The Changing Face of Trigeminal Neuralgia

A Narrative Review

Stine Maarbjerg MD, PhD; Rafael Benoliel BDS (Hons)

Headache. 2021;61(6):817-837.

Gamma Knife

GKS radiosurgery is a minimally invasive technique that precisely delivers radiosurgical doses of 70–90 Gray units to the trigeminal nerve root at the point of vascular compression. The technique relies on accurate MRI mapping and sequencing. If no compressing vessels are identified, the site of exit of the trigeminal nerve from the pons or other preselected position on the trigeminal nerve is treated.

A recent pooled analysis reveals that 30%–66% of patients are pain free at 4–11 years after GKS.^[57] Comparing GKS with glycerol rhizotomy injection, it was concluded that despite greater facial numbness and a higher failure rate, glycerol provided more rapid pain relief than GKS. Indeed, the percentage of patients with GKS becoming pain free often increases over time (~24 months), suggesting cumulative effects.^[209–211] GKS shows better long-term pain relief with less treatment-related morbidity than glycerol rhizotomy and may be indicated in patients who are poor candidates for MVD.^[212,213] Although posterior fossa surgery (MVD or partial nerve section) was shown to be superior to GKS over a mean follow-up duration of about 2 years,^[213,214] there are reports that GKS may be the procedure of choice for recurrent CTN.^[215] There are insufficient data at present to assess the long-term outcomes or complications of GKS, particularly the unknown effects of radiation in the area of the trigeminal root. With GKS, better outcomes are associated with higher dosages that, however, induce higher rates of sensory loss.^[138]

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Table 1. Subtypes of trigeminal neuralgia and their coding as per the International Classification of Headache Disorders, 3rd edition (ICHD-3)
13.1 Pain attributed to a lesion or disease of the trigeminal nerve
13.1.1	Trigeminal neuralgia (TN)		Note: Clinically established
	13.1.1.1	Classical TN (CTN)
		13.1.1.1.1	CTN, purely paroxysmal
		13.1.1.1.2	CTN with concomitant continuous pain
	13.1.1.2	Secondary TN (STN)
		13.1.1.2.1	TN attributed to multiple sclerosis
		13.1.1.2.2	TN attributed to space-occupying lesion
		13.1.1.2.3	TN attributed to other cause
	13.1.1.3	Idiopathic TN (ITN)
		13.1.1.3.1	ITN, purely paroxysmal
		13.1.1.3.2	ITN with concomitant continuous pain

Table 2. Diagnostic criteria for trigeminal neuralgia
Diagnostic criteria		Notes
A	Recurrent paroxysms of unilateral facial pain in the distribution(s) of one or more divisions of the trigeminal nerve, with no radiation beyond,¹ and fulfilling criteria B and C	In a few patients, pain may radiate to another division, but it remains within the trigeminal dermatomes Classical trigeminal neuralgia may be preceded by a period of atypical continuous pain termed "pretrigeminal neuralgia" in the literature Pain is overwhelmingly unilateral and does not cross the midline. Bilateral pain may indicate disease (e.g., multiple sclerosis) Most patients suffer pain in the distribution of the second or third division or both Pain may be accompanied by spasm of the facial muscles Periods of remission from days to years may occur
B	Pain has all of the following characteristics: 1. Lasting from a fraction of a second to 2 min 2. Severe intensity 3. Electric shock-like, shooting, stabbing, or sharp in quality	Duration can change over time, with paroxysms becoming more prolonged. A minority of patients will report attacks predominantly lasting for >2 min Attack duration, distribution, etc. may vary between patients but are highly consistent within cases, that is, attacks are stereotyped in the individual patient Pain may become more severe over time Mild autonomic symptoms such as lacrimation and/or redness of the eye may be present
C	Precipitated by innocuous stimuli within the affected trigeminal distribution	Some attacks may be, or appear to be, spontaneous, but there must be a history or finding of pain provoked by innocuous stimuli to meet this criterion. Ideally, the examining clinician should attempt to confirm the history by replicating the triggering phenomenon. However, this may not always be possible because of the patient's refusal, awkward anatomical location of the trigger, and/or other factors A short gap between trigger and pain may be observed (latency). Following an attack, a refractory period occurs where pain cannot be triggered
D	Not better accounted for by another ICHD-3 diagnosis	Other causes are ruled out by history, physical examination, and special investigations. Imaging (preferably MRI) should be done to exclude secondary causes and, in the majority of patients, to demonstrate neurovascular compression of the trigeminal nerve (i.e., establish classical trigeminal neuralgia) Sensory testing may reveal mild deficits in the distribution of the trigeminal nerve

Note: With permission from the International Headache Society.

Table 3. Diagnostic criteria for classical trigeminal neuralgia
Criteria		Comments
A	Recurrent paroxysms of unilateral facial pain fulfilling criteria for 13.1.1 Trigeminal neuralgia	Typically nerve root atrophy and/or displacement due to neurovascular compression (NVC), which are independently associated with the signs and symptoms of trigeminal neuralgia. Classical trigeminal neuralgia is caused by neurovascular compression, most frequently by the superior cerebellar artery. The common site of neurovascular compression is at the root entry zone, with compression by an artery more clearly associated with symptoms than compression by a vein. MRI techniques to measure volume and cross-sectional area of the root are available. Atrophic changes may include demyelination, neuronal loss, changes in microvasculature, and other morphological changes
B	Demonstration on MRI or during surgery of neurovascular compression (not simply contact), with morphological changes in the trigeminal nerve root
Diagnostic criteria for classical trigeminal neuralgia, which is purely paroxysmal or with concomitant continuous facial pain
Purely paroxysmal		With concomitant continuous facial pain
A	Recurrent paroxysms of unilateral facial pain fulfilling criteria for 13.1.1.1 Classical trigeminal neuralgia	Recurrent paroxysms of unilateral facial pain fulfilling criteria for 13.1.1.1 Classical trigeminal neuralgia
B	Pain-free between attacks in the affected trigeminal distribution	Concomitant continuous or near-continuous pain between attacks in the affected trigeminal distribution

Note: With permission from the International Headache Society.

