Glossopharyngeal Neuralgia – Causes, Symptoms, Treatment

Glossopharyngeal neuralgia (GN) is a rare pain? syndrome that affects the glossopharyngeal nerve (the ninth cranial nerve that lies deep within the neck)  and causes sharp, stabbing pulses of pain in the back of the throat and tongue, the tonsils, and the middle ear.  The excruciating pain of GN can last for a few seconds to a few minutes, and may return multiple times in a day or once every few weeks.  Many individuals with GN relate the attacks of pain to specific trigger factors such as swallowing, drinking cold liquids, sneezing, coughing, talking, clearing the throat, and touching the gums or inside the mouth.  GN can be caused by compression of the glossopharyngeal nerve, but in some cases, no cause is evident.  Like trigeminal neuralgia, it is associated with multiple sclerosis?.  GN primarily affects the elderly.

Glossopharyngeal neuralgia (GN) is a rare and pain? syndrome in the sensory distribution of the ninth cranial nerve also known as the glossopharyngeal nerve. As per ICHD-3 (International Classification of Headache? Disease- 3) classification, glossopharyngeal neuralgia is a disorder characterized by a brief episodic unilateral pain, with sharp and stabbing in character, with abrupt onset and cessation, in the glossopharyngeal nerve distribution (angle of the jaw, ear, tonsillar fossa and the tongue base). It also involves the pharyngeal and auricular branches of CN X. Pain is commonly triggered by coughing, talking and swallowing. Pain in glossopharyngeal neuralgia follows a relapsing and remitting pattern. It falls under the International Classification of Diseases (ICD) category as ICD-10-CM-G52.1.[rx]

Pathophysiology

The glossopharyngeal nerve is a mixed sensorimotor nerve that exits the brainstem from the upper medulla. From that point, it leaves the skull through the jugular foramen along with the vagus and accessory nerves. It continues its path between the internal jugular vein and the internal carotid artery as it descends and then continues beneath the styloid process. It then curves to make an arch on the side of the neck as it passes under the hyoglossus muscle to its final distribution of the base of the tongue, the palatine tonsil, and glands of the mouth. A motor efferent supplies the stylopharyngeus muscle which is essential in swallowing. Sensory afferents provide information from the inner surface of the tympanic membrane, the upper pharynx as well as the posterior one-third of the tongue. Another important branch is the one to the carotid body and sinus is known as Hering’s nerve. It communicates with the vagus nerve and carries information from chemoreceptors in the carotid body and baroreceptors in the carotid sinus; this is important clinically as activation of the visceral sensory branch of the glossopharyngeal neuralgia can activate the vagus nerve (tractus solitarius and dorsal motor nucleus) and produce a reflex arrhythmia?. This vagal activation may explain the cardiac-related syncopal episodes sometimes associated with glossopharyngeal neuralgia.  Overall the glossopharyngeal nerve is a very small nerve that runs deep in the neck, and it is sometimes resected accidentally during open neck dissections. For this same reason, it is often called ‘the neglected cranial nerve.’ Any infectious, inflammatory, or compressive etiologies across the glossopharyngeal nerve’s path from the end organs to the brainstem may result in hyperexcitability of the nerve and produce pain?.[5][7][8]

Causes of Glossopharyngeal Neuralgia

Essential or idiopathic? glossopharyngeal neuralgia is where etiology is unknown.[rx][rx]

Secondary causes of glossopharyngeal neuralgia include:

• Vascular compression mainly at the nerve root: the most common cause
• Demyelinating diseases: e.g., multiple sclerosis?
• Inflammatory and autoimmune? diseases: e.g., Sjogren disease
• Intraoral and peritonsillar infections
• Intracranial space-occupying lesions especially medullary tumors or tumors originating from CP angle
• Posterior fossa and cervical? malformations
• Eagle syndrome or stylalgia: If the styloid process is over 25mm or stylohyoid ligament? is calcified they can cause compression of the glossopharyngeal nerve
• Oropharyngeal cancers include carcinoma of the tongue and benign? tumors like schwannomas.

