UpToDateOfficial reprint from UpToDate® www.uptodate.com ©2018 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Wolters Kluwer Health Trigeminal neuralgia Authors:Zahid H Bajwa, MDCharles C Ho, MDSajid A Khan, MDSection Editors:Jeremy M Shefner, MD, PhDJerry W Swanson, MD, MHPEDeputy Editor:John F Dashe, MD, PhD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Aug 2018. | This topic last updated: Jun 01, 2018. INTRODUCTION — Trigeminal neuralgia (TN) is characterized by recurrent brief episodes of unilateral electric shock-like pains, abrupt in onset and termination, in the distribution of one or more divisions of the fifth cranial (trigeminal) nerve that typically are triggered by innocuous stimuli [1].

An overview of TN is presented here. Other causes of facial pain are discussed separately. (See “Overview of craniofacial pain”.)

ANATOMY — The trigeminal nerve (figure 1) is the sensory supply to the face and the sensory and motor supply to the muscles of mastication. It has three major divisions:

●Ophthalmic (V1)

●Maxillary (V2)

●Mandibular (V3)

The nerve starts at the midlateral surface of the pons, and its sensory ganglion (gasserian ganglion) resides in Meckel cave in the floor of the middle cranial fossa.

EPIDEMIOLOGY — TN is a rare condition that affects women more than men. The annual incidence of TN is 4 to 13 per 100,000 people [2,3]. Despite its low incidence, TN is one of the more frequently seen neuralgias in the older adult population. The incidence increases gradually with age; most idiopathic cases begin after age 50, although onset may occur in the second and third decades or, rarely, in children [4].

The male-to-female prevalence ratio of TN ranges from 1:1.5 to 1:1.7 [5,6]. This female predominance may be related to the increased longevity of women compared with men. Rare familial cases have been reported, but the vast majority of patients have sporadic disease [7].

Although data are not entirely consistent, hypertension may be a risk factor for the development of TN [5,8-10]. There is also some evidence that migraine is a risk factor for TN [11].

ETIOLOGY AND PATHOGENESIS — Most cases of TN are caused by compression of the trigeminal nerve root, usually within a few millimeters of entry into the pons (the root entry zone) [12]. Compression by an aberrant loop of an artery or vein is thought to account for 80 to 90 percent of cases [12-14]. (See 'Classification' below.)

Other causes of TN via nerve compression include vestibular schwannoma (acoustic neuroma), meningioma, epidermoid or other cyst, or, rarely, a saccular aneurysm or arteriovenous malformation [15-21].

The mechanism by which compression of the nerve leads to symptoms appears to be related to demyelination in a circumscribed area around the compression [22,23]. Precisely how demyelination results in the symptoms of TN is not entirely clear. Demyelinated lesions may set up ectopic impulse generation, possibly causing ephaptic transmission. Ephaptic cross-talk between fibers mediating light touch and those involved in pain generation could account for the precipitation of painful attacks by light tactile stimulation of facial trigger zones [12]. Furthermore, alteration of afferent input may disinhibit pain pathways in the spinal trigeminal nucleus.

Evidence for a role of central pain mechanisms includes the presence of refractory periods after a triggered episode, trains of painful sensations after a single stimulus, and latency from the time of stimulation to the onset of pain [24]. In addition, electrophysiologic evidence of central sensitization of trigeminal nociceptive processing has been observed in patients with atypical TN who have concomitant chronic facial pain [25].

Demyelination of one or more of the trigeminal nerve nuclei may also be caused by multiple sclerosis or other structural lesions of the brainstem. In multiple sclerosis, a plaque of demyelination typically occurs in the root entry zone of the trigeminal nerve [26,27], although vascular compression also has been noted in these patients [27,28].

Classification — In the International Classification of Headache Disorders, Third Edition (ICHD-3), TN is divided into classic (or classical) TN, secondary TN, and idiopathic TN [1].

●Classic TN encompasses cases related to vascular compression [1]. The rationale is as follows. TN found to be related to compression of the trigeminal nerve by a vascular loop, as demonstrated by surgery, should strictly be regarded as secondary. However, most patients do not have surgery, and it is often uncertain as to whether they have primary or secondary neuralgia. For this reason, the ICHD-3 uses the term “classical” instead of “primary” for patients with a typical history of TN who have a presumed or demonstrated vascular source of compression as the cause.

●Secondary TN caused by an underlying disease such as multiple sclerosis or a tumor along the trigeminal nerve.

