Laryngeal Reinnervation

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CHAPTER 68 Laryngeal Reinnervation

George S. Goding

Key Points

• Ideal rehabilitation of unilateral vocal fold paralysis would involve restoration of vocal fold movement, position, bulk, and tone.
• Complete recovery from unilateral paralysis can happen only through the spontaneous and appropriate regeneration of the recurrent laryngeal nerve.
• Reinnervation options for laryngeal paralysis include (1) the neuromuscular pedicle procedure, (2) ansa hypoglossi–recurrent laryngeal nerve anastomosis, and (3) direct implantation of a nerve (ansa hypoglossi) into the denervated muscle.
• Laryngeal reinnervation as yet does not result in coordinated movement of the vocal fold and is used clinically for unilateral paralysis.

Complete recovery from laryngeal denervation may occur with spontaneous and appropriate regeneration of the recurrent laryngeal nerve (RLN). Surgical intervention cannot reliably provide appropriate vocal fold movement or the rapid and fine adjustments required for continuous vocal fold symmetry. Vocal cord medialization and augmentation allow for improved positioning of the paralyzed vocal fold. The RLN, however, supplies both adductor and abductor laryngeal muscles. Reinnervation procedures designed to generate muscle movement must bypass the main trunk of the nerve and address individual muscles directly or at the most distal branches of the RLN. Reinnervation at the level of the RLN trunk can provide improvement in laryngeal muscle tone and mass.

In 1909, Horsley1 reported the first successful vocal cord reinnervation. He performed a neurorrhaphy of the RLN in a patient who had been shot in the neck, who had nearly complete recovery of laryngeal function. A number of writers have independently reported recurrent nerve repairs with return of function.2–4

In most cases vocal fold motion does not return after RLN anastomosis. Instead, a laryngeal synkinesis occurs with adductor and abductor nerve fibers nonselectively innervating the laryngeal muscles.5–8 The result of this neuromuscular mismatching is that counteracting forces are applied to the arytenoid by all the muscles innervated by the RLN and little or no functional movement occurs.9 An inspiratory medial bulging is seen that is thought to arise by the inappropriate activation of the thyroarytenoid muscle by abductor axons. The majority of RLN repairs, however, are incapable of producing abduction and adduction in functional coordination with the respiratory cycle.

The activity of the phrenic nerve during inspiration makes it an excellent candidate for reinnervation of the posterior cricoarytenoid (PCA) muscle. A similar muscle fiber–type profile between the diaphragm and the PCA also exists.10 Abductor mobility of the vocal fold had been obtained in multiple animal models.11–15 Experimental reinnervation with the phrenic nerve after a 9-month delay is successful but the functional recovery is reduced.16 Attempts at creating vocal fold motion with phrenic nerve reinnervation in humans, however, were unsuccessful.17

Because of the inability to consistently obtain cyclical motion of the vocal cords in coordination with respiration, reinnervation at the level of the nerve trunk has not gained acceptance as a clinical modality for bilateral vocal cord paralysis.18 Selective innervation of individual laryngeal muscles (in particular the PCA muscle) by neuromuscular transfer technique,19 selective anastomosis,20,21 or direct nerve implantation22,23 is required.

Although desirable, cyclical vocal cord motion is not mandatory for the successful rehabilitation of unilateral vocal cord paralysis. This fact has led to the successful use of vocal cord medialization techniques to improve the primary functions of the larynx (closure, respiration, and phonation). The vocal cord medialization techniques currently in use include thyroplasty, arytenoid adduction, and vocal fold injection. Laryngeal reinnervation at the level of the RLN can also take advantage of the resultant synkinesis to provide vocal fold position, bulk, and tone.

The two most common reinnervation techniques that have been applied to the problem of laryngeal paralysis in patients are the neuromuscular pedicle (NMP) and the ansa cervicalis–recurrent laryngeal nerve (ansa-RLN) anastomosis. The two techniques take advantage of the same donor nerve (ansa cervicalis), but otherwise they differ.

The NMP procedure, developed in the 1970s, involves placement of the distal portion of the ansa cervicalis branch to the omohyoid muscle along with a small block of muscle into a denervated laryngeal muscle. The procedure is indicated in patients with either unilateral or bilateral vocal fold paralysis, with different muscles being treated in each case. Depending on the success of reinnervation and the nature of the stimulus, there is a potential for recovery of vocal fold motion. In patients with unilateral vocal fold paralysis, the technique can be combined with a thyroplasty.24

The ansa-RLN anastomosis as an attempt to restore vocal fold movement was first reported by Frazier25 in 1924 and Frazier and Mosser26 in 1926. The current use of the technique was reported in 1986.27 An end-to-end anastomosis of the proximal ansa cervicalis nerve to the distal stump of the RLN is performed. The procedure is indicated for unilateral paralysis because vocal fold motion is not restored. Instead, muscle tone is restored to the entire hemilarynx, providing appropriate vocal fold position, bulk, and tone. The result is the potential for a near normal vocal ability.

Physiologic and Anatomic Issues in Laryngeal Reinnervation

There is substantial evidence that reinnervated muscle takes on the characteristics of the donor nerve (see Talmadge28 for review). This process appears to happen as the reinnervating nerve imposes a pattern of activity on the muscle fibers it contacts. Thus the selection of a donor nerve should ideally take into account the fiber type and contraction characteristics of the muscle to be reinnervated.

