Epidemiology

• Most commonly, episodes occur after the age of 40.
• There is annual incidence of about 27 cases per 100,000.^[1][2]
• It is more common in females.
• There may also be a genetic predisposition, as there have been observations of familial clustering. However, the exact method of transmission is unclear, although there is a lack of penetrance.^[3]
• 2-4% of patients will actually have multiple sclerosis (MS).

Aetiology

• Compression: blood vessels may press on the trigeminal nerve as it leaves the brainstem at its cerebellopontine nerve root. Compression of the nerve leads to demyelination. This results in spontaneous generation of electric impulses. This probably accounts for up to 90% of cases that were originally classified as idiopathic.^[1]
• Degeneration: some have postulated it to be part of the ageing process, as with increasing age the brain atrophies, leading to redundant arterial loops which can cause compression.^[4]
• Myelin sheath infiltration: for example, tumour or amyloidosis.
• Idiopathic.

Presentation

• There may be preceding symptoms, eg tingling or numbness.
• Patients may have certain triggers that set the pain paroxysm off (see table below).
• This is followed by sharp, severe, shock-like pains.
• These pains are usually on one side in the cheek or face but pain can involve the eyes, lips, nose and scalp.
• Episodes are intermittent but can last days, weeks or months on end and then not return for months or even years.
• 3-5% of patients will have bilateral pains.

Triggers

• Vibration.
• Skin contact, eg shaving, washing.
• Brushing teeth.
• Oral intake.
• Exposure to wind.

Atypical trigeminal neuralgia (TN)

This subgroup of patients have relentless underlying pain like a migraine associated with superimposed stabbing pains. There may also be an intense burning sensation. This condition is particularly difficult to treat.

Differential diagnosis

• Dental pathology.
• Temporomandibular joint dysfunction.
• Migraine.
• Temporal arteritis (TN rarely affects the forehead alone).
• Cluster headaches.
• MS and other disorders of myelin.
• Overlying aneurysm of a blood vessel.
• Tumour in posterior fossa, eg meningiomas.
• Arachnoid cyst at the cerebellopontine angle.^[5]
• Postherpetic neuralgia after shingles

Investigations

The diagnosis is clinical and it can be difficult to make. No investigations are required initially unless there is uncertainty regarding the diagnosis. Patients who are referred on for specialist review will usually have a brain MRI scan - this is to document the presence of compression and look for other intracranial causes of trigeminal neuralgia (TN) (5-10% of patients, eg aneurysm, MS).^[5] There should be a lower threshold for earlier investigations in the following groups: younger patients, atypical symptoms, focal neurology and poor response to initial therapy.^[1]

Management

Unfortunately, there is no definative cure at present (relapses and reoccurences occur); although newer surgical procedures are promising.

Management involves three aspects:

• Support and education
• Medical
• Surgical

Support and education

• Patients need to be made aware that the condition is not life-threatening.
• There is a need, however, also to express empathy towards severity of the condition.
• Education as to the causes and potential therapies.
• Reassurance and support groups.

Medical

• Typical analgesics and opioid analgesics are unfortunately not effective.
• Carbamazepine has the most evidence for efficacy and should be used first-line.^[1] It should be tried initially and the dose titrated to achieve pain control. There is consensus that oxcarbazepine is also an effective treatment in trigeminal neuralgia (TN), although there is a lack of RCT-based data to confirm this.^[2]
• If it fails to relieve the pain or adverse effects develop, then gabapentin can be tried, although there is a lack of evidence for its use in TN. Their effects may be enhanced with baclofen and clonazepam - however, the efficacy is not well-established and, to date, studies only involve a small number of patients.^[6]
• Once patients have been in remission for one month, the drug should be gradually withdrawn.
• Tricyclic antidepressants, eg low-dose amitriptyline - the data supporting their use at present are lacking.
• Other drugs that might be used in a specialist setting include lamotrigine and baclofen, although lamotrigine needs to be titrated over many weeks and has limited value in severe pain.

Failure of these agents should prompt a review of the diagnosis and, if pain control cannot be achieved or drugs cause unacceptable adverse effects, surgical options should be considered.

