Trigeminal neuralgia

INTRODUCTION — 

Trigeminal neuralgia (TN) is a condition that is characterized by recurrent brief episodes of unilateral electric shock-like pains that are abrupt in onset and termination, occur in the distribution of one or more divisions of the fifth cranial (trigeminal) nerve, and are typically 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".)

ETIOLOGY AND PATHOPHYSIOLOGY

Anatomy — The trigeminal nerve provides sensation to the face and portions of the mouth as well as motor control to the muscles of mastication. It has three major divisions:

●Ophthalmic (V1)

●Maxillary (V2)

●Mandibular (V3)

The trigeminal nerve originates in the dorsolateral pons from three sensory nuclei and one motor nucleus that have cell bodies extending from the midbrain to the upper cervical spinal cord. The pontine trigeminal fibers traverse to the midlateral surface of the pons and extend into the subarachnoid space typically adjacent to the superior cerebellar artery. The nerve then travels to the Meckel cave in the floor of the middle cranial fossa where its sensory ganglion (gasserian ganglion) lies and then divides into three main divisions. The ophthalmic (V1) and maxillary (V2) branches extend through the cavernous sinus (figure 1), and the ophthalmic branch exits the skull at the superior orbital fissure while the maxillary branch exits the skull through the foramen rotundum. The mandibular (V3) branch continues along the floor of the middle cranial fossa and exits the skull through the foramen ovale.

The ophthalmic branch provides sensation to the forehead, cornea, and tip of the nose; the maxillary branch provides sensation to the cheeks, lateral nose, upper lip, and upper teeth/gingiva; the mandibular branch provides sensation to the chin, lower lip, part of the external ear, anterior two-thirds of the tongue, and lower teeth/gingiva (figure 2).

Mechanisms — Several distinct mechanisms can produce TN. Compression of the trigeminal nerve root is the main causal mechanism of TN, but brainstem lesions account for a small proportion of cases [2]. Other cases of TN may be idiopathic with no structural cause found despite advanced imaging or surgical exploration. Central sensitization and/or genetic susceptibility may contribute to these cases [3-5].

●Compression of the trigeminal nerve root – Most cases of TN are caused by compression of the trigeminal nerve root, usually within a few millimeters of entry into the pons [6]. The transition from central oligodendroglial myelination to peripheral Schwann cell myelination at this root entry zone may account for a susceptibility to compression [7].

Compression by an aberrant loop of an artery or vein is thought to account for 80 to 90 percent of cases [6,8-11]. 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 [12-18].

The mechanism by which compression of the nerve leads to symptoms appears to be related to demyelination in a circumscribed area around the compression [19,20]. Precisely how demyelination results in the symptoms of TN is not entirely clear. Demyelinated lesions may set up ectopic impulse generation, or the apposition of aberrantly myelinated axons may lead to 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 [6]. Furthermore, alteration of afferent input may disinhibit pain pathways in the spinal trigeminal nucleus.

●Brainstem lesions – Central lesions of the brainstem such as tumors or demyelinating plaques may also contribute to TN when pontine trigeminal pathways are involved.

Tumors of the central nervous system that may present with TN include [21]:

•Meningioma

•Squamous cell carcinoma

•Lymphoma

•Schwannoma

Demyelination of one or more of the trigeminal nerve pathways may be caused by inflammatory conditions such as multiple sclerosis [22]. In multiple sclerosis, a plaque of demyelination typically occurs adjacent to the pontine surface in the root entry zone of the trigeminal nerve [23,24].

●Central sensitization – Evidence for a role of central pain mechanisms includes the presence of refractory periods after a triggered TN attack, trains of painful sensations after a single stimulus, and latency from the time of stimulation to the onset of pain [25]. In addition, electrophysiologic evidence of central sensitization of trigeminal nociceptive processing at brainstem trigeminal nuclei has been observed in some patients with TN who have concomitant chronic facial pain [3]. In other cases, patients with brainstem lesions present years before the onset of TN symptoms suggest a role for chronic inflammation or central sensitization to the development of TN [26].

●Genetic susceptibility – The observation of clinical benefit with some sodium channel antagonists has led to the hypothesis that abnormal sodium channel physiology may contribute to the pathogenesis of TN. Some studies have found abnormal expression of sodium channels in patients with TN [4,27]. In addition, small cohort studies and hospital registries of patients with TN have identified an apparent inherited occurrence of TN in some families [28,29].

EPIDEMIOLOGY — 

TN is a rare condition with an overall prevalence of <0.1 percent in the general population [30-32]. The annual incidence of TN is 4 to 13 per 100,000 people [30,33]. Despite its low incidence, TN is one of the more frequently seen neuralgias in the older adult population.

TN affects females more frequently than males [21,34]. The female-to-male prevalence ratio of TN ranges from 1.5:1 to 1.7:1 [34,35]. This female predominance in this chronic condition may be related to the longer lifespan of females. The incidence of TN increases gradually with age; most idiopathic and classic TN cases begin after age 50 years, although onset may occur in the second and third decades or, rarely, in children [21,36].

Possible risk factors for the development of TN include hypertension and migraine [35,37-40]. Rare familial cases have been reported, but the vast majority of patients have sporadic disease [41,42].

CLINICAL FEATURES

Paroxysmal facial pain

●Character of pain – TN is characterized by paroxysmal, stereotyped attacks of usually intense, stabbing pain. The pain is often described as electric, shock-like, sharp, or stabbing and is usually maximal at or near onset.

Some patients with longstanding TN may also have continuous dull pain that is present between paroxysms of pain. It is usually milder than the paroxysmal attacks and is typically characterized as dull or tingling, though the intensity and quality may fluctuate [32]. In a cohort of 158 patients with TN from a tertiary headache center, concomitant persistent pain was present in about one-half of patients [34].

Mild sensory loss may be reported in rare patients with TN due to compressive lesion such as a tumor [10]. However, prominent sensory loss should prompt evaluation for alternative diagnoses, such as trigeminal neuropathy. (See 'Differential diagnosis' below.)

