Bilateral Vocal Fold Paralysis: Etiology, Diagnosis and Treatment Options — A Clinical Case
Greta Ona Andrijauskaitė¹, Vilmantė Vaitekėnaitė¹, Dr. Andrius Matulevičius¹˒², Dr. Arnoldas Morozas¹˒²
¹Vilnius University Faculty of Medicine
²Vilnius University Hospital Santaros Klinikos
Introduction
Bilateral vocal fold paralysis (BVFP) is the most common cause of dysphonia in elderly individuals. The most common etiological factors of BVFP affecting the vocal folds innervated by the vagus nerve (n. vagus) or its branch, the recurrent laryngeal nerve (n. laryngeus recurrens), are iatrogenic and oncological in nature.
The most recommended diagnostic procedures for BVFP are fiberoptic laryngoscopy, direct laryngoscopy, and laryngeal electromyography. Surgical treatment methods for BVFP include tracheostomy, arytenoidectomy, cordotomy, lateralization, and reinnervation.
Tracheostomy is the most common treatment method for BVFP. Despite its drawbacks, this method is considered an effective initial short-term treatment for BVFP. Both arytenoidectomy and cordotomy are irreversible surgical treatment methods for BVFP that widen the airway but are often complicated by voice changes and airway narrowing due to the formation of granulation tissue and scarring.
Compared with the latter two methods, lateralization significantly improves lung ventilation, reduces the risk of aspiration, and preserves voice quality, making it recommended for patients who are expected to recover laryngeal function or who wish to avoid tracheostomy. Other new methods for treating BVFP are still under investigation and are therefore not recommended for routine clinical practice.
BVFP Etiology
The incidence of BVFP increases with age. This may be because older individuals are more likely to have oncological and neurological diseases (1). In fact, 72% of cases of dysphonia in older patients are caused by vocal fold paralysis (2). However, the exact prevalence of this pathology remains unknown because of diagnostic challenges.
Bilateral vocal fold paralysis most commonly develops due to iatrogenic causes, when the vagus nerve (n. vagus) or its branch, the recurrent laryngeal nerve (n. laryngeus recurrens), is damaged during surgery (2). Thyroidectomy accounts for a large proportion of surgical causes, up to 90% according to various authors. Although this remains the predominant cause, some authors have noted a decreasing trend in such cases, which is associated with improvements in surgical techniques (3). In rarer cases, BVFP may also develop after other neck and thoracic surgical procedures (2).
The second most common cause of BVFP is damage to the vagus or recurrent laryngeal nerve due to tumor spread. This is most commonly caused by tumors in the mediastinum and lung region, including tumors of the lungs, esophagus, and thyroid, as well as metastases. Vocal fold paralysis may also be caused by radiation therapy for head and neck tumors because blood flow around the nerves within the radiation field deteriorates, leading to fibrotic changes and subsequent nerve dysfunction and damage (1).
Other relatively common causes include intubation trauma, which causes mechanical compression of the recurrent laryngeal nerve, and idiopathic causes. The literature also contains data on vocal fold paralysis triggered by neurotropic viruses. For example, cases associated with Herpes simplex, Varicella zoster, and Epstein-Barr infections have been described (2, 4). Cases have also been reported in which paralysis was caused by a systemic disease, such as sarcoidosis, or neurological diseases, including multiple sclerosis and amyotrophic lateral sclerosis (2).
BVFP Diagnosis
Bilateral recurrent laryngeal nerve damage is characterized by stridor and a history of thyroidectomy. The voice may remain normal, with the vocal folds observed in a medial-paramedial position (5).
The literature most commonly recommends assessing the following laboratory parameters: potassium and calcium ions, blood glucose concentration, antineutrophil cytoplasmic antibody concentration, laboratory diagnostic markers of venereal diseases, Lyme disease titer, a skin test for tuberculosis, uric acid concentration, rheumatoid factor activity, antinuclear antibody concentration, and erythrocyte sedimentation rate (6).