Table 4. Diagnostic criteria for secondary trigeminal neuralgia
Criteria		Comments
A	Recurrent paroxysms of unilateral facial pain fulfilling criteria for 13.1.1 Trigeminal neuralgia, either purely paroxysmal or associated with concomitant continuous or near-continuous pain	In many cases, clinically indistinguishable from classical or idiopathic trigeminal neuralgia Clinical examination shows sensory changes in a significant proportion of these patients
B	An underlying disease has been demonstrated known that is to be able to cause, and explaining, the neuralgia	1. Recognized causes are tumor in the cerebellopontine angle, arteriovenous malformation, and multiple sclerosis (MS)
C	Not better accounted for by another ICHD-3 diagnosis 1. Recognized causes are tumour in the cerebellopontine angle, arteriovenous malformation and multiple sclerosis 2. MRI is best equipped to detect an underlying cause for Secondary trigeminal neuralgia. Other investigations may include neurophysiological recording of trigeminal reflexes and trigeminal evoked potentials, suitable for patients who cannot undergo MRI	2. MRI is best equipped to detect an underlying cause for 13.1.1.2 Secondary trigeminal neuralgia. Other investigations may include neurophysiological recording of trigeminal reflexes and trigeminal evoked potentials, suitable for patients who cannot undergo MRI
Most common forms of secondary trigeminal neuralgia
Trigeminal neuralgia attributed to MS		Trigeminal neuralgia attributed to space-occupying lesion
A	Recurrent paroxysms of unilateral facial pain fulfilling criteria for 13.1.1 Trigeminal neuralgia	Recurrent paroxysms of unilateral facial pain fulfilling criteria for 13.1.1 Trigeminal neuralgia
B	B. Both of the following: 1. MS has been diagnosed 2. An MS plaque at the trigeminal root entry zone or in the pons affecting the intrapontine primary afferents has been demonstrated by MRI, or its presence is suggested by routine electrophysiological studies showing impairment of the trigeminal pathways	Both of the following: 1. A space-occupying lesion in contact with the affected trigeminal nerve has been demonstrated 2. Pain has developed after identification of the lesion or led to its discovery
C	Not better accounted for by another ICHD-3 diagnosis	Not better accounted for by another ICHD-3 diagnosis

Note: A third type is defined by ICHD: "Trigeminal neuralgia attributed to other cause." This is designed to be a flexible diagnosis that may include various causes of secondary TN with criteria that clearly link the disorder to the signs and symptoms.
With permission from the International Headache Society.

Table 5. Diagnostic criteria for idiopathic trigeminal neuralgia
Criteria		Comments
A	Recurrent paroxysms of unilateral facial pain fulfilling criteria for 13.1.1 Trigeminal neuralgia, either purely paroxysmal or associated with concomitant continuous or near-continuous pain	A contact between a blood vessel and the trigeminal nerve and/or nerve root is a common finding on neuroimaging in healthy subjects. When such a contact is found in the presence of 13.1.1 Trigeminal neuralgia but without evidence of morphological changes (e.g., atrophy or displacement) in the nerve root, the criteria for 13.1.1.1 Classical trigeminal neuralgia are not fulfilled and the condition is considered idiopathic
B	Neither 13.1.1.1 Classical trigeminal neuralgia nor 13.1.1.2 Secondary trigeminal neuralgia has been confirmed by adequate investigation including electrophysiological tests and MRI
C	Not better accounted for another ICHD-3 diagnosis	Electrophysiological tests nor MRI showing significant abnormalities
Diagnostic criteria for idiopathic trigeminal neuralgia, which is purely paroxysmal or with concomitant continuous facial pain
Purely paroxysmal		With concomitant continuous facial pain
A	Recurrent paroxysms of unilateral facial pain fulfilling criteria for 13.1.1.3 Idiopathic trigeminal neuralgia	Recurrent paroxysms of unilateral facial pain fulfilling criteria for 13.1.1.3 Idiopathic trigeminal neuralgia
B	Pain-free between attacks in the affected trigeminal distribution	Concomitant continuous or near-continuous pain between attacks in the affected trigeminal distribution

Note: With permission from the International Headache Society.

Table 6. Drugs commonly used in the treatment of trigeminal neuralgia
Drug	Initial dose (mg)	Target dose (mg)^a	#Dose increase (titration)	Schedule
Carbamazepine	100–200	1200–1800	100–200 mg/2 days	x2–4/days
Carbamazepine-CR	200–400	1200	Usually transfer from regular format at equivalent dose	x2/days
OXC	300	1200–2400	300–600 mg/week	x2–3/days
Baclofen	5–15	30–60	5 mg/3 days	x3/days
Gabapentin	300	900–2400	300 mg/2–3 days	x3/days
Pregabalin	150	300–600	50 mg/2–3 days	x2–3/days
Lamotrigine	25	400–600	25–50 mg/week	x1–2/days