Glossopharyngeal Neuralgia

Glossopharyngeal neuralgia is a rare cranial neuralgia of sudden, brief, severe stabbing pain in the throat, tonsil, base of the tongue or deep in the ear, in the territory of the glossopharyngeal nerve and sometimes the vagus. Attacks are triggered by swallowing, coughing, talking or yawning, and a minority are accompanied by bradycardia, asystole or syncope.

The incidence is about 0.2 to 0.7 in every 100,000 people each year, roughly 1% of that of trigeminal neuralgia. Onset is usually after 50 years, men and women are affected about equally, and the left side is slightly more often involved.

Causes. Most cases are classical, from neurovascular compression of the nerve root at the brainstem, usually by the posterior inferior cerebellar artery. Secondary causes include cerebellopontine angle and parapharyngeal tumours, Eagle syndrome (elongated styloid process), multiple sclerosis, oropharyngeal carcinoma, and trauma or surgery.

Course. Attacks come in clusters with remissions of weeks to years, and tend to become more frequent over time.

Pathophysiology.

Focal demyelination at the root entry zone, usually from vascular contact, causes ectopic impulse generation and ephaptic transmission between afferent fibres.

Spread of discharge to the vagal dorsal motor nucleus and the nucleus tractus solitarius explains the cardiovascular reflex effects.

• Paroxysmal electric or stabbing pain lasting seconds to 2 minutes, in the posterior tongue, tonsil, pharynx or beneath the angle of the jaw, often radiating to the ear.
• Triggers: swallowing, chewing, coughing, talking, yawning, and cold liquids.
• No pain between attacks, or a dull background ache in some; normal neurological examination in the classical form.
• Bradycardia, hypotension, syncope, seizure like events or cardiac arrest during attacks in a minority.
• Weight loss from fear of eating and drinking.

Red flags.

• Syncope, bradycardia or asystole with attacks.
• Sensory loss, cranial nerve deficit, dysphagia, hoarseness or a neck mass.
• Constant pain, weight loss, haemoptysis or other signs of malignancy.
• Onset under 40 years or other signs of demyelination.

• Clinical diagnosis from the pain character, site and triggers.
• MRI of the brain and skull base with high resolution heavily T2-weighted sequences and MR angiography, to show neurovascular contact and to exclude tumour and demyelination.
• Topical local anaesthetic spray to the tonsil and pharynx abolishes the pain and supports the diagnosis.
• ECG and ambulatory cardiac monitoring when syncope or palpitations occur.
• CT of the skull base and styloid process when Eagle syndrome is possible; nasopharyngoscopy for mucosal lesions.

Differential diagnosis. Trigeminal neuralgia, nervus intermedius neuralgia, Eagle syndrome, tonsillitis and peritonsillar abscess, oropharyngeal and nasopharyngeal carcinoma, superior laryngeal neuralgia, temporomandibular disorder, occipital neuralgia and cardiac syncope.

• Carbamazepine, first line: 100 mg orally twice daily, increased by 100 mg every 2 days to a usual 400 to 800 mg daily in 2 to 3 divided doses. Maximum 1600 mg daily. Monitor sodium, full blood count and liver function at baseline and during titration; check HLA-B*1502 before starting in people of at risk Asian ancestry; stop at the first rash. Avoid in atrioventricular block, bone marrow depression and porphyria; reduce dose in hepatic impairment and older adults; it lowers the effect of oral contraceptives and is teratogenic (folic acid 5 mg daily before conception).
• Oxcarbazepine as an alternative: 300 mg orally twice daily, increased by 300 mg every 3 days to a usual 600 to 1200 mg daily in 2 divided doses. Maximum 2400 mg daily. Monitor sodium and rash. Halve the starting dose when creatinine clearance is under 30 mL/min; use caution in hepatic impairment; reduces the effect of oral contraceptives.
• Gabapentin 300 mg orally at night on day 1, 300 mg twice daily on day 2, then 300 mg three times daily on day 3, increased by 300 mg every 3 to 7 days to 900 to 2400 mg daily in 3 divided doses. Maximum 3600 mg daily. Monitor sedation, dizziness, peripheral oedema, mood and misuse. Adjust for renal function: creatinine clearance 50 to 79 mL/min, 600 to 1800 mg daily; 30 to 49 mL/min, 300 to 900 mg daily; 15 to 29 mL/min, 150 to 600 mg daily; under 15 mL/min, 150 to 300 mg daily. Avoid in pregnancy unless benefit outweighs risk.
• Bradycardia or asystole with attacks: atropine 0.5 mg intravenously, repeated every 3 to 5 minutes to a maximum of 3 mg, with continuous ECG; monitor heart rate and rhythm; avoid in angle closure glaucoma and urinary retention; use caution in tachyarrhythmia. A pacemaker may be needed.
• Microvascular decompression is the preferred surgery for classical disease that is drug resistant, with a good chance of lasting relief; rhizotomy of the glossopharyngeal nerve and upper vagal rootlets is an alternative when no vessel is found.
• Treat secondary causes: tumour, demyelination, Eagle syndrome (styloidectomy).
• Dietary support during flares: soft, tepid food, and nutrition review.

Monitoring. Review at 2 to 4 weeks, then every 3 months; check sodium and blood count on carbamazepine; attempt slow dose reduction after 3 to 6 months of remission.

Referral and escalation. Neurology for diagnosis; neurosurgery for drug resistant pain; cardiology for syncope or asystole; urgent admission for cardiac arrest or recurrent syncope.

Special groups. Older adults: start low and titrate slowly because of falls and hyponatraemia. Women of childbearing potential: plan pregnancy and avoid carbamazepine where possible.