Location of pain – The pain of TN is strictly limited to the distribution of the trigeminal nerve (figure 3). The pain most often involves the V2 and/or V3 divisions of the trigeminal nerve [1]. However, isolated involvement of the V1 subdivision occurs in <5 percent of patients with TN [34].

TN is typically unilateral. Occasionally, the pain becomes bilateral over time, though rarely on both sides simultaneously [43]. In a review of 439 patients with TN, symptoms were unilateral in 81 percent [21]. Bilateral involvement increases suspicion for a secondary cause of TN, such as multiple sclerosis and connective tissue disorders such as Sjögren's disease, sarcoidosis, or systemic lupus erythematosus [21,44].

●Associated autonomic or motor symptoms – Cranial 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 [34,45,46]. These features are typically mild and intermittent but may accompany attacks of pain in up to 67 percent [47,48]. Although this is known to occur in TN, the presence of prominent or severe autonomic features suggests the possibility of an alternative diagnosis mimicking TN, such as one of the trigeminal autonomic disorders: short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or 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".)

Facial muscle spasms can sometimes be observed during attacks of severe pain. This finding gave rise to the older term for this disorder, "tic douloureux." However, motor involvement with TN is uncommon, and prominent or isolated facial spasms suggest alternative diagnoses related to facial nerve impairment. (See "Nonepileptic paroxysmal disorders in adolescents and adults", section on 'Hemifacial spasm, blepharospasm, and Meige syndrome'.)

●Duration – Paroxysms of pain usually last from one to several seconds, but some patients report attacks that persist for up to two minutes, rarely even longer [49].

●Frequency – Attacks may occur repetitively, anywhere from zero to more than 50 times a day [2,32,50]. Following an attack, patients typically have a refractory period of several minutes during which a paroxysm cannot be provoked. TN pain does not typically awaken patients at night, but exceptions may occur [51].

●Triggers – Nearly all patients with TN experience triggered pain from activation of structures innervated by the trigeminal nerve [2,32,50,52,53]. Trigger zones in the distribution of the affected nerve are common and are often located near the midline of the face. Slight tactile activation of these zones often triggers an attack, leading patients to protect these areas [54]. Trigger zones can sometimes be demonstrated on physical examination. Common triggers of TN paroxysms include [34,49,54]:

•Light touch

•Talking

•Chewing

•Brushing teeth

•Washing the face

•Wind/cold air

•Smiling and/or grimacing

Some TN attacks may be spontaneous, but patients typically also have triggered attacks [49]. Patients who have episodic facial pain without triggered attacks should be evaluated for other conditions. (See 'Differential diagnosis' below.)

Temporal course — The course of TN is variable. Many patients have a relapsing-remitting pattern with pain-free intervals that often last for several months, but remissions can range from weeks to years in some patients [35,50]. However, TN attacks typically recur. (See 'Prognosis' below.)

Some series describe patients with a history of "pretrigeminal neuralgia" who report a history of a dull, continuous, aching pain in the jaw that evolves over time into TN [55-57]. This preceding milder pain is sometimes initially suspected to have a dental origin, and unnecessary dental procedures have been performed in some cases [58].

DIAGNOSIS AND EVALUATION — 

The diagnosis of TN is based upon the characteristic clinical features, primarily paroxysms of pain in the distribution of the trigeminal nerve. Once the diagnosis of TN is suspected on clinical grounds, diagnostic evaluation should be performed to help determine the underlying cause and guide management as well as to identify secondary causes that may require cause-specific treatment (algorithm 1).

Clinical diagnosis — The diagnosis of TN is made in patients with compatible clinical features. 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

Determining the cause — 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, neuroimaging is necessary to help determine the mechanism (algorithm 1) [59].

Clinical features may be similar whether patients have TN from neurovascular compression, tumor, or other cause [2]. Patients presenting at younger ages and/or with objective trigeminal sensory loss or bilateral involvement appear to be at higher risk of secondary TN [10]. 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 features (sensory loss, bilateral involvement, younger age) does not rule out a secondary cause for TN.

For selected patients with atypical clinical features and those with nondiagnostic imaging, we also perform trigeminal reflex testing to help confirm the diagnosis. (See 'Imaging' below and 'Other testing' below.)

Imaging — For all patients with the clinical diagnosis of TN, we recommend brain magnetic resonance imaging (MRI) with and without contrast and magnetic resonance angiography (MRA) to help identify neurovascular compression or a structural brain lesion (eg, tumor in the cerebellopontine angle, demyelinating lesions) [10,21,59-61]. Head computed tomography (CT) and CT angiography may be performed as alternative imaging modalities when MRI and MRA are unable to be performed. However, higher resolution with MRI and MRA enables better visualization of the trigeminal nerve and small adjacent lesions.

●MRI protocol – We typically perform high-resolution MRI with thin cuts through the region of the trigeminal ganglion and heavy T2 weighting (eg, three-dimensional [3D] T2-weighted MRI using constructive interference in steady-state [CISS] fusion study with the addition of intravenous contrast) and 3D T1 postcontrast sequences for optimal visualization of the trigeminal nerve in its cisternal and cavernous segments along with 3D time-of-flight MRA for optimal visualization of the arteries, in agreement with guidelines [32,59,62-64].

●Imaging findings

•Confirmation of neurovascular compression – For patients with a clinical diagnosis of TN prior to MRI, mere contact of a vessel with the trigeminal nerve on imaging is insufficient to diagnose neurovascular compression as the cause. Rather, there is a consensus that the diagnosis requires imaging confirmation of morphologic changes such as dislocation, distortion, atrophy, or compression of the trigeminal nerve at its origin from the pons (image 1) [1,32].

In a 2014 meta-analysis of nine blinded case-control studies, neurovascular contact of the trigeminal nerve on MRI/MRA was more frequent with symptomatic nerves compared with asymptomatic nerves (89 versus 36 percent) [11]. Anatomic change (ie, atrophy, distortion, or flattening) of the trigeminal nerve on MRI at the site of vascular contact was more frequent with symptomatic nerves (53 versus 9 percent, odds ratio 11.8, 95% CI 7.79-17.89). Trigeminal root contact alone had a sensitivity and specificity of 66 and 90 percent, respectively. When trigeminal root contact and nerve atrophy coexisted, sensitivity was lower (52 percent), but specificity was increased to 100 percent.