●Idiopathic TN.

Painful trigeminal neuropathy encompasses a separate category of conditions that cause predominantly continuous or near-continuous facial pain in the distribution of the trigeminal nerve [1]. Examples include:

●Painful trigeminal neuropathy attributed to acute herpes zoster

●Trigeminal postherpetic neuropathy

●Painful post-traumatic trigeminal neuropathy

●Painful trigeminal neuropathy attributed to other disorder

●Idiopathic painful trigeminal neuropathy

CLINICAL FEATURES — TN is defined clinically by paroxysmal, stereotyped attacks of usually intense, sharp, superficial, or stabbing pain in the distribution of one or more branches of the fifth cranial (trigeminal) nerve (figure 2).

The pain of TN tends to occur in paroxysms and is maximal at or near onset. Facial muscle spasms can be seen with severe pain. This finding gave rise to the older term for this disorder, tic douloureux. The pain is often described as electric, shock-like, or stabbing. It usually lasts from one to several seconds, but may occur repetitively. A refractory period of several minutes during which a paroxysm cannot be provoked is common. Some patients with longstanding TN may have continuous dull pain that is present between paroxysms of pain. Unlike some other facial pain syndromes, TN typically does not awaken patients at night.

TN is typically unilateral. Occasionally the pain is bilateral, though rarely on both sides simultaneously [29]. The distribution of pain most often involves the V2 and/or V3 subdivisions of the trigeminal nerve [1]. Autonomic symptoms, usually mild or moderate, can occur in association with attacks of TN in the V1 trigeminal distribution, including lacrimation, conjunctival injection, and rhinorrhea [6,30,31]. However, isolated involvement of the V1 subdivision occurs in <5 percent of patients with TN [6]. The presence of autonomic features, particularly when prominent or severe, is suggestive of the syndromes of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA). (See 'Differential diagnosis' below and “Short-lasting unilateral neuralgiform headache attacks: Clinical features and diagnosis”.)

Trigger zones in the distribution of the affected nerve may be present and are often located near the midline. Lightly touching these zones often triggers an attack, leading patients to protect these areas [32]. Trigger zones can sometimes be demonstrated on physical examination. Other triggers of TN paroxysms include chewing, talking, brushing teeth, cold air, smiling, and/or grimacing [6,32].

Some patients have a history of “pretrigeminal neuralgia,” a dull, continuous, aching pain in the jaw that evolves over time into TN [33-35]. This brief, milder pain is sometimes suspected to have a dental origin, and unnecessary dental procedures have been performed in some cases [36]. On the other hand, TN can be precipitated by dental procedures (eg, dental extraction), resulting in increased confusion about the precise etiology of this problem [33].

The course of TN is variable, as discussed below. (See 'Prognosis' below.)

DIAGNOSIS — The diagnosis of TN is based upon the characteristic clinical features described above, primarily paroxysms of pain in the distribution of the trigeminal nerve. Once the diagnosis of TN is suspected on clinical grounds, a search for secondary causes should be undertaken (algorithm 1).

For all patients with suspected TN or those with recurrent attacks of pain limited to one or more divisions of the trigeminal nerve and no obvious cause (eg, herpes zoster or trigeminal nerve trauma), we recommend neuroimaging to help distinguish classic TN (ie, idiopathic TN or TN caused by vascular compression) from secondary TN (ie, painful trigeminal neuropathy caused by structural brain lesion other than vascular compression). Neuroimaging of the brain can be done with magnetic resonance imaging (MRI) or computed tomography (CT), though MRI with and without contrast is much preferred because its higher resolution enables imaging the trigeminal nerve and small adjacent lesions.

Patients with trigeminal sensory loss or bilateral involvement are probably at higher risk of secondary TN [37]. Younger age is also probably associated with a higher risk of secondary TN. However, age is not a clinically useful predictor for distinguishing classic TN from secondary TN because there is considerable age overlap. In addition, absence of any of these clinical features (sensory loss, bilateral involvement, younger age) does not rule out a secondary cause for TN.

Electrophysiologic testing does not clearly distinguish classic TN from secondary TN and has no established role in the diagnostic evaluation of TN. However, a 2008 guideline suggested that trigeminal reflex testing was probably useful for distinguishing classic TN from secondary TN, while trigeminal evoked potentials were not useful for making this distinction [37].

