The etiology of UVFP involves dysfunction of either the brainstem nuclei, the vagus nerve, or the recurrent laryngeal nerve (RLN) supplying the involved side of the larynx (Fig. 69.1
). Corticobulbar fibers from the cerebral cortex descend through the internal capsule and synapse on the motor neurons in the nucleus ambiguus. The nucleus ambiguus is the area within the brainstem (medulla) from which arise the fibers that will contribute to the vagus nerve. Lower motor neurons leave the nucleus ambiguus and travel laterally, exiting the medulla between the olive and the pyramid as a series of eight to ten rootlets. These rootlets coalesce into a single nerve root, known as the vagus nerve, which then exits the skull base via the jugular foramen. The vagus nerve descends in the carotid sheath, giving off three major branches: the pharyngeal branch, the superior laryngeal nerve, and the RLN. The SLN supplies sensation to the glottic and supraglottic larynx, as well as motor input to the cricothyroid (CT) muscle, which controls vocal fold lengthening and pitch. The RLN arises from the vagus nerve in the upper chest and loops under the aortic arch (left) or subclavian artery (right) and ascends back into the neck, traveling in the tracheoesophageal groove. The nerve enters the larynx posteriorly, adjacent to the CT joint. The RLN innervates the ipsilateral posterior cricoarytenoid (PCA), interarytenoid (IA) (an unpaired muscle), lateral cricoarytenoid (LCA), and thyroarytenoid (TA) muscles. Thus, the RLN supplies all of the intrinsic laryngeal muscles with the exception of the CT muscle. Ipsilateral RLN transection results in nearcomplete vocal fold immobility. (The ipsilateral CT muscle does not contribute to vocal fold adduction or abduction). It is important to remember, however, that the IA muscle is unpaired, and contralateral RLN input to the IA can lead to some adduction of the vocal fold on the paralyzed side (Fig. 69.2
The causes of unilateral VFP are myriad, but can be broken down into categories to highlight the relevant pathophysiology (2
). These are shown in (Table 69.1
In the past, nonlaryngeal malignancy was generally cited as the most common cause of UVFP, while iatrogenic nerve injury likely represented the most common cause for otolaryngologic referral. Recently, a large retrospective study over 20 years demonstrated a reversal of this trend, such that iatrogenic surgical trauma has now become the most common etiology for unilateral vocal fold immobility (3
Traditionally, thyroidectomy was often thought to account for most of these iatrogenic cases. However, more recent data have shown that nonthyroid surgeries such as carotid endarterectomies and anterior cervical spine
surgery are the causative etiology approximately twice as often as thyroidectomy, 31% versus 16% of all causes, respectively (3
). Merati et al. (4
) also reported a 47.6% rate of iatrogenic injury in 84 patients with acute vocal fold motion impairment, including 27.5% following cervical spine procedures and 15% after thyroidectomy. While iatrogenic VFP caused by anterior cervical spine surgery is clearly on the rise, it is unclear whether this increase is caused by a change in surgical technique or by a rise in the overall number of these surgeries being performed. The overall incidence of this complication has previously been reported to be around 1% but more recent studies have found a higher rate (11%) of early persistent RLN palsy (5
). Netterville et al. (6
) has noted that the complication is almost exclusively right-sided and is probably caused by a stretch injury of the RLN by the Cloward retractor. The shorter, more oblique course of the right RLN seems to predispose it to injury (6
). Other common iatrogenic surgical causes of UVFP include esophagectomy, thymectomy, neck dissection, mediastinoscopy, and cardiothoracic surgery, including aortic surgery, coronary artery bypass grafting, and pulmonary lobar resection (2
). Endotracheal intubation (9
), prolonged nasogastric tube placement, and even esophageal stethoscope placement have been implicated as occasional causes of VFP (Table 69.2
Figure 69.1 Illustration of the neural pathway for the nerves controlling laryngeal function, beginning in the central nervous system (CNS), and terminating with the RLN in the endolarynx. From Academy of Otolaryngology-Head and Neck Surgery: Patient of the Month Program, Volume 31, Number 7. Simpson CB: Breathy dysphonia. Hamilton, Ontario: BC Decker Inc., 2002, with permission.
Figure 69.2 Intrinsic laryngeal musculature and innervation schematic. Note the bilateral innervation of the IA muscle by the RLN. From Rosen CA, Simpson CB. Operative techniques in laryngology. New York, NY: Springer, 2008, with permission.
TABLE 69.1 UNILATERAL VOCAL FOLD IMMOBILITY: CAUSES
Iatrogenic (surgical trauma)
Adapted from Rosenthal LHS, Benninger MS, Deeb RH. Vocal fold immobility: a longitudinal analysis of etiology over 20 years. Laryngoscope 2007;117:1864-1870, with permission.