•Structural lesions – Imaging evidence of secondary TN includes structural lesions along the trigeminal nerve pathway such as cerebellopontine angle tumors, arteriovenous malformations, and areas of demyelination within the pons (image 2) [21,22,65].

•Patients with idiopathic TN – Idiopathic TN refers to patients with TN who do not have apparent neurovascular compression or other structural lesions impacting the trigeminal nerve. This includes patients with a vascular loop adjacent to or in contact with the trigeminal nerve that does not cause compression or other morphologic change. (See 'Classification based on underlying cause' below.)

However, anatomic variations that do not meet criteria for classic or secondary TN may also be found in some patients. In one series of 30 patients with idiopathic TN, the mean trigeminal-pontine angle on axial imaging was found to be narrower on the symptomatic side (40 versus 49 degrees) [66]. This finding may suggest mild anatomic distortion or compression not visible on standard neuroimaging, such as due to a thickened arachnoid membrane [67].

Other testing

●Trigeminal reflex testing is a neurodiagnostic procedure that involves electrical stimulation to assess the integrity of the branches of the trigeminal nerve using side-to-side comparisons of the ophthalmic, maxillary, and mandibular divisions of the trigeminal nerve. Reflex testing is seldom used in contemporary clinical practice but may be useful for select patients with a clinical diagnosis of TN but nondiagnostic imaging (including those unable to have a brain MRI/MRA).

Trigeminal reflex testing is often normal in most patients with TN but may show abnormal responses in many of those with secondary TN or mimics such as trigeminal neuropathy. Findings have been used to identify patients with secondary TN, while other nerve testing like trigeminal evoked potentials have been nondiagnostic [10,59]. In a guideline review of 628 patients with TN from 10 studies, trigeminal reflex testing had a sensitivity and specificity of 94 and 87 percent, respectively, for the diagnosis of secondary TN [10,68].

●Dental evaluation including examination and panoramic or periapical radiographs may be warranted for patients with new onset facial pain who have exclusively intraoral triggers or other atypical features suggestive of an odontogenic cause to symptoms. (See "Complications, diagnosis, and treatment of odontogenic infections", section on 'Diagnosis'.)

Classification based on underlying cause — Patients with TN may be classified by the underlying mechanism typically identified on imaging (see 'Imaging' above). The ICHD-3, defines several subtypes of TN according to the underlying cause [1]:

●Classic (or classical) TN – Classic TN refers to symptoms due to neurovascular compression (not simply contact) with morphologic changes in the trigeminal nerve root, demonstrated on imaging or surgery. Classic TN is the most common mechanism, accounting for up to 75 percent of cases [49].

●Secondary TN – Secondary TN is defined as TN caused by an underlying structural condition. Recognized causes include multiple sclerosis, cerebellopontine angle tumor, and arteriovenous malformation. Secondary TN accounts for approximately 15 percent of cases [10,32].

●Idiopathic TN – Idiopathic TN refers to patients who meet diagnostic criteria for TN, but no clear underlying cause is identified on neuroimaging or other diagnostic tests. Idiopathic TN accounts for approximately 10 percent of cases [11,69]. This includes patients with imaging that shows a vessel that touches but does not compress or distort the symptomatic trigeminal nerve. However, some of these patients who undergo surgical treatment may be reclassified as having classic TN if morphologic changes are found intraoperatively.

DIFFERENTIAL DIAGNOSIS — 

The differential diagnosis of TN includes other conditions that cause trigeminal distribution facial pain, including cranial neuropathies and other causes of cranial pain as well as dental conditions that cause oral or facial pain.

Trigeminal neuropathy — Painful trigeminal neuropathy is a condition distinct from TN, defined as facial pain in the distribution(s) of one or more branches of the trigeminal nerve caused by another condition that produces nerve damage [1]. Conditions that may cause trigeminal neuropathy include:

●Acute herpes zoster

●Postherpetic neuralgia

●Trauma (post-traumatic trigeminal neuropathy)

Painful trigeminal neuropathy may also be idiopathic. (See "Overview of craniofacial pain", section on 'Painful trigeminal neuropathy'.)

Unlike TN, trigeminal neuropathy produces predominantly continuous or near continuous pain and is described most often as burning or squeezing or as a pins and needles sensation. Brief paroxysms of pain may occur but are not predominant. Sensory deficit in the trigeminal nerve territory is common in trigeminal neuropathy and is uncommon or mild in TN.

In most cases, painful trigeminal neuropathy can be distinguished from TN by a history that identifies an antecedent infection or other cause for neuropathy and examination that reveals constant facial pain that does not worsen with light tactile stimulation and a fixed sensory deficit in a trigeminal distribution compared with the contralateral side. Of note, isolated involvement of the V1 subdivision occurs in <5 percent of patients with TN [34], while V1 is most commonly affected by postherpetic neuralgia. (See "Postherpetic neuralgia".)

Dental causes of pain — TN may sometimes be confused with dental causes of pain. These may include:

●Dental caries or fracture

●Periodontal abscess

●Pulpitis

(See "Epidemiology, pathogenesis, and clinical manifestations of odontogenic infections".)

Dental pain is usually described as continuous, intraoral pain that is dull or throbbing, whereas TN pain is typically intermittent pain and sharp. However, symptoms may vary according to the severity and acuity of the dental condition, and it can be difficult to differentiate by history alone. Careful evaluation of all of the triggers can sometimes be helpful. Both dental pain and TN can be triggered by oral manipulations such as chewing and brushing the teeth, however TN is typically also triggered by light touch over the skin supplied by the affected dermatome. If the patient is presenting with only intraoral triggers, additional evaluation should be considered to rule out dental pain. (See 'Other testing' above.)

In some cases, TN can be precipitated by dental procedures (eg, dental extraction), resulting in increased confusion about the precise etiology of the patient’s symptoms [55].

Other causes of headache and craniofacial pain — Several uncommon causes of headache and craniofacial pain may also mimic idiopathic TN. They are typically distinguished by specific clinical features.

