Refer to: Adour KK, Hilsinger RL lr, Byl FM, Herpes simplex

polyganglionitis. Otolaryngol Head Neck Surg

88:270-274 (May-June) 1980.

HERPES SIMPLEX POLYGANGLIONITIS

KEDAR K. ADOUR, MD, RAYMOND L. HILSINGER, JR, MD, and FREDERICK M. BYL, MD,
Oakland, California

Evidence suggests that many cranial nerve syndromes, such as migraine headache,
acute vestibular neuronitis, globus hystericus, carotidynia, acute facial paralysis (Bell's
palsy), and Meniere's disease, are caused by the neurotropic herpes simplex virus
(HSV). Because transitory cranial nerve dysfunction during acute HSV infection can be
asymptomatic but often occurs in conjunction with mucocutaneous vesicles, we tested
five subjects with herpes labialis for cranial nerve dysfunction. Four of the subjects had
hypesthesia of the trigeminal nerve (which recurred in two); four, hypesthesia of the
glossopharyngeal nerve; and two, hypesthesia of the second cervical nerve. Three of
the subjects had positional or spontaneous nystagmus (which recurred in one); one of
the subjects had a unilateral, decreased caloric response of 50%. Unilateral weakness
of the cricothyroid muscle or the palate occurred in three of the subjects (and recurred
in one). Volitional electromyograms were normal in all the subjects, but two of the sub-
jects had increased facial nerve latency (which recurred in one). Similar findings of an
acute, transitory nature should suggest to the clinician a viral polyganglionitis caused
by HSV infection.

MANY cranial nerve syndromes,' including migraine
headaches, acute vestibular neuronitis, globus hysteri-
cus, carotidynia, acute facial paralysis (Bell's palsy),2and
Meniere's disease.' are forms of acute recurrent cranial
neuritis; we have suggested that the probable causative
agent is the herpes simplex virus (HSV).'-] The cranial
nerve dysfunction seen in our patients included
hypesthesia, increased facial nerve latency, abnormal
electronystagmographic (ENG) examination results,
and motor paralysis of the trigeminal, facial, and vagus
cranial nerves; some of these findings were
asymptomatic. Because approximately 40% of these
patients had mucocutaneous herpetic vesicles during
acute symptoms, we hypothesized that similar cranial
nerve abnormalities should be present in some patients
with active herpetic vesicles but no clinical symp-
toms."] The results of our study to test volunteers with
acute mucocutaneous herpes simplex vesicles for
evidence of cranial nerve dysfunction are reported.

Submitted for publication Aug 1, 1979. SUBJECTS AND METHODS

From the Cranial Nerve Research Clinic, Department of Otolaryn-
gology, Kaiser-Permanente Medical Center, Oakland, Calif.
Presented at the 1979 Annual Meeting of the American Academy of
Otolaryngology, Dallas, Oct 7-11.
Reprint requests to Department of Otolaryngology, Kaiser-Permanente
Medical Center, 280 w MacArthur Blvd, Oakland, CA 94611 (Dr
Adour).
The subjects for our study were five volunteer
women employees aged from 22 to 34 years. Each had a
past history of recurrent herpes labialis and active
mucocutaneous vesicles and had come to our oto-
laryngology clinic for evaluation. There was some
selection bias, ie, all the subjects had symptoms of pain

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 HERPES SIMPLEX POLYGANGLIONITIS

and paresthesia severe enough to seek aid, and patients
with systemic disease such as diabetes, connective
tissue disorder, pregnancy, and sarcoidosis were ex-
cluded from the study. Informed consent was obtained
from each subject after the nature of the procedure
had been fully explained.
Following a complete history and an examination of
the ears, nose, and throat, the cranial nerves were
tested for dysfunction. Unilateral superior laryngeal
nerve palsy was determined by indirect, and confirmed
by direct, laryngoscopic examination. The trigeminal
and upper cervical nerves were tested for sensitivity to
pinprick, light touch, and electrical stimulation. The
glossopharyngeal nerve was tested by applying a cotton
applicator on the posterior part of the pharynx to test
the ability to initiate the gag reflex and by determining
the sensation level to square-wave electrical stimula-
tion. The findings were considered positive when they
could be reproduced and when statements of the
patients were not changed by contrasuggestion. All
findings were confirmed by at least two examiners.
Electromyography was performed by using a multi-
channel recorder with a fiberoptic direct recorder.
In a previous study group of 172 volunteers, the facial
nerve conduction latency measured from the stylo-
mastoid foramen to the corner of the mouth had
averaged 2.48±0.38 rnsec.! A facial nerve latency of 3.5
msec is the upper limit of a normal response; a latency
of 4.0 msec is prolonged.
The ENG examination for spontaneous and positional
nystagmus, as well as caloric response to cold water,
was performed with a dual-channel, dc recorder. A
caloric response difference of 20% between sides was
considered abnormal.'
During each initial examination, serum was drawn to
determine complement fixation titers to herpes sim-
plex and herpes zoster viruses. All patients were reex-
amined weekly for four weeks, and all tests were
repeated at the end of three weeks, when there were
no mucocutaneous vesicles. Two subjects were re-
tested when the mucocutaneous vesicles recurred.
FINDINGS
Four of the five subjects had hypesthesia of one or
more divisions of the trigeminal nerve. The condition
subsided within three weeks, but was found to have
recurred in two of the subjects who had initially re-
turned for reevaluation because of recurrence of
herpes labialis (Table). Two subjects had transitory glos-
sopharyngeal hypesthesia; testing for hypesthesia of
the vagus nerve was excluded because it was difficult to
evaluate the laryngeal area of the hypopharynx. Four
patients had glossopharyngeal hypesthesia (found in-
itially in two subjects and on the return visits of both
the retested subjects). One subject had hypesthesia of
the second division of the cervical nerve.
Three subjects had abnormal ENG recordings, which
indicated either spontaneous or positional nystagmus,
and one of these had a unilateral decreased caloric
response of 50%. All the findings returned to normal,
although spontaneous nystagmus did recur in one of
the two subjects retested (patient 1).

