Trigeminal Neuralgia: Symptoms, Causes and Treatment

According to the ICHD-3 classification the diagnosis requires recurrent attacks of one-sided facial pain in the distribution of at least one branch of the trigeminal nerve, without radiation beyond it. The pain has at least three of four features: it occurs in attacks lasting from a fraction of a second to 2 minutes, it is severe, it is electric-shock-like, shooting, stabbing or sharp in quality, and it is precipitated by innocuous stimuli on the side of the pain. The second (cheek, upper lip, gum) and third branch (jaw, lower lip, tongue) are most often affected; the first (forehead, eye) less often.

The basic difference from other headaches and facial pains lies in the brevity and 'triggerability' of the attacks: cluster pain lasts a quarter of an hour to hours and comes with tearing and motor restlessness (we write about it in a separate article), migraine lasts hours and has a different character, and toothache is usually constant or throbbing and reacts to cold and heat. It is also worth remembering shingles, which can lead to persistent postherpetic neuralgia in the facial area — we write about shingles separately.

The classification proposed in 2016 by an international group of experts on neuropathic pain (Cruccu et al., Neurology) distinguishes three categories. This distinction is of practical importance because it affects further management and the choice of procedure.

In short: the classical form is associated with neurovascular conflict, the secondary with another disease, and the idiopathic with no discernible cause. The 2019 EAN guideline recommends using this classification (with the division into primary — classical or idiopathic — and secondary) and cautions that merely showing a vessel in contact with the nerve does not confirm the diagnosis, because such contacts are also seen in people without pain; it serves rather in deciding whether and when to refer the patient for microvascular decompression.

The first layer is neurovascular conflict. In the classical form a loop of an artery (most often the superior cerebellar artery) or a vein compresses the root of the trigeminal nerve just where it leaves the brainstem, in the zone where the fibres lose their central-type myelin sheath. Pulsation of the vessel causes gradual demyelination and damage to the fibres. In multiple sclerosis similar foci of demyelination arise in the brainstem, and tumours or cysts may compress the nerve from outside — these are the secondary forms.

The second layer is the altered excitability of the damaged fibres. The demyelinated segment of the nerve becomes a focus of ectopic discharges and 'cross-talk' between fibres (so-called ephapses): a touch stimulus, which is normally carried by non-pain fibres, is wrongly 'redirected' to pain fibres, producing pain from touch. This explains why drugs that block sodium channels, such as carbamazepine and oxcarbazepine, suppress the excessive discharges and are first-choice drugs. This is a model based mainly on neurophysiological and operative studies; not every case has a visible vascular compression, and not every compression causes pain.

Many patients in the first months go through visits to several dentists, sometimes with unnecessary root canal treatment or tooth extraction, after which the pain does not go away. It is a classic mistake, because the attacks of neuralgia are projected onto the cheek, jaw and gums, imitating toothache, and are triggered precisely by eating or touch.

The diagnosis of neuralgia rests on history and neurological examination, but imaging plays a key role in establishing the cause. The EAN guideline recommends performing magnetic resonance imaging (with a combination of three high-resolution sequences) as part of the work-up of every patient, because no clinical feature rules out secondary neuralgia. When MRI is impossible, assessment of the trigeminal reflexes can be used. We write about the examination itself in the entry on magnetic resonance imaging.

The age of onset, involvement of the first branch or lack of response to treatment are not enough to distinguish the secondary form from the classical one — as the earlier 2008 AAN-EFNS position reminds us. Clues pointing to secondary neuralgia are a sensory deficit on the face, involvement of both sides and abnormal trigeminal reflexes. That is why an MRI is done almost always, even in people with a typical picture.

Both the 2019 EAN guideline and the earlier 2008 AAN-EFNS guideline name carbamazepine (stronger evidence) or oxcarbazepine (better tolerability) as first-line drugs. Both block sodium channels in hyperexcitable fibres. The dose is increased gradually under a doctor's supervision, and the effect is usually seen within a few days.

This result is an important lesson in humility: carbamazepine is the first-choice drug in neuralgia mainly because it has worked in clinical practice for decades and meets the criteria of the guidelines, not because large, long randomised trials exist. Adverse effects are common: drowsiness, dizziness, balance disturbance, nausea, and, less often, dangerous ones — rashes, hyponatraemia, changes in the blood count and liver. The drug has many interactions (among others with hormonal contraception, anticoagulants and some antibiotics), so it requires monitoring, and it must not be stopped abruptly or the dose changed without a doctor. Oxcarbazepine has somewhat fewer interactions but can also lower the sodium level.

If first-line drugs are not enough or are not tolerated, the guidelines list lamotrigine, gabapentin, pregabalin, baclofen, phenytoin and botulinum toxin type A as stand-alone or add-on options; the evidence for these drugs is weaker and based on fewer studies. In an acute exacerbation in hospital, fosphenytoin or lidocaine can be given intravenously. The choice of subsequent steps belongs to the neurologist.

The EAN guideline recommends offering a procedure when pain is not adequately controlled by drugs or treatment is poorly tolerated. Microvascular decompression (MVD) — opening the skull behind the ear and moving the vessel away from the nerve with a pad — is the first-choice procedure in classical neuralgia. Neuroablative procedures (among others percutaneous balloon compression, thermocoagulation, glycerol rhizolysis, stereotactic radiosurgery such as Gamma Knife) destroy part of the fibres and are preferred when MRI shows no neurovascular contact or when the patient is not suitable for major surgery.

What follows? Procedures can give years of relief, but each carries its own risk: decompression is a neurosurgical operation with a risk of complications (among others hearing problems, haematomas, cerebrospinal fluid leakage), and procedures that destroy the nerve often cause facial numbness and recurrences. The choice of procedure therefore depends on age, general health, the MRI picture and the patient's preference, and should be made at a centre experienced in treating neuralgia. The review mentioned rests on non-randomised studies, so we treat its conclusions as preliminary. The guidelines also recommend offering psychological and nursing support alongside treatment.

Secondary trigeminal neuralgia may be one of the symptoms of multiple sclerosis (MS): foci of demyelination in the brainstem or in the nerve root lead to the same attacks as in the classical form. In younger patients, especially with bilateral pain or other neurological symptoms (sensory, visual or balance disturbance), the neurologist usually widens the work-up to include MRI of the whole nervous system. On the other hand, the vast majority of people with neuralgia do not have MS.

In MS, drug treatment relies on the same drugs, and the role of surgery is more uncertain — the 2008 AAN-EFNS guideline states explicitly that the role of surgery versus pharmacotherapy in MS patients remains unclear, and newer reviews examine the effectiveness of balloon compression and radiosurgery in this group. We write about the link between MS and vitamin D deficiency in a separate article, but that knowledge does not bear directly on the treatment of facial pain.

Trigeminal neuralgia is one of those diseases in which the right diagnosis is nearly equivalent to a way out of the impasse: the characteristic pain can be treated with drugs and, when they fail, with effective procedures. The greatest losses come from delays, unnecessary dental procedures and waiting it out alone. It is sensible to rely on the guidelines: MRI for everyone, carbamazepine or oxcarbazepine as the first step, a quick referral to a neurosurgical centre when drugs are not enough, and psychological support. At the same time it is worth remembering that the evidence for the drugs is weaker than their place in the recommendations suggests.