●SUNCT/SUNA – Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA) are types of trigeminal autonomic cephalalgias. SUNCT/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. In patients with SUNCT and SUNA, cranial autonomic features are often more prominent than in TN, and refractory periods between attacks are not present. However, some experts suggest that SUNCT, SUNA, and TN are related conditions that exist on a continuum [70]. (See "Short-lasting unilateral neuralgiform headache attacks: Clinical features and diagnosis".)

●Glossopharyngeal neuralgia – Patients with glossopharyngeal neuralgia may report paroxysms of pain while brushing their teeth or chewing or swallowing food, similar to patients with TN. However, the trigger site in glossopharyngeal neuralgia is the posterior pharynx, rather than oral or facial structures innervated by the trigeminal nerve. In addition, patients may also report pain in extratrigeminal regions such as the posterior tongue and middle ear. (See "Glossopharyngeal neuralgia".)

●Nervus intermedius neuralgia – The nervus intermedius is a branch of the facial nerve (cranial nerve VII) that can produce triggered neuralgic pain in the auditory canal. Pain may radiate to trigeminal regions of the face in some patients, but prominent inner ear pain usually identifies nervus intermedius neuralgia. (See "Nervus intermedius neuralgia".)

●Cluster-tic syndrome – Cluster-tic syndrome is a combination of cluster headache with coexistent TN. Such patients meet diagnostic criteria for both TN and cluster headache and may require treatment directed at both conditions. (See "Overview of craniofacial pain", section on 'Cluster-tic syndrome'.)

●Primary stabbing headache – Primary stabbing headache is characterized by transient, sharp jabbing pains that typically occur in frontal or parietal cranial locations, including within trigeminal dermatomes in some patients. Most of the stabs of pain last only a few seconds and occur at irregular intervals from one to many times each day. Symptoms are spontaneous, rather than triggered, in primary stabbing headache, and the extratrigeminal location of some or all attacks can also help differentiate from TN. (See "Primary stabbing headache".)

●First bite syndrome – First bite syndrome is a paroxysmal facial pain or cramping induced by the first bite of a meal with subsequent lessening on further bites [71,72]. Pain can also be precipitated by smelling food. First bite syndrome can be distinguished from TN due to its association with deep parotid lesions, prior surgery that included neck dissection, and lack of cutaneous triggers.

TREATMENT — 

The approach to symptomatic treatment of TN starts with preventive pharmacotherapy for all patients (algorithm 2). Adjunctive rescue therapy may be needed for short-term pain relief during the initial titration of preventive therapies or severe bouts of breakthrough pain. Surgical management is reserved for patients with symptoms that are unresponsive to one or more medications, depending on the underlying cause.

In addition, cause-specific treatment is warranted for patients with secondary TN. (See 'Cause-specific management for secondary TN' below.)

Preventive pharmacotherapy for all patients — Daily preventive pharmacologic therapy is the cornerstone of treatment for patients with classic or idiopathic TN. Although placebo-controlled trials are lacking for the treatment of secondary TN (ie, TN caused by multiple sclerosis or nonvascular compression), it is reasonable to treat the pain associated with secondary TN using the same medications used for classic or idiopathic TN [59]. In our clinical experience, patients with secondary TN often respond well to these drugs.

Initial preventive medications — For most patients with TN who require pain control, we recommend initial therapy with either carbamazepine or oxcarbazepine. Some reports indicate these medications provide significant pain relief in up to 90 percent of patients [2]. Both medications are generally well tolerated, especially with a gradual titration, but the risk of sedation and dizziness or adverse effects from drug interactions may be higher with carbamazepine, and the incidence of hyponatremia may be higher with oxcarbazepine. For patients with an inadequate response within several weeks of achieving a typical therapeutic dose or those with an intolerance to initial choice of therapy, we add or switch to an alternative agent in another class. (See 'Alternatives and adjuncts to initial pharmacotherapy' below.)

Carbamazepine — Carbamazepine is the best studied treatment for classic TN and is established as effective [2,10,43,73].

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

●Adverse effects – Adverse effects of carbamazepine include nausea, vomiting, diarrhea, hyponatremia, rash, pruritus, drowsiness, dizziness, blurred or double vision, lethargy, and headache. Slow titration may minimize these effects. Carbamazepine-induced leukopenia is common, but it is usually benign. Rare but serious adverse effects of carbamazepine include agranulocytosis, aplastic anemia, Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic failure, drug reaction with eosinophilia and systemic symptoms (DRESS), dermatitis/rash, serum sickness, pancreatitis, lupus syndrome, and hypogammaglobulinemia. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects", section on 'Carbamazepine'.)

We suggest testing for the HLA-B*15:02 allele in genetically at-risk populations (ie, those with East Asian or South Asian ancestry) before initiating treatment with carbamazepine. The HLA-B*15:02 allele is a genetic susceptibility marker that is associated with an increased risk of developing Stevens-Johnson syndrome and/or toxic epidermal necrolysis. 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.

Four randomized, controlled trials with a total of 147 patients have established the effectiveness of carbamazepine (200 to 1200 mg daily) for TN [74-77]. A systematic review and practice parameter published in 2008 from the American Academy of Neurology (AAN) and European Federation of Neurological Societies (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 [10]. 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.

Oxcarbazepine — Oxcarbazepine is an effective drug for TN and one that some experts prefer over carbamazepine, citing better tolerability and decreased risk of drug interactions [32,78,79].

●Dosing – Oxcarbazepine is started at a dose of 150 to 300 mg twice daily. The dose can be increased as tolerated in 300 mg increments every three days to a total daily dose of 1200 to 1800 mg, often given as two divided doses or once daily if using the extended-release tablet.

●Adverse effects – Adverse effects of oxcarbazepine are similar to carbamazepine and include hyponatremia, nausea, vomiting, diarrhea, rash, pruritus, drowsiness, dizziness, blurred or double vision, lethargy, and headache. Rare but serious hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and multiorgan hypersensitivity have been associated with oxcarbazepine use, usually within the first few weeks of starting the drug. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects", section on 'Oxcarbazepine'.)

As with carbamazepine, we suggest testing for the HLA-B*15:02 allele in genetically at-risk populations (ie, those with East Asian or South Asian ancestry) before initiating treatment with oxcarbazepine. Oxcarbazepine and carbamazepine should be avoided in patients carrying the HLA-B*15:02 allele unless the estimated benefits clearly outweigh the risks.

