Trigeminal Neuralgia

RUDOLPH M. KRAFFT, MD, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio

Trigeminal neuralgia is an uncommon disorder characterized by recurrent attacks of lancinat-

ing pain in the trigeminal nerve distribution. Typically, brief attacks are triggered by talking,
chewing, teeth brushing, shaving, a light touch, or even a cool breeze. The pain is nearly always
unilateral, and it may occur repeatedly throughout the day. The diagnosis is typically deter-
mined clinically, although imaging studies or referral for specialized testing may be necessary
to rule out other diseases. Accurate and prompt diagnosis is important because the pain of tri-
geminal neuralgia can be severe. Carbamazepine is the drug of choice for the initial treatment
of trigeminal neuralgia; however, baclofen, gabapentin, and other drugs may provide relief
in refractory cases. Neurosurgical treatments may help patients in whom medical therapy is
unsuccessful or poorly tolerated. (Am Fam Physician. 2008;77(9):1291-1296. Copyright © 2008
American Academy of Family Physicians.)

T
rigeminal neuralgia was first 1 and 2 percent, making it the most common
described at the end of the first associated disease.2 Patients with hyperten-
century and was later given the sion have a slightly higher incidence of tri-
name “tic douloureux” because geminal neuralgia than does the general
of the distinctive facial spasms that often population.2 There is no racial predilection.2
accompany the attacks. The International Trigeminal neuralgia is generally sporadic,
Headache Society has published criteria for although there have been reports of the dis-
the diagnosis of classical and symptomatic ease occurring in several members of the
trigeminal neuralgia (Table 1).1 In classi- same family. Spontaneous remission is pos-
cal trigeminal neuralgia, no cause of the sible, but most patients have episodic attacks
symptoms can be identified other than vas- over many years.
cular compression. Symptomatic trigeminal
neuralgia has the same clinical criteria, but Pathophysiology
another underlying cause is responsible for It has been proposed that the symptoms of
the symptoms. Trigeminal neuralgia may trigeminal neuralgia are caused by demy-
involve one or more branches of the tri- elination of the nerve leading to ephaptic
geminal nerve (Figure 1), with the maxillary transmission of impulses. Surgical speci-
branch involved the most often and the oph- mens have demonstrated this demyelination
thalmic branch the least.2,3 The right side of and close apposition of demyelinated axons
the face is affected more commonly than the in the trigeminal root of patients with tri-
left (ratio of 1.5:1), which may be because of geminal neuralgia.5 Results from experi-
the narrower foramen rotundum and fora- mental studies suggest that demyelinated
men ovale on the right side.2-4 axons are prone to ectopic impulses, which
The annual incidence of trigeminal neural- may transfer from light touch to pain fibers
gia has been reported as 4.3 per 100,000 pop- in close proximity (ephaptic conduction).5
ulation, with a slight female predominance Current theories regarding the cause
(age-adjusted ratio of 1.74:1).2 Primary care of this demyelination center on vascular
physicians might expect to encounter this compression of the nerve root by aberrant
condition two to four times over the course or tortuous vessels. Pathologic and radio-
of a 35-year career. The peak incidence is at logic studies have demonstrated proximity
60 to 70 years of age, and classical trigeminal of the nerve root to such vessels, usually
neuralgia is unusual before age 40 years.2,3 the superior cerebellar artery.5 Relief of
The incidence of trigeminal neuralgia in symptoms by surgical techniques that sepa-
patients with multiple sclerosis is between rate the offending vessels from the nerve

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Trigeminal Neuralgia
SORT: KEY RECOMMENDATIONS FOR PRACTICE

Evidence
Clinical recommendation rating References

Physicians should obtain magnetic resonance imaging in all patients with suspected trigeminal neuralgia. C 3, 11-13
Carbamazepine (Tegretol) should be the initial treatment for patients with classical trigeminal neuralgia A 15, 16, 41
because it has been found to be successful in most cases and no other medication has been shown to
be superior in large studies.
Surgical options should be considered for patients who have persistent pain after trials with several C 12-14
medications or who have a relapse after initial success with medical treatment.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited quality patient-oriented evidence; C = consensus, disease-
oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 1205 or http://
www.aafp.org/afpsort.xml.

