Neuralgias are paroxysmal pain in the distribution of a particular
nerve. The pain is typically maximal at onset and lancinating, and
may be described as “electric shocks” or “jabbing.” There
may be a single sharp pain, or repetitive pains in succession. The
pain may be so brief as to last but an instant, or for several seconds.
There is usually a refractory period after the severe pain, during which
pain does not occur. Some neuralgic conditions have trigger zones
(areas that, when stimulated, provoke an attack) or other triggers.
Careful history taking often reveals other pain occurring as well,
such as continuous aching, burning, or throbbing. Inquiry must be
made about all the sensations that occur, because some patients
mention only the severe exacerbations. Response to treatment may
provide a clue to diagnosis, but can also be misleading. “Diagnostic
blocks” in the setting of facial pain do not necessarily
define the site from which the pain arises because of overlap of
cranial nerves V, IX, and X (which converge on the spinal trigeminal
nucleus and the tractus solitarius).
The best-known facial neuralgia is trigeminal neuralgia, which
is discussed in detail in this chapter and, in many ways, serves
as a model for understanding other neuralgias causing facial pain.
Trigeminal neuralgia is a severe, (usually) unilateral facial
pain, characterized by lancinating pains in the distribution of
one or more divisions of the trigeminal nerve. Although onset may occur
in the second and third decades, the majority of cases begin in
middle and old age. With an annual incidence rate of 4 to 5 per
100,000, it is one of the most frequently seen neuralgias in the elderly.1 The
pain may be so excruciating that facial muscle spasms can be seen,
hence the older term, tic douloureux.
The facial pain tends to occur in paroxysms and is maximal at
or near onset. The severe exacerbations tend to last from one to
several seconds, but may occur in volleys. There may also be a coexisting
continual deep or dull pain. Patients may or may not, therefore,
have pain-free periods.
Trigeminal neuralgia most often involves the second and third
divisions of the trigeminal nerve (V2 and V3),
but can include or be limited to the first division, as well. Trigger
zones may be present. Often, lightly touching these areas will trigger
a paroxysm, and patients tend to protect these areas. Other triggers
may include chewing, talking, brushing teeth, cold air, or smiling
and grimacing. A refractory period of several minutes typically
follows an episode, during which a paroxysm cannot be provoked.
In occasional patients, the pain may be bilateral, but not on both
This condition may be idiopathic (primary), or symptomatic (secondary).
Idiopathic implies no known underlying condition, but in point of
fact most idiopathic cases are the result of vascular compression
of the trigeminal nerve near its entry into the pons. Symptomatic
causes include multiple sclerosis, tumors, and basilar artery aneurysm
Unlike some other facial pain conditions, trigeminal neuralgia
typically does not awaken patients at night. Some patients have
a history of so-called pretrigeminal neuralgia, which is said to
be dull, continuous, aching pain in the jaw, evolving eventually
into trigeminal neuralgia. This brief, milder pain is sometimes
suspected to have a dental origin, and dental procedures are performed. Because
trigeminal neuralgia is sometimes precipitated by dental procedures
(e.g., dental extraction), confusion about etiology has resulted.5
The pathophysiology of trigeminal neuralgia is not fully elucidated.
Demyelinative lesions of trigeminal fibers appear to set up ectopic
impulses and ephapses. This 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 some latency from the time of stimulation to
the onset of pain.6
Clinically, certain features of the history help in making the
diagnosis. Paroxysms of pain in the distribution of the trigeminal
nerve, especially if trigger points are present, are typical. The
examination may reveal these trigger zones, which often are near
the midline. If sensory loss is present, a mass lesion is more likely.
In younger patients (20 to 40 years old) with trigeminal neuralgia, multiple
sclerosis should be considered. A demyelinative lesion in the pons
would explain bilateral symptoms.
Once the diagnosis is suspected on clinical grounds, a careful
search for ipsilateral dental pathology should be undertaken (oral
surgery consultation should be considered). Magnetic resonance imaging
(MRI) and magnetic resonance angiography (MRA) should be performed
to look for evidence of demyelinating lesions, a mass lesion in
the cerebellopontine angle, or an ectatic blood vessel (rarely seen
with MRA). The differential diagnosis includes SUNCT, cluster-tic
syndrome, jabs and jolts syndrome, and other neuralgias, all of
which are discussed later in this chapter.