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 [10]. In the pooled analysis, both medications were equally effective, with a >50 percent reduction of attacks in 88 percent or more of patients in both treatment groups.

Alternatives and adjuncts to initial pharmacotherapy — For patients with TN with an inadequate response or intolerance to carbamazepine and oxcarbazepine, we switch to or add an alternative preventive treatment such as gabapentin, lamotrigine, or baclofen. Some patients whose symptoms did not respond to initial pharmacotherapy may benefit from alternative or adjunctive medications, based on the authors’ clinical experience.

However, other experts initiate early surgical referral for patients whose symptoms do not respond to initial pharmacotherapy, arguing that they may be unlikely to respond to alternative agents [32,80]. Early surgical referral may also allow time to plan for surgical options while response to alternative pharmacotherapies is being assessed during titration. (See 'Surgery for refractory TN' below.)

There is limited evidence to support specific alternative treatments for patients with TN. The 2008 AAN/EFNS practice parameter concluded that baclofen, lamotrigine, and pimozide are possibly effective for TN [10]. There are weak data to support botulinum toxin injections. A 2019 systematic review from the European Academy of Neurology concluded that lamotrigine, gabapentin, botulinum toxin type A, pregabalin, baclofen, and phenytoin can be used as monotherapy or as adjuncts with first-line therapy (carbamazepine or oxcarbazepine) [59]. However, the quality of supporting evidence was low to very low.

●Gabapentin – Gabapentin may be started at 100 to 300 mg once daily and increased by 300 mg every third day as needed and tolerated up to a typical therapeutic dose of 900 mg/day and a maximum dose of 2400 mg/day given in three divided doses. Gabapentin is generally well tolerated when titrated slowly but may cause sedation, dizziness, and weight gain.

Gabapentin was shown to be possibly effective and to have fewer side effects when compared with carbamazepine in a 2016 meta-analysis of 16 randomized trials [81]. However, all studies were rated as having poor methodologic quality. Nevertheless, gabapentin is an attractive choice due to its better tolerability compared with first-line agents, relative lack of drug interactions, and a low risk of liver or kidney toxicity [59].

●Lamotrigine – The titration schedule for lamotrigine varies by the presence of concomitant medications that affect its metabolism:

•For patients not taking other antiseizure medications, the initial dose is 25 mg once daily; the does may be increased to 50 mg once daily after two weeks and then by 50 mg increments every one to two weeks as tolerated and needed to a typical daily maximum of 400 mg.

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

•For patients taking an antiseizure medication that inhibits hepatic enzymes (eg, valproate), the initial daily dose of lamotrigine is 12.5 to 25 mg every other day. The titration transitions to daily dosing at subsequent intervals, with increases of 25 mg every two weeks as needed to a maximum of 200 mg daily.

Lamotrigine is dosed once daily as an extended-release formulation and twice daily (in divided doses) as an immediate-release formulation. Rash and nausea are common adverse effects, and serious rashes may occur if dose escalation is too rapid. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects", section on 'Lamotrigine'.)

In a double-blind, placebo-controlled crossover study of 14 patients with TN that was refractory to carbamazepine or phenytoin, adjunctive therapy with lamotrigine (400 mg daily) was beneficial for improvement on a composite outcome index [82]. Similarly, an open-label study found that lamotrigine was beneficial in 11 of 15 patients with TN once the 400 mg dose was reached [83]. However, the clinical utility of lamotrigine for severe pain is limited by the need to titrate the dose over many weeks, given the risk of rash and other serious adverse effects [84].

●Baclofen – Baclofen is typically started at 5 to 10 mg once daily and increased by 10 mg up to every three days to a typical daily maximum dose of 80 mg, given in three to four divided doses. Drowsiness, nausea, and dyspepsia are common adverse effects. The drug should be discontinued slowly since seizures and hallucinations have been reported upon withdrawal.

Limited evidence from a small double-blind crossover trial suggests that baclofen is beneficial for TN [85]. Treatment with baclofen 40 to 80 mg daily resulted in a reduction in paroxysm frequency in 7 of 10 patients with typical TN, compared with 1 of 10 who received placebo. The utility of baclofen is limited by adverse effects, which typically prevent a sufficient oral dose needed to achieve beneficial pain reduction [32].

●Botulinum toxin injections — Botulinum toxin injections may be beneficial for patients with TN, although data are limited. A 2024 systematic review and meta-analysis identified 23 studies including four small placebo-controlled randomized controlled trials with a total of 178 patients that evaluated the use of botulinum toxin A for TN [86]. Pain improvement, assessed by change in the visual analog scale (VAS) rating, was greater with botulinum toxin than sham injections at 4-, 8-, and 12-week follow-up (mean differences -2.6, -2.5, and -4.1, respectively). In the pooled analysis of single-arm studies, botulinum toxin treatment was associated with a reduction in mean VAS scores and attack frequency. However, small patient numbers limit the confidence in these results, and further study is required.

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

•Tizanidine at 2 to 4 mg once daily 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 [87]. Tizanidine has been used at doses up to 24 mg daily for spasticity, but the utility of this dosing in TN is uncertain.

•Pregabalin is a gabapentinoid similar to gabapentin that may be used for patients with TN. It is started at 25 mg daily and titrated to a usual therapeutic daily dose of 150 to 600 mg, given in two or three divided doses. In an open-label study of 53 patients with TN, pregabalin was associated with partial or complete pain relief in 74 percent at eight-week follow-up [88].

•Phenytoin is most commonly used for acute rescue therapy for TN but may also be used as preventive therapy [89]. Phenytoin is usually started at a dose of 15 mg/kg given in three divided doses and titrated to effect and guided by serum phenytoin concentration levels. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects", section on 'Phenytoin and fosphenytoin'.)

•Pimozide, a dopamine receptor antagonist, was more effective than carbamazepine in a randomized, double-blind crossover trial of 48 patients with refractory TN [90,91]. There were no dropouts among patients taking pimozide. Pimozide dosing ranges from 2 to 12 mg once daily. 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.