If no other cause is identified, imaging recommendations include computed tomography covering the entire course of the vagus nerve, from the base of the skull to the upper mediastinum (6, 7). Magnetic resonance imaging is not recommended as a routine examination for diagnosing BVFP. Pulmonary function testing is useful for detecting upper airway obstruction, assessing its severity, and monitoring the patient after treatment. Acoustic analysis is useful for evaluating voice recovery over time. Neurological examinations and/or consultation with a neurologist help differentiate central nervous system or neuromuscular diseases that may cause bilateral vocal fold paralysis (6).
Three diagnostic procedures are recommended for BVFP: fiberoptic laryngoscopy, direct laryngoscopy, and laryngeal electromyography (EMG). Fiberoptic laryngoscopy is the principal method of clinical assessment. A variant of this method, stroboscopic video laryngoscopy, can provide additional information about vocal fold movement disorders, such as asymmetry of the mucosal wave.
Laryngoscopy in patients with BVFP reveals immobile vocal folds. During laryngoscopy, it is also important to examine not only the posterior regions of the vocal folds and arytenoid cartilages but also the subglottic part of the larynx, trachea, and main bronchus for possible subglottic stenosis, tumors, or other abnormalities.
Laryngeal EMG provides information about the transverse arytenoid and posterior cricoarytenoid muscles and should be performed after administering topical analgesic medication, most commonly in children (6). In patients diagnosed with BVFP, laryngeal EMG provides useful information for differentiating fixation from paralysis and other disorders, as well as for identifying neuromuscular diseases or peripheral neuropathy (6, 7).
EMG may be performed as early as 2 days after the onset of BVFP for differential diagnosis. The baseline assessment can be used as a prognostic tool. The examination should be performed within 30 days of the development of BVFP, or within 30–60 days when there is a secondary cause. Laryngeal EMG can help predict poor recovery of vocal fold function in approximately 90% of cases (6).
Treatment
Surgical methods for treating BVFP can be divided into 4 main groups:
- Resection of anatomical structures (tracheostomy, arytenoidectomy, cordotomy).
- Modification and redistribution of existing structures (lateralization) with minimal tissue removal.
- Redistribution of existing structures (lateralization) without tissue resection.
- Restoration or replacement of the absent innervation of the laryngeal muscles (reinnervation) (8).
Tracheostomy
Tracheostomy is one of the most commonly used surgical methods for treating BVFP. Despite its effectiveness, patients increasingly reject this method because of the associated care requirements and aesthetic concerns (9). Tracheostomy creates an open wound that not only requires long-term postoperative care but may also cause psychosocial problems for patients.
According to recent studies, the cost-effectiveness of tracheostomy is inferior to that of endoscopic treatment methods, such as cordotomy and arytenoidectomy. Nevertheless, tracheostomy is still recommended as an effective initial short-term treatment for BVFP (10).
Arytenoidectomy
Removal of the arytenoid cartilages is an irreversible surgical method for treating BVFP in which the glottis is widened along the transverse axis, thereby facilitating breathing. This method is widely used either alone or in combination with partial removal of the vocal fold (arytenoid cordectomy) (8).
Open arytenoidectomy was introduced at the beginning of the 20th century, while the procedure was first performed endoscopically in 1948. This method was proposed by Thornell, and his technique remains the most widely accepted (9). During Thornell's endoscopic arytenoidectomy, a temporary tracheostomy is created, and a small mucosal incision is made in the region of the arytenoid cartilage. The incision is extended into the aryepiglottic fold (plica aryepiglottica), allowing the cartilage to be removed (8).
This technique and its various modifications provide good results in improving respiratory function. Endoscopic arytenoidectomy was subsequently improved through the use of a CO₂ laser. This provides greater incision precision, better hemostasis, and less postoperative edema (11).
Despite maximum efforts to preserve as many anatomical structures as possible, most patients experience voice changes after arytenoidectomy. Granulation tissue and scars may also form and once again narrow the airway, resulting in the need for one or more revision procedures (10). To reduce the risk of scar and granulation tissue formation, patients are advised to receive antireflux medication before surgery (11).
Cordotomy
Like arytenoidectomy, cordotomy is an irreversible surgical treatment for BVFP based on tissue removal to widen the airway. During cordotomy, soft tissues of the larynx are removed, including parts of the vocal folds, the vocal ligament, or the thyroarytenoid muscle (10).
