Botulinum Toxin
Botulinum toxin 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.
In spasmodic dysphonia, laryngeal muscles spasm because too many or the wrong type of signals travel from the brain through the nerves to the muscles. Botulinum toxin (BTX), a biologic product, is injected directly injected into the affected muscles. BTX blocks these nerve signals, reducing the number and severity of the spasms.
Use of BTX specifically for SD began in 1984, and since then it has been used to treat thousands of people with SD with its efficacy and safety documented in numerous medical publications. Furthermore, the American Academy of Otolaryngology & Head and Neck Surgery has documented its use for SD in a policy statement. Its use by physicians to treat SD is termed “off-label.” Many other medicines are used successfully off-label and FDA approval does not limit a physician’s use of a medicine.
BTX exists in a number of forms, but only types A and B are available commercially. Both are administered similarly but have different dosing, onset of action, and length of activity. The majority of people with SD receive BTX type A; therefore, the remainder of this discussion focuses on this type.
How is BTX Injected for SD?
BTX needs to be injected with a needle directly into the desired muscle for effect. The higher the dose, the weaker the muscle becomes, but this must be balanced with consideration for possible side-effects.
Most physicians inject BTX through the skin of the neck, and many use an EMG (electromyography) machine to help with correct placement. Some physicians do not use EMG and others deliver the medicine using a special curved needle through the mouth, sometimes using an endoscope to help guide them.
The majority of physicians administer the medicine in an office setting without any special preparation. Physicians may inject the affected muscles on one side (unilateral injections), or both sides (bilateral injections), together at one or separately in two sittings.
Successful results occur with all types of injection. It all depends on the specifics of the nerve and muscle interaction, which may not be fully known until several injections later. During this time of trial and error, the physician chooses and modifies the route, dose, and side based on his or her clinical experience and discussions with the patient about the symptoms and the results from the previous injection.
In AdSD the target muscles are often the TA, although some practitioners prefer to dose the LCA as well.
These muscles are active in closing the larynx; weakening them prevents the voice breaks associated with AdSD.
People with AbSD typically receive injections in the PCA. Weakening the muscles that open the larynx keeps the vocal cords closer together, thus preventing the breathy voice breaks associated with this subtype.
Persons with tremor may have their laryngeal strap muscles injected for improvement. The strap muscles, located in the neck, support the voice box and are often affected in tremor. In certain circumstances, the other smaller muscles such as the CT or the IA may be injected as well.
What is the Dosage?
A wide variety of doses are used, but most people receive less than five units per muscle. In their review of 901 patients, Blitzer, et. al., found the average dose per muscle at about three units of BTX type A.
While about 90 percent of AdSD patients are successfully treated with BTX, only one-half to two-thirds with AbSD find BTX treatment helpful. This perhaps occurs because physicians consciously limit the dose delivered to the PCA, as these muscles are also intricately involved in respiration.
A large dose delivered to these muscles could cause a patient to experience difficulty with breathing. Many physicians stage the dose from side to side or only inject one side in patients with AbSD for this reason.
What do I Expect After the Injection?
Following injection, the patient may experience some slight discomfort at the injection site, but this is typically quite minimal. Bruising is uncommon. The BTX does not begin to work for about two days. After this short time, the targeted muscles weaken and the person may experience some changes.
In AdSD, patients often develop a weak voice with an airy or breathy quality. Some describe a voice that sounds like Mickey or Minnie Mouse. Rarely, the patient may have some temporary swallowing difficulty, especially with liquids. This only occurs with higher dosing and the person can usually compensate by following simple instructions from the physician or speech pathologist. Once these effects pass, the voice strengthens and becomes more fluent, that is, without breaks. The weak voice generally lasts only for a few days. The stronger voice lasts about three months.
Following this, the effect of the BTX wears away and the voice symptoms recur. Most physicians try to minimize the negative effects of weak voice and maximize the good voice. The physician depends on patients relaying their experiences so that the doses can be appropriately adjusted. Some patients keep a diary to chart their voice between injections.
People with AbSD may experience a similar period of BTX effect, but have less of the ups and downs in the beginning.
As injection of the PCA can lead to some restriction of breathing, it is important that patients inform the doctor how they felt so that good voice can be balanced with good breathing.
Some considerations for non-response to BTX include antibody development, inappropriate dosage, inaccurate delivery/placement of the toxin (missing the spot), incorrect diagnosis, disease progression, or co-existence of some other neurological disorder. Best outcomes for BTX therapy involve time, and a team effort between the patient and the treating doctor.