A radiologic review of hoarse voice from anatomic and neurologic perspectives
The differential diagnosis for hoarseness is extensive and includes a multitude of etiologies that span a large geographic area from the brainstem to the mediastinum. Therefore, localizing a causative lesion can be extremely difficult for clinicians and radiologists alike. In this review, we will first discuss the normal anatomy of the larynx and its innervation via the vagus and recurrent laryngeal nerves. We will then proceed with a guided tour of the various infectious/inflammatory, neoplastic, congenital, and traumatic/iatrogenic causes of hoarseness subdivided by anatomic location (brainstem, skull base, carotid sheath, thyroid, larynx, and superior mediastinum). Along the way, we will discuss the various cross-sectional imaging modalities best suited to detect the often subtle signs of recurrent laryngeal nerve injury. With thorough knowledge of these entities, radiologists can impact patient care by suggesting the appropriate imaging test and tailoring their search patterns to detect the subtle findings of laryngeal dysfunction.
KeywordsHoarseness Vocal cord dysfunction Recurrent laryngeal nerve Larynx
Computed tomography angiography
Hypertrophic olivary degeneration
Human papilloma virus
Inferior olivary nucleus
Magnetic resonance angiography
Positron emission tomography
Posterior inferior cerebellar artery
Recurrent laryngeal nerve
Squamous cell carcinoma
Time of flight
Vocal cord paralysis
The clinical symptom of hoarseness carries with it an extensive differential diagnosis, which is not confined to neoplastic etiologies.
The anatomic course of the recurrent laryngeal nerves differs bilaterally, which impacts the geographic extent of imaging coverage required to diagnose causative lesions.
Laryngeal dysfunction can be caused by lesions located anywhere from the brainstem to the mediastinum.
Dysphonia affects one-third of people at some point in their lifetime, and an estimated one in 13 adults experiences hoarse voice annually . Hoarse voice is often used interchangeably with dysphonia; however, the former is a symptom while the latter is a clinical diagnosis. Dysphonia is a broad term for impaired vocal production, including altered quality, pitch, loudness, or effort. Causes for dysphonia can be divided into organic and functional etiologies. Organic dysphonia is due to a physiologic change in vocal production, and is further divided into structural and neurogenic dysphonia. Structural etiologies impact a physical change upon the mechanism of vocal production (i.e., the larynx), while neurogenic etiologies effect via the nervous system (i.e., vagus or recurrent laryngeal nerve or their nuclei). Functional dysphonia is due to vocal overuse or abuse, and can have overlap with organic dysphonia.
Any hoarseness not readily attributable to a benign cause (such as an acute upper respiratory infection) and lasting more than 4 weeks should be further evaluated; this is especially important when there are additional coexisting symptoms such as dysphagia, odynophagia, cough, hemoptysis, unilateral ear/throat pain, neck mass, weight loss, or if there are significant risk factors for head and neck cancer . The first line of investigation is laryngoscopy; however, diagnostic imaging comes into play if a cause is not identified or if further evaluation is warranted.
The biomechanics of phonation is a complex process which can be altered by a wide range of local and systemic processes, many which are not readily apparent on laryngoscopy. The head and neck radiologist must be familiar with the anatomy and pathology of the larynx, as well as the complex supporting laryngeal network. Here, we will briefly review the normal anatomy of the structures of phonation, as well as the course of the vagus and recurrent laryngeal nerves, then present important etiologies of dysphonia with case examples by location.
Anatomy of the larynx
Innervation of the larynx and vocal cord paralysis
Differential diagnosis of vocal cord dysfunction by location
Squamous cell carcinoma
Differential diagnosis of vocal cord dysfunction by etiology
Intrinsic vocal fold lesions
Vocal cord paralysis
Compression of CN X or RLN—mediastinal causes
Compression of CN X or RLN—thyroid mass
Compression of CN X or RLN—skull base
Traumatic Injury to CN X or RLN
Neurodegenerative disorders (i.e., ALS, Parkinsons)
Lesions and disorders of the larynx
The laryngeal ventricles of Morgagni are paired structures of the larynx residing between the vocal and vestibular folds; the saccule is an appendageal diverticulum extending vertically from the ventricle between the vestibular fold and the thyroid cartilage, and is responsible for producing mucus that lubricates the vocal cords. Cystic dilatation of the saccule is termed a laryngocele, which may be developmental due to failure of regression after birth, and can also be seen in persons who experience high throat pressures, such as wind musicians, glass blowers, and those with excessive coughing . These are often asymptomatic and found incidentally, but occasionally can present with hoarseness and stridor. Symptoms may be episodic due to intermittent filling and resultant one-way valve effect, or due to infection .
