Botulinum Toxin for Laryngeal Dystonia 

Updated: Dec 20, 2016
Author: Jayita Poduval, MS, MBBS, DNB(ENT), DORL; Chief Editor: Arlen D Meyers, MD, MBA 

Overview

Background

Laryngeal dystonia (LD) is a muscle-contraction disorder of the larynx and laryngeal musculature. It was once referred to as spasmodic dysphonia (SD), which refers to a group of dystonias, or muscle-contraction disorders, in which involuntary muscle movements in a particular organ or region of the body interfere with normal function. However, the term spasmodic dysphonia is an inaccurate description of laryngeal dystonia, since no lesion in the pyramidal or extrapyramidal tract has yet been identified to account for the spasticity.[1]

Other synonyms of historical significance for laryngeal dystonia have included spastic aphonia, spastic dysphonia, phonic laryngeal spasm, coordinated laryngeal spasm, mogiphonia, laryngeal stuttering, and nervous hoarseness.

Although Traube is believed to have coined the term “spasmodic dysphonia” in 1871, further extensive studies using electromyography and, subsequently, the use of botulinum toxin to treat laryngeal dystonia in 1986 are credited to Blitzer and his colleagues.[2]

Laryngeal dystonias are classified according to the specific muscle(s) involved, into 4 distinct types, as follows:[1]

  • Adductor type: This type accounts for most cases of laryngeal dystonia, around 80%. In this condition, the true vocal cords close intermittently and irregularly during connected speech, resulting in voice breaks and a strained, strangled voice quality and effortful speech.

  • Abductor type: This type is rare and causes a soft, whispery voice due to increased breathiness and vocal air escape. Complete aphonia can occur in severe cases.

  • Mixed type: This has features of both adductor and abductor types.

  • Adductor laryngeal breathing dysphonia (ALBD): In this condition, the voice is normal, but there is an inspiratory stridor, which may persist and complicate swallowing, leading to paroxysmal cough and dysphagia.

Laryngeal dystonia is characterized by the severe impairment of connected speech without associated problems with singing, humming, or laughing or related activities such as yawning, yelling, or sneezing.

Laryngeal dystonia is usually precipitated by stress and may be temporarily controlled with alcohol, tranquilizers, and/or sedatives. It must be distinguished from essential voice tremor, functional aphonia, malingering, and neurological diseases. Associated focal dystonias in other areas may be seen, such as torticollis, blepharospasm, hemifacial spasm, strabismus, and writer’s cramp.[3]

Laryngeal dystonia is significantly more common in female than in males, and its peak age of onset is 35-45 years. Familial clustering has been reported.

A detailed history and thorough physical examination are essential to diagnose the condition and to rule out other neurological lesions.[1] Investigations of choice in laryngeal dystonia are fiberoptic laryngoscopy and laryngeal videostroboscopy. Other tests include aerodynamic, acoustic, perceptual, and spectral voice analysis.

Laryngeal dystonias result from poorly coordinated muscle movement; therefore, treatment involves weakening one side of the agonist and antagonist groups of muscle.[1] Although laryngeal dystonias have no known cure, various pharmacological, surgical, and physiotherapeutic options may be used for treatment.[1] Injection of botulinum toxin (BT) is now the criterion standard of treatment.

Indications

Indications for botulinum toxin treatment of laryngeal dystonias include the following:

  • Laryngeal dystonia: Adductor laryngeal dystonia, adductor laryngeal breathing dystonia (ALBD), abductor laryngeal dystonia, persistent laryngeal dystonia after recurrent laryngeal nerve (RLN) section[1]

  • Essential voice tremor[4]

  • Vocal cord granuloma[4]

Contraindications

Contraindications to botulinum toxin treatment of laryngeal dystonia are as follows:

  • Pregnancy, lactation

  • Very young age (neonates, infants)

  • Motor neuron disease, neuromuscular disorders

  • Concomitant aminoglycoside use

  • Untreated gastroesophageal reflux disease

Outcomes

The response of botulinum toxin treatment of laryngeal dystonias is typically better in younger patients.