Nerve Characteristics

The RLN contains 1000 to 4000 motor axons, efferent axons, and sympathetic and parasympathetic secretomotor fibers, depending on the level at which the count is made. The RLN gives off branches to the cricopharyngeus and upper esophageal muscles29 as well as a sensory branch that communicates with the superior laryngeal nerve prior to entering the larynx. Five hundred to a thousand fibers are in the motor branches of the RLN.30 Before branching within the laryngeal framework, the motor fibers to the various muscles are intermixed throughout the RLN nerve trunk, making selective reinnervation at this level impractical.31 The anterior motor branch of the RLN enters the larynx posterior to the cricothyroid joint. The first branches that emerge from the RLN innervate the PCA muscle and often have connections to the midline interarytenoid muscle. The branch to the PCA muscle has characteristics of a slow-twitch motor nerve, with axons containing 200 to 250 muscle fibers in each motor unit.32 The interarytenoid muscle also receives a separate branch from each RLN, resulting in bilateral innervation. The terminal branches of the RLN innervate the lateral cricoarytenoid (LCA) and thyroarytenoid (TA) muscles. The axons in this branch are more characteristic of fast-twitch fibers, with motor unit sizes of 2 to 20 muscle fibers.33 In some larynges a connection between the superior laryngeal and the terminal fibers of the RLN can be seen within the TA.34

Except for proprioceptive fibers carried within the nerve, the ansa cervicalis is a purely motor derivative of the ventral rami of the cervical plexus. Fibers from the first cervical nerve join the hypoglossal nerve until it curves anteroinferiorly. At this point the first cervical nerve fibers leave the hypoglossal nerve to form the superior root of the ansa cervicalis. The geniohyoid and thyrohyoid are supplied entirely by these fibers. The branch to the superior belly of the omohyoid muscle typically originates from the superior loop of the ansa cervicalis. Because of its proximity to the thyroid ala and infrahyoid position, this branch has been frequently used as a donor for reinnervation using the NMP technique. The other strap muscles receive motor fibers from second and third cervical nerves primarily via the inferior root of the ansa cervicalis. The lower portions of the sternothyroid and sternohyoid muscles receive terminal nerves that branch off the loop of the ansa cervicalis as it passes deep to the omohyoid muscle.35

Muscle Fibers in General

The performance of a particular muscle depends on the character of the individual muscle fibers it contains. On the basis of their histochemical and contraction properties, the fibers of skeletal muscle can be classified as slow fatigue-resistant (type 1), fast fatigue-resistant (type 2A), or fast fatigable (type 2B). Several other classifications and subtypes exist (see Staron36 for review). Type 1 fibers are characterized by a low peak tension, slow contraction time, a low threshold of recruitment, fatigue resistance, and a dependence on aerobic metabolism. Muscles that are required to produce low tension over a prolonged period generally have a high proportion of type 1 fibers. Type 2 fibers are found to play a prominent role in muscles that can generate high tension for short periods. Type 2B fibers have a fast contraction time and can generate a higher tension. They are more easily fatigued, have a higher threshold of activation, and depend on anaerobic metabolism. Type 2A fibers are intermediate in tension, fatigability, and threshold, and they make use of both aerobic and anaerobic metabolism. The laryngeal muscles also have a high-velocity, low-tension fiber types (2L or mixed fiber type) that may be similar to those found in extraocular and jaw-closing muscles.37–40

Most mammalian skeletal muscles are made up of multiple fiber types. Because of these combinations the various whole muscles have a variety of contraction and relaxation characteristics. The peak contraction time of the extraocular muscles is the fastest and that of the soleus muscle is the slowest.

Laryngeal Muscles

Activity of the PCA muscle is synchronous with inspiration and precedes activation of the diaphragm by 40 to 100 msec.41 The amount of activity varies directly with ventilatory resistance. Activity of the PCA produces lateral turning of the arytenoid, resulting in abduction of the vocal fold. Loss of PCA muscle tone results in instability of the arytenoid cartilage. On the basis of gross anatomy42 and innervations,43 the PCA muscle in humans can be divided into a horizontal compartment and a vertical/oblique compartment.43 Some researchers have reported that the PCA in laryngectomy specimens consists of nearly equal percentages of type 1 and type 2 fibers.44 A similar ratio is seen in the primate PCA.45 Other writers have found the PCA to have a higher percentage of type 1 fibers.10 The remainder of the muscle fibers appears to be mostly of the intermediate (type 2A) variety. These findings are consistent with the peak contraction time of the PCA, which is approximately 40 msec.

Reinnervation occurs most easily at the sites of the original motor end plates. It is possible that placement of a reinnervating NMP near a large population of motor end plates could improve the end result.46 The motor end plates of the human PCA muscle are distributed in a loosely arranged arc in the midportion of the muscle. The density of end plates is higher in the deeper portions of the PCA.

TA activity increases with phonation and reflex protection of the airway. Contraction of the TA is critical to the fine control of the mass and tension of the phonating edge of the vocal fold. Atrophy of the TA muscle results in a reduced vocal cord volume and glottic incompetence. Paralysis of the LCA and interarytenoid muscles severely compromises the ability to adduct and stabilize the vocal process of the arytenoid. Bilateral innervation of the interarytenoid muscle is not sufficient to compensate for this loss.

The TA and LCA are faster muscles. Their peak contraction times of 14 msec (TA) and 19 msec (LCA) make them some of the more rapid muscles in the body.45,47 The composition of muscle fibers in the TA is approximately 40% type 1, 55% type 2A, and 5% type 2B. The higher frequency of oxidative fibers characterizes the muscle as having aerobic metabolism, resistance to fatigue, and fast contraction.48 The faster response characteristics of these muscles are appropriate for their phonatory and protective functions.

The pattern of motor end plate distribution in the TA and cricothyroid (CT) muscles is more diffuse than that in the PCA. In the CT muscle the majority of the motor end plates are in the medial two thirds of the muscle49 while in the TA the end plates are scattered throughout the muscle.50 Placement of a NMP, or a direct nerve implant in precise locations, therefore, may offer a limited advantage in reinnervating the PCA and CT muscles. These diffuse patterns differ from skeletal muscles elsewhere in the body where they form a narrow band at the midpoint of the muscle.49

Both adductor and abductor laryngeal muscles contribute to the position and stability of the arytenoid cartilage.51 Restoration of adductor and abductor muscle tone should allow appropriate arytenoid position and stability.