Trigeminal neuralgia is usually successfully treated with medication
(Table 25-1). Carbamazepine is felt to be the most effective medication.
Baclofen, phenytoin, valproate, pimozide, and clonazepam have utility
as well, alone or in various combinations.7 Misoprostol,
a prostaglandin E analogue, has been reported as effective in trigeminal
neuralgia caused by multiple sclerosis.8 Gabapentin
and lamotrigine have also been reported to be useful, although there
is less clinical experience with these agents.9,10
Table 25-1 Medications
for Trigeminal Neuralgia
Neuroleptic medications, including chlorpromazine and perphenazine,
have been used successfully in intractable cases, and novel neuroleptics
such as olanzapine and quetiapine are being tried as well. Tizanidine
has been used in selected cases. Topiramate has been suggested,
because other anticonvulsant medication has been effective.
We have found carbamazepine to be the most useful of all the
available drugs. If doses are started low, especially in the elderly
(e.g., 50 mg b.i.d.) and advanced gradually, the drug is highly
efficacious with few side effects, and few patients develop tolerance.
If pain control is insufficient, baclofen may be added. If the patient
is desperate for immediate pain relief, intravenous infusion of
phenytoin or fosphenytoin (250 to 500 mg at no more than 50 mg/min,
monitoring pulse and blood pressure) may be rapidly effective, although
many patients quickly develop tolerance to the drug. Nonetheless,
intravenous phenytoin may afford immediate temporary relief while
oral carbamazepine therapy is begun. This maneuver may also enable
the physician to better examine the patient with a sensitive face.11 Details
of the use of these medications may be found elsewhere in this book
(see Chaps. 62, 63, and 64). Rarely, there are spontaneous permanent
remissions of trigeminal neuralgia. More often, the illness tends
to wax and wane in terms of severity and frequency of exacerbations.
Therefore, in patients achieving good relief of pain with medications,
periodic attempts to gradually withdraw these drugs are warranted.
For patients refractory to therapy with drugs, various surgical
procedures may have efficacy. Janetta has popularized microvascular
decompression, the dissection away from the trigeminal nerve of
various vascular structures, often an ectatic superior cerebellar
artery.12 Long-term outcome is good (over 80% pain-free),
but this procedure does involve an intracranial approach with a
small morbidity and mortality rate. Other procedures directed against
the trigeminal nerve include percutaneous radiofrequency rhizotomy,
glycerol rhizolysis, and balloon compression. Complications include
anesthesia dolorosa (a central pain disorder resulting from hypersensitization
of the second-order spinal trigeminal nucleus neuron) and keratitis,
as well as facial weakness caused by injury of the facial nerve.
More recently, excellent results with minimal morbidity have been reported
with gamma knife therapy.13 For patients unable
or unwilling to tolerate more aggressive surgical procedures, peripheral
nerve root avulsion may provide relief. Although often temporarily
effective, nerves often regenerate and pain recurs.
Tenser has noted that after surgery for trigeminal neuralgia,
herpes simplex virus reactivation occurs in 17% to 94% of
patients. The speculation is that altered function of cranial nerve
V (CNV) underlies the beneficial response to the various surgical
manipulations (injury to the trigeminal root ganglion).14
In summary, patients suffering from trigeminal neuralgia deserve
a careful evaluation, especially to exclude symptomatic causes such
as multiple sclerosis or a cerebellopontine angle mass. Ipsilateral
dental pathology should be sought. Pain relief can usually be achieved
through aggressive pharmacologic therapy, surgery or both.
It has been reported that the pains of trigeminal neuralgia and
cluster headache may coexist.15 In the cluster-tic
syndrome, there are three types of pain. One component of the pain
resembles trigeminal neuralgia—paroxysmal, extremely brief,
and severe. The second component is more similar to cluster headache,
although of variable length, with autonomic phenomena (lacrimation, rhinorrhea).
The third type of pain is a mixture of the first two. This pain
may be provoked by trigger points or moving the neck.