Benign inflammatory laryngeal lesions
Squamous cell carcinoma
Squamous cell carcinoma (SCC) is by far the most common (98%) primary tumor of the larynx, and can also secondarily involve the larynx when the primary is elsewhere in the oropharynx. SCC generally occurs in men over 50 and was previously associated with smoking and alcohol abuse; however, SCC related to human papilloma virus (HPV) is now more prevalent, and is seen in the younger population with better prognosis. Classification is based on subsite of location in relation to the glottis—supraglottic (20–30%), glottic (50–60%), subglottic (5%), and transglottic (spanning two or more subsites)—and presentation depends on the subsite involved. Glottic lesions often present earlier with dysphonia or aspiration, while subglottic lesions typically present with dyspnea and/or stridor. Purely supraglottic lesions are asymptomatic, thus usually present later with symptoms due to lymphadenopathy or trans-spatial spread, such as tender neck mass, sore throat, dysphagia/odynophagia, or referred ear pain.
Small lesions may be treated locally with laser or radiation ablation; larger tumors usually necessitate laryngectomy and radiation therapy, although supraglottic tumors without vocal cord fixation may be treated with voice-sparing surgery. Compared to similarly staged SCC elsewhere in the head and neck, laryngeal SCC portends a better prognosis, but 15–20% will develop a second primary site SCC that is most certainly fatal.
Recurrent respiratory papillomatosis
Hypertrophic olivary degeneration
The dentato-rubro-olivary tract, also known as the myoclonic or Guillain-Mollaret triangle, connects the inferior olivary nucleus (ION) in the medulla to the ipsilateral red nucleus in the midbrain and contralateral dentate nucleus in the cerebellum via the central tegmental, olivocerebellar/olivodentate, and dentorubral tracts. A lesion disrupting any of these pathways can result in deafferentation of the inferior olivary nucleus, either contralateral (lesion of the superior or inferior cerebellar peduncle) or ipsilateral (lesion of the central tegmentum). Due to trans-synaptic degeneration, there is cytoplasmic vacuolar degeneration, along with glial hypertrophy and astrocytic proliferation, initially resulting in enlargement of the ION; this hypertrophy is unique to these lesions, although the olive eventually becomes atrophic. Often the offending lesion is hemorrhagic, but may be ischemic or demyelinating .
The classic clinical finding in hypertrophic olivary degeneration (HOD) is palatal myoclonus, which is involuntary rhythmic movement involving the oropharynx, typically the levator palatini but may also include the larynx; ocular myoclonus and tremor or ataxia of the upper extremity may also be present. Symptoms usually present several months after the primary insult, but the patient may also be asymptomatic.
Lateral medullary syndrome
Lesions at the jugular foramen
The jugular foramen is situated at the junction between the petrous temporal and occipital bones and is divided into two compartments. The pars nervosa is smaller and anteromedial, and contains the inferior petrosal sinus and CN IX. The pars vascularis is larger and posterolateral, and contains the jugular bulb and CNs X and XI.
Paragangliomas, or glomus tumors, are slow-growing vascular neoplasms that arise from the neural crest, histologically equivalent to pheochromocytomas of the adrenal gland, and are intimately associated with neurovascular structures. Although extra-adrenal paragangliomas are most common in the head and neck, they are rare, accounting for approximately 0.5% of all head and neck tumors. Most are sporadic, but with new discoveries of genetic markers, it is now thought that up to 30% may be familial. Incidence slightly favors women, and diagnosis is typically during the third through fifth decades. Most are benign, and malignancy is determined by the presence of metastatic lesions as there is no histologic difference. The vast majority are not vasoactive; symptomatology is usually determined by location.
Paragangliomas are named for their location of origin; the four most common primary sites in the head and neck are at the tympanic membrane (glomus tympanicum), jugular fossa (glomus jugulare), within the carotid sheath (glomus vagale), and at the carotid bifurcation (glomus caroticum or carotid body tumor). These tumors have the propensity for trans-spatial spread; for example, a glomus jugulotympanicum tumor involves both the skull base and middle ear. Glomus jugulare tumors tend to present as pulsatile tinnitus and hearing loss, although lower cranial nerve symptoms such as hoarse voice can be present as well. Glomus vagale tumors occur along the vagus nerve and are accompanied by VCP approximately half of the time.