The CT muscle participates in deep inspiration, expiration and phonation. The CT is innervated by the superior laryngeal nerve and is not addressed by ansa-RLN reinnervation. Cricothyroid contraction pulls the vocal process in an anterior and slightly medial direction. This anterior pull is offset by the stabilizing effect of PCA and LCA contraction.

Infrahyoid Muscles

The ansa cervicalis provides motor supply to the infrahyoid muscles and is the most commonly used donor nerve in laryngeal reinnervation. The peak contraction times of the thyrohyoid and sternothyroid muscles are approximately 50 msec.52 Approximately two thirds of the muscle fibers are type 1.53 The infrahyoid muscles have enzyme profiles similar to those of limb muscles and lack the faster mixed fibers found in the laryngeal muscles.54

In the hope of obtaining vocal fold movement, the activity of the various infrahyoid muscles has been examined. The strap muscles extending below the larynx function as accessory muscles of inspiration in varying degrees. The sternohyoid muscle has consistently shown little to no consistent activity with respiration. In the canine, a regular contraction of the sternothyroid muscle is seen with quiet respiration, but all strap muscles lack phasic activity in the primate. With greater airway resistance and hypoxia, inspiratory activity in the primate is greatest in the omohyoid, followed by the sternothyroid muscle .55 The sternothyroid in labored respiration can result in vocal cord lateralization even if the larynx is paralyzed, by means of the sternothyroid muscle’s effect on the laryngeal skeleton.56

The thyrohyoid muscle can similarly assist in adduction of the vocal cords. Medial positioning of the vocal folds is assisted by this muscle’s action of displacing the thyroid cartilage upward. On the basis of activity relative to the respiratory cycle, the nerve supply to the sternothyroid and omohyoid muscles would be acceptable candidates for use in reinnervation for laryngeal abduction. The thyrohyoid muscle’s activity makes its branch of the ansa cervicalis nerve an appropriate choice for laryngeal adduction. Because specific laryngeal muscles are not reinnervated in isolation with the ansa-RLN anastomosis, the activation patterns of the infrahyoid muscles become less meaningful with this technique. Denervation of an infrahyoid muscle does occur and may result in a change in vocal quality immediately after surgery. Sacrifice of the sternothyroid muscle can result in a decrease of lateral pull on the thyroid ala and a medialization effect. The opposite effect can occur with sacrifice of the thyrohyoid muscle.

The infrahyoid muscles are a less than perfect histochemical match to the recipient laryngeal muscles. After reinnervation for unilateral vocal fold paralysis with the ansa cervicalis, changes in the fiber type composition of the laryngeal muscles would be expected.

Effects of Denervation

With denervation, the area of sensitivity to acetylcholine, which is limited to the end plate region in the intact muscle, spreads out over most of the external membrane.57 Denervation also eliminates both the trophic and activity-related influences on the muscle, resulting in muscle atrophy. Without reinnervation there is progressive atrophy and eventual destruction of the muscle despite an adequate supply of all nutrients.

Reinnervation becomes less effective the longer a muscle is denervated. The different laryngeal muscles appear to atrophy at different rates that vary with the muscles’ fiber composition. In a study on primate larynges, the faster TA muscle showed a far greater reduction in fiber size than the slower CT or PCA muscle. By 8 weeks of denervation, however, all laryngeal muscles were fibrosed.58 Muscle atrophy in human skeletal muscles apparently proceeds at a slower pace, with muscles surviving at least 3 years after denervation. Successful laryngeal reinnervation has been claimed as much as 50 years after onset of laryngeal paralysis.59 It is possible that some nerve sprouting occurs, resulting in a low-grade but functionless innervation that preserves the muscle’s ability to be reinnervated.60 Innervation of laryngeal muscles can also come from misdirected reinnervation from autonomic nerves.61

Restoration of Function

Successful regeneration of injured nerves requires (1) a neuron responding to the injury with the metabolic changes necessary to support axonal regrowth, (2) an environment around the injured axon that permits axon growth, and (3) guidance clues for restoration of function.

Regeneration is pointless unless the regenerating axons grow back to reinnervate the original targets. Motor axons preferentially reinnervate distal motor branches of a severed nerve. The specificity is gained primarily through pruning of misdirected fibers.62 Some evidence for a neurotrophic mechanism of directional nerve regrowth exists,63 but the usual outcome of nerve injury suggests the specificity is low. A major problem is that after division of a nerve, a functional specificity in motoneuron regeneration for the original muscle does not exist.64–66 The result, in a regenerating nerve supplying several muscles such as the RLN, is synkinesis.

Muscle fiber types can change under the influence of activation pattern67 and altered innervation.68 The changes following reinnervation with a different donor nerve may be related to a different pattern of activity imposed by the new nerve supply. Fiber type grouping is thought to be a result of this process.69 Mechanisms for directing the regenerating motor axons within a single muscle leading slow- and fast-twitch axons to the appropriate muscle fibers have some influence on reinnervation.70 The effect, however, is not enough to prevent changes in muscle fiber type. Reinnervation with a new donor nerve would be expected to change the fiber type composition of the reinnervated muscle and thus its contraction characteristics.

The Neuromuscular Pedicle

The NMP technique attempts to transfer a nerve with a portion of its motor units intact to a denervated muscle. Preservation of motor units is brought about by the inclusion of a small block of muscle at the distal end of the donor nerve. This inclusion distinguishes the technique from nerve anastomosis, implantation of a nerve stump, and direct electrical stimulation of muscle fibers.