Diagnostic criteria — The International Classification of Headache Disorders, Third Edition (ICHD-3) diagnostic criteria for TN are as follows [1]:

●A) Recurrent paroxysms of unilateral facial pain in the distribution(s) of one or more divisions of the trigeminal nerve, with no radiation beyond, and fulfilling criteria B and C

●B) Pain has all of the following characteristics:

•Lasting from a fraction of a second to two minutes

•Severe intensity

•Electric shock-like, shooting, stabbing or sharp in quality

●C) Precipitated by innocuous stimuli within the affected trigeminal distribution

●D) Not better accounted for by another ICHD-3 diagnosis

The ICHD-3 further defines several subtypes of TN [1]:

●Classic (or classical) TN, which develops without apparent cause other than neurovascular compression, fulfilling the criteria above and requiring demonstration on MRI or during surgery of neurovascular compression (not simply contact), with morphological changes in the trigeminal nerve root. Most patients with classic TN will have a purely paroxysmal form without persistent background facial pain (ie, they are pain-free between attacks in the affected trigeminal distribution). Occasional patients who fulfill criteria for classic TN may have continuous or near-continuous facial pain of moderate intensity in the affected area, thereby meeting ICHD-3 criteria for classic TN with concomitant continuous facial pain, also known as atypical TN or TN type 2

●Secondary TN, defined as TN caused by an underlying disease. Recognized causes include multiple sclerosis, cerebellopontine angle tumor, and arteriovenous malformation.

●Idiopathic TN, defined as TN with neither electrophysiological tests nor MRI showing significant abnormalities.

Painful trigeminal neuropathy, distinct from TN, is defined as facial pain in the distribution(s) of one or more branches of the trigeminal nerve that is caused by another disorder and is indicative of neural damage [1]. Unlike TN, the pain is predominantly continuous or near continuous, and is described most often as burning or squeezing, or a pins and needles sensation. Brief paroxysms of pain may occur but are not predominant.

Neuroimaging — Neuroimaging with head MRI (or CT if MRI is not an option) is useful for identifying the small proportion of patients who have a structural lesion (eg, tumor in the cerebellopontine angle, demyelinating lesions including multiple sclerosis) as the cause of TN [37-39]. In addition, high-resolution MRI and magnetic resonance angiography (MRA) may be useful for identifying vascular compression as the etiology of classic TN [40], but the utility of these studies has not been established.

We recommend obtaining brain MRI with and without contrast to rule out a causative structural brain lesion for all patients presenting with suspected TN. High-resolution MRI with thin cuts through the region of the trigeminal ganglion and heavy T2 weighting (eg, a constructive interference in steady-state [CISS] fusion study), is the preferred imaging modality if available. Patients with trigeminal sensory loss, patients with bilateral symptoms, and those younger than 40 years may have a higher risk of secondary TN.

In a 2014 meta-analysis of nine blinded case-control studies, the following observations were noted [41]:

●Neurovascular contact of the trigeminal nerve on MRI/MRA was significantly more frequent with symptomatic nerves compared with asymptomatic nerves (89 versus 36 percent) [41]. Among individual studies, the accuracy of neurovascular compression on MRI for detecting symptomatic nerves showed a moderate variation in sensitivity (75 to 95 percent) and a large variation in specificity (26 to 86 percent).

●Anatomic change (ie, atrophy, distortion, or flattening) of the trigeminal nerve on MRI at the site of vascular contact was significantly more frequent with symptomatic nerves (53 versus 9 percent) [41]. Among individual studies, the accuracy of anatomic change for detecting symptomatic nerves showed a wide variation in sensitivity (20 to 74 percent) and a moderate variation in specificity (79 to 100 percent).

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of TN includes the conditions discussed above (see 'Classification' above) that cause classic TN and secondary TN, mainly compression of the trigeminal nerve by a vascular loop or a nonvascular space-occupying lesion, and demyelination from multiple sclerosis in the pons or root entry zone of the trigeminal nerve.

Although less likely to be confused with TN, the differential diagnosis also includes various causes of painful trigeminal neuropathy, such as acute herpes zoster, postherpetic neuralgia, and trauma to the trigeminal nerve. In most cases, painful trigeminal neuropathy can be distinguished from TN by a thorough history and examination. Of note, isolated involvement of the V1 subdivision occurs in <5 percent of patients with TN [6], while V1 is most commonly affected by postherpetic neuralgia (see “Postherpetic neuralgia”). Neuroimaging, preferably with brain magnetic resonance imaging (MRI), can discern the presence of demyelination or mass lesion as the cause of TN.