Cluster-tic syndrome usually afflicts patients between 20 and
70 years old. It may exist in chronic or episodic forms (remissions
and recurrences). Medical therapy is usually unsuccessful, although when
surgery (microvascular decompression or trigeminal rhizotomy) relieves
the neuralgia, the cluster-like pain may be lessened and become
more responsive to therapy.
The differential diagnosis includes SUNCT, which is discussed
later in this chapter. Secondary (symptomatic) SUNCT has been reported
as a result of arteriovenous malformation in the cerebellopontine
angle, and secondary cluster-tic syndrome has been seen associated
with an ectatic basilar artery running deep into the cerebellopontine
cistern.16,17 We feel it is possible that so-called
cluster-tic syndrome and SUNCT may actually be the same condition.
Glossopharyngeal neuralgia is defined as paroxysmal pain in areas
supplied by cranial nerves IX and X (CN IX, X). There are numerous
analogies to trigeminal neuralgia, with which it occasionally coexists.
This entity is much less common than trigeminal neuralgia. Age
of onset ranges from childhood to old age, although middle age is
most frequent. This condition usually occurs as paroxysmal, severe,
unilateral pain involving the ear, larynx, tonsil, or tongue. It
is almost never bilateral. Triggers include chewing, swallowing,
coughing, speaking, yawning, certain tastes, and touching the neck
or external auditory canal (rarely the pre- or postauricular areas).18
The pain typically radiates upward from the oropharynx toward
the ear. The duration of the severe paroxysms is seconds to minutes,
but there may also be a low-grade, constant, dull background pain.
Up to several dozen attacks may occur each day, some of which awaken
the patient from sleep. Some episodes are associated with strenuous
coughing or hoarseness.
Similar to trigeminal neuralgia, glossopharyngeal neuralgia may
occur in a pattern of bouts lasting weeks to months, alternating
with longer periods of remission. Severe attacks may be associated
with bradycardia and asystole, resulting in syncope.19 Presumably,
in these cases, input from CN IX into the tractus solitarius has
an effect on the dorsal motor nucleus of X.
Also, similar to trigeminal neuralgia, there are idiopathic and
secondary (symptomatic) forms. Presumably, in the idiopathic form,
peripheral demyelinization results in brainstem discharges. Alternatively,
vascular compression of CN IX and X may occur at the nerve root
entry zone by the vertebral artery or posterior inferior cerebellar
artery. Symptomatic causes include cerebellopontine angle tumor,
brainstem demyelinative lesions, peritonsillar abscess, carotid
aneurysm, and Eagle’s syndrome (in which CN IX is compressed
laterally against an ossified stylohyoid ligament).20
The evaluation of a patient suspected of suffering from glossopharyngeal
neuralgia incudes a careful history, especially inquiring about
the presence of trigger factors and nocturnal awakening. All aspects
of an attack need to be recorded. MRI and MRA are appropriate, because
approximately 25% of cases of glossopharyngeal neuralgia
result from secondary causes, such as brainstem mass lesions. Plain
skull films might reveal an ossified stylohyoid ligament in Eagle’s syndrome.
Medical therapy of glossopharyngeal neuralgia is essentially
the same as for trigeminal neuralgia (see Table 25-1). Additionally,
the application of local anesthetics to the oropharynx may be both diagnostic
and therapeutic. Injection of local anesthetic into the region of
the stylohyoid ligament can be diagnostic if Eagle’s syndrome
is strongly considered. Patients failing drug therapy may be candidates
for surgical treatment. Procedures include intracranial sectioning
of CN IX along with the upper three to four rootlets of CN X at
the jugular foramen, or vascular decompression.20
The differential diagnosis of glossopharyngeal neuralgia includes
so-called geniculate neuralgia (nervus intermedius neuralgia of
Hunt), which is discussed later in this chapter. The obvious overlap
of clinical features between the two conditions fosters suspicions
that they may actually be variations of the same condition.
The superior laryngeal nerve is a branch of CN X that runs adjacent
to the carotid bifurcation and supplies the cricothyroid muscle
of the larynx. A lesion of this nerve produces a weak, hoarse voice.