Reinnervation with the Neuromuscular Pedicle

Successful reinnervation with an NMP depends partly on the ability of the transplanted axons to reach receptive sites on the recipient muscle fibers and partly on the ability of the muscle fibers to accept innervation from foreign nerves. With partial denervation of the transferred nerve, the remaining intact motor neurons develop sprouts that provide reinnervation preferentially at the original end plate sites of the denervated muscle fibers.71,72 This phenomenon is important to successful transfer of the NMP, because a portion of the nerve fibers in an NMP may have an intact motor unit.73 Axon sprouting results in a larger number of motor fibers innervated by each nerve. Mature nerve terminals appear to be limited in functional expansion to three to five times the normal terminal field.74

Laboratory Investigations

In early experiments a block of muscle containing the terminal branches of the recurrent laryngeal nerve was removed and reimplanted into the larynx.73,75 A small portion of muscle was incorporated at the distal end of the transferred nerve to transfer intact nerve fibers. The short time to functional recovery (2 to 6 weeks) was thought to be secondary to the avoidance of degeneration and regeneration before effective reinnervation.

In 1973, reinnervation of the canine larynx with an NMP derived from the ansa cervicalis nerve and its insertion into the sternohyoid muscle was described.76 The technique was modified because of the unavailability of the RLN in most cases of laryngeal paralysis and the unsuitability of preserving a portion of the larynx in the presence of cancer.77 Return of function was seen at approximately 6 weeks after surgery. Reinnervation could be successful up to 6 months after denervation.78

Evidence for reinnervation with the NMP has included muscle response to pedicle stimulation, demonstration of neural tracer in the central motor nuclei of the donor nerve,79 and glycogen depletion in fiber of reinnervated muscles.80 Successful use of the NMP technique in animal models has been reported by multiple researchers.19,81–85 In their studies, electrical stimulation of the transferred nerve or induction of greater respiratory effort was required to produce gross motion.

In other studies, the presence of vocal fold movement under hypercarbic conditions was not associated with evidence of reinnervation by either direct stimulation86–88 or histologic evaluation.88 Other maneuvers, such as division of the inferior pharyngeal constrictor86 or of the superior laryngeal nerve or the strap muscles,87 were effective in eliminating the observed vocal fold motion. Postoperative scarring, which could stabilize the arytenoid and lateral tethering of the arytenoid to the thyroid cartilage, is a potential explanation for vocal fold motion not related to reinnervation.89

A modification of the NMP technique involves using a transferred NMP as a means of providing access to a denervated muscle for long-term electrical stimulation.90–92 A cuffed electrode can be placed around the nerve component of an implanted NMP. This should avoid deterioration at the electrode-muscle interface. Successful pacing was accomplished for the sternothyroid90 and PCA91 muscles with the use of tracheal motion with respiration as the triggering signal.

Indications

Bilateral Paralysis

The NMP technique can be considered for any patient with bilateral vocal cord paralysis that has persisted for 6 months59 to a year.93 In practice, however, only half of such patients are suitable candidates.94 Fixation or limitation of the cricoarytenoid joint is the most common contraindication, affecting approximately one third of patients.93 Direct laryngoscopy and palpation of the arytenoids prior to proceeding with the NMP procedure is recommended.

The ansa cervicalis nerve and its insertion into the appropriate strap muscle must be available for this technique. Any prior surgery or trauma that may have injured the ansa cervicalis should be carefully reviewed. Other causes of airway obstruction should be resolved before reinnervation.93

Central nervous system disease resulting in vocal cord paralysis is a relative contraindication. Tucker93 has reported only a 40% to 50% success rate in patients with such diseases, which may also disrupt the function of the ansa cervicalis nerve.

Finally, the laryngeal muscles must be able to accept reinnervation. Although successful reinnervation has been reported after 22 and 50 years of denervation, muscle atrophy probably plays a role in hampering the outcome. The incidence of cricoarytenoid fixation may increase with time95 but this finding has not been confirmed hstologically.96

Unilateral Paralysis

Consideration of reinnervation is usually delayed in patients with unilateral paralysis until enough time has passed to make spontaneous recovery unlikely. In patients who have difficulty with aspiration, vocal fold injection has been recommended. Prior injection of polytetrafluoroethylene (Teflon) into the vocal cord, however, has had a poor vocal result.97 The procedure has also been limited to patients who require above-average vocal quality.

Like patients with bilateral vocal cord paralysis who are being considered for an NMP procedure, the patient with unilateral paralysis must be able to tolerate the procedure, and the ansa cervicalis nerve must be intact, the selected adductor muscle must be in suitable condition for reinnervation, and there must be a mobile arytenoid muscle on the paralyzed side. Inability to visualize the larynx by normal endoscopic methods, which precludes transoral injection, is an additional indication for NMP reinnervation.97

Technique

The description of the NMP procedure below is that first described by Tucker59with modifications by other writers as noted (Fig. 68-1).77,93,95,98

image

Figure 68-1. Neuromuscular pedicle (NMP). A, NMP harvested from omohyoid muscle. The branch of the ansa cervicalis nerve to the omohyoid is removed with a 2- to 3-mm attached block of muscle. SCM, sternocleidomastoid muscle. B, NMP placed into the posterior cricoarytenoid muscle after rotation of the larynx and separation of the fibers of the inferior constrictor for the treatment of bilateral paralysis. C, NMP placed into the lateral cricoarytenoid muscle via a window in the thyroid ala for the treatment of unilateral paralysis.

In Bilateral Paralysis

When performed in a patient with bilateral paralysis, the procedure begins with laryngoscopy and palpation of the arytenoids with the patient under general anesthesia and muscular paralysis but with no endotracheal tube. Once it is determined the arytenoids are freely mobile, the patient is intubated, and a tracheotomy is performed if one is not already present.