•Tocainide is an antiarrhythmic drug that was reported to be similarly effective as carbamazepine at two weeks in a crossover trial of 12 patients with TN [92]. Tocainide is not available in the United States, and availability elsewhere may be limited.

Duration of successful pharmacotherapy — For patients with resolution of TN symptoms while taking preventive pharmacotherapy, we offer an attempt to gradually wean after a sustained pain-free interval of at least six to eight weeks on medication; some authors wait for at least six months before attempting a wean. The taper schedule varies according to the medication and dose but should be slow.

Some patients with TN may have remissions for weeks to months or even years, and periodic weaning can reduce exposure to adverse effects or drug interactions with TN pharmacotherapy. However, the patient should be aware that future pain recurrence is likely and would require restarting the medication. (See 'Prognosis' below.)

Acute rescue therapy for patients with breakthrough pain — Some patients with frequent attacks may warrant acute rescue therapy for short-term rapid pain relief. Rescue therapy may be used during the initial titration of preventive pharmacotherapy, as an adjunct for patients with breakthrough attacks, or as a bridge for patients with refractory pain awaiting surgical treatment options.

We frequently start with a short-term increase in dose of preventive medications, provided the patient is not already taking the maximal dose. For other patients with breakthrough pain, we individualize medication selection, using risk profile of available agents, prior response to acute therapies, and severity of attacks to help guide among options. Limited low-quality data suggest that intranasal or intravenous infusions of lidocaine, subcutaneous injections of sumatriptan, intravenous phenytoin or fosphenytoin, or intravenous lacosamide can provide analgesia for patients with TN [59,93,94].

●Additional dose of preventive medication – For patients who achieve symptomatic relief with preventive therapy but develop breakthrough attacks and are not already taking the maximum dose, a short-term increase in dosing may provide additional benefit. As an example, an additional carbamazepine dose of 50 to 100 mg may be given for breakthrough pain, typically using the oral suspension or chewable tablet. (See 'Carbamazepine' above.)

●Lidocaine – Lidocaine may be given for acute exacerbations of TN by intranasal aerosol or intravenous administration.

•Lidocaine administered intranasally or intraorally as a 2.4 percent aerosol (32 mg per dose) was reported effective in a retrospective study of 152 patients in China with severe pain from TN [95]. Pain resolution or a greater than 50 percent improvement was reported at 15 and 30 minutes in 78 and 70 percent, respectively. Adverse effects were mild, including numbness, bitter taste, and burning in the affected area; no cardiovascular or other systemic adverse effects were reported. Repeat administration for pain recurrence was common, and response rate was lower among patients taking high doses of carbamazepine or oxcarbazepine and those with TN symptoms affecting the ophthalmic (V1) division of the trigeminal nerve. Similar short-term benefit was reported in a small placebo-controlled trial of 25 patients with TN using intranasal lidocaine 8 percent (16 mg) [96].

Lidocaine nasal sprays are not commercially available in the United States but may be prepared by a compounding pharmacy.

•Lidocaine administered by intravenous infusion at 5 mg/kg over one hour showed some benefit for up to 24 hours after infusion in a placebo-controlled crossover trial of 20 patients [97]. Intravenous lidocaine administration requires continuous cardiac monitoring with electrocardiogram (ECG) and frequent blood pressure checks.

●Sumatriptan – The benefit of sumatriptan at 3 mg given by subcutaneous injection was shown in a small placebo-controlled crossover trial, with improvement persisting for a mean duration of approximately eight hours [98]. Subcutaneous sumatriptan followed by oral sumatriptan 50 mg daily for one week may provide a longer duration of analgesia [99].

●Phenytoin – Phenytoin or fosphenytoin treatment has been associated with improvement in TN in case reports and small case series [94,100-103]. The phenytoin dose is 250 to 1000 mg given intravenously at no more than 50 mg/minute (150 mg phenytoin equivalents [PE]/minute for fosphenytoin) [100]. Alternative weight-based single dosing is 15 mg/kg given over 30 to 120 minutes [100,104].

●Lacosamide – In a retrospective observational study of patients with TN presenting to an emergency department, resolution of acute symptoms following an intravenous infusion of lacosamide was reported in 49 of 63 patients (78 percent) [94]. Infusion dose ranged from 50 to 400 mg; adverse effects were mild.

●Peripheral nerve block – Limited data suggest nerve block using an anesthetic with or without a glucocorticoid directed to the symptomatic trigeminal nerve roots may provide short-term pain relief [105-108]. In a series of 72 patients with TN who received local injections with lidocaine (0.25 mL at 2 percent concentration) plus triamcinolone 10 mg, a ≥50 percent reduction in pain severity was reported in nearly 80 percent of patients at one-month follow-up [109]. In another small series of nine patients with medically refractory TN who received local injections with bupivacaine and lidocaine, partial or complete pain relief was reported by 5 patients at one- to eight-month follow up [105]. However, the longer-term benefit of these treatments is uncertain.

Surgery for refractory TN — Surgical referral is warranted for patients with TN symptoms refractory to one or more preventive medications. For patients with TN refractory to medical therapy, it is reasonable to discuss options for surgical therapy using microvascular decompression, rhizotomy, or stereotactic radiosurgery [2].

The decision to pursue surgery for TN varies by underlying cause, availability of surgical expertise, and patient preferences. Patients whose symptoms are refractory to a therapeutic trial of initial therapy may elect to pursue surgery when neuroimaging shows clear evidence of an underlying structural lesion, such as neurovascular compression among those with classic TN. Others may prefer therapeutic trials of two or more preventive medications before considering surgical options, such as those with idiopathic TN who lack a radiographically apparent structural cause and patients at high risk for surgery.

Choice of procedure — The choice among surgical options is influenced by underlying cause of TN, adverse effect profile of the available techniques, and expertise of the local center.

●Patients with classic TN – For patients with neurovascular compression identified on neuroimaging (see 'Imaging' above) who are able to tolerate major surgery, we suggest microvascular decompression rather than another surgical procedure. Microvascular decompression appears to be an effective procedure for properly selected patients with classic TN.