Following the introduction of endoscopic laser arytenoidectomy, this method was soon adapted for cordotomy. However, despite improvements in respiratory function, these procedures caused the same complications as laser arytenoidectomy: voice changes and airway narrowing due to the formation of granulation tissue and scarring, resulting in the need for revision surgery in approximately 30% of patients (8).
Compared with arytenoidectomy, endoscopic laser cordotomy is less traumatic and less likely to cause aspiration and is therefore a preferred method for the long-term treatment of BVFP. Cordotomy is proposed as an alternative to tracheostomy at the time of diagnosis; however, it should be noted that better ventilatory function is achieved with tracheostomy (10).
Laterofixation (Lateralization) of the Vocal Fold and/or Arytenoid Cartilage
Vocal fold lateralization is a useful, minimally invasive, and potentially reversible treatment for BVFP. In recent years, it has been successfully used in both adults and children. The reversibility of its effects has contributed to the popularity of this method.
During lateralization surgery, a longitudinal incision is made lateral to the affected vocal fold, which is then retracted and secured with sutures, thereby widening the glottis.
Laterofixation may be performed alone or in combination with endoscopic procedures, such as arytenoidectomy (12). Compared with arytenoidectomy and cordotomy, lateralization provides better results in improving ventilatory function, preventing aspiration, and preserving voice quality (10). Postoperative hoarseness is inevitable but may decrease over time, while more serious complications of lateralization are rare (12). The rate of revision surgery after lateralization is 10–30%.
Lateralization is recommended for patients in whom recovery of laryngeal function is expected or who wish to avoid tracheostomy (10).
Reinnervation
None of the tissue resection-based methods used to treat BVFP can restore the principal functions of the larynx: ensuring unobstructed airflow, vocalization, and swallowing. To achieve better treatment outcomes, reinnervation methods have therefore been investigated. The first attempts began as early as a century ago (10).
Attempts have been made to reinnervate the posterior cricoarytenoid muscle (m. cricoarytenoideus posterior; PCA), the only muscle that abducts the vocal folds, using other nerves, such as the phrenic nerve (n. phrenicus). This nerve is considered the most suitable because of its homogeneous population of motor neurons active during inspiration. However, such surgery may cause diaphragmatic paralysis, further worsening already impaired respiratory function (13).
Bilateral reinnervation of the PCA muscles using the left hemiphrenic nerve has been sufficiently successful in restoring vocal fold abduction during inspiration, preserving the preoperative level of phonation without causing swallowing disorders, and improving patients' quality of life (14). Although reinnervation is a promising treatment for BVFP in animal studies, the results of clinical studies in humans have been inconsistent, and further studies are therefore required before conclusions can be drawn (11).
Laryngeal Pacemakers and Functional Electrical Stimulation
Functional electrical stimulation of paralyzed laryngeal muscles began to be investigated more than 3 decades ago (15). Laryngeal pacemakers consist of afferent and efferent components. The afferent component provides the information required to coordinate muscle contractions with inspiration. Phrenic nerve activity, changes in intrathoracic pressure, or expansion of the chest signal inspiration to the afferent component of the laryngeal pacemaker, causing stimulation of the posterior cricoarytenoid muscle to abduct the vocal folds.
The efferent component of the laryngeal pacemaker is connected to the nerve (n. vagus or n. laryngeus recurrens) at the neuromuscular junction or directly to the denervated muscles. When electrodes are connected directly to denervated muscles, regeneration of damaged axons does not need to be considered.
Zealear and co-authors performed the first unilateral laryngeal stimulation in 7 patients with BVFP by implanting a commercial pacemaker and electrodes (16). Based on postoperative ventilatory and voice outcome assessments, unilateral stimulation was more effective than superior or posterior cordotomy.
A clinical study of unilateral stimulation conducted by Mueller and colleagues in 9 patients with BVFP, using minimally invasive electrodes activated by an external stimulator attached to the chest wall, demonstrated improved ventilation without any adverse effect on voice quality (17).
Thus, an external stimulator may significantly improve postoperative ventilation. However, further studies are needed to more accurately assess the balance between potential harm and benefit for patients (25).