The success rate approaches 85%-90% and is higher in adductor laryngeal dystonia than in abductor laryngeal dystonia. Essential voice tremor is associated with the poorest success rate.[1]

Injections into the posterior cricoarytenoid (PCA) muscle are technically more difficult than into the thyroarytenoid and lateral cricoarytenoid (TA/LCA) and may be less satisfactory in patients with abductor laryngeal dystonia, since the PCA muscle is more difficult to access and/or some patients believed to have abductor laryngeal dystonia actually have the mixed type (ie, a combination of adductor and abductor laryngeal dystonia).[4]

Large or repeated doses may cause resistance by formation of antibodies; this may occur in about 3%-10% of patients and is also related to younger age and booster doses. It may be treated by using another serotype (eg botulinum toxin B).[1]

 

Periprocedural Care

Pre-Procedure Planning

Equipment

Botulinum toxin treatment of laryngeal dystonias involves the following:

  • Flexible fiberoptic laryngoscope with distal chip for a two-person approach or a rigid 70° telescope for a one-person approach[4]

  • C-mount camera

  • Video monitor for visualization

  • Curved Abraham canula for delivery of topical lidocaine and vocal fold palpation

  • Needles for percutaneous injection (1.5 inch and 23, 25, or 27 gauge)

  • Flexible fine-gauge injection needle for use with working channel in flexible laryngoscope

  • Electromyographic (EMG) device

Along with the botulinum toxin to be injected, an assortment of syringes and needles, topical and infiltration anesthesia, ground and reference electrodes, alcohol swabs, cotton pledgets, and orotracheal injection device (when necessary) may be needed.[4]

Patient Preparation

Anesthesia

Percutaneous electromyography (EMG)–guided botulinum toxin for laryngeal dystonia: Local anaesthesia is optional.

Percutaneous indirect laryngoscopy-guided botulinum toxin for laryngeal dystonia: The cricothyroid membrane is punctured for administration of local anesthesia, instilling approximately 3 mL of 4% lidocaine into the airway.

Positioning

The patient is positioned in semirecumbent position with the chin elevated and head extended.

Monitoring & Follow-up

Late Sequelae

Late sequelae of botulinum toxin treatment of laryngeal dystonia may include the following:

  • Denervation atrophy

  • Fibrosis

  • EMG changes

Side Effects

Side effects may include the following:

  • Breathy dysphonia

  • Hoarseness

  • Swallowing difficulties (including aspiration)

  • Pain

  • Flulike symptoms

Complications

Complications may include the following:

  • Dysphagia

  • Airway compromise

  • Generalized weakness

 

Technique

Approach Considerations

Keep in mind that the lethal dose of botulinum toxin is 2800-3000 U in a 70-kg male.[5]

Percutaneous Electromyography-Guided Botulinum Toxin Treatment of Laryngeal Dystonia

The EMG-guided method is quicker and more accurate than the method using percutaneous indirect laryngoscopy but is technically more difficult, apart from the necessity of having an EMG apparatus and skill in interpreting the readings and results.[4]

The EMG electrodes are attached to the patient’s skin so as not to obstruct the access area for injection and connected to the EMG machine.

Adductor dysphonia

In adductor dysphonia, the TA-LCA muscle complex is identified with EMG-guided localization. The TA-LCA muscle complex on either side is injected with equivalent amounts of the toxin.

The patient is asked to breathe quietly and to try not to swallow during the procedure. The injection needle may be bent up by 30° to 45° to facilitate access to the injection site, especially in females.[4] The EMG needle is inserted through the cricothyroid membrane approximately 2-3 mm off of the midline toward the side to be injected and advanced superiorly and laterally (see image below).

Needle inserted into the cricoarytenoid muscle for Needle inserted into the cricoarytenoid muscle for botulinum toxin injection.

Entry into the airway produces a characteristic “buzz” in the EMG signal that should alert the surgeon to redirect the needle more laterally or even to restart. The needle is maneuvered within the tissue until the tip lies in an area of crisp motor unit potentials found with EMG. This indicates the position of the muscle complex.

The patient is asked to phonate, and, when a brisk recruitment and a full interference pattern confirm placement, the botulinum toxin is injected (see image below). For optimal localization of the injection, a prephonatory burst of EMG activity must be obtained.[4] In the treatment of adductor laryngeal dystonia with botulinum toxin, unilateral injection into the thyroarytenoid muscle is preferable to bilateral injection in order to avoid complete loss of voice in the immediate post-treatment period.[6]

Laryngeal electromyography recording during inject Laryngeal electromyography recording during injection of botulinum toxin.

Abductor dysphonia

In abductor laryngeal dystonia, the PCA muscle is localized and injected. The PCA muscle on only one side is injected at a time to minimize the risk of airway obstruction and stridor.