Surgery

Most of the improvements in the management of TN have occurred because of advances in surgical treatments. Surgery involves either relieving pressure on the trigeminal nerve or damaging it to prevent any pain transmission.

There are various types of surgical procedures that can be used in TN:

• Rhizotomy - the aim is to damage the trigeminal nerve. This is an alternative to the more invasive decompression. These methods include:
  • Percutaneous glycerol rhizotomy (under a local anaesthetic).
  • Percutaneous balloon compression rhizotomy (under a general anaesthetic.)^[7]
  • Radiofrequency rhizotomy (performed under sedation).
  These procedures are good in the frail elderly patient or those with comorbidities but, unfortunately, the effects are short-lived and symptoms usually recur. They are usually associated with some level of sensory loss and can be repeated if necessary.
• Stereotactic radiosurgery (gamma knife) - this is also a form of rhizotomy that uses radiation targeted at the trigeminal nerve root and thus injures it. Pain relief is usually delayed for a few days and there can be associated facial numbness. At present, the number of locations providing this treatment is limited.^[1]
  National Institute for Health and Clinical Excellence (NICE) guidance on the use of stereotactic surgery in trigeminal neuralgia:^[8]

  • Surgery to be considered if severe pain or side-effects from medication.
  • A systematic review commissioned by NICE reported that between 33% to 90% achieved immediate pain relief with this procedure - only an average of 14% had recurrence of symptoms at 18 months.
• Microvascular decompression:
  • Blood vessels are compressing the trigeminal nerve and lifting these blood vessels away reduces the pressure. This requires a general anaesthetic. The approach is behind the ear into the posterior fossa on the affected side. Patients are usually assessed by MRI beforehand to look for the presence of compression.
  • 90% of patients obtain pain relief, with over 80% still pain-free at one year.^[9]
  • This procedure, however, is not without risks and the average mortality associated with the operation is 0.2%. There is a risk of a cerebrovascular event, deafness and even death.^[10][11] The rates of complication depend on the surgeon's expertise.
  • Up to 4% of patients have major problems, such as CSF leaks, infarcts or haematomas.^[9] Aseptic meningitis is the most common complication (11%). Diplopia due to IVth or VIth nerve damage is often transient and VIIth nerve palsy is rare. Sensory loss occurs in 7% of patients. The major long-term complication is ipsilateral hearing loss, which can be as high as 10%.

Percutaneous microballoon compression is safe for elderly patients.^[7] However, nearly all procedures cause some numbness and, in a few, this can be associated with intense pain obviating the whole point of the surgery ("anaesthesia dolorosa").

Complementary therapies

Due to the lack of curative measures, the use of complementary therapies in trigeminal neuralgia (TN) has evolved quite rapidly. These include the following:

• Transcutaneous electrical nerve stimulation (TENS).
• Acupuncture.
• Biofeedback.
• Vitamin therapies, eg vitamin B.
• Nutritional therapies, eg garlic.

There is no evidence available that supports the use of these measures.

When and who to refer

Refer the patient if:

Patients should be referred to a specialist, who may be a neurologist, neurosurgeon or pain relief specialist.

Management plan for a patient with trigeminal neuralgia

• Patient education.
• Encourage the use of a pain diary.
• Carbamazepine is first-line, gradually titrating the dose until pain resolves.
• Warn patients of sedative side-effects and watch for adverse effects.
• However, the underlying process will continue and pain usually recurs.
• Investigations are only indicated if there is presence of any other focal neurology - otherwise, the diagnosis is clinical.
• If pain resolves then, after a period, reduce doses of medication with a plan to stop the drug.
• If pain recurs, restart or increase the dose.
• If this does not work or the patient is not suitable for drug therapy, refer for specialist review.

Complications

The pain of trigeminal neuralgia (TN) can be so intense that it can lead to a poor quality of life due to mental and physical incapacity. Patients may require psychosocial input, eg counselling.

Prognosis

One third of patients will have mild symptoms and some will only ever have one episode.^[1] Many people have periods of remission with no pain for months or years. There is anecdotal evidence that in many people it becomes more severe and less responsive to treatment with time.^[2]