Key points

Introduction

Botulinum toxin is a natural neurotoxin produced by clostridial bacterial species that causes muscular paralysis. The primary mechanism of action of the toxin is via inhibition of calcium-dependent exocytosis and release of acetylcholine at the neuromuscular junction. Other indirect mechanisms of action may also explain the clinical effect of the toxin. Inhibition of intramuscular gamma motor neurons and lack of feedback to motor neurons due to muscle weakening may have an effect on afferent feedback to the central nervous system. The effect of botulinum toxin is reversible because the nerve terminals do recover the ability to release acetylcholine into the neuromuscular junction.

There are seven serotypes of the botulinum toxin; only type A and type B have been developed for clinical use in humans:

• •
  

  Type A has the longest duration of effect and diffuses less from the point of injection compared with type B. These differences may be secondary to differences in the preparation of the toxin as opposed to inherent differences in the serotypes themselves.

  
  
• •
  

  The dosing differs significantly between type A and type B preparations. The focus of information in this article is based on the use of type A (Botox, Allergan Irvine, USA; Dysport, Ipsen, Ltd, Slough, UK).

There are numerous indications for botulinum toxin injection in the treatment of laryngeal disorders. The most common use of botulinum toxin is for the treatment of spasmodic dysphonia (SD), a focal dystonia affecting the laryngeal musculature. SD is classified as primarily adductor (ADSD), abductor (ABSD), or of a mixed nature. Distinguishing between these conditions can often be subtle and difficult (a fully detailed discussion of this is beyond the scope of this article). This determination is essential to the effective treatment with targeted botulinum toxin injections, which is the mainstay of management for this condition. The thyroarytenoid-lateral cricoarytenoid (TA-LCA) muscle complex is targeted for ADSD while the posterior cricoarytenoid (PCA) muscle is targeted for ABSD.

Essential tremor and age-related disease that involves involuntary muscle contraction can affect the upper aerodigestive tract muscles with varying degrees of impact on voice production. Symptoms can range from mild to severe vocal disability. Systemic pharmacologic intervention for vocal tremor is generally ineffective; however, botulinum toxin injections have proven to be helpful in selected patients. Tremor can also be observed in other neurologic conditions, such as Parkinson’s disease, and can coexist with SD.

Plica ventricularis refers to hyperfunction of the supraglottic larynx and excessive adduction of the false vocal folds with phonation, resulting in poor voice quality. This may arise secondary to an underlying pathologic condition at the level of the true vocal folds that is resulting in glottal insufficiency or impaired vocal fold vibration. However, it may also be functional in origin. Traditional management typically involves a combination of treatment of any underlying cause at the level of the true vocal folds and aggressive voice therapy. Voice therapy aims to teach patients to reduce false vocal fold phonation and resume phonation with the true vocal folds; however, some patients may continue to have problems despite aggressive therapy. In these cases, weakening the contraction of the false folds, that is, the aryepiglottic muscle, via a botulinum toxin injection may help facilitate more effective therapy.

The use of botulinum toxin has been recently described as a potential treatment of patients with bilateral vocal fold paralysis and posterior glottic stenosis. By weakening the TA-LCA muscle complex, the PCA muscle has less opposition and can lead to a more lateralized position of the vocal folds, thus improving the caliber of the airway. Although this technique had good success in treating patients with bilateral vocal fold paralysis, results in patients with PGS were mixed.

The management of vocal fold granulomas can be challenging and typically involves voice therapy and aggressive management of laryngopharyngeal reflux. Surgery plays a minimal role because it is often ineffective. Various investigators have found that botulinum toxin injection into the ipsilateral vocal fold can be an effective adjunctive treatment of recalcitrant granulomas by preventing forceful contact between the arytenoids during phonation and coughing.

Paradoxic vocal fold motion is characterized by the inappropriate adduction of the true vocal folds during inspiration. There are a wide range of proposed causes and treatments (further discussion is beyond the scope of this article). It is often a very difficult condition to treat effectively and botulinum toxin injections have been proposed as an effective adjunctive treatment in severe or refractory cases.

Botulinum toxin injections into the cricopharyngeus muscle can also be effective in the treatment of dysphagia secondary to increased tone and delayed relaxation of this muscle. This technique can also be used as a predictor for which patients will benefit from a surgical cricopharyngeal myotomy.

Botulinum toxin injections are contraindicated in patients who are pregnant or breastfeeding, have concurrent neuromuscular diseases (eg, myasthenia gravis), are receiving concurrent aminoglycoside treatment, or have a known sensitivity to botulinum toxin or any of the compounds contained in the toxin preparation.

Introduction

Botulinum toxin is a natural neurotoxin produced by clostridial bacterial species that causes muscular paralysis. The primary mechanism of action of the toxin is via inhibition of calcium-dependent exocytosis and release of acetylcholine at the neuromuscular junction. Other indirect mechanisms of action may also explain the clinical effect of the toxin. Inhibition of intramuscular gamma motor neurons and lack of feedback to motor neurons due to muscle weakening may have an effect on afferent feedback to the central nervous system. The effect of botulinum toxin is reversible because the nerve terminals do recover the ability to release acetylcholine into the neuromuscular junction.

There are seven serotypes of the botulinum toxin; only type A and type B have been developed for clinical use in humans:

• •
  

  Type A has the longest duration of effect and diffuses less from the point of injection compared with type B. These differences may be secondary to differences in the preparation of the toxin as opposed to inherent differences in the serotypes themselves.