TN may sometimes be confused with dental causes of pain. Dental pain is usually continuous, intraoral pain that is dull or throbbing, whereas classic TN is typically intermittent pain and sharp. However, classic TN is often triggered by oral manipulations such as chewing and brushing the teeth, which can suggest a dental cause and lead patients to present for dental care prior to seeking a medical evaluation. Furthermore, some patients have a phase of “pretrigeminal neuralgia” characterized by atypical symptoms (eg, jaw or tooth pain) that might mimic dental pain. (See 'Clinical features' above.)

Several uncommon causes of headache and craniofacial pain, including short-lasting unilateral neuralgiform headache attacks, cluster-tic syndrome, and primary stabbing headache, should also be considered in the differential diagnosis of TN.

●Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA) are characterized by sudden brief attacks of severe unilateral head pain in orbital, periorbital, or temporal regions, accompanied by ipsilateral cranial autonomic symptoms. Attacks may be triggered by a number of factors, including skin contact. Given the short, stabbing nature of the attacks, the cutaneous triggering, and the association of cranial autonomic symptoms with pain in the trigeminal V1 distribution, the differentiation between SUNCT, SUNA, and TN can be difficult. Some argue that the degree of cranial autonomic features in SUNCT and SUNA is greater than in TN, while others suggest that SUNCT, SUNA, and TN are related conditions that exist on a continuum [42]. (See “Short-lasting unilateral neuralgiform headache attacks: Clinical features and diagnosis”.)

●Cluster-tic syndrome is a combination of cluster headache with coexistent TN. (See “Overview of craniofacial pain”, section on 'Cluster-tic syndrome'.)

●Primary stabbing headache is characterized by transient, sharp jabbing pains that occur at variable locations within trigeminal and cervical dermatomes. Most of the stabs of pain last only a few seconds and occur at irregular intervals from one to many times each day. The extratrigeminal location of some or all attacks can differentiate primary stabbing headache from TN. (See “Primary stabbing headache”.)

MEDICAL THERAPY — Pharmacologic therapy is the first-line initial treatment for most patients with classic TN (caused by neurovascular compression) and patients with idiopathic TN. Surgery is reserved for patients who are refractory to medical therapy.

Carbamazepine is the best studied treatment for classic TN and is established as effective [37,43,44]. Side effects can be a problem but are generally manageable, particularly if low doses are prescribed initially with gradual titration.

A systematic review and practice parameter published in 2008 from the American Academy of Neurology (AAN) and the European Federation of Neurological Societies (EFNS) concluded that carbamazepine is effective for controlling pain in patients with TN, oxcarbazepine is probably effective, and baclofen, lamotrigine, and pimozide are possibly effective [37]. There are limited data and uncertain effectiveness regarding other drugs that have been used for TN, including botulinum toxin injections, clonazepam, gabapentin, phenytoin, tocainide, tizanidine, and valproate.

Periodic attempts to gradually withdraw these drugs are warranted in patients achieving relief of pain with oral medications.

No placebo-controlled trials have evaluated the treatment of secondary TN (ie, TN caused by a structural lesion such as multiple sclerosis or nonvascular compression). Treatment of the underlying condition (eg, multiple sclerosis) is recommended, if feasible. In addition, it is reasonable to treat the pain associated with secondary TN using the same medications that are employed in classic TN. In our clinical experience, patients with secondary TN often respond well to these drugs.

Carbamazepine — Four randomized, controlled trials with a total of 147 patients have established the effectiveness of carbamazepine (200 to 2400 mg daily) for TN [45-48].

A systematic review and practice parameter published in 2008 from the AAN and EFNS noted that the treatment response in these trials was robust, with complete or near complete pain control attained in 58 to 100 percent of patients on carbamazepine, compared with 0 to 40 percent of patients on placebo [37]. For the outcome of important pain relief, the number needed to treat was <2. However, carbamazepine was sometimes poorly tolerated, with numbers needed to harm for minor and severe adverse events of 3 and 24, respectively.

The usual starting dose of carbamazepine is 100 to 200 mg twice daily. The dose can be increased gradually in increments of 200 mg daily as tolerated until sufficient pain relief is attained. The typical total maintenance dose is 600 to 800 mg daily, given in two divided doses for tablets and extended-release capsules, or four divided doses when for oral suspension. The maximum suggested total dose is 1200 mg daily.