Symptoms of Glossopharyngeal Neuralgia

Patients describe an attack as burning or jabbing pain?, or as an electrical shock that may last a few seconds or minutes. Swallowing, chewing, talking, coughing, yawning or laughing can trigger an attack. Some people describe the feeling of a sharp object lodged in the throat. The pain usually has the following features:

The pain? usually has the following features:

• Affects one side of the throat
• Can last several days or weeks, followed by a remission? for months or years
• Occurs more frequently over time and may become disabling

About 10% of patients also have potentially life-threatening episodes of heart irregularities caused by involvement of the nearby vagus nerve, such as:

• slow pulse
• sudden drop in blood pressure
• fainting (syncope)
• seizures

Diagnosis? of Glossopharyngeal Neuralgia

History and Physical

The ICHD-3 provides the following diagnostic criteria for glossopharyngeal neuralgia[rx]:

A. Recurrent paroxysmal painful attacks in unilateral glossopharyngeal nerve distribution and should fulfill the criterion.

B. Pain? should have all the following characteristics:

• Duration – Pain? lasts from a few seconds to about 2 minutes
• Intensity – Severe
• Type of pain? – Sharp, stabbing, shooting or electrical shock-like sensations
• Precipitating factors – The pain is precipitated or exacerbated by coughing, yawning, swallowing or talking

C. Pain should not be accounted for by any other ICHD-3 diagnosis.

The physical examination of patients with glossopharyngeal neuralgia is generally benign, and the painful areas do not show any signs of sensory abnormalities for both light touch and pinprick. Sometimes glossopharyngeal neuralgia is associated with dysesthesias and/or hyperalgesia in the affected areas. If there is an absent cough or gag reflex, a detailed investigation into the etiology of the pain is necessary. In some rare cases, glossopharyngeal neuralgia and trigeminal neuralgia can occur concurrently.[rx]

Evaluation

The diagnosis of glossopharyngeal neuralgia is mainly clinical and should meet all criteria as mentioned in ICHD-3. A detailed history and physical examination of the patient is therefore mandatory. A thorough ENT examination is necessary including a throat exam and neck palpation. All the patients should have basic laboratory evaluations include complete blood count, basic metabolic panel, and erythrocyte sedimentation rate, anti-nuclear antibodies to rule out any underlying infection, inflammation, malignancy or temporal arteritis.

Persistent symptoms are infrequent and warrant further investigation. Complications including syncope should have a cardiology evaluation with an echocardiogram and Holter monitoring.

The primary role of imaging is to identify potential causes of nerve compression at the base of the skull.

• Computed tomography (CT) – CT scans do not show the nerve directly but can identify an elongated and ossified styloid process in the axial images.[rx]
• X-Ray – An elongated and heavily calcified styloid process can be present on the cervical spine plain radiograph on the lateral view.[rx]
• Magnetic Resonance Imaging (MRI) – Neurovascular compression of the glossopharyngeal nerve is most visible on MRI. Thin section T2 weighted images are ideal for seeing pathology. An MRI with contrast should be performed to see any abnormal enhancement of the nerve, vessels, or surrounding structures. The most common vascular source of nerve compression is from the posterior inferior cerebellar artery (PICA). The vertebral artery and anterior inferior cerebellar artery are the second and third most common culprit vessels. The MRI can also show demyelinating brain lesions, tumors in the posterior fossa, or any malformations.
• Magnetic resonance angiogram (MRA) – MRA should also be done to evaluate for avascular loop compressing on the nerve root entry zone.[rx]

Treatment of Glossopharyngeal Neuralgia

Medical management –  Glossopharyngeal neuralgia is usually responsive to pharmacotherapy especially with carbamazepine or oxcarbazepine.

Carbamazepine – Starting dose 200 mg/day in a single dose (extended-release), or two divided doses (immediate-release tablet) or in four divided doses (oral solution). Increase the dose gradually with increments of 200 mg/day as needed. If the dose exceeds 200mg per day, it is advisable to administer extended-release capsules in two divided doses. Maintenance dose – 400 to 800 mg daily in two divided doses (immediate-release tablet) forms) or four divided doses (oral solution); maximum dose: no be more than 1,200 mg/day.