Botulinum Toxin
Botulinum toxin injections into the cricothyroid muscle (m. cricothyroideus) reduce vocal fold tension, thereby causing lateralization of the vocal folds and widening of the glottis (10, 11). In BVFP, botulinum toxin may be used to block abnormally increased innervation of the adductor muscles by inspiratory motor neurons (18). In this way, the remaining active inspiratory motor neurons of the abductor muscles would become more effective in opening the glottis.
Marie and co-authors were the first to describe the effectiveness of botulinum toxin injections into the bilateral adductor muscles in the treatment of BVFP (19). Improved ventilation was observed in this patient (19).
Zealear and co-authors also used botulinum toxin in studies of human laryngeal stimulation to suppress the activity of the vocal fold adductor muscles while stimulating them electrically (20). The researchers observed that reducing stimulation of the adductor muscles improved pulmonary ventilation (20). A subsequent study involving 11 patients with BVFP and respiratory impairment showed that pulmonary ventilation improved after botulinum toxin injections into the adductor muscles (18).
Neuromodulatory Effect of Electrical Stimulation in Promoting Selective Reinnervation of the Denervated PCA Muscle
It has long been established that electrical stimulation improves the functional recovery of denervated muscles by accelerating axonal regeneration and muscle reinnervation before significant atrophy develops (21). Research by Zealear et al. demonstrated that electrical stimulation of the posterior cricoarytenoid muscle (PCA) promotes selective reinnervation of denervated laryngeal muscles while simultaneously preventing the development of synkinesis (22).
This is a significant finding because, without prevention of synkinesis in the denervated PCA, up to 70% of patients with bilateral vocal fold paralysis, despite successful reinnervation, ultimately develop synkinetically paralyzed vocal folds (10).
Gene Therapy
The possibility of gene therapy for patients with bilateral vocal fold paralysis (BVFP) emerged with the identification of several growth factors that promote neuronal survival and growth. The introduction of genes encoding such growth factors could protect neurons from degeneration and promote their regeneration after injury (11).
These genes typically encode neurotrophic factors that promote neuronal survival or growth factors that stimulate muscle cell proliferation and differentiation (23). Therapeutic genes are delivered by vector injections into the recurrent laryngeal nerve or laryngeal muscles. There, they are taken up by muscle cells or transported retrogradely along axonal pathways to neuronal cell bodies.
Once these genes enter the nuclei of target cells, they produce peptides that promote recurrent laryngeal nerve regeneration, synapse formation, and muscle growth (24). This technique could potentially be applied to neurodegenerative diseases such as amyotrophic lateral sclerosis or in cases of recurrent laryngeal nerve injury (11). However, the lack of an effect on synkinesis and the fact that studies have so far been conducted only in animal models limit its use in clinical practice (23).
Stem Cell Therapy
Stem cell transplantation is known as a treatment method that allows tissue regeneration. For example, autologous stem cells can be isolated from a small piece of a patient's tissue and grown to a sufficient mass before being reimplanted. Muscle stem cells have the potential to promote the regeneration of atrophied muscle mass and provide a better environment for reinnervation (25). Similar to gene therapy, the application of stem cell therapy for patients with BVFP is limited as it does not protect against synkinesis. Little is currently known about its effect on laryngeal muscle reinnervation, so further research is needed before this treatment method can be more widely implemented.
Table 1 summarizes the advantages and disadvantages of various BVFP treatment methods.