Adverse effects of carbamazepine include drowsiness, dizziness, nausea, and vomiting; slow titration may minimize these effects. Carbamazepine-induced leukopenia is not uncommon, but it is usually benign; aplastic anemia is a rare side effect. (See “Antiseizure drugs: Mechanism of action, pharmacology, and adverse effects”, section on 'Carbamazepine'.)

The HLA-B*15:02 allele is a genetic susceptibility marker in Asians that is associated with an increased risk of developing Stevens-Johnson syndrome and/or toxic epidermal necrolysis. Screening for this allele in patients with Asian ancestry is recommended before to starting carbamazepine. If genetic testing results are positive for the presence of at least one copy of the HLA-B*15:02 allele, carbamazepine should be avoided.

Oxcarbazepine — The 2008 AAN/EFNS practice parameter identified several randomized controlled trials that compared oxcarbazepine (600 to 1800 mg daily) with carbamazepine in 178 patients with TN [37]. In the pooled analysis, both medications were equally effective, with a >50 percent reduction of attacks achieved by 88 percent or more of patients in both treatment groups.

Oxcarbazepine can be started at a total dose of 600 mg daily, given in two divided doses. The dose can be increased as tolerated in 300 mg increments every third day to a total dose of 1200 to 1800 mg daily. As with carbamazepine, we suggest testing for the HLA-B*15:02 allele in genetically at-risk populations (ie, those with Asian ancestry) before initiating treatment with oxcarbazepine. Oxcarbazepine, carbamazepine, and phenytoin should be avoided in patients carrying the HLA-B*15:02 allele unless the estimated benefits clearly outweigh the risks.

Baclofen — Limited evidence from a small double-blind crossover trial suggests that baclofen is beneficial for TN [49]. Treatment with baclofen 40 to 80 mg daily resulted in a reduction in paroxysms in 7 of 10 patients with typical TN, compared with 1 of 10 who received placebo [49].

The starting dose of baclofen is 15 mg daily given in three divided doses, with gradual titration to a maintenance dose of 50 to 60 mg per day. Sedation, dizziness, and dyspepsia can occur with treatment, and the drug should be discontinued slowly since seizures and hallucinations have been reported upon withdrawal.

Lamotrigine — In a double-blind, placebo-controlled crossover study of 14 patients with TN that was refractory to carbamazepine or phenytoin, adjunct therapy with lamotrigine (400 mg daily) was beneficial for improvement on a composite outcome index [50]. Patients continued taking either carbamazepine or phenytoin for the duration of the trial.

Similarly, an open-label study found that lamotrigine was beneficial in 11 of 15 patients with TN once the 400 mg dose was reached [51]. However, the clinical utility of lamotrigine for severe pain is limited by the need to titrate the dose over many weeks [43].

In patients who are not taking other anticonvulsants, lamotrigine is typically started at 25 mg daily for the first two weeks, and then increased to 50 mg daily for weeks 3 and 4. The dose is then titrated to effect, increasing by 50 mg daily every one to two weeks. The suggested total dose of 400 mg daily is given in two divided doses.

For patients taking an anticonvulsant drug that induces hepatic enzymes (eg, carbamazepine, phenytoin, or primidone), the initial dose of lamotrigine is 50 mg once daily, titrating upward as needed to 100 mg once daily at week 3, 200 mg once daily at week 5, 300 mg once daily at week 6, and 400 mg once daily at week 7.

For patients taking valproate, the initial dose of lamotrigine is 12.5 to 25 mg every other day, with increases of 25 mg every two weeks as needed to a maximum of 400 mg per day.

Other medications — Several other drugs have shown some evidence of efficacy for TN in small, generally lower-quality controlled trials:

●Pimozide, a dopamine receptor antagonist, was more effective than carbamazepine in a randomized, double-blind crossover trial of 48 patients with refractory TN [52,53]. There were no dropouts among patients taking pimozide. However, pimozide is seldom used for TN because it has many potentially serious side effects, including sedation, arrhythmias, anticholinergic effects, acute extrapyramidal symptoms, and parkinsonism.

●Topical lidocaine given by intraoral application was more effective than placebo for pain reduction in a two-week, randomized crossover trial of 24 subjects with TN whose pain was most severe in the mouth [54]. However, blinding may have been compromised because of the bitter taste or numbness perceived by some patients when treated with lidocaine.

