospasm and cervical dystonia. Botulinum neurotoxin type-B is approved in the US for the treatment of cervical dystonia. Both type A and type B are used extensively to treat the various forms of dystonia. The regulations of the FDA allow physicians to use approved medications for conditions other than the specified indications. This is called "off-label" use.

No studies have been done to examine the effects of botulinum neurotoxin during pregnancy. It is generally recommended that women not receive botulinum neurotoxin injections while pregnant.

Methods

Injections of botulinum neurotoxin should only be performed by a physician who is trained to administer this treatment. The physician needs to know the clinical features and study the involuntary movements of the person being treated. The physician doing the treatment may palpate (touch) the muscles carefully, trying to ascertain which muscles are over-contracting and which muscles may be compensating. In some instances, such as in the treatment of spasmodic dysphonia/laryngeal dystonia, a team approach including other specialists may be required.

For selected areas of the body, and particularly when injecting muscles that are difficult or impossible to palpate, guidance using an electromyograph (EMG) may be necessary. For instance, when injecting the deep muscles of the jaw, neck, or vocal cords, an EMG-guided injection may improve precision since these muscles cannot be readily palpated. An EMG measures and records muscle activity and may help the physician locate overactive muscles.

Injections into the overactive muscle are done with a small needle, with one to three injections per muscle. Discomfort at the site of injections is usually temporary, and a local anesthetic is sometimes be used to minimize any discomfort associated with the injection.

It normally takes several days for the effects of the botulinum neurotoxin to become apparent. The benefit peaks in approximately four weeks and lasts three to four months. Temporary side effects for both types A and B may include muscle weakness, flu-like symptoms, pain at the injection site, and dry mouth. Patients should feel free to ask their physician about additional side effects that may be specific to the body area that is to be injected--for example, temporary difficulty swallowing may occur in patients injected for laryngeal or cervical dystonias, but is highly unlikely for someone getting injected for writer's cramp. If a patient experiences side effects, adjusting the dosage or site of injection for future treatments may help avoid these effects. There is some evidence that side effects may be more prevalent in people treated with type B.

An important difference between the different brands of botulinum neurotoxin is the number of units needed for treatment and how much toxin is in a 'unit' of each product. The units used to measure dosage are not consistent among the commercially produced toxins, and the products are not interchangeable.

Optimizing results

Like many aspects of treating dystonia, injecting botulinum neurotoxin as much art as it is science. It is in your best interest to locate the most well-trained and experienced doctor you can find. Before making an appointment to receive botulinum neurotoxin injections, ask the office personnel which doctor will be doing the injections, where he/she was trained, and how many other patients he/she has injected for the form of dystonia for which you are being treated. The Dystonia Medical Research Foundation can help you locate the nearest, most experienced physician. Travel may be required to access the most appropriate specialist.

The success of a botulinum neurotoxin injection depends upon:

  • The dose used
  • The specific sites in the muscles where the product is injected
  • The experience of the physician giving the injection
  • Clear communication between physician and patient, so that both parties understand and agree on the specific symptoms that are being treated and what can be expected as a result of an injection.

Because of the multiple factors that determine the success of a botulinum neurotoxin injection, a person might require being injected on two or three separate occasions before the optimal benefit is achieved. All of the factors listed above must be aligned for the best result, and this may take some time to perfect.

Based on over a decade of clinical experience, patients who respond well to botulinum neurotoxin may continue treatment over the course of many years without side effects from long-term use.

Immunity

Because botulinum neurotoxin is a biological product, it is possible for the body to create antibodies and develop immunity to the effects of the toxin. Measures are in place to guard against immunity:

  • The 'recipes' for manufacturing botulinum neurotoxins have been refined to reduce the chances of the body forming antibodies
  • Physicians use the smallest dose needed to get a positive result
  • Injections are typically not repeated more often than every 3-4 months
  • Physicians generally use one serotype at a time rather than alternate or mix type A and type B

An important distinction must be made between individuals who have become immune to the neurotoxin and individuals who have not had an optimal treatment: Someone who has become immune to botulinum neurotoxin does not react at all to the product. This is very different from someone who gets some results from the injections but not the results they were hoping for or expecting. If a person is getting any results at all then there is hope that the way the botulinum neurotoxin is administered can be adjusted to get a good result.

If you are receiving botulinum neurotoxin injections and getting some result but not the result you expected or unacceptable side effects, ask your physician about the specific symptoms that concern you. Treatment with botulinum neurotoxin may require a trial period to establish the appropriate dose, injection sites, and targeted symptoms but it is a very adaptable treatment that can create a dramatic benefit. A physician may test a patient for immunity by injecting a tiny amount of botulinum neurotoxin into the brow muscle and observing the effect.

In some cases, an individual who has previously been successfully treated with botulinum neurotoxin begins to experience a loss in benefit. Several factors could be responsible for this change. The nature and pattern of muscle contractions may change over time, thus necessitating an adjustment in the site of injection and dosage. If deep muscles become involved, it may be difficult to access those muscles.  If you notice a change in how your symptoms respond to botulinum neurotoxin, discuss these changes with your doctor.

Reimbursement resources

There are programs in place to help people access botulinum neurotoxin and to assist patients with or without medical insurance achieve appropriate reimbursement for their treatment. Click here to learn more.

 

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