A horizontal incision is made near the lower border of the thyroid cartilage. The anterior border of the sternocleidomastoid muscle is exposed and retracted laterally. Dissection of the anterior belly of the omohyoid muscle and the fascia overlying the internal jugular vein is completed. The branch of the ansa cervicalis supplying the anterior belly of the omohyoid muscle can be identified in either of the following two ways: (1) by finding the main trunk of the ansa cervicalis as it crosses the internal jugular vein and tracing it proximally and distally until the appropriate branch is recognized or (2) by mobilizing the medial border of the omohyoid near its attachment to the hyoid and dissecting in a medial to lateral direction along the muscle. The nerve is usually accompanied by a small arterial vessel, which is preserved. If the nerve is injured, the branch to the sternothyroid is also acceptable.89,99

After the point of entry into the muscle is determined, dissection of the nerve is continued distally until its terminal branches are identified. This may require an additional 2 to 3 mm of dissection from the entrance of the nerve into the muscle. A block of muscle large enough to include the terminal branches (usually 2-3 mm on a side) is dissected free with the attached nerve. The muscle block is kept as small as possible because it will act as a free graft. The proximal portion of the omohyoid branch of the ansa cervicalis is mobilized, with care taken to preserve the accompanying vessel.

The lateral margin of the thyroid cartilage is identified and is used to rotate the larynx toward the opposite side. With the dissection kept close to the lateral edge of the thyroid ala, the fibers of the inferior constrictor are bluntly separated. Dissection is continued until either the pyriform sinus is encountered or the PCA muscle is seen. The mucosa of the pyriform sinus is bluntly displaced superiorly if necessary. The PCA muscle can be recognized from its fibers, which pass at right angles to those of the inferior constrictor.

The NMP is then sutured to the PCA with two or three sutures of 5-0 nylon. Abrasion of the surface of the PCA is not necessary for reinnervation to occur. Closure of the fibers of the inferior constrictor muscle is not necessary. A drain is placed, and the wound is closed in layers. Postoperative antibiotics are not routinely used.

Unilateral Paralysis

The direct laryngoscopy and harvesting of the NMP are the same for unilateral vocal cord paralysis as for bilateral paralysis. No tracheotomy is performed. The recipient muscle in unilateral paralysis is the LCA, and the second portion of the operation varies accordingly.

The thyroid cartilage on the denervated side is exposed, and the lower half of the perichondrium of the thyroid cartilage is incised in the midline. A posteriorly based perichondrial flap exposing the lower half of the thyroid ala is created. A block of thyroid cartilage is removed from this area, leaving the underlying perichondrium and the inferior margin of the thyroid cartilage intact. The inner perichondrium is incised to expose the denervated LCA muscle, and the NMP is sutured in place with two or three sutures of 5-0 nylon. The outer perichondrial flap may be sutured back in place, and the wound is closed in layers with a drain. One modification consists of placement of two pedicles (each from a separate strap muscle) into the recipient muscle.100

Intravenous dexamethasone has been given to reduce laryngeal edema in the early recovery period after NMP in unilateral vocal paralysis.99 Voice rest and postoperative antibiotics are not necessary.

Reported Results

In 1976, Tucker77 reported using the NMP in humans for bilateral vocal fold paralysis. All five patients he studied demonstrated vocal cord abduction with inspiration within 6 to 8 weeks after the procedure. In two patients with a marked improvement in exercise tolerance, vocal cord motion was not seen without an increased respiratory effort. In 1978, Tucker59 reviewed 45 cases of NMP laryngeal reinnervation for bilateral vocal cord paralysis, reporting an 88.8% (40/45) success rate. Duration of follow-up ranged from 3 months to 4 years, and duration of paralysis ranged from 6 months to 50 years. The time to return of function varied from 6 to 12 weeks.

In 1982, Tucker93 divided results of NMP reinnervation for bilateral vocal cord paralysis into three categories. In approximately 40% of his cases, airway improvement was accompanied by visible motion of the vocal cord with inspiratory effort; 20% of patients had no airway improvement. The remaining patients had airway improvement but little vocal cord motion. Most of the patients in this last group demonstrated vocal cord motion or tonic abduction only with increased respiratory demand. A second NMP procedure to the opposite PCA muscle has been performed successfully in patients in whom the first procedure had an inadequate result.93

A review of 214 patients with bilateral vocal cord paralysis demonstrated a 74% long-term success rate.94 In 48% of patients, tracheotomy was performed at the time of reinnervation. Success was defined as decannulation with improved airway that did not limit regular daily activities or exacerbate acute upper respiratory disease. Minimum follow-up was 2 years. Six-month results showed an 89% success rate, but 31 patients had subsequent deterioration of the airway. In a majority of patients with late failure who were evaluated, fixation of the cricoarytenoid joint was identified.

In 1977, Tucker reported the use of the NMP procedure in 9 patients with unilateral vocal cord paralysis.98 Recovery of adductive function was seen 2 to 12 weeks after surgery in all of the patients. Only 6 patients had a satisfactory improvement in vocal quality, and a subsequent polytetrafluoroethylene injection was required in the other 3. In a subsequent report on the use of the NMP in unilateral vocal cord paralysis, improvement was found in 25 of 27 patients undergoing a NMP procedure to the LCA.99

In a 1989 study, NMP procedures for unilateral paralysis were reported to have a success rate of 88%.94 Success was established by voice improvement, vocal cord adduction, and change in cord tension with elevated pitch. Voice results were noted to improve for several months and were aided by the addition of speech therapy.

May and colleagues101 reported their results with the NMP procedure in 1980. Of 8 patients undergoing NMP reinnervation of the PCA for airway obstruction only 3 experienced improvement; 13 of 15 patients with disordered phonation and/or deglutition were improved by NMP reinnervation of the LCA. Applebaum and associates100 reported successful results in all 6 of their patients undergoing the NMP technique. Four of the patients had bilateral vocal cord paralysis, with 1 requiring a tracheostomy. Dyspnea and stridor were relieved in all 4 patients, in whom vocal cord movement was seen only after physical exertion.