The patient is seated upright, and the surgeon palpates the posterior border of the thyroid cartilage on the side to be injected. Using counterpressure from the other 4 fingers on the opposite side of the thyroid cartilage, the larynx is gently rotated to expose its posterior aspect. The needle pierces the skin along the lower half of the posterior border of the thyroid cartilage and is advanced until it stops against the posterior surface of the cricoid. The needle is then pulled back slightly, and the patient is asked to sniff to confirm placement.[4] When this produces brisk recruitment, the toxin is injected.

Percutaneous Indirect Laryngoscopy-Guided Botulinum Toxin Treatment of Laryngeal Dystonia

The cricothyroid membrane is punctured for administration of local anesthesia, instilling approximately 3 mL of 4% lidocaine into the airway. The nasal cavity is anesthetized, and a flexible laryngoscope, attached to a video monitor, is inserted through the nasal cavity and advanced to a level slightly above the vocal folds. An assistant keeps the scope in position to provide exposure and visual feedback during the procedure.

A 1-mL syringe filled with botulinum toxin is attached to a 27-gauge needle, and the needle is placed through the cricothyroid membrane near the midline under video monitoring to confirm the location of the needle tip in the subglottic airway. The needle is angled posterolaterally, and the posterior one third of the membranous vocal fold is injected. The opposite vocal fold is then injected using the same approach.

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Mechanism of action of botulinum toxin. Mechanism of action of botulinum toxin.

Neuromuscular Blockers, Botulinum Toxins

Class Summary

Botulinum toxin exists in up to 8 different forms: A, B, C1, C2, D, E, F, and G; A and B types are the most commonly used.[1]

Botulinum toxin A is available in the United States as BOTOX® (Allergan) and in Europe as Dysport (Speywood), while botulinum toxin B is known as Myobloc in the United States and Neurobloc in Europe. Only type A is used extensively in laryngology,[4] and all dosages and parameters of use mentioned herein are with regard to the brand BOTOX®.

Botulinum toxin affects the neuromuscular junction by binding presynaptically and blocking the release of the neurotransmitter acetylcholine, thereby preventing muscle contraction in the innervated area. It causes a temporary paresis or paralysis that may be reversed by the production of new axon terminals and the production of new cellular proteins (see image below).[1]

Botulinum toxin exists in nature as a clostridial neurotoxin that is extracted from fermented culture media, precipitated, purified, and crystallized with ammonium sulfate.[1, 4] It is commercially prepared as a single-chain polypeptide that is inert and must be converted into a double chain to achieve potency.[1] The double chain has a heavy chain that is required for intracellular binding and transportation and a light chain that has zinc endopeptidases that disrupt the proteins involved in the release of acetylcholine into the postsynaptic cleft.[1]

To be effective, BOTOX® is diluted in preservative-free saline and used within 4 hours of reconstitution.[1] It is stored at a temperature below 20°C, and with a pH maintained between 4.2 and 6.8. It must not be stirred, shaken, or frozen and should not be mixed with preservatives.[1] BOTOX® is dispensed in 100-U vials and is usually used in a concentration of 2.5-10 U/0.1 mL (ie, one vial may be diluted in 1-4 mL of saline).[1]

Approximately 0.1-0.2 mL may be injected into one vocal cord. Effects of BOTOX® start in 24-72 hours, maximizing at about 2 weeks. The action may last from 3-6 months.[1]

Onabotulinumtoxin A (BOTOX®)

This is one of several toxins produced by Clostridium botulinum. It blocks neuromuscular transmission through a 3-step process, described below.

Step 1

BOTOX® binds to the motor nerve terminal. The binding domain of the type A molecule appears to be the heavy chain, which is selective for cholinergic nerve terminals.

Step 2

BOTOX® is internalized via receptor-mediated endocytosis, a process in which the plasma membrane of the nerve cell invaginates around the toxin-receptor complex, forming a toxin-containing vesicle inside the nerve terminal. After internalization, the light chain of the toxin molecule, which has been demonstrated to contain the transmission-blocking domain, is released into the cytoplasm of the nerve terminal.

Step 3

BOTOX® blocks acetylcholine release by cleaving SNAP-25, a cytoplasmic protein that is located on the cell membrane and that is required for the release of this transmitter. The affected terminals are inhibited from stimulating muscle contraction. The toxin does not affect the synthesis or storage of acetylcholine or the conduction of electrical signals along the nerve fiber.