13.1 Introduction

For over 30 years, botulinum neurotoxin (BoNT) has been the gold-standard treatment for spasmodic dysphonia. Since it was first publicized in mainstream society, the use of BoNT has grown at a staggering rate, with toxin being utilized in almost every field of medicine. Within the field of laryngology, the use of BoNT has also found a multitude of uses other than for spasmodic dysphonia. Almost any type of hyperkinetic or compensatory behavior found can be treated with the use of this toxin with a high degree of success, a low side-effect profile, and significant patient satisfaction. Toxin has been injected into the laryngopharynx for vocal tics, stuttering, vocal tremor, ventricular dysphonia, bilateral vocal fold paralysis, tracheoesophageal speech failure, as well as many other applications. By using toxin, many of these symptoms are controlled more easily, often requiring less systemic medication. Also, toxin is used as an adjunct to other types of traditional therapy, such as voice therapy and swallowing therapy, and even to surgical interventions. Additionally, because of the physiologic effects of weakening muscle, the toxin can be used to “rebalance” the larynx. In cases of bilateral vocal fold paresis, selectively weakening the adductor muscles can provide an adequate airway and help avoid a surgical intervention. Patients with vocal fold granulomas can benefit from toxin injection to help decrease the traumatic forces of the posterior glottis, thus decreasing the recurrence of granuloma and helping with resolution of persistent granulomas. In almost every situation of hyperfunction of the laryngeal and extralaryngeal musculature, BoNT can be used to help ameliorate symptoms and provide significant, reproducible relief for patients.

As with most patients presenting with hyperfunctional disorders of the larynx, the primary diagnostic modality is laryngoscopy with or without stroboscopy. A detailed evaluation of the laryngopharyngeal structures demonstrates any abnormalities of function, including laryngeal closure, pharyngeal contraction, vocal fold motion, and laryngeal elevation. Additionally, anatomic abnormalities are visualized, indicating such findings as benign vocal fold mucosal disease, vocal fold granulomas, and excessive muscular tension. Typically, no further workup is necessary other than a thorough history and a physical examination of the head and neck.

Although BoNT may be very successful for a variety of hyperkinetic laryngeal disorders, care must be taken to evaluate the larynx in a systematic and critical manner. We have used selective chemodenervation for a variety of conditions such as muscle tension dysphonia, laryngeal tremor, paradoxical vocal fold motion (frequently referred to as vocal cord dysfunction), spastic dysarthria, arytenoid rebalancing, idiopathic chronic cough, and contact granulomas, and results can be variable. The following considerations should accompany the decision-making process when considering selective laryngeal chemodenervation using BoNT in these less common laryngeal disorders.

1. 
   

   The specificity of injections may be inadequate due to inherent difficulties with site localization and the inevitable diffusion of BoNT to adjacent muscles within the relatively narrow injection field of the larynx.

   
   
2. 
   

   Diagnostic criteria and our ability to determine the root cause of some laryngeal disorders with existing technology is an inexact science. Clinical examination and visualization during phonation is a rough guide to laryngeal activity. Visualization of the larynx with the endoscope allows a single angle of view that limits evaluation of inferior and deeper structures. In the case of muscle tension dysphonia and vocal hyperfunction, the true vocal folds are often obscured by the function of the supraglottic structures. Other tools such as laryngeal electromyography (LEMG) may be a more sensitive instrument; however, in its current state, LEMG is still an imprecise tool. The technique to perform EMG-guided injection of BoNT has been described extensively in Chapter 6.

   
   
3. 
   

   A variety of dysfunction produces the same clinical appearance. For instance, muscle tension dysphonia can be the end result of hyperfunction of certain laryngeal muscle groups, hypofunction of others, paresis, poor coordination, inadequate or disruptive sensory feedback, or anatomic pathology.

   
   
4. 
   