Paragangliomas can be imaged with a number of modalities, including CT, MRI, and nuclear medicine studies . The intimate association of glomus tympanicum and jugulare with structures of the temporal bone and skull base lends well to the use of CT; aggressive tumors may result in bony destruction with a moth-eaten appearance. On MRI, these tumors are classically described as “lightbulb bright” on T2-weighted imaging due to extensive vascularity and “salt and pepper” due to flow voids. Avid enhancement is seen with both iodinated and gadolinium contrast. Due to their avidity for tumors of neuroendocrine origin, a number of radionuclides can be used to identify paragangliomas: 111In-pentreotide and 68Ga-DOTATATE for somatostatin receptor positivity, 18F-fluorodeoxyglucose (18F-FDG) for metabolic activity, and 123I-metaiodobenzylguanidine (123I-MIBG) and 18F-fluorodopamine (18F-FDA) for catecholamine production.
Lesions of the carotid space
The carotid space, also known as the poststyloid compartment of the parapharyngeal space, is one of the deep spaces of the neck, spanning from the skull base to the aortic arch. It is enclosed by all three layers of the deep cervical fascia, termed the carotid sheath. It is bordered anterolaterally by the sternocleidomastoid muscle, anteromedially by the parapharyngeal space and visceral space, and posteriorly by the prevertebral space. Its primary contents are the carotid artery, internal jugular vein, and vagus nerve, but also contains other lower cranial nerves (CN IX, XI, XII) superiorly, sympathetic nerves (cervical sympathetic plexus anteriorly and ansa cervicalis posteriorly), and the deep cervical lymph node chain. Lesions tend to be neurovascular in origin but can arise from any of these components ; given the confined space, these can all affect the vagus nerve and lead to dysphonia.
Benign nerve sheath tumors
Of the cranial nerve schwannomas, the vast majority (90%) are of the vestibular branch of the vestibulocochlear nerve (CN VIII), but can also affect the trigeminal nerve (CN V), facial nerve (CN VII), or lower cranial nerves (CN IX-XII). Vagal nerve schwannomas have a slight female predominance and usually present in middle age, although they can occur at any age. These tumors most often present as an asymptomatic slow-growing palpable neck mass; however, the second most common presentation is hoarseness. The most specific sign for vagal nerve schwannoma is paroxysmal cough induced by palpation or manipulation of the mass, due to stimulation of the vagal nerve . Treatment is surgical resection; preservation of the vagus nerve can be difficult; however, schwannomas tend to be more easily resected since they arise from the myelin surrounding the entire nerve and are often eccentric to the nerve itself, rather than neurofibromas which arise from the perineurium surrounding individual fascicles and thus can be entwined in the fibers [20, 22].
Lesions of the mediastinum
Traumatic/iatrogenic nerve injury
Laryngeal carcinoma often has a better prognosis than a similarly staged head and neck squamous cell carcinoma of another primary site. Presenting symptoms depend on the laryngeal subsite involved.
Infiltrative laryngeal lesions such as papillomatosis and amyloidosis are benign but progressive, resulting in dysphonia and/or airway obstruction and frequently requiring multiple treatments due to extent and recurrence.
A well-positioned brainstem lesion may affect either the inferior olivary nucleus (hypertrophic olivary degeneration) or nucleus ambiguous (lateral medullary syndrome), leading to classic constellations of higher-order neuronal symptoms including dysphonia.
Multiple lower cranial neuropathies should trigger search for a lesion at the skull base, particularly at the jugular foramen.
The vagus nerve is confined within the carotid sheath as it courses down the neck, rendering it susceptible to injury from neck trauma or neck mass.
The whole spectrum of thyroid disease can result in dysphonia due to the gland’s position below the larynx.
The recurrent laryngeal nerve can be either stretched or compressed by lesions in the superior mediastinum, resulting in vocal cord paralysis.
Knowledge of these different lesions put into clinical context will help the radiologist narrow the differential diagnosis and guide the clinician to proper ordering of tests.
The authors acknowledge Nadya Kiriyak for contribution of original illustrations and Sarah Klingenberger for annotation of images.
Availability of data and material
Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
SM drafted the manuscript. AP drafted annotations for the images and illustrations. AB participated in the design, collection of images, and editing of the manuscript. All authors read and approved the final manuscript.
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Consent for publication
The authors declare that they have no competing interests.
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