●Tizanidine appeared to be more effective than placebo in a small one-week trial, but patients who continued the drug in follow-up developed recurrent attacks of TN within one to three months [55].

●Tocainide was as effective as carbamazepine at two weeks in a crossover trial of 12 patients with TN [56].

Small open-label studies have suggested benefit with a number of medications used for TN [57]:

●Phenytoin [58] and intravenous phenytoin [59]

●Fosphenytoin [60]

●Valproic acid [61,62]

●Gabapentin [63]

●Pregabalin [64,65]

●Clonazepam [66,67]

●Topiramate [68]

●Misoprostol, in patients with TN and multiple sclerosis [69]

However, these agents have not been studied in controlled trials, and their effectiveness in TN is not established [70].

Although there are no controlled data regarding the efficacy of opioids in TN specifically, we have used them in patients with acute exacerbations of pain lasting for days to weeks. Opioids may help make the pain bearable while more effective long-term treatments take effect. Our experience with opioids suggests partial analgesia with central side effects (particularly sedation) when these drugs are used alone, as high doses of morphine, hydromorphone, or oxycodone are usually required. In combination with other neuropathic analgesics, opioids seem to be more effective at lower doses.

Refractory pain — There is only limited evidence to support treatment alternatives for patients with TN who are refractory to first-line medical therapy. There are weak data to support botulinum toxin injections (see 'Botulinum toxin injections' below). Among oral drugs, some patients who fail carbamazepine monotherapy may benefit from combination therapy with gabapentin, lamotrigine, topiramate, baclofen, or tizanidine. Intravenous infusion of phenytoin, fosphenytoin, or lidocaine may provide analgesia while oral medications are titrated [59,71]. Phenytoin and fosphenytoin are dosed at 250 to 1000 mg intravenously [59] at no more than 50 mg/minute and lidocaine is given at 100 to 300 mg [71] over one-half hour while monitoring pulse and blood pressure. Nevertheless, there are no randomized controlled trials comparing monotherapy with combination therapy for TN.

Botulinum toxin injections — Botulinum toxin injections may be beneficial for patients with medically refractory TN, although data are limited. A 2014 literature review identified only two small randomized controlled trials that evaluated the use of botulinum toxin for TN [72]. The largest trial randomly assigned 42 patients who failed medical treatment for TN to either onabotulinumtoxinA injections or placebo (saline) injections into skin or mucosa in the regions where pain was experienced [73]. At 12 weeks, the group assigned to botulinum toxin injections showed significant reductions in mean pain scores and attack frequency compared with the placebo group. In addition, the number of responders (defined by a ≥50 percent decrease in pain score) was significantly greater for the botulinum toxin group than for the placebo group (68 versus 15 percent). However, small patient numbers and other concerns about the quality of this trial limit the strength of these findings [74].

SURGICAL THERAPY — Patients with TN who are refractory to medical therapy are candidates for surgery. A variety of surgical methods have been employed to relieve the symptoms of TN. The major types of procedures are [43]:

●Microvascular decompression for TN caused by compression of the trigeminal nerve root

●Ablative procedures, including:

•Rhizotomy with radiofrequency thermocoagulation, mechanical balloon compression, or chemical (glycerol) injection

•Radiosurgery

•Peripheral neurectomy and nerve block

However, few surgical treatments for TN have been studied in controlled trials, and most of the evidence comes from observational studies [75].

A systematic review and practice parameter published in 2008 from the American Academy of Neurology (AAN) and the European Federation of Neurological Societies (EFNS) concluded that microvascular decompression, percutaneous procedures on the gasserian ganglion (rhizotomy), and gamma knife radiosurgery are possibly effective in the treatment of TN [37]. Evidence for peripheral neurectomy was considered negative or inconclusive.

The AAN/EFNS noted that definitive conclusions regarding the relative effectiveness of surgical techniques for TN are precluded by the lack of studies directly comparing them [37]. Indirect comparisons of the findings from different surgical studies suggest that microvascular decompression has a longer duration of pain control than other surgical interventions for TN.

Microvascular decompression is invasive, although the overall mortality and complication rates are low. Ablative procedures are less invasive, but recurrence may be more common. The incidence of facial numbness is higher with rhizotomy procedures than with microvascular decompression or gamma knife radiosurgery.