For isolated unilateral recurrent laryngeal paralysis, May and Beery97 reported improvement in the voice in 19 of 20 (95%) patients treated with NMP implantation into the LCA muscle. Observable movement of the reinnervated cord was seen in only 1 patient, suggesting that enhanced muscle tone or a slight change in position was responsible for voice improvement. The degree of voice improvement was substantially less in patients with multiple cranial nerve deficits or vocal cord fixation.

Complications

The main complication of the NMP technique is failure to obtain a satisfactory result. Many of the patient selection factors listed previously as contraindications are a result of these experiences. Relatively few operative complications associated with the NMP procedure are described. In 214 patients undergoing an NMP procedure for bilateral vocal cord paralysis, Tucker99 noted only four complications. Three were wound infections, and the fourth was related to the previously placed tracheotomy. No complications were reported in 73 patients undergoing NMP for unilateral paralysis. No operative complications were reported in other series.97,100

Future of the Neuromuscular Pedicle Procedure

Despite its successful use in a few writers’ experiences, widespread use of the NMP has not materialized. Reinnervation can occur with implantation of an NMP into denervated muscle, but the ansa cervicalis continues to be an imperfect source for neural input. Even in the absence of movement with respiration, the NMP can maintain muscular tone.

The NMP can provide a mechanism to access a denervated muscle for long-term pacing.90,91 With electrical pacing, the options for a potential triggering source and the stimulus for muscle contraction are increased, providing a potentially more effective treatment of airway impairment secondary to bilateral vocal fold paralysis.

Ansa Cervicalis–Recurrent Laryngeal Nerve Anastomosis

The current use of the ansa-RLN anastomosis is in unilateral vocal fold paralysis. No motion of the reinnervated vocal fold with respiration or phonation is expected. A variation of this technique involves a hypoglossal nerve–RLN anastomosis.102,103 Use of the ansa cervicalis as a donor nerve has gained the widest acceptance because of the lower morbidity associated with the sacrifice of this nerve.

Advantages

The procedure is relatively easy to perform in an unoperated neck for any surgeon familiar with head and neck anatomy. The primary difficulty is associated with identifying the appropriate nerves when excessive scar is present. There is typically no “learning curve” with respect to the ultimate vocal result, because fine adjustments of vocal fold position are not required. In contrast, the ultimate vocal result for vocal cord injection and thyroplasty is determined at the time of surgery and depends on the expertise of the surgeon.

The ansa-RLN procedure provides tone, position, and bulk to the denervated muscles, resulting in less asymmetry between the normal and reinnervated vocal cords. This result offers the opportunity for an outstanding rehabilitation of unilateral vocal cord paralysis. Improvement in vocal quality can also continue to occur after the initial improvement seen during the first year after surgery.

The sacrifice of the sternothyroid muscle is clinically insignificant and may theoretically improve vocal function. The resting tone of the sternothyroid muscle slightly lateralizes the normal vocal cord.56 Loss of this tone may result in a slight medialization of the paralyzed vocal cord and an improvement in vocal quality early after surgery.60

The procedure is primarily extralaryngeal and can be reversed by division of the anastomosis at a later time. Because the thyroid ala and intrinsic muscles of the larynx are not violated, the subsequent use of vocal fold injection or thyroplasty is not limited. The impact of the delay prior to reinnervation can be reduced when the procedure is combined with injection of absorbable material into the vocal fold at the time of surgery. No permanent implant material is used, so the potential for implant migration or foreign body reaction at the level of the vocal cord is eliminated.

Disadvantage

The ansa-RLN transfer procedure requires a deeper level of dissection in the neck and typically takes longer to perform than thyroplasty or vocal fold injection. The time for completion of the ansa-RLN is estimated at 2 hours.104 Although thyroplasty is typically performed with the patient under sedation and vocal fold injection can be performed in the clinic, ansa-RLN anastomosis is performed under general anesthesia.

The possibility of spontaneous recovery of vocal fold function is eliminated with the division of the RLN prior to ansa-RLN anastomosis. It is important to wait until the possibility of spontaneous recovery is minimal before performing this procedure.

There is a delay of 5 to 9 months before substantial improvement in the voice occurs, in addition to the several-month delay of waiting for the possibility of spontaneous recovery before the procedure is performed. Often an initial improvement can be seen as early as 3 to 4 months after surgery. Improvement, however, can continue for several years.

The procedure requires one intact ansa cervicalis and the intact distal stump of the RLN. This requirement can be difficult to satisfy after thyroid surgery or impossible after bilateral neck surgery in which the ansa cervicalis is sacrificed. In cases of unilateral neck surgery the contralateral ansa cervicalis can be used. Unlike in thyroplasty, the consequences of performing the procedure on the wrong (nonparalyzed) side are severe. With division of the only remaining intact RLN, a bilateral vocal fold immobility and resultant airway obstruction are likely consequences.

Surgical Indications and Contraindications

Ansa-RLN anastomosis is indicated for the treatment of unilateral vocal fold paralysis in which there is minimal chance for spontaneous recovery. The most common waiting period prior to consideration of reinnervation is 12 months. The distal stump of the RLN must be available for anastomosis. In the presence of extensive scar, the RLN can be found behind the cricothyroid joint. A donor nerve must also be available. The ansa cervicalis, however, can be prepared from either the ipsilateral or contralateral side. The patient must be able to tolerate both general anesthesia and the wait for substantial improvement from reinnervation.

Absolute contraindications include glottic airway compromise, bilateral vocal fold paralysis, absence of the distal RLN, bilateral absence of the ansa cervicalis, and poor general health.