further strengthens this hypothesis. Demyelination has nerve and the generation of ectopic impulses that are
also been demonstrated in cases of trigeminal neuralgia spread ephaptically to precipitate the typical attack.
associated with multiple sclerosis or tumors affecting
the nerve root. Diagnosis
Multiple other causes of trigeminal neuralgia have The diagnosis of trigeminal neuralgia should be consid-
been described, including amyloid infiltration, arterio- ered in all patients with unilateral facial pain. Accurate
venous malformations, bony compression, and small and prompt diagnosis is important because the pain of
infarcts in the pons and medulla. In most of these situ- trigeminal neuralgia can be severe. Other diagnoses must
ations, demyelination may also be an underlying cause. also be considered, particularly in patients with atypical
Most investigators now accept the theory that classical features of the disease or “red flags” in the history or phys-
trigeminal neuralgia results from vascular compression ical examination (Table 2). In addition, it is important to
of the nerve root. This leads to demyelination of the distinguish classical from symptomatic trigeminal neu-
ralgia for the purpose of treatment. Symptomatic trigemi-
nal neuralgia is always secondary to another disorder, and
Table 1. IHS Diagnostic Criteria treatment should focus on the underlying condition.
for Trigeminal Neuralgia
HISTORY
Classical
Because trigeminal neuralgia is a clinical diagnosis, the
A. Paroxysmal attacks of pain lasting from a fraction of a second
to two minutes, affecting one or more divisions of the
patient’s history is critical in the evaluation. Patients with
trigeminal nerve, and fulfilling criteria B and C trigeminal neuralgia present with a primary description
B. Pain has at least one of the following characteristics: of recurrent episodes of unilateral facial pain. Attacks
1. Intense, sharp, superficial, or stabbing last only seconds and may recur infrequently or as often
2. Precipitated from trigger zones or by trigger factors as hundreds of times each day; they rarely occur during
C. Attacks are stereotyped in the individual patient sleep. The pain is generally severe, and is described as a
D. There is no clinically evident neurologic deficit stabbing, sharp, shock-like, or superficial pain in the dis-
E. Not attributed to another disorder tribution of one or more of the trigeminal nerve divisions.
Symptomatic Patients generally are asymptomatic between episodes,
A. Paroxysmal attacks of pain lasting from a fraction of a second although some patients with long-standing trigeminal
to two minutes, with or without persistence of aching between neuralgia have a persistent dull ache in the same area.
paroxysms, affecting one or more divisions of the trigeminal Talking, smiling, chewing, teeth brushing, and shaving
nerve, and fulfilling criteria B and C
have all been implicated as triggers for the pain. Even a
B. Pain has at least one of the following characteristics:
breeze touching the face may cause a paroxysm of pain
1. Intense, sharp, superficial, or stabbing
in some patients. In trigger zones—small areas near the
2. Precipitated from trigger zones or by trigger factors
nose or mouth in patients with trigeminal neuralgia—
C. Attacks are stereotyped in the individual patient
minimal stimulation initiates a painful attack. Patients
D. A causative lesion, other than vascular compression, has been
demonstrated by special investigations and/or posterior fossa with trigeminal neuralgia can pinpoint these areas and
exploration will assiduously avoid any stimulation of them. Not all
patients with trigeminal neuralgia have trigger zones, but
IHS = International Headache Society. trigger zones are nearly pathognomonic for this disorder.
Information from reference 1. The patient’s history is also important for ruling out
other causes of facial pain. Because of the association

1292 American Family Physician www.aafp.org/afp Volume 77, Number 9 V May 1, 2008
Trigeminal Neuralgia

Ophthalmic
division

Trigeminal trigeminal neuralgia have stereotyped

ganglion attacks; a change in the location, severity, or
quality of the pain should alert the physician
Maxillary to the possibility of an alternative diagnosis.
division
PHYSICAL EXAMINATION
The physical examination in patients with
trigeminal neuralgia is generally normal.
Therefore, physical examination in patients
Mandibular with facial pain is most useful for identifying
division
abnormalities that point to other diagno-
ses. The physician should perform a careful
ILLUSTRATION BY RENEE CANNON