Although surgical therapy for TN is generally well tolerated, a feared complication is painful post-traumatic trigeminal neuropathy (anesthesia dolorosa), a condition characterized by persistent, painful anesthesia or hypesthesia in the denervated region [1]. It can be more intolerable than the pain from classic TN itself [76]. This risk warrants careful decision-making when considering surgical treatment for TN. (See “Overview of craniofacial pain”, section on 'Painful post-traumatic trigeminal neuropathy (anesthesia dolorosa)'.)

Anesthesia dolorosa most frequently occurs as a complication of rhizotomy or thermocoagulation for TN, but is rarely, if ever, a complication of gamma knife surgery.

Microvascular decompression — Microvascular decompression is a major neurosurgical procedure that involves craniotomy and the removal or separation of various vascular structures, often an ectatic superior cerebellar artery, away from the trigeminal nerve [77].

The 2008 AAN/EFNS practice parameter identified five studies of microvascular decompression for TN [78-82] that used independent outcome assessment [37]. The practice parameter concluded that initial pain relief was attained in 90 percent of patients, but that pain-free rates declined by one, three, and five years to 80, 75, and 73 percent, respectively.

The average mortality was approximately 0.2 percent. However, major adverse events, such as cerebrospinal fluid leaks, infarction, or hematoma, occurred in up to 4 percent of patients [37].

The most common complication was aseptic meningitis in 11 percent of patients [37]. Long-term hearing loss occurred in up to 10 percent of patients, and sensory loss occurred in 7 percent.

Rhizotomy — Rhizotomy encompasses a number of percutaneous surgical techniques that are performed by passing a cannula through the foramen ovale, followed by lesioning of the trigeminal ganglion or root using one of several options [83]:

●Radiofrequency thermocoagulation rhizotomy, which creates a lesion by application of heat

●Mechanical balloon compression, which uses a Fogarty catheter to compress the gasserian ganglion

●Chemical (glycerol) rhizolysis, which involves the injection of 0.1 to 0.4 mL of glycerol into the trigeminal cistern

The 2008 AAN/EFNS practice parameter identified four uncontrolled case series that used independent outcome assessment of these procedures [37], including two reports of radiofrequency thermocoagulation [84,85], one report of glycerol rhizolysis [86], and one of balloon compression [87]. The AAN/EFNS found that initial pain relief was achieved in 90 percent of patients, but that pain-free rates declined by one year to 68 to 85 percent, by three years to 54 to 64 percent, and by five years to approximately 50 percent [37].

The major perioperative complication after rhizotomy procedures is meningitis, mainly aseptic, seen in 0.2 percent [37]. Mortality is rare. Postoperative dysesthesia, described as a burning, heavy, or aching feeling, occurs in 12 percent. Longer-term sequelae include trigeminal distribution sensory loss in nearly one-half of patients, anesthesia dolorosa in approximately 4 percent, and corneal numbness with risk of keratitis in 4 percent.

Radiosurgery — Gamma knife radiosurgery produces lesions with focused gamma radiation [88]. (See “Stereotactic cranial radiosurgery”, section on 'Gamma Knife'.)

The therapy is aimed at the proximal trigeminal root since targeting the gasserian ganglion produced poor results [89]. The aiming of the beams is carried out with a stereotactic frame and magnetic resonance imaging (MRI). The doses used are 70 to 90 grays (Gy). The beams cause axonal degeneration and necrosis [89]. Pain relief with gamma knife surgery occurs after a lag time of approximately one month [89,90].

The 2008 AAN/EFNS practice parameter [37] identified one randomized controlled trial of gamma knife surgery for TN that compared two different treatment regimens [91] and found no important differences. In addition, the AAN/EFNS [37] identified three case series with independent outcome assessment [92-94]. Complete pain relief at one year was found in up to 69 percent of patients, and at three years in 52 percent [37]. An earlier systematic review found that approximately 75 percent of patients reported complete relief within three months, but the proportion decreased to 50 percent by three years [95].

New or worsened facial sensory impairment occurred in 9 to 37 percent, with more bothersome sensory loss or paresthesia found in 6 to 13 percent of patients [37]. However, anesthesia dolorosa is rarely, if ever, a complication of gamma knife surgery.

Linear accelerator radiosurgery has been evaluated for the treatment of TN in retrospective case series [96,97], but no prospective studies or controlled trials are available. (See “Stereotactic cranial radiosurgery”, section on 'Linac'.)