The other neuropathic pain medicines recommended by the International Association for the Study of Pain (IASP) are as below:

• Gabapentin (100 to 5000mg/day in 1 to 4 divided doses),
• Duloxetine (20 to 90mg/day),
• Valproic acid (125-2500mg/day in 1 to 2 divided doses),
• Clonazepam (0.5-8mg/day),
• Lamotrigine (50 to 500mg/day in 1 to 2 divided doses),
• Baclofen (10 to 80mg/day in 1 to 4 divided doses),
• Phenytoin (200 to 600mg/day in 1 to 3 divided doses),
• Pregabalin (75 to 500mg/day in 1 to 2 divided doses) and
• Topiramate (50 to 1000mg/day in 1 to 2 divided doses)

As a general rule, these medications should be started at low doses and titrated up as needed based on their effectiveness, tolerability, and side effects. This pain condition often shows a relapsing-remitting course, and so medication can be tapered down to a low maintenance dose. Combining two or more medications with different mechanisms of action can help achieve better pain relief while avoiding side effects. A short course of opioids can be useful for intractable pain.

Adjuvant care: Cold and hot compresses, physical therapy, and psychological counseling are all options in addition to medical therapy. The success rate is variable but can be helpful.[rx]

Interventional pain management techniques

Glossopharyngeal nerve blocks merit consideration for both diagnostic and therapeutic purposes. This block can be an option in conjunction with pharmacotherapy. A diagnostic block with a local anesthetic should be tried first to confirm the origin of the pain. If diagnostic blocks are successful, chemical neurolysis or thermal radiofrequency ablation can be performed on the nerve. Chemical neurolytic agents such as alcohol, glycerol, or phenol are typical choices. Radiofrequency ablation is typically performed at the jugular foramen to target the inferior petrous ganglion of Andersch. Accurate needle placement is critical as life-threatening bradycardia and hypotension can occur if the vagus nerve gets stimulated during the procedure. There are two common approaches to block the glossopharyngeal nerve: the intraoral and extra-oral approaches. The extra-oral technique is preferred since it is safe and easy to perform. Complications are not uncommon with glossopharyngeal neuralgia blocks. The glossopharyngeal nerve is in the vicinity of the internal jugular vein, and the carotid artery and intravascular injection can easily occur. The concomitant block of the recurrent laryngeal nerve may cause hoarseness of the voice. Always avoid bilateral glossopharyngeal nerve blocks at the same time to avoid complete vocal cord paralysis. Blockade of the vagus nerve may result in tachycardia and hypertension via blockade of parasympathetic fibers.[rx][rx][rx]

Surgical Therapy

Once the patient becomes refractory or intolerant to medications, surgery is the next treatment option. However, surgical therapy is associated with high morbidity of the patients and is limited to younger patients. These surgical procedures for the lesions may be classified as follows:

• Extracranial, such as direct surgical neurotomies or percutaneous radiofrequency thermal rhizotomy[rx–rx]
• Intracranial, such as a direct section of glossopharyngeal and vagal nerves in the cerebellopontine angle[rx,rx]
• Central procedures, such as percutaneous or open trigeminal tractotomy-nucleosome or nucleus caudalis DREZ operation

These days, the best-established surgical treatments are MVD of vascular roots[rx–rx] and a rhizotomy of the glossopharyngeal nerve with upper vagal nerve roots.[rx] In essential GPN, the primary pathology, being vascular compression of the nerve roots, responds well to MVD. However, in secondary GPN, first, address the underlying pathology: Tumor resection, posterior fossa decompression in Chiari malformation, embolization of an arteriovenous malformation, coagulation of choroid plexus overgrowth, fistulectomy for Eagle’s Syndrome.[34] In secondary GPN, when MVD is not possible, the intracranial root section is considered curative and is most widely employed. In the largest case series by Rushton et al.[9] and in a smaller series by Taha et al.,[rx] there were no recurrences after a preganglionic section of the ninth and upper tenth nerve roots. However, sectioning of cranial nerve fibers IX–X, open or percutaneous tractotomy-nucleosome is followed by severe and persistent dysphonia and dysphagia.[rx,rx,rx] This is because all neural destructive or ablative procedures carry the risk of neuritis, deafferentation pain, and neurovascular injury.[rx]