examination of the head and neck, with an

emphasis on the neurologic examination.
The ears, mouth, teeth, and temporoman-
dibular joint (TMJ) should be examined for
problems that might cause facial pain.
The finding of typical trigger zones verifies
Figure 1. Trigeminal nerve.
the diagnosis of trigeminal neuralgia. Patients
with classical trigeminal neuralgia have a
between trigeminal neuralgia and multiple sclerosis, normal neurologic examination. Sensory abnormalities
patients should be asked about other neurologic symp- in the trigeminal area, loss of corneal reflex, or evidence
toms, particularly those common in multiple sclerosis of any weakness in the facial muscles should prompt the
(e.g., ataxia, dizziness, focal weakness, unilateral vision physician to consider symptomatic trigeminal neuralgia
changes). An evaluation for other diagnoses is indicated or another cause of the patient’s symptoms.
in younger patients, because classical trigeminal neural-
ANCILLARY TESTING
gia is unusual in persons younger than 40 years.3
Trigeminal neuralgia pain is nearly always unilateral. Laboratory studies generally are not helpful in patients
In rare cases of bilateral trigeminal neuralgia, individ- with typical symptoms of trigeminal neuralgia. Occasion-
ual attacks are usually unilateral, with distinct episodes ally, TMJ or dental radiographs may be useful when TMJ
involving each side of the face at separate times. Symp- syndrome or dental pain is in the differential diagnosis.
toms are always confined to the trigeminal nerve distri- Magnetic resonance imaging (MRI) of the brain is use-
bution, with most cases involving the second or third ful to look for multiple sclerosis, tumors, or other causes
division, or both. The asymptomatic period between of symptomatic trigeminal neuralgia, and it should be
attacks is important to distinguish classical trigeminal performed in the initial evaluation of all patients pre-
neuralgia from other causes of facial pain, as well as senting with trigeminal neuralgia symptoms. One study
from symptomatic trigeminal neuralgia. Patients with found that specific clinical variables may be helpful in
determining the likely utility of MRI, which may be use-
ful in prioritizing MRI studies when there is limited MRI
capacity.6 Some studies have indicated that MRI may pre-
Table 2. Atypical Features Suggesting
dict surgery outcomes based on findings of neurovascular
Symptomatic Trigeminal Neuralgia or
an Alternative Diagnosis
contact or the volume of the affected trigeminal nerve.7-9
One recent study demonstrated that trigeminal reflex
Abnormal neurologic Hearing loss or abnormality
testing could distinguish classical from symptomatic
examination Numbness
trigeminal neuralgia with a sensitivity of 96 percent
Abnormal oral, dental, Pain episodes persisting and a specificity of 93 percent.10 Trigeminal reflex test-
or ear examination longer than two minutes ing involves electrical stimulation of the divisions of the
Age younger than 40 years Pain outside of trigeminal trigeminal nerve and measurement of the response with
Bilateral symptoms nerve distribution standard electromyography apparatus. This testing is
Dizziness or vertigo Visual changes not readily available to most physicians, and its indica-
tions and clinical utility are still unclear.

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Trigeminal Neuralgia
Table 3. Differential Diagnosis of Trigeminal Neuralgia

