Weisenberg first described
glossopharyngeal neuralgia (GPN) in 1910, but it
was Harris in1921, who reported the first
idiopathic case and coined the term
"glossopharyngeal neuralgia" . The syndrome is
manifested by paroxysms of excruciating pain in
the posterior pharynx, tonsillar fossa, and base
of the tongue, often radiating to the external
auditory canal or the neck. The pathogenesis of
GPN is unknown but probably involves both
central and peripheral mechanisms. Pain is in
the distribution of the glossopharyngeal nerve
but may include the territory of the auricular
and pharyngeal branches of the vagus nerve.
Chewing, talking, swallowing, or yawning
triggers pain. The clinical manifestations
of GPN resemble trigeminal neuralgia (TN). We
report four MS patients with GPN, three of whom
were treated with carbamazepine.
Patient 1. A 43 year-old
Hispanic-American woman was diagnosed with MS in
1990. She remained stable until May 1995 when
she experienced two generalized tonic-clonic
seizures. Shortly thereafter she experienced
severe knifelike pain radiating into her right
ear. The pain was always unilateral, lasting a
few seconds. Painful paroxysms occurred
frequently and were triggered by chewing and
swallowing. Seizure control was attempted with
phenytoin but failed. Carbamazepine was
initiated with escalation of the dose to 1g
daily with subsequent control of seizures. At
this dose of carbaniazepine, relief of
pharyngeal pain occurred.
Patient 2. A 63-year-old man with a 27
year history of relapsing-remitting MS was
stable when in 1985 he experienced onset of
paroxysinal lancinating pain involving his left
ear, base of the tongue, and tonsillar fossa.
Each paroxysm lasted a few seconds and was
triered by chewing and yawning. Two
neurosurgeons and in oral maxillofacial surgeon
concurred with the diagnosis of GPN. Treatment
with carbamazepine 600 mg daily resulted in pain
relief after 4 weeks. One attempt to Withdraw
carbaniazepine caused recurrence of pain, which
responded to reinstitution of the drug.
Patient 3. A 54-year-old man with a
35-year history of MS presented in February 1998
complaining of recurrent attacks of severe,
sharp pain localized to the posterior pharynx,
tonsillar region, and base of the tongue. Pain
radiated to the left ear and was precipitated by
chewing and swallowing. No hearing loss,
tinnitus, or vertigo was present. An
otolaryngologist concurred with a diagnosis of
GPN. He had a prompt salutary response to
carbamazepine at a dosage of 300 mg daily.
Patient 4. A 22-year-old woman with
rapidly progressive MS was admitted to the
hospital because of new-onset nausea, vomiting,
and severe ataxia. Four years earlier she had
experienced numbness of her lower extremities
accompanied by dizziness. A few months later she
developed right-side optic neuritis and weakness
of her left hand, and was diagnosed with MS.
During the next 2 years she had multiple
relapses with limited responses to IV
methylprednisolone or adrenocorticotrophin
hormone (ACTH). In Januarv 1999 she had severe,
sharp pain involving her left ear more than
throat and tonsillar fossa, occurring several
times daily. Each painful episode was triggered
by chewing and lasted for less than a minute.
The patient declined treatment with
carbamazepine but pain abated after 10 days of 1
mg IV synthetic ACTH and 8 mg/kg cyclophosph
mide treatment daily.
Results. Of a population of 8000
patients seen at the MS Center, University of
Miami during a 20-year period, we identified
four patients (two men and two women) with GPN:
an incidence of 0.5:1000 MS patients. The
average age of the patients was 47 years (range,
21 to 35 years) and the duration of MS ranged
from 4 to 36 years. Onset of GPN in our MS
patients was manifested by the sudden onset of
unilateral sharp, lancinating pain in the ear,
base of the tongue, and tonsillar fossa.
Patients reported that the duration ofthe
painful paroxysms usually lasted a second or
less but could last to a few seconds.
Occasionally pain was described by patients as
lasting a "few minutes." Duration of pain
witnessed in the clinic was always very brief,
but the pain could appear repeatedly.
Anticipation of the pain caused great anxiety in
the MS patient who reported longer duration of
pain. Pain-free intervals lasted hours to days.
In our serics, GPN was not associated with
bradycardia, or hypotension, as has been
reported. In no instance was GPN the initial
manifestation of MS.
All patients underwent brain MRI during and
after the development of GPN. Brain MRI did not
reveal any pathology in the medulla nor
involvement or compression ofthe
glossopharyngeal nerve by neoplasms, infection,
or anomalous blood vessels.
Three patients were treated with
carbamazepine with complete relief of pain. A
fourth patient declined carbamazepine but pain
resolved gradually during ACTH and
cylophosphamide administration. In the last 9
months this patient has remained pain free.
Carbamazepine withdrawal in one male patient was
associated with relapse of GPN within 1 week,
but reintroduction of carbamazepine relieved the
pain. The average follow-up of three patients on
carbamazepine was 6 years (range, 1.5 to 14
vears), during which they tolerated the
medication well.
Discussion. GPN may, uncommonly,
complicate MS, as illustrated in our patients.
GPN has been attributed to vascular compression
of the nerve root entry zone, resulting in
demyelination and ephaptic transmission. This
hypothesis has served as a rationale for
microvascular surgical decompression.
Alternatively, vascular compression of a nerve
has been hypothesized to induce repetitive
activation of primary afferents in the nerve and
has led to hyperactivity and hyperexcitability
in the central neurons. Activation of
N-methyl-D-aspartic acid receptor has been
invoked as another possible explanation.
However, in MS patients, other potential causes
should be considered. Oppenhelm has described
demyelinating plaques at the root entry zone as
the potential cause of paroxysmal TN in MS
patients. It is likely that similar root entry
zone lesions of the glossopharyngeal nerve are
associated with ephaptic conduction and underlie
the pathogenesis of GPN.
Atypical facial pain may mimie some of the
clinical features of both TN and GPN. Atypical
facial pain is eliminated from the differential
diagnosis by the brevity of the recurrent severe
pain experienced by our patients as well as the
precise localization of their pain. Atypical
facial pain is usually persistent, deep, and
aching, and is often bilateral. Although
sometimes more severe, the pain lacks the
typical sharp lancinating character oft he
paroxysms seen in our patients with GPN.
The incidence of GPN in our patient
population (0.5:1,000) is in contrast to that of
TN, which has an incidence of 40:1000 (4%) MS
patients. Although the numbers reveal the rarity
of GPN in the MS population, our observations
reveal approximately the same ratio of TN to GPN
in the general population. In the general
population. incidence of GPN is 0.2 to 1.31% of
that of TN. The population-based study of GPN in
Rochester, MN, revealed peak incidence rates in
the sixth through eighth decades. This
observation shows that GPN, although less
frequent than TN, may occur at a younger age and
early in the course of MS suggests that similar
mechanisms may be operative. Anecdotal reports
on treatment of GPN in patients without MS
suggest benefit may be obtained from the use of
carbamazepine, phénytoin or baclofen
indoses similar to those used to treat TN. In
our series GPN was responsive to carbamazepine
and identification of MS patients with GPN is
warranted.