Stem Cell TherapyStem cell transplantation is known as a treatment method that enables tissue regeneration. For example, autologous stem cells can be isolated from a small sample of a patient's tissue and grown to a sufficient mass before being reimplanted. Muscle stem cells have the potential to promote the regeneration of atrophied muscle tissue and provide a more favorable environment for reinnervation (25). Similar to gene therapy, the application of stem cell therapy in patients with BVFP is limited because it does not protect against synkinesis. Little is currently known about its effects on laryngeal muscle reinnervation; therefore, further research is needed before this treatment method can be implemented more widely. Table 1 summarizes the advantages and disadvantages of various BVFP treatment methods. Table 1. Advantages and Disadvantages of BVFP Treatment Methods
Clinical CaseA 77-year-old woman consulted a physician because of bothersome hoarseness and shortness of breath. The onset of the patient's illness was in 2012, when scintigraphy raised suspicion of an adenoma of the right lower parathyroid gland secreting parathyroid hormone. Its blood concentration was 194.4 ng/l; the normal value should be [value missing in the provided text]. According to her medical history, the patient underwent radiation therapy for a hemangioma on the left side of her face when she was only 2 years old. Several years later, poorly healing wounds developed in this area, resulting in several plastic surgical procedures involving soft tissue and skin grafts. At the age of 16, the patient was diagnosed with diffuse enlargement of the thyroid gland, but she felt well at the time and no treatment was administered. Three years later, in 1961, because of frequent palpitations, general weakness, and shortness of breath, she underwent thyroid nodule resection. In 1983, the patient was diagnosed with recurrent nodular goiter, and in 1987, following an increase in neck size, repeat thyroid nodule resection was performed. In 1991, the patient underwent hysterectomy because of multiple fibroids and cysts. In 1992, a nodule was detected in the right thyroid lobe, resulting in hospitalization in the endocrinology department for evaluation of thyroid function and treatment. Because of micrognathia, the patient had a lower jaw prosthesis. Cataracts were diagnosed, and both eyes were operated on: the right eye in 2015 and the left eye in 2018. Left shoulder joint arthrosis and compressive vertebral deformities were also diagnosed. The patient currently has primary arterial hypertension and takes nebivolol and enalapril. Because of respiratory insufficiency and speech difficulties caused by BVFP, the patient was scheduled for surgery. Preoperative laryngoscopy revealed a mobile epiglottis and an immobile left vestibular fold and left arytenoid cartilage. The left vocal fold was completely immobile, while the mobility of the right vocal fold, arytenoid cartilage, and vestibular fold was reduced. The vocal folds were pale, with no glottal closure, and the left fold was in a paramedian position. The glottal opening was considered insufficient for breathing. On January 10, 2019, the patient underwent microlaryngoscopic partial left vocal fold cordectomy using a CO₂ laser under microscopic control. To improve visualization of the left vocal fold, part of the vestibular fold was also removed. After surgery, repeat laryngoscopy revealed a swollen, reddened, and partially mobile right vocal fold with smooth edges and surface. The left vocal fold had been partially removed, and the remaining part was immobile and reddened, with an uneven surface covered with fibrin. The surrounding tissues were slightly swollen. After removal of the tracheostomy tube, the patient experienced inspiratory dyspnea. Breathing without the tracheostomy tube was possible but remained insufficient. During fiberoptic bronchoscopy on January 14, 2019, limited mobility of the arytenoid cartilage was observed, and fibrin was present on the left vocal fold. When viewed from below, after mucus and fibrin had been suctioned from the left vocal fold, a gap between the folds was observed that was expected to be sufficient once the edema subsided. The trachea and visible bronchial lumens were clear, and no tracheal strictures were observed. As her overall condition improved, the patient was discharged for further outpatient treatment.
Publication "Internistas" No. 2, 2020 |
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LITERATURE
1. Myssiorek D. Recurrent laryngeal nerve paralysis: anatomy and etiology. Otolaryngol Clin North Am. 2004 Feb;37(1):25–44, v.
2. Reiter R, et al. Etiology, diagnosis, differential diagnosis and therapy of vocal fold paralysis. Laryngorhinootologie. 2014 Mar;93(3):161–73.
3. Chen H-C, et al. Etiology of vocal cord paralysis. ORL J Oto-Rhino-Laryngol Its Relat Spec. 2007;69(3):167–71.
4. Dupuch V, et al. Bilateral vocal cord abductor paralysis associated with primary herpes simplex infection: a case report. Eur Ann Otorhinolaryngol Head Neck Dis. 2012 Oct;129(5):272–4.
5. Wareing, Michael J, et al. Chapter 32. Vocal Cord Paralysis. CURRENT Diagnosis & Treatment in Otolaryngology-Head & Neck Surgery, 3e Ed. Anil K. Lalwani. New York, NY: McGraw-Hill, 2012, http://accessmedicine.mhmedical.com/content.aspx?bookid=386§ionid=39944070.
6. Bilateral Vocal Fold Paralysis Workup: Laboratory Studies, Imaging Studies, Other Tests. Available online: https://emedicine.medscape.com/article/863885-workup#showall.