Features that differentiate from trigeminal

Diagnosis neuralgia
treatment of trigeminal neuralgia is pro-
Cluster headache Longer-lasting pain; orbital or supraorbital; may
cause patient to wake from sleep; autonomic vided in Figure 2.12
symptoms
Dental pain (e.g., caries, Localized; related to biting or hot or cold foods; Treatment
cracked tooth, pulpitis) visible abnormalities on oral examination The initial treatment of choice for trigemi-
Giant cell arteritis Persistent pain; temporal; often bilateral; jaw nal neuralgia is medical therapy, and most
claudication patients have at least temporary relief with
Glossopharyngeal Pain in tongue, mouth, or throat; brought on by
the use of selected agents. Patients who have
neuralgia swallowing, talking, or chewing
no response to or who relapse with medical
Intracranial tumors May have other neurologic symptoms or signs
therapy should be considered for surgical
Migraine Longer-lasting pain; associated with photophobia
and phonophobia; family history treatment.12-14 Surgery may also be consid-
Multiple sclerosis Eye symptoms; other neurologic symptoms ered for patients who are intolerant of medi-
Otitis media Pain localized to ear; abnormalities on cal treatment.
examination and tympanogram
MEDICAL TREATMENT
Paroxysmal hemicrania Pain in forehead or eye; autonomic symptoms;
responds to treatment with indomethacin Carbamazepine (Tegretol) has been studied
(Indocin) extensively in trigeminal neuralgia, with one
Postherpetic neuralgia Continuous pain; tingling; history of zoster; often
meta-analysis finding good evidence for its
first division
effectiveness.15 A Cochrane review confirmed
Sinusitis Persistent pain; associated nasal symptoms
that carbamazepine is effective for the treat-
SUNCT Ocular or periocular; autonomic symptoms
Temporomandibular Persistent pain; localized tenderness; jaw
ment of trigeminal neuralgia.16 The number
joint syndrome abnormalities needed to treat has been calculated at 2.5 for
Trigeminal neuropathy Persistent pain; associated sensory loss trigeminal neuralgia. The number needed to
harm for minor adverse events is 3.7, which
SUNCT = shorter lasting, unilateral neuralgiform, conjunctival injection, and tearing. was calculated using data for all conditions.16
Information from reference 11. Some authors have suggested that car-
bamazepine is useful as a diagnostic trial
for classical trigeminal neuralgia. Lack of
DIFFERENTIAL DIAGNOSIS response would suggest symptomatic trigeminal neu-
Some disorders that might be included in the differential ralgia or another diagnosis, both of which are less likely
diagnosis of trigeminal neuralgia are listed in Table 3.11 A to respond to the drug. Dosages used have ranged from
careful examination may disclose local findings indica- 100 to 2,400 mg per day, with most patients responding
tive of otitis, sinusitis, dental disorders, or TMJ dysfunc- to 200 to 800 mg per day in two or three divided doses.
tion. A history of persistent pain or pain that occurs Carbamazepine should be the initial treatment for
episodically in attacks lasting longer than two minutes patients with classical trigeminal neuralgia. Other medi-
eliminates classical trigeminal neuralgia and should lead cations may be tried if carbamazepine is unsuccessful or
to a search for other diagnoses. The pain of glossopha- provides only partial relief. These may be substituted or
ryngeal neuralgia, which may be triggered by talking or added to carbamazepine as necessary. Baclofen (Liore-
swallowing, is located in the tongue and pharynx. sal) in dosages of 10 to 80 mg daily has been shown to be
Symptomatic trigeminal neuralgia is usually caused by useful.17 Additional medications with reported success in
multiple sclerosis or by tumors arising near the trigeminal smaller studies or case reports include phenytoin (Dilan-
nerve root. A history of previous neurologic symptoms tin), lamotrigine (Lamictal), gabapentin (Neurontin),
and typical findings on MRI assist with the diagnosis of topiramate (Topamax), clonazepam (Klonopin), pimo-
multiple sclerosis. Tumors involving the trigeminal nerve zide (Orap), and valproic acid (Depakene).13,18-23 Most
usually cause additional symptoms or examination find- patients will respond, at least temporarily, to single or
ings that suggest the combination therapy with these agents.
diagnosis, and these A variety of other medications and modalities have
The initial choice of treat- tumors are gener- been tried for treatment of trigeminal neuralgia. There
ment for trigeminal neural- ally visible on MRI. are small studies reporting success with botulinum toxin
gia is medical therapy. An algorithm for type A (Botox) in some patients,24 and one case report
the diagnosis and of relief being experienced after an accidentally high