The relative contraindications to ansa-RLN anastomosis include limitations of time, voice, and surgery. Time limitations primarily focus on the delay after surgery for the voice improvement. Is the wait worthwhile for the patient? Time can be limited by either social or work considerations or by the patient’s life expectancy. If the patent’s life expectancy is less than 5 years, the delay for improvement with reinnervation may not be worthwhile. The procedure also appears to be less successful in the elderly and in patients who have had paralysis for several decades. Voice limitations focus on the fact that ansa-RLN anastomosis fixes only the position, bulk, and tone of the paralyzed vocal fold. Is there other pathology that will limit the voice result, such as dysarthria associated with multiple cranial nerve defects or stroke? Other vocal fold pathology that will limit the ultimate result, such as the presence of a vocal fold scar, web, or polyp, must be considered. If a near-normal voice is not the anticipated result, the use of ansa-RLN anastomosis should be considered carefully. Fixation of an arytenoid in a lateral position also has an adverse effect on the expected outcome.

Surgical considerations also come into play when prior surgery has occurred in the area of the RLN. Is there extensive scarring or atrophy of the nerve? The possibility of not finding an adequate nerve for anastomosis must be considered, and alternative plans for intraoperative management reviewed with the patient.

Surgical Technique

An incision in a natural crease of the neck is made below the level of the cricoid cartilage, often at the level of a thyroidectomy incision (Fig. 68-2). The incision need not cross the midline, and 4 cm is usually adequate. The strap muscles are separated vertically in the midline, and the RLN is identified in the tracheoesophageal groove. The nerve is dissected to its entrance into the larynx. In the presence of local scar tissue, the RLN can be found behind the cricothyroid joint. A vessel loop can be placed around the nerve. The anterior border of the sternocleidomastoid muscle is identified. The ansa cervicalis nerve can be identified along the lateral border of the sternothyroid muscle, at the level of the omohyoid muscle, or along the internal jugular vein.

image

Figure 68-2. Ansa cervicalis to recurrent laryngeal nerve (RLN) anastomosis. A, Exposure of branch to sternohyoid muscle. B, Exposure of RLN in the tracheoesophageal groove. C, Ansa-RLN anastomosis.

After both nerves are identified and the distal RLN is confirmed to be intact, the ansa cervicalis nerve and RLN are transected. Each nerve should be divided inferiorly enough to allow a tension-free anastomosis. A tunnel deep to the sternohyoid and sternothyroid muscles connects the two operative sites and facilitates the anastomosis. The anastomosis is performed with the use of 9-0 or 10-0 nylon sutures. Two or three epineural sutures are adequate. Magnification with either a surgical microscope or loupes can be used. The wound is closed in layers with an appropriate drain.

An absorbable material can be injected at the time of surgery to provide an initial improvement in vocal quality. After 2 to 3 months the voice may deteriorate to the preoperative level. At 4 to 6 months after surgery, a gradual improvement in vocal quality begins. On laryngeal examination after ansa-RLN transfer, the reinnervated cord is immobile or demonstrates only minimal movement. The procedure produces a synkinesis that allows the mobile vocal fold to approximate the reinnervated fold in the midline.

Clinical Results

Ansa-RLN anastomosis has produced near-normal vocal quality in most reports. The initial two reports by Crumley and colleagues27,105 described success in two patients and four patients. In one of these patients the contralateral ansa cervicalis nerve served as the donor nerve. No motion of the reinnervated vocal fold was seen in reinnervated patients. The vocal improvement was believed to be secondary to precise positioning of the reinnervated vocal fold. Reinnervation of the of PCA, LCA, and TA muscles appears to provide the needed tone to stabilize and position the arytenoid properly.51

A series of 20 patients undergoing ansa-RLN anastomosis was reviewed by Crumley60 in 1991. Vocal quality was judged to be normal or near normal in 18 of 20 cases. In the one failure, identification of the RLN was in doubt secondary to local scar formation from multiple prior procedures. A second patient demonstrated improvement but to a lesser extent. Lateralization of the arytenoid and the patient’s age (65 years) were cited as possible factors contributing to the lesser result. Several patients in whom the delay between injury and reinnervation exceeded 8 years had successful results.

Ansa-RLN anastomosis was successful in two elderly patients (66 and 71 years old) following resection of mediastinal tumors with early reinnervation.106 Zheng and coworkers107 presented eight cases with one disappointing result. They used an anterior branch of the RLN. Slight improvement was seen early after surgery, with additional improvement seen at 2 to 3 months. Electromyographic confirmation was obtained in five patients. Passive arytenoid mobility was important in achieving good results and was related to the one substandard result.

Similar results in terms of mean phonation time and vocal fold position are seen after a direct anastomosis of the RLN, a free nerve graft reconstructing the RLN, a vagus nerve–RLN anastomosis, and an ansa-RLN anastomosis performed during the course of thyroid surgery.108 The ansa-RLN anastomosis has several advantages over other means of reconstruction of a divided RLN during the course of thyroid or other neck surgery. These include the requirement of only one anastomosis performed at a relatively accessible level in the neck, a relatively short time to recovery because the anastomosis is close to the larynx, and availability when the RLN is injured within the mediastinum. Performing the anastomosis behind the thyroid cartilage108 as well as using the contralateral ansa cervicalis as a donor nerve109 improves the chances of successful reconstruction.

Olsen and colleagues110 performed a quantitative analysis of 12 patients with ansa-RLN anastomosis for unilateral vocal fold paralysis. Improvement in vocal quality was demonstrated. Results of acoustic analyses in postoperative patients were similar to those in a control group of normal subjects. Patients with isolated vocal fold paralysis had the best results. Improvement in overall severity, roughness, and breathiness of the patient’s voice more than 6 months following ansa-RLN anastomosis has also been demonstrated.111 The greatest improvement was seen with breathiness measures. Postoperative electromyographic studies of patients undergoing reinnervation with an ansa-RLN anastomosis as well as NMP implantation into the TA have shown activation of the reinnervated muscle with speech and head elevation.112 Head elevation maneuvers that directly activate the strap muscles were routinely found to result in greater activation of the TA and LCA muscles. Activation of the TA muscles with speech was found to increase with time.