The nerve may be involved by local disease of the carotid or injured
by carotid endarterectomy.21
Clinically, the patient suffers paroxysmal pain that radiates
from the throat to the ear or eye, similar to the pain of glossopharyngeal
neuralgia. There is generally hoarseness. The episodes last seconds
to minutes, and may occur spontaneously, or be triggered by coughing,
swallowing, or speaking. During severe paroxysms, the patient temporarily
may be rendered mute.
On examination, hoarseness of speech, and a trigger point superolateral
to the thyroid cartilage may be noted. The differential diagnosis
includes glossopharyngeal neuralgia, geniculate neuralgia, and carotidynia
(all discussed elsewhere in this chapter). Local blockade of the
nerve is diagnostic. Some patients respond to carbamazepine and
possibly other drugs used for neuralgias. Neurectomy may be curative.21
Acute herpes zoster (shingles) often causes facial pain, especially
affecting V1. The varicella zoster virus persists in sensory
nerve ganglia, and may cause a painful rash. Postherpetic neuralgia
is variably defined as pain that persists (anywhere from 1 to 6
months) after the rash has healed. Although treatment of acute zoster
with acyclovir, valacyclovir, famciclovir, steroids, pain medications,
and even sympathetic nerve blocks may shorten the duration and alleviate
the immediate pain, none has been clearly proven to prevent the
occurrence of postherpetic neuralgia. Age is the major risk factor.
Patients younger than 40 years of age rarely develop postherpetic
neuralgia, whereas more than 75% of patients older than
age 70 years are afflicted.22 Lesser risk factors
include diabetes mellitus, V1 involvement, and other immunologic
Clinically, there is usually scarring and pigmentary changes
in the affected dermatome. The pain is constant and variably aching,
burning, lancinating, or itchy. The mechanism of the pain is likely deafferentation
pain. Pathologically, there are degenerative changes in the involved
axons, dorsal ganglion, and even the dorsal horn of the spinal cord.
Patients complain of allodynia (pain with non-noxious stimulus)
in the affected area.23
Because this condition preferentially affects the elderly, treatment
can be difficult. Unlike trigeminal neuralgia, anticonvulsants are
usually ineffective. Amitriptyline is the single most useful agent,
although the anticholinergic side effects may be troublesome. Beginning
with a low dose (e.g., 10 mg) and slowly escalating toward 75 mg
at bedtime may improve tolerance. If side effects are troublesome,
either nortriptyline or doxepin, which have fewer anticholinergic
side effects, may be substituted (both are available in liquid form,
allowing very gradual dose titration if necessary). Approximately
60% of patients obtain significant relief with these agents.24,25
Many other agents have been anecdotally reported to benefit patients
with postherpetic neuralgia. These include controlled-release oxycodone,
capsaicin cream, topical lidocaine gel, EMLA cream, and gabapentin.
With persistence, pain relief can usually be achieved. Fortunately,
for most patients, the pain eventually spontaneously remits, for
the majority in less than 3 years.
Numerous neuralgias have been described as causes of facial pain.
However, some share many features with other conditions, and it
is likely that some of these conditions simply share several names.
Of these, Raeder’s paratrigeminal syndrome is the best
Raeder’s syndrome consists of constant, unilateral,
burning facial pain with hypesthesia or dysesthesia, or both, in
the distribution of the trigeminal nerve, most often V1,
plus oculosympathetic paresis (ptosis and miosis). This syndrome
may be caused by carotid artery dissection. It may also occur with
trauma, mass or lesion of the middle cranial fossa, syphilis, and
sinusitis. In the absence of these underlying conditions, it is
generally a self-limited process, remitting in weeks to months.26
Sphenopalatine neuralgia (with numerous other synonyms, including
greater superficial petrosal neuralgia) is described as unilateral,
episodic, perinasal facial pain with nasal congestion.27 Most
of these cases closely resemble cluster headache, and the existence
of this neuralgia as a separate diagnostic entity is questionable.
The same may be said for geniculate neuralgia (or nervus intermedius
neuralgia of Hunt). This condition has been described as lancinating
pains deep in the ear with a trigger zone in the external auditory
canal.28 The existence of geniculate neuralgia
as a separate entity also has been called into question. The similarities
with the better-accepted diagnosis—glossopharyngeal neuralgia—are