1294 American Family Physician www.aafp.org/afp Volume 77, Number 9 V May 1, 2008
Trigeminal Neuralgia

discharge from a transcutaneous electrical nerve stim- was insufficient evidence from randomized controlled
ulation unit.25 Topical capsaicin (Zostrix) was helpful trials to show significant benefit from non-antiepileptic
for trigeminal neuralgia pain in one open-label trial,26 drugs in patients with trigeminal neuralgia.32
and intramuscular sumatriptan (Imitrex) was benefi-
cial in one small, single-dose study.27 One recent study SURGICAL TREATMENT
found that intranasal lidocaine (Xylocaine) significantly Surgical procedures may be percutaneous or open. The
decreased second-division trigeminal neuralgia pain choice of procedure should be made after patient preference
for more than four hours.28 Acupuncture, high-dose and the experience of the surgeon have been considered
dextromethorphan (Delsym), and topical ophthalmic and the potential risks and benefits of each procedure have
anesthetic have been tried unsuccessfully in small tri- been evaluated. Most procedures provide effective short-
als.29-31 A recent Cochrane review concluded that there term relief, but studies suggest that recurrence is likely
within several years for many patients.33-40
Percutaneous techniques include glycerol
Diagnosis and Treatment of Trigeminal Neuralgia injection, balloon compression, radiofre-
quency rhizotomy, and gamma knife stereo-
Patient with unilateral, episodic facial pain
tactic radiosurgery. These techniques offer
the advantage of being relatively noninvasive,
History and physical examination being outpatient procedures or requiring
consistent with trigeminal neuralgia? only a short hospital stay, and lacking life-
threatening adverse effects. However, they
may provide less long-lasting relief than the
Yes No
more invasive techniques and have a higher
MRI; especially if atypical symptoms, Evaluate for other causes incidence of sensory loss, which may cause
abnormal examination, or age < 40 years
the patient significant discomfort and can be
extremely difficult to treat.
Abnormal? Open techniques include partial trigemi-
nal rhizotomy and microvascular decom-
pression. These procedures involve posterior
Yes No
fossa exploration with its attendant risks,
Treat underlying disorder Medical therapy with including stroke, meningitis, and death,
carbamazepine (Tegretol)
although the reported incidence of these
complications with microvascular decom-
Resolution of pain? pression is less than 2 percent. Microvascular
decompression appears to provide the longest
lasting relief, with persistent relief at 10 years
Yes No
in more than 70 percent of patients.36,41,42 It
Continue treatment Add second agent has low risks of symptom recurrence and
sensory loss, and is therefore a good choice
Resolution of pain?
for young, healthy patients, who have lower
risks of adverse outcomes with the invasive
surgery involved.
Yes No
The author thanks Brian Selius, DO, and Azfar Ahmed,
Continue treatment Surgical therapy MD, for their assistance in the preparation and review of
the manuscript.

Trial without medication after The Author

several symptom-free months
RUDOLPH M. KRAFFT, MD, is an associate professor of
family medicine at Northeastern Ohio Universities Col-
lege of Medicine in Rootstown and director of the Fam-
Figure 2. Algorithm for the diagnosis and treatment of trigeminal ily Medicine Residency at St. Elizabeth Health Center in
neuralgia. (MRI = magnetic resonance imaging.) Youngstown, Ohio. He received his medical degree from
Information from reference 12. Jefferson Medical College of Thomas Jefferson University,

May 1, 2008 V Volume 77, Number 9 www.aafp.org/afp American Family Physician 1295
Trigeminal Neuralgia

Philadelphia, Pa., and completed a residency in family medicine at St. Vin- trigine (lamictal) in refractory trigeminal neuralgia: results from a dou-
cent Health Center in Erie, Pa. ble-blind placebo controlled crossover trial. Pain. 1997;73(2):223-230.
20. Cheshire WP. Defining the role for gabapentin in the treatment of tri-
Address correspondence to Rudolph M. Krafft, MD, FAAFP, 1053 Bel- geminal neuralgia: a retrospective study. J Pain. 2002;3(2):137-142.
mont Ave., Youngstown, OH 44504 (e-mail: rudolph_krafft@hmis. 21. Gilron I, Booher SL, Rowan JS, Max MB. Topiramate in trigeminal neu-
org). Reprints are not available from the author. ralgia: a randomized, placebo-controlled multiple crossover pilot study.
Author disclosure: Nothing to disclose. Clin Neuropharmacol. 2001;24(2):109-112.
22. Lechin F, van der Dijs B, Lechin ME, et al. Pimozide therapy for trigeminal
neuralgia. Arch Neurol. 1989;46(9):960-963.
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1296 American Family Physician www.aafp.org/afp Volume 77, Number 9 V May 1, 2008