●Patients with secondary TN – The selection of surgical procedure to treat medically refractory secondary TN should be individualized. Observational data, mainly single-center case series, suggest that some patients with multiple sclerosis and TN experience at least short-term improvement with interventions including microvascular decompression [110-112], gamma knife radiosurgery [113], and percutaneous ganglion lesioning [114,115].

Patients with structural causes of secondary TN may also warrant surgical treatment to manage the underlying cause, such as those with cerebellopontine angle tumors. (See 'Cause-specific management for secondary TN' below.)

●Patients with idiopathic TN – Surgery may benefit some patients with idiopathic TN (ie, no abnormalities on neuroimaging), but data are limited. Percutaneous ablation procedures may be preferred when imaging shows no neurovascular contact [7]. However, surgical exploration may identify vascular compression that was not evident on MRI, providing a rationale for microvascular decompression. In cases where no compressive vessel is found, a partial rhizotomy may be performed, sparing the V1 division. Other ablative strategies for refractory idiopathic TN include radiosurgery with gamma knife or rhizotomy with radiofrequency, balloon, or glycerol.

●Patients with TN at high surgical risk – Patients with medically refractory TN symptoms who are felt to be at a high surgical risk due to concomitant medical comorbidities may be candidates for percutaneous ablation procedures like gamma knife stereotactic radiosurgery or radiofrequency thermocoagulation rhizotomy [116,117].

Surgical techniques — Surgical procedures for TN include microvascular decompression (of the impacted trigeminal nerve root) and ablative procedures. Microvascular decompression is commonly used for patients with classic TN, the most frequent causal mechanism. While the procedure is invasive, the overall mortality and complication rates are low. Ablative procedures are often less invasive and used for patients without neurovascular compromise or those unable to tolerate open surgery, but recurrence may be more common. However, few surgical treatments for TN have been studied in controlled trials, and most of the evidence comes from observational studies [118]. Definitive conclusions regarding the relative effectiveness of surgical techniques for TN are precluded by the lack of studies directly comparing them [10].

●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 [119].

Microvascular decompression appears to be the most effective surgical technique for classic TN, although comparative randomized trials are lacking [32,59]. The 2008 AAN/EFNS practice parameter identified five studies of microvascular decompression for TN [120-124] that used independent outcome assessment [10]. 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. Indirect comparisons of the findings from different surgical studies suggested that microvascular decompression has a longer duration of pain control than other surgical interventions for TN. The average mortality was approximately 0.2 percent; major perioperative adverse events, such as cerebrospinal fluid leaks, infarction, or hematoma, occurred in up to 4 percent of patients, while aseptic meningitis complicated 11 percent [10]. Long-term hearing loss occurred in up to 10 percent of patients, and sensory loss occurred in 7 percent. Similar results were reported in a 2024 retrospective study of 1025 patients with TN who underwent microvascular decompression using autologous muscle, with high rates of sustained pain relief at 1, 5, 10, 15, and 20 years (97, 90, 85, 82, and 81 percent, respectively) [125]. In this cohort, durable pain relief was likely among patients with an arterial rather than venous source of nerve compression.

●Rhizotomy – Rhizotomy encompasses several percutaneous surgical techniques that are performed by passing a cannula from the surface through the foramen ovale and to the trigeminal nerve under fluoroscopic or CT guidance. The trigeminal ganglion or root is then lesioned using one of several options [126,127]:

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

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

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

A small trial of 30 patients with TN found percutaneous radiofrequency ablation reduced pain at one month [128]. The 2008 AAN/EFNS practice parameter identified four uncontrolled case series that used independent outcome assessment of these procedures [10], including two reports of radiofrequency thermocoagulation [129,130], one report of glycerol rhizolysis [131], and one of balloon compression [132]. 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 [10].

The major perioperative complication after rhizotomy procedures is meningitis, mainly aseptic, seen in 0.2 percent [10]. There is also a risk of maxillary artery injury and dural laceration overlaying Meckel cave, which could lead to oculomotor nerve injury via thermocoagulation or inadvertent injection of glycerol into the middle cranial fossa [32]. Mortality is rare. Postoperative dysesthesia, described as a burning, heavy, or aching feeling, occurs in 12 percent [10]. 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. The incidence of facial numbness is higher with rhizotomy procedures than with microvascular decompression or gamma knife radiosurgery.

●Radiosurgery – Stereotactic radiosurgery uses gamma or x-rays delivered to imaging-defined targets to produce therapeutic lesions [133]. For TN radiosurgery, the therapy is aimed at the proximal trigeminal root since targeting the gasserian ganglion produced poor results [80]. The aiming of the beams is typically carried out with a stereotactic frame and MRI. The doses used are 70 to 90 grays (Gy) [134]. The beams cause axonal degeneration and necrosis [80]. Pain relief with gamma knife surgery occurs after a lag time of approximately one month [80,135].

The 2008 AAN/EFNS practice parameter [10] identified one randomized controlled trial of gamma knife surgery for TN that compared two different treatment regimens [136] and found no important differences. In addition, in three case series [137-139] with independent outcome assessment, complete pain relief was found in up to 69 percent of patients at one year and 52 percent at three years [10]. 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 [140]. In one retrospective study of 871 patients who underwent radiosurgery for refractory TN, the initial response rate was 82 percent, but nearly 50 percent of patients had pain recurrence and underwent a second procedure at a median of 44 months follow-up [134].

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 [10]. However, anesthesia dolorosa is rarely, if ever, a complication of gamma knife surgery.

Other radiosurgery techniques have been evaluated for the treatment of TN in retrospective case series, including linear accelerator radiosurgery [141,142] and pulsed radiofrequency [143-145], but randomized trials are warranted to better assess comparative short- and longer-term benefits and risks of these techniques. (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. However, the AAN/EFNS practice parameter and subsequent reviews have noted that the evidence regarding peripheral techniques for the treatment of TN is either negative or inconclusive [10,32].

Although surgical therapy for TN is generally well tolerated, a feared complication is painful posttraumatic 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 [146]. Anesthesia dolorosa most frequently occurs as a complication of rhizotomy or thermocoagulation for TN but may also be an uncommon complication of gamma knife surgery. This risk warrants careful decision making when considering surgical treatment for TN. (See "Overview of craniofacial pain", section on 'Painful post-traumatic trigeminal neuropathy'.)