Peripheral neurectomy — Peripheral neurectomy can be performed on the branches of the trigeminal nerve, which are the supraorbital, infraorbital, alveolar, and lingual nerves. Neurectomy is accomplished by incision, alcohol injection, radiofrequency lesioning, or cryotherapy. Cryotherapy involves freezing of the nerve using special probes, in theory to selectively destroy the pain fibers.

The AAN/EFNS practice parameter noted that the evidence regarding peripheral techniques for the treatment of TN is either negative or inconclusive [37].

PROGNOSIS — The course of TN is variable. Episodes may last weeks or months, followed by pain-free intervals. Recurrence is common, and some patients have concomitant persistent background facial pain. Most often, the condition tends to wax and wane in severity and frequency of pain exacerbations. However, there are no pure natural history studies of TN, most likely because the severity of the pain leads to intervention [43].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See “Society guideline links: Neuropathic pain”.)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topic (see “Patient education: Trigeminal neuralgia (The Basics)”)

SUMMARY AND RECOMMENDATIONS

●Trigeminal neuralgia (TN) is divided by presumed etiology into classic TN, secondary TN, and idiopathic TN. Classic TN encompasses cases related to vascular compression of the trigeminal nerve. Secondary TN is defined as TN caused by an underlying disease, such as multiple sclerosis and compression of the trigeminal nerve by a space-occupying lesion. (See 'Etiology and pathogenesis' above.)

●TN is defined clinically by sudden, usually unilateral, severe, brief, stabbing or lancinating, recurrent episodes of pain in the distribution of one or more branches of the fifth cranial (trigeminal) nerve. (See 'Clinical features' above.)

●The diagnosis of TN is based upon the characteristic clinical features. Sensory loss, bilateral involvement, and younger age are associated with a higher risk of secondary TN (painful trigeminal neuropathy). (See 'Diagnosis' above.)

●For all patients with suspected TN, we recommend neuroimaging to help distinguish classic TN from secondary TN (algorithm 1). Magnetic resonance imaging (MRI) is the preferred imaging method because of its higher resolution compared with computed tomography (CT). (See 'Neuroimaging' above.)

●The differential diagnosis of classic TN includes conditions that cause classic TN and secondary TN, mainly compression of the trigeminal nerve by a vascular loop or a nonvascular space-occupying lesion, and demyelination from multiple sclerosis in the pons or root entry zone of the trigeminal nerve (see 'Classification' above). Uncommon causes of headache and craniofacial pain in the differential include short-lasting unilateral neuralgiform headache attacks, cluster-tic syndrome, and primary stabbing headache. In addition, TN can sometimes be confused with dental causes of pain. Although less likely to be confused with TN, the differential diagnosis also includes various causes of painful trigeminal neuropathy, such as acute herpes zoster, postherpetic neuralgia, and trauma to the trigeminal nerve. (See 'Differential diagnosis' above.)

●Pharmacologic therapy is used for initial treatment of most patients with TN. (See 'Medical therapy' above.)

•For patients with classic or idiopathic TN who require pain control, we recommend carbamazepine as initial therapy (Grade 1A). (See 'Carbamazepine' above.)

•For patients with classic or idiopathic TN who require pain control who do not respond to or tolerate carbamazepine, we recommend oxcarbazepine (Grade 1B). (See 'Oxcarbazepine' above.)

•For patients with classic or idiopathic TN who are refractory to or intolerant of carbamazepine and oxcarbazepine, we suggest switching to treatment with baclofen (Grade 2C). Alternatively, lamotrigine can be used as add-on therapy. (See 'Baclofen' above and 'Lamotrigine' above.)

•For patients with classic or idiopathic TN who are refractory to the first- and second-line agents listed above, a number of other medications with limited evidence of benefit may be considered. The choice among these agents is driven by patient preference, side effect profile, cost, and clinician familiarity. (See 'Other medications' above and 'Refractory pain' above.)

While no medications have been established as effective for the treatment of secondary TN, patients with secondary TN often respond well to the same medications that are employed in classic and idiopathic TN. In addition, treatment of the underlying condition causing secondary TN is recommended, if feasible. (See 'Medical therapy' above.)

●For patients with TN refractory to medical therapy, it is reasonable to discuss options for surgical therapy using microvascular decompression (for TN caused by compression of the trigeminal nerve root), various types of rhizotomy, or gamma knife radiosurgery. The decision to have surgery and the choice among surgical options will be influenced by individual circumstances including patient preference, adverse effect profile of the available techniques, and expertise of the local center. (See 'Surgical therapy' above.)

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