  
  
• •
  

  The dosing differs significantly between type A and type B preparations. The focus of information in this article is based on the use of type A (Botox, Allergan Irvine, USA; Dysport, Ipsen, Ltd, Slough, UK).

There are numerous indications for botulinum toxin injection in the treatment of laryngeal disorders. The most common use of botulinum toxin is for the treatment of spasmodic dysphonia (SD), a focal dystonia affecting the laryngeal musculature. SD is classified as primarily adductor (ADSD), abductor (ABSD), or of a mixed nature. Distinguishing between these conditions can often be subtle and difficult (a fully detailed discussion of this is beyond the scope of this article). This determination is essential to the effective treatment with targeted botulinum toxin injections, which is the mainstay of management for this condition. The thyroarytenoid-lateral cricoarytenoid (TA-LCA) muscle complex is targeted for ADSD while the posterior cricoarytenoid (PCA) muscle is targeted for ABSD.

Essential tremor and age-related disease that involves involuntary muscle contraction can affect the upper aerodigestive tract muscles with varying degrees of impact on voice production. Symptoms can range from mild to severe vocal disability. Systemic pharmacologic intervention for vocal tremor is generally ineffective; however, botulinum toxin injections have proven to be helpful in selected patients. Tremor can also be observed in other neurologic conditions, such as Parkinson’s disease, and can coexist with SD.

Plica ventricularis refers to hyperfunction of the supraglottic larynx and excessive adduction of the false vocal folds with phonation, resulting in poor voice quality. This may arise secondary to an underlying pathologic condition at the level of the true vocal folds that is resulting in glottal insufficiency or impaired vocal fold vibration. However, it may also be functional in origin. Traditional management typically involves a combination of treatment of any underlying cause at the level of the true vocal folds and aggressive voice therapy. Voice therapy aims to teach patients to reduce false vocal fold phonation and resume phonation with the true vocal folds; however, some patients may continue to have problems despite aggressive therapy. In these cases, weakening the contraction of the false folds, that is, the aryepiglottic muscle, via a botulinum toxin injection may help facilitate more effective therapy.

The use of botulinum toxin has been recently described as a potential treatment of patients with bilateral vocal fold paralysis and posterior glottic stenosis. By weakening the TA-LCA muscle complex, the PCA muscle has less opposition and can lead to a more lateralized position of the vocal folds, thus improving the caliber of the airway. Although this technique had good success in treating patients with bilateral vocal fold paralysis, results in patients with PGS were mixed.

The management of vocal fold granulomas can be challenging and typically involves voice therapy and aggressive management of laryngopharyngeal reflux. Surgery plays a minimal role because it is often ineffective. Various investigators have found that botulinum toxin injection into the ipsilateral vocal fold can be an effective adjunctive treatment of recalcitrant granulomas by preventing forceful contact between the arytenoids during phonation and coughing.

Paradoxic vocal fold motion is characterized by the inappropriate adduction of the true vocal folds during inspiration. There are a wide range of proposed causes and treatments (further discussion is beyond the scope of this article). It is often a very difficult condition to treat effectively and botulinum toxin injections have been proposed as an effective adjunctive treatment in severe or refractory cases.

Botulinum toxin injections into the cricopharyngeus muscle can also be effective in the treatment of dysphagia secondary to increased tone and delayed relaxation of this muscle. This technique can also be used as a predictor for which patients will benefit from a surgical cricopharyngeal myotomy.

Botulinum toxin injections are contraindicated in patients who are pregnant or breastfeeding, have concurrent neuromuscular diseases (eg, myasthenia gravis), are receiving concurrent aminoglycoside treatment, or have a known sensitivity to botulinum toxin or any of the compounds contained in the toxin preparation.

Preoperative planning, preparation, and patient positioning

Botox is supplied as a vacuum-dried concentrated powder in 100-unit vials and it is reconstituted with sterile normal saline. The authors prefer to use 4.0 mL of saline for the reconstitution, which provides a dose of 2.5 U/0.1 mL. This can be further diluted based upon the dose required; the preferred injection volume is 0.1 to 0.2 mL per vocal fold.

Some investigators prefer not to use local anesthesia for percutaneous injections. The authors, however, have found that the use of a small amount of injected 1% lidocaine in the skin and subcutaneous tissue improves patient comfort. Topical anesthesia of the larynx is typically not required, unless the planned approach involves the electrode needle piercing the endolaryngeal mucosa (eg, for PCA muscle injections; see later discussion).

Percutaneous injections should be guided via electromyography to maximize the accuracy of injection location. Needle placement is crucial to achieve accurate distribution of the toxin. The EMG machine must be appropriately set-up and calibrated along with placement of ground and reference electrodes before starting any injection procedure and the physician must be comfortable with basic EMG interpretation to use this technique. EMG-guided injections should be done with a 26-gauge or 27-gauge needle electrode. Injections can be done without EMG guidance by using laryngoscopic or visual guidance; however, the latter technique is less precise, in the opinion of the authors. EMG guidance allows for more precise injections, which should maximize the efficacy of the injected dose. Information here is focused on EMG-guided percutaneous techniques.

Counseling the patient regarding the nature of the procedure and expected time course of postinjection effects (see later discussion) is essential to maximize patient comfort and to minimize the risk of complications. The authors prefer patients to be in a comfortable seated position for all injections. The physician can be positioned on either side of the patient depending in the location of the injection and the physician’s dominant hand.