7. Weinberger, Paul M, David J. Terris. Otolaryngology: Head & Neck Surgery. CURRENT Diagnosis & Treatment: Surgery, 14e Ed. Gerard M. Doherty. New York, NY: McGraw-Hill, 2014, http://accessmedicine.mhmedical.com/content.aspx?bookid=1202§ionid=71517698.
8. Sapundzhiev N, et al. Surgery of adult bilateral vocal fold paralysis in adduction: history and trends. Eur Arch Oto-Rhino-Laryngol Off J Eur Fed Oto-Rhino-Laryngol Soc EUFOS Affil Ger Soc Oto-Rhino-Laryngol - Head Neck Surg. 2008 Dec;265(12):1501–14.
9. Young VN, Rosen CA. Arytenoid and posterior vocal fold surgery for bilateral vocal fold immobility. Curr Opin Otolaryngol Head Neck Surg. 2011 Dec;19(6):422–7.
10. Li Y, et al. Current Treatment Options for Bilateral Vocal Fold Paralysis: A State-of-the-Art Review. Clin Exp Otorhinolaryngol. 2017 Sep;10(3):203–12.
11. Rubin AD, Sataloff RT. Vocal Fold Paresis and Paralysis. Otolaryngol Clin North Am. 2007 Oct 1;40(5):1109–31.
12. Damrose EJ. Suture laterofixation of the vocal fold for bilateral vocal fold immobility. Curr Opin Otolaryngol Head Neck Surg. 2011 Dec;19(6):416–21.
13. Marina MB, et al. Laryngeal reinnervation for bilateral vocal fold paralysis. Curr Opin Otolaryngol Head Neck Surg. 2011 Dec;19(6):434–8.
14. Song W, et al. Treatment of bilateral vocal cord paralysis by hemi-phrenic nerve transfer. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2017 Apr 7;52(4):245–52.
15. Obert PM, et al. Use of direct posterior cricoarytenoid stimulation in laryngeal paralysis. Arch Otolaryngol Chic Ill 1960. 1984 Feb;110(2):88–92.
16. Zealear DL, et al. Electrical pacing of the paralyzed human larynx. Ann Otol Rhinol Laryngol. 1996 Sep;105(9):689–93.
17. Mueller AH, et al. Laryngeal pacing via an implantable stimulator for the rehabilitation of subjects suffering from bilateral vocal fold paralysis: A prospective first-in-human study. The Laryngoscope. 2016;126(8):1810–6.
18. Ekbom DC, et al. Botulinum toxin injections for new onset bilateral vocal fold motion impairment in adults. The Laryngoscope. 2010 Apr;120(4):758–63.
19. Marie JP, et al. Bilateral laryngeal movement disorder and synkinesia: value of botulism toxin. Apropos of a case]. Rev Laryngol - Otol - Rhinol. 1998;119(4):261–4.
20. Zealear DL, et al. Electrically stimulated glottal opening combined with adductor muscle botox blockade restores both ventilation and voice in a patient with bilateral laryngeal paralysis. Ann Otol Rhinol Laryngol. 2002 Jun;111(6):500–6.
21. Williams HB. The value of continuous electrical muscle stimulation using a completely implantable system in the preservation of muscle function following motor nerve injury and repair: an experimental study. Microsurgery. 1996;17(11):589–96.
22. Zealear DL, et al. Stimulation of denervated muscle promotes selective reinnervation, prevents synkinesis, and restores function. The Laryngoscope. 2014 May;124(5):E180-187.
23. Bijangi-Vishehsaraei K, et al. Microarray Analysis Gene Expression Profiles in Laryngeal Muscle After Recurrent Laryngeal Nerve Injury. Ann Otol Rhinol Laryngol. 2016 Mar;125(3):247–56.
24. Heavner SB, et al. Dysfunction of the recurrent laryngeal nerve and the potential of gene therapy. Ann Otol Rhinol Laryngol. 2007 Jun;116(6):441–8.
25. Dirja BT, et al. Potential of laryngeal muscle regeneration using induced pluripotent stem cell-derived skeletal muscle cells. Acta Otolaryngol (Stockh). 2016;136(4):391–6.