TABLE 69.2 SURGICAL OR IATROGENIC CAUSES OF VFP
Surgery or Procedure
Mechanism of Nerve Injury or Relevant Anatomy
Anterior cervical spine
Retraction; stretch injury of RLN (right more common) (6)
RLN injury in tracheoesophageal groove
Vagal injury during dissection
RLN injury, usually left
Coronary artery bypass grafting
1. Retraction or direct injury to vagus or RLN during internal mammary artery harvest for grafting (8)
2. Hypothermic nerve injury from ice cardioplegia (7)
Usually left upper lobe or RLN injury
Possible pressure neuropraxia from compression of anterior rami of RLN caused by a high-riding endotracheal cuff in the subglottis (9)
RLN, recurrent laryngeal nerve.
Nonlaryngeal malignancies are another common cause of unilateral VFP. The most common scenario involves bronchiogenic carcinoma of the lung associated with a left RLN paralysis. The cause in these cases is usually mediastinal spread of the malignancy into the aortopulmonary window. These paralyses rarely resolve spontaneously, and deserve early intervention. Other nonlaryngeal malignancies include thyroid, esophageal, and skull base (i.e., paraganglioma) tumors. Because of the common association of nonlaryngeal malignancies with VFP, it is imperative that all unexplained VFP cases be evaluated by means of an appropriate imaging study that looks at the full course of the cervicothoracic vagus and RLN (1
The neurologic event most commonly associated with unilateral VFP is stroke, usually of the brainstem. In these patients, however, other neurologic symptoms (e.g., paraplegia) or additional cranial nerve (CN) involvement are the rule, and isolated unilateral VFP in this setting is highly unlikely (1
). Many of these patients have severe dysphagia and aspiration caused by ipsilateral laryngopharyngeal sensory and motor deficits. Such patients can be challenging to treat, and may fail to improve despite adequate medialization surgery of the paralyzed vocal fold.
Uncommon neurologic causes of VFP include Arnold-Chiari malformation, amyotrophic lateral sclerosis (ALS), Guillain-Barré syndrome, Eaton-Lambert syndrome,
Parkinson disease, Shy-Drager syndrome, progressive bulbar palsy, myasthenia gravis, multiple sclerosis, and postpolio syndrome. Almost all of these disorders will have other obvious signs of progressive neurologic disease in addition to unilateral VFP and, in many cases, the neurologic condition has already been diagnosed before the patient presents with voice complaints. Most of these progressive neurologic conditions present with much more complicated (yet often subtle) findings on head and neck examination, such as a bowed vocal fold or vocal fold atrophy (Parkinson, ALS, postpolio syndrome), unexplained vocal fatigue with subtle reduced vocal fold mobility (myasthenia gravis in particular), vocal spasms (ALS), tongue fasciculations (ALS), and dysarthria (ALS, bulbar palsy). It is important to obtain a neurology consultation when a progressive neurologic disease is suspected.
Idiopathic and miscellaneous causes of unilateral VFP are also seen frequently. A few case reports suggest that “idiopathic” UVFP may be caused by herpes simplex infection (HSV1) of the vagus nerve or its branches. The injury is presumed to be an inflammatory neuropathy, similar to the cranial neuritis observed with Bell palsy (10
). Although this theory is widely regarded as true, little scientific data have been published to demonstrate that HSV neuritis is the causative agent in “idiopathic” UVFP.
In addition, no studies exist that evaluate the benefit of corticosteroids or antiviral medications in the treatment of this condition. Limited data are available to document the natural history of this “idiopathic” UVFP, although Blau and Kapadia (11
) reported spontaneous recovery in approximately 50%. Dworkin and Treadway (12
) also described spontaneous recovery in 25% of patients with more than 3-month follow-up. It is apparent that additional study is needed to evaluate the cause and treatment of “idiopathic” UVFP. Lastly, it is important to remember that idiopathic UVFP is a diagnosis of exclusion, once a detailed history and appropriate imaging studies fail to demonstrate a cause.
Rarely, medications can cause VFP. The most notorious substances are the Vinca alkaloids (vincristine and vinblastine), which are known to cause neurotoxicity. The VFP in this case is dose related and usually resolves over a 4- to 6-week period after stopping or adjusting the dose of the medication. Both unilateral and bilateral VFP have been reported (13
). Cisplatinum, also a potential source of neurotoxicity, has been implicated as a cause of reversible bilateral VFP (14
Systemic diseases can (also rarely) cause vocal fold immobility, because of either paralysis or joint fixation. Such diseases include gout, sarcoidosis, tuberculosis, rheumatoid arthritis, and hypothyroidism (only in cases of myxedema) (16
). Again, these systemic diseases would be expected to have myriad symptoms in addition to unilateral vocal fold immobility, and these conditions should not
be suspected in cases of isolated VFP.
In the case of endotracheal intubation leading to unilateral vocal fold mobility, it is important to rule out the possibility of arytenoid cartilage dislocation or subluxation as the true cause of an immobile vocal fold. This is best done with laryngeal electromyography (LEMG) (see below and also Chapter 70
.) Other traumatic causes of VFP include blunt or penetrating injuries to the neck.