With the refinements of microsurgical and anesthesiological techniques (Brainstem evoked potentials), MVD has proven to be an effective and safe available treatment and should be considered the first-line treatment in drug-resistant GPN.[rx] In a study by Resnic et al.,[rx] MVD provided complete pain relief in 76% of the cases and substantial improvement in a further 16%. Sampson et al.[rx] found pain relief of more than 10 years by MVD, hence indicating its efficacy and safety even on long term follow-up. MVD should be considered when a patient experiences typical GPN symptoms and has a PICA loop near the glossopharyngeal nerve[rx] and especially in patients with isolated symptom of throat pain.[rx]

Recently, various case reports have been published, which have shown beneficial effects of pulsed radiofrequency neurolysis (PRN) and gamma knife surgery (GKS). PRN is a non-destructive neuromodulatory method to treat both, idiopathic and secondary GPN.[rx,rx] Short pulses of radiofrequency energy, delivered at a constant temperature, produce central and peripheral neuromodulatory effects.[rx,rx] In GKS system, an 80 Gy dose is stereotactically directed to the isocenter with MR imaging-based target localization and 4-mm collimation.[rx,rx] It might serve as a potential alternative to other percutaneous techniques and surgical options for patients with secondary GPN. Stereotactic radiosurgery (SRS) with GKS system offers a less-invasive option for patients with GPN. Till date, Pollock and Boes have reported the largest series of patients (5 patients), with suspected GPN being treated with SRS directed at the glossopharyngeal and vagus nerves, within the jugular foramen with a failure rate of 40%.[rx] These new techniques offer a promising direction that might spare patients from pain and potential morbidity of surgery.

There are several surgical modalities used for the treatment of glossopharyngeal neuralgia based on the etiology of the pain. The compression of the glossopharyngeal nerve by a vascular structure is the most common cause of secondary glossopharyngeal neuralgia. Microvascular decompression (MVD) of the glossopharyngeal nerve is the most widely used surgical modality to correct vascular compression of the nerve. Alternatively, a resection of the glossopharyngeal nerve alone or with branches of the vagus nerve can also be performed.

Extracranial techniques are percutaneous radiofrequency rhizotomy and direct surgical resection. These techniques are ideal in patients with essential glossopharyngeal neuralgia who failed medical management but unable to tolerate an open intracranial resection. Resection of the ipsilateral styloid process also known as fistulectomy is a therapeutic option for Eagle syndrome. The physician must rule out other central causes of glossopharyngeal neuralgia before pursuing this surgery.

Intracranial techniques include rhizotomy or an intracranial root resection of the glossopharyngeal nerve and/or vagus nerves from its origin in the brainstem at the cerebellopontine angle. Persistent dysphagia and hoarseness of voice are the most common complications if these surgeries. Stereotactic radiosurgery with gamma knife surgery provides a less-invasive option, but data on safety and efficacy is limited.[rx][rx][rx][rx]

Complications

Syncope and cardiac dysrhythmias: When the glossopharyngeal nerve gets irritated, it sends feedback via the dorsal motor nucleus of the Xth nerve. These signals also stimulate the nucleus tractus solitarius in the midbrain. Thus, during the acute glossopharyngeal neuralgia attack, abnormal stimulation produces amplified vagal response, which, in turn, results in bradycardia, hypotension, and cardiac dysrhythmias. These autonomic changes cause cerebral hypoperfusion, slow waves on EEG, seizures, and syncope. Convulsive movements, limb clonus, automatic smacking movements of the lips, and upward turning of the eyes are signs of cerebral hypoxia.

The cardiovascular complications occur during the painful episodes or immediately after the pain symptoms resolve. Management of glossopharyngeal neuralgia pain attacks with drugs and/or surgical treatment can help manage these complications. Some patients only develop cardiovascular manifestations of glossopharyngeal neuralgia without painful paroxysms, also known as non-neurologic glossopharyngeal neuralgia. These patients can receive therapy with glossopharyngeal nerve avulsion or microvascular decompression.[rx][rx]