   A well-defined management algorithm incorporating selective chemodenervation for these conditions does not exist. Individual practitioners are using BoNT without a clear constructive clinical model, resulting in a wide range of injection techniques and therapies. Instead of treating botulinum injections like a surgical tool, it is perceived as a medication with a specific pharmacologic action. BoNT should be viewed as an instrument with properties of cutting or severing a nerve. In this chapter, we discuss our general experience and collective expertise with these disorders; however, use of this “chemical knife” correctly requires an individualized plan of care and treatment.

   
   
5. 
   

   Response to treatment is gauged by the outcome of the voice, resolution of the dysfunction, granuloma, or cough. Our guidelines are meant as suggestive dosing which may vary depending on severity of the symptom. If the initial injection fails to improve the symptom and there are no significant side effects, a repeat injection can be performed typically with one half the dose.

13.2 Bilateral Vocal Fold Paralysis

Bilateral vocal fold paralysis can be a devastating consequence of neck surgery, brainstem disease, or systemic disease that often leaves a patient with severe debilitation including shortness of breath and stridor with airway compromise. It is imperative to differentiate bilateral cricoarytenoid joint ankylosis or posterior glottic web as a complication of intubation from true bilateral vocal fold paralysis. Laryngeal EMG followed by examination under anesthesia to evaluate for posterior glottic stenosis (PGS) and/or cricoarytenoid joint ankylosis, if EMG is normal, is an effective technique to establish the correct diagnosis. Patients often require airway intervention ranging from suture lateralization, simple posterior vocal fold cordotomy, or tracheotomy. While some laryngologists advocate waiting for at least 1 year from the onset of the bilateral immobility before performing a destructive laryngeal procedure to create an adequate airway to allow for laryngeal patency and removal of a tracheotomy tube, others intervene sooner if signs of chronic denervation are present on laryngeal EMG, or if the mechanism of injury suggests poor prognosis. However, when patients have bilateral vocal paresis with possible return of function given the mechanism or favorable EMG findings, alternative treatments with BoNT are considered. Nimodipine is a promising adjunctive treatment that has been shown to increase the likelihood of neural regeneration, although multicenter human studies have not yet been performed. ¹

Many patients who are newly diagnosed with airway compromise due to bilateral paresis or paralysis may be stable at rest or moderately symptomatic without distress. In this situation, a tracheotomy can possibly be avoided, removed early, or capped, by using BoNT injection into either unilateral or bilateral thyroarytenoid and lateral cricoarytenoid (TA/LCA) muscle complex. By inhibiting the adductory function during reinnervation, the abductor muscles can contract unopposed, often leading to a larger airway caliber that allows for better airflow. In one study, 10 of 11 patients obtained substantial relief from airway obstruction after either bilateral or unilateral followed by bilateral BoNT injection into the TA/LCA complex which can result in increased airway patency at rest and with activity. ²

In addition to injecting the TA/LCA complex, recent intervention has focused on the cricothyroid muscles. In a pediatric case series, a small incision to expose the cricothyroid muscles with subsequent direct intramuscular injection of 4 to 10 units (U) of BoNT resulted with decannulation of five of six patients, with a larger airway caliber reported postinjection. ³ A small adult series of three patients using transcutaneous cricothyroid muscle injections of BoNT ranging from 2.5 to 3 U was used to treat their bilateral vocal fold paralysis with success in avoiding tracheotomy and alleviating symptoms of dyspnea. ⁴

Another use of BoNT in patients with bilateral vocal fold paralysis pertains to those with implantable laryngeal stimulators within the posterior cricoarytenoid (PCA) muscle. By weakening the opposing adductory forces with chemical denervation, the airway patency was increased, alleviating the symptoms of dyspnea. Thus, by using electrical stimulation and chemical denervation, this group was able to decannulate patients with longstanding bilateral vocal fold paralysis. ⁵

Typical treatment utilizing BoNT involves bilateral injections of the thyroarytenoid muscles utilizing the standard EMG-guided anterior neck approach; 2.5 U of toxin is injected bilaterally as the initial dose. A second dose of 0.5 to 1 U can be injected 2 to 3 weeks after the initial dose if there has been little or no response. Typical side effects can range from no ill effects to severe breathiness and occasional coughing while drinking liquids. Gross aspiration is possible but has not occurred in our experience. Patients with severe airway compromise or progressive compromise despite BoNT injection are not good candidates for this type of medical intervention, and airway security is the primary concern.