Chhetri and colleagues113 reported that the addition of ansa-RLN anastomosis to arytenoid adduction did not result in better acoustic results than arytenoid adduction alone. All patients in their series had significant perceptual improvement in voice, but these investigators questioned the relationship of surgical repositioning of the arytenoid and reinnervation in unilateral paralysis.

Direct Nerve Implant

Early in the 20th century, direct implantation of a nerve into a denervated muscle was shown to produce successful reinnervation in experimental models.114–116 Insertion of a nerve ending into skeletal muscle results in the establishment of neuromuscular junctions.117,118 Using multiple implants distributed over a wide area increases the effectiveness of reinnervation with the direct nerve implantation technique.119 Direct nerve implants have been successfully used in 10 patients, with active muscle movement occurring in all 10 patients.120 A short period of denervation, a healthy donor nerve, and a wide distribution of nerve fibers entering the muscle had a positive effect on the outcome.

Early experiments investigating direct nerve implantation also examined the value of the technique in laryngeal reinnervation.121,122 Direct implantation of the RLN into the PCA muscle was successfully performed in the canine and proposed as a promising method for reinnervation.4,123

Comparisons of the NMP procedure with direct implantation of the ansa cervicalis nerve into denervated muscle have shown mixed results. Meikle and associates82 showed no advantage of one method over the other, whereas Hall and colleagues83 found the NMP procedure to produce stronger evoked contractions and to involve a shorter time to return of function. Both groups judged that their results were consistent with the action of the NMP as a source for multiple direct nerve implants rather than a predominant reliance on transfer of intact motor units. Because of the need to support a distal muscle pedicle, the NMP procedure was inferior to the direct nerve implantation when the reinnervation procedure was extended with a cable graft.84

Direct nerve implantation of the TA muscle was performed in ten patients with unilateral paralysis.124 Improvement of voice was seen in eight, with a return to “normal” or “great improvement” in 6 patients. Reinnervation was supported by electromyography in all four patients tested.

A variant of this technique, in which a nerve acts as a conduit from an innervated muscle to the contralateral, denervated muscle (muscle-nerve-muscle), has been successfully used.125 Selective cricothyroid reinnervation with a muscle-nerve-muscle graft from the contralateral cricothyroid was used in combination with ansa-RLN anastomosis in three patients (Fig. 68-3). All patients had improved voice and electromyographic evidence of cricothyroid muscle reinnervation.

image

Figure 68-3. Muscle-nerve-muscle graft between the innervated and denervated cricothyroid muscle.

SUGGESTED READINGS

Chhetri DK, Gerratt BR, Kreiman J, et al. Combined arytenoid adduction and laryngeal reinnervation in the treatment of vocal fold paralysis. Laryngoscope. 1999;109:1928-1936.

Crumley RL, Izdebski K, McMicken B. Nerve transfer versus Teflon injection for vocal cord paralysis: a comparison. Laryngoscope. 1988;98:1200-1204.

Crumley RL. Update: ansa cervicalis to recurrent laryngeal nerve anastomosis for unilateral laryngeal paralysis. Laryngoscope. 1991;101:384-388.

Crumley RL, Izdebski K. Voice quality following laryngeal reinnervation by ansa hypoglossi transfer. Laryngoscope. 1986;96:611-616.

El-Kashlan HK, Carroll WR, Hogikyan ND, et al. Selective cricothyroid muscle reinnervation by muscle-nerve-muscle neurotization. Arch Otolaryngol Head Neck Surg. 2001;127:1211-1215.

Lee WT, Milstein C, Hicks D, et al. Results of ansa to recurrent laryngeal nerve reinnervation. Otolaryngol Head Neck Surg. 2007;136:450-454.

Maronian N, Waugh P, Robinson L, et al. Electromyographic findings in recurrent laryngeal nerve reinnervation. Ann Otol Rhinol Laryngol. 2003;112:314-323.

Miyauchi A, Matsusaka K, Kawaguchi H, et al. Ansa-recurrent nerve anastomosis for vocal cord paralysis due to mediastinal lesions. Ann Thorac Surg. 1994;57:1020-1021.

Miyauchi A, Matsusaka K, Kihara M, et al. The role of ansa-to-recurrent-laryngeal nerve anastomosis in operations for thyroid cancer. Eur J Surg. 1998;164:927-933.

Miyauchi A, Yokozawa T, Kobayashi K, et al. Opposite ansa cervicalis to recurrent laryngeal nerve anastomosis to restore phonation in patients with advanced thyroid cancer. Eur J Surg. 2001;167:540-541.

Olson DE, Goding GS, Michael DD. Acoustic and perceptual evaluation of laryngeal reinnervation by ansa cervicalis transfer. Laryngoscope. 1998;108:1767-1772.

Su WF, Hsu YD, Chen HC, et al. Laryngeal reinnervation by ansa cervicalis nerve implantation for unilateral vocal cord paralysis in humans. J Am Coll Surg. 2007;204:64-72.

Tucker HM. Reinnervation of the paralyzed larynx: a review. Head Neck Surg. 1979;1:235-242.

Tucker HM. Long-term results of nerve-muscle pedicle reinnervation for laryngeal paralysis. Ann Otol Rhinol Laryngol. 1989;98:674-676.

Zheng H, Li Z, Zhou S, et al. Update: laryngeal reinnervation for unilateral vocal cord paralysis with the ansa cervicalis. Laryngoscope. 1996;106:1522-1527.

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