Cause-specific management for secondary TN — Patients with secondary TN may require management of the underlying cause distinct from symptomatic management of TN symptoms. In some cases, treatment of the underlying cause may improve TN symptoms. These entities include the following:

●Demyelinating plaque (see "Overview of disease-modifying therapies for multiple sclerosis" and "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): Treatment and prognosis")

●Cerebellopontine angle tumors (see "Management of known or presumed benign (WHO grade 1) meningioma", section on 'Large or symptomatic tumors' and "Vestibular schwannoma (acoustic neuroma)", section on 'Management' and "Uncommon brain tumors", section on 'Epidermoid cyst' and "Etiology of hearing loss in adults", section on 'Cholesteatoma' and "Cholesteatoma in children", section on 'Surgical treatment')

●Arteriovenous malformations (see "Brain arteriovenous malformations", section on 'Management of the AVM')

PROGNOSIS — 

The course of TN is variable. Patients may have episodes that persist for weeks or months, followed by pain-free intervals of weeks to years. However, most remissions last for only a few months [35,50]. In one observational study of 186 patients with TN, apparent remission permitting medications to be discontinued occurred in 28 percent by two-year follow up, but most patients continued with symptomatic management [147]. Most often, the condition tends to wax and wane in both severity and frequency of pain exacerbations, and most patients require long-term treatment for symptom management [78]. Some patients have intermittent episodes along with chronic baseline facial pain. However, there are no pure natural history studies of TN, most likely because the severity of the pain leads to intervention [84].

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 5^th to 6^th 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 10^th to 12^th 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 email 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

●Characteristic features – TN is characterized by paroxysmal, stereotyped attacks of usually intense, stabbing unilateral pain in the distribution of one or more branches of the fifth cranial (trigeminal) nerve (figure 3). The pain most often involves the V2 and/or V3 divisions of the trigeminal nerve. Slight tactile activation of structures innervated by the trigeminal nerve often trigger an attack. (See 'Clinical features' above.)

●Clinical diagnosis – The diagnosis of TN is made clinically in patients with compatible features that fulfill diagnostic criteria. (See 'Clinical diagnosis' above.)

●Evaluation – For all patients with the clinical diagnosis of TN, neuroimaging is necessary to help determine the underlying cause (algorithm 1). (See 'Determining the cause' above.)

•Imaging – We recommend brain MRI with and without contrast and magnetic resonance angiography (MRA) to help identify neurovascular compression or a structural brain lesion (eg, tumor in the cerebellopontine angle, demyelinating lesions) as the cause of TN. (See 'Imaging' above.)

•Classification – Patients with TM may be classified by the underlying cause. (See 'Classification based on underlying cause' above.)

-Classic TN – Classic TN refers to symptoms due to neurovascular compression (not simply contact) with morphologic changes in the trigeminal nerve root demonstrated on imaging or surgery (image 1).

-Secondary TN – Secondary TN is defined as TN caused by an underlying structural condition. Recognized causes include multiple sclerosis, cerebellopontine angle tumor, and arteriovenous malformation (image 2).

-Idiopathic TN – Idiopathic TN refers to patients who meet diagnostic criteria for TN, but no clear underlying cause is identified on neuroimaging or other diagnostic tests.

●Differential diagnosis – The differential diagnosis of TN includes other conditions that cause trigeminal distribution facial pain, including cranial neuropathies and other causes of cranial pain as well as dental conditions that cause oral or facial pain. (See 'Differential diagnosis' above.)

●Management – The approach to symptomatic treatment of TN starts with daily preventive pharmacotherapy for all patients (algorithm 2). Adjunctive rescue therapy may be needed for short-term pain relief during the initial titration of preventive therapies or severe bouts of breakthrough pain. Surgical management is reserved for patients with symptoms that are unresponsive to one or more medications, depending on the underlying cause. In addition, cause-specific treatment is warranted for patients with secondary TN.

•Initial pharmacotherapy – For most patients with TN who require pain control, we recommend initial therapy with either carbamazepine or oxcarbazepine over other options (Grade 2C). These agents have been shown to be effective in several placebo-controlled clinical trials but have not been systematically compared with other agents. (See 'Initial preventive medications' above.)

For patients with TN with an inadequate response or intolerance to initial pharmacotherapy, we switch to or add an alternative preventive treatment such as gabapentin, lamotrigine, or baclofen. (See 'Alternatives and adjuncts to initial pharmacotherapy' above.)

•Acute rescue therapy for breakthrough pain – Several options may be used as rescue therapy for breakthrough attacks. We frequently start with a short-term increase in dose of preventive medications provided the patient is not already taking the maximal dose. Other options include intranasal or intravenous infusions of lidocaine, subcutaneous injections of sumatriptan, intravenous phenytoin or fosphenytoin, or intravenous lacosamide. We individualize medication selection, using risk profile of available agents, prior response to acute therapies, and severity of attacks to help guide among options. (See 'Acute rescue therapy for patients with breakthrough pain' above.)

•Surgery for refractory cases – Surgical referral is warranted for patients with TN symptoms refractory to one or more preventive medications. (See 'Surgery for refractory TN' above.)

-For patients with classic TN refractory to one or more preventive medications, who are able to tolerate major surgery, we suggest microvascular decompression (Grade 2C). Microvascular decompression appears to be an effective procedure for properly selected patients with classic TN, although adverse events are a risk, and the benefit wanes over time.

-The selection of surgical procedure to treat medically refractory TN in patients with secondary or idiopathic TN and those who are unable to tolerate surgery should be individualized. Options include microvascular decompression, rhizotomy, or stereotactic radiosurgery. However, efficacy of these interventions is uncertain in these patients, and benefits may not be durable; in addition, interventions have a risk for serious complications.

●Prognosis – Patients may have episodes that persist for weeks or months followed by pain-free intervals of weeks to years. Recurrence is common. Most often, the condition tends to wax and wane in severity and frequency of pain exacerbations. (See 'Prognosis' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Zahid H Bajwa, MD, who contributed to earlier versions of this topic review.