13.3 Tracheoesophageal Speech Failure

Loss of voice after total laryngectomy is an unavoidable morbidity. However, with the widespread use of a tracheoesophageal puncture (TEP) and voice prosthesis, patients can develop and maintain the ability to communicate. A major disappointment occurs when that ability is lost again because of dysfunction of the prosthesis from fungal infection, dislodgement, and hyperfunction of the cricopharyngeus (even if CP myotomy was performed at the time of the laryngectomy), or pharyngoesophageal segment, preventing normal airflow through the TEP. In addition, some laryngectomy patients initially fail an insufflation test of the pharyngoesophageal segment, demonstrating hyperfunction of this segment and likely poor TEP function.

The use of BoNT had been shown to be an excellent adjunct in the treatment of these hyperfunctional disorders of the pharyngoesophageal segment. By paralyzing the hyperfunctional muscle fibers, airflow through the TEP and pharyngoesophageal segment is enhanced, resulting in fluent esophageal speech. In cases where the etiology of failure of the TEP is uncertain, BoNT injection into the inferior constrictor and cricopharyngeal fibers can provide diagnostic information by either its success or failure. If successful at ameliorating the problem, BoNT can also be administered for long-term treatment. BoNT may be administered transcutaneously to the suprastomal region using EMG guidance, although scar tissue often prevents robust signal; 50 U is the typical starting dose delivered bilaterally in equal doses. The injection can also be performed without EMG, if the plunger of the syringe is withdrawn prior to injection to prevent inadvertent intravascular or intraluminal injection. The practitioner should be aware of the medialized position of the carotid arteries following total laryngectomy. If there is no response, up to another 50 U can then be administered. The cricopharyngeus muscle is identified by finding baseline activity at rest, which diminishes with a swallow with prompt return of function after the swallow. ⁶ Side effects are rare and may include some dysphagia from weakened constrictor muscles from toxin diffusion. Because of the alaryngeal state, there is no risk of aspiration or airway compromise.

13.4 Benign Vocal Fold Disease

Benign vocal fold disease such as vocal fold nodules, polyps, cysts, granulomas, and hemorrhages all share a common etiologic factor: trauma. Chronic overuse of the voice, vocal abuse, acute phonatory trauma from coughing and yelling, and excessive Valsalva maneuver can all lead to thickening of the epithelium of the vocal folds, subepithelial fibrosis, and vocal hemorrhage. In many of these cases, voice therapy is the gold standard of treatment. Other cases require microsurgical intervention using a microflap technique of removal to optimize vocal outcome. However, often patients are reluctant to undergo surgery, and surgery does entail some small risk of long-term dysphonia. In certain circumstances, in patients with recurrent vocal fold benign disease, or dysphonia that persists despite voice therapy and surgery, BoNT can be used as an adjunct to temporarily weaken the adductor forces of the glottis to allow for healing or resolution of the benign vocal fold disease. By using this technique, there is no risk to the superficial lamina propria from surgical trauma. In addition, patients can continue undergoing voice therapy to help prevent recurrent lesions. Some patients can develop a temporary breathiness inherent in injecting the adductor muscles with BoNT. Though typically temporary, these periods of breathiness can be decreased by serial injections of lower doses of BoNT. The typical starting dose is 0.5 U of toxin delivered by EMG-guided injection into the thyroarytenoid muscle. If no change in voice is noted, an additional booster of 0.5 U can be attempted. Side effects are typical for BoNT injection and include breathiness and possible aspiration. Mild breathiness for a few weeks is ideal, as this gives time for the mucosal pathology to resolve. With ongoing voice therapy, these lesions can actually regress and often do not recur once behavioral changes have been made.