SUMMARY OF CRANIAL NERVE ABNORMALITIES IN FIVE PATIENTS WITH

MUCOCUTANEOUS HERPES SIMPLEX VIRUS (HSV) VESICLES·

HYPESTHESIA MOTOR INVOLVEMENT

GLOSSO- CERVICAL
TRIGEMINAL PHARYNGEAL NERVE, FACIAL VAGAL
NERVE NERVE 2ND DIVISION NERVE NERVE ENG
PATIENT

, R+ NRt NR NR NR Positional nystagmus

(Retested at 2 mol L+ L+ NR NR R+ (Palate) Spontaneous nystagmus

2 L+ NR NR L(FNL=4.0)t L+ (Palate and NR

vocal cord)

(Retested at 7 mol L+ L+ NR L(FNL=4.0) L+ (Palate) NR

3 NR R+ NR NR L+ (Vocal cord) NR

4 R+ NR NR NR NR Positional nystagmus,
50% decrease on left
5 R+ R+ R+ NR NR Spontaneous nystagmus

'All tests returned to normal in four weeks.

tNormal response.
tFacial nerve latency.

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 ADOUR ET AL
None of the subjects complained of vertigo, but the
one with a unilateral decreased caloric response felt
"unsteady and nauseated."
Unilateral weakness of the palate (Fig 1) or crico-
thyroid muscle (vagus nerve) was found in three sub-
jects, all of whom recovered after three weeks. In
patient 2, weakness of the palate recurred, but no ab-
normality was detected in the cricothyroid muscle.
Fig 1.-Unilateral right palatal weakness becomes more apparent
when longue i s used to stretch palatal folds (8yl's sign) as
demonstrated in a pat ient not in th is study.
Volitional EMG recordings were normal in all the
subjects, but one (patient 2) had increased facial nerve
latency during the acute episode with vesicles and had
unilateral fungiform papillitis of the tongue on the af-
fected side, which indicated inflammation of the
chorda tympani branch of the facial nerve (geniculate
ganglionitis) . The facial nerve latency returned to nor-
mal and again became abnormal during recurrence of
the herpetic vesicles.
All patients had herpes simplex complement fixation
titers (1:32) in the acute and convalescent sera. We
noted no diagnostic increases in complement fixation
antibody titers to herpes simplex or varicella virus.
DISCUSSION
The finding of cranial nerve dysfunction in acute
mucocutaneous herpes simplex infection that cleared
spontaneously and reappeared during reactivation of
the virus was not unexpected and supports our hy-
272 Otolaryngol Head Neck Surg 88:270-274 (May-June) 1980
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pothesis that the HSV is the cause of multiple cranial
nerve syndromes. The suggestion that migraine head-
ache and Meniere's disease are two spectrums of one
disease entity is not news': when symptoms of both
diseases overlap, the term "basilar migraine" is applied.
Similarly, after examining five cases of polyneuritis with
facial paralysis, Antoni" offered the term "acute infec-
tious polyneuritis cerebra lis acustica tacialis," which
localized the disease to the proximal part of the nerves
with predilection for the cranial sensory ganglia.
Sufficient clinical and experimental knowledge
about HSV has been generated to associate it with
cranial nerve syndromes, even though the possibility
exists that a yet unknown virus or pathophysiologic
mechanism may be the primary disease that causes
reactivation of HSV. Nevertheless, this neurotropic
virus has been cultured from the vagal.? trigerninal.w
and second cervical ganglia? in unselected human
cadavers, thus giving further credence to the relation-
ship of HSV with acute and chronic diseases of the cen-
tral nervous system . Further, the known pathophysiol-
ogy of HSV offers a more plausible explanation for the
symptomatology, the clinical course, and the
epidemiology of migraine headache and of Meniere's
disease than possible previously with the classic
descriptions of vascular instability and cochlear
hydrops, respectively.
When a patient recovers from a primary HSV infec-
tion, the virus subsides to latency in the cranial and
spinal ganglia (Fig 2), where it is protected from cir-
culating antibodies. Because the HSV reactivation and
replication begins in the ganglion cells, every case of
recurrent HSV infection starts as ganglionitis. The virus
only then passes down the axons to induce the forma-
tion of herpetic vesicles in the skin or mucous mem-
branes, but this represents merely the " lip of the vol-
cano"; treatment directed to the mucocutaneous le-
sions alone is incomplete unless the topical agent can
migrate to the source of the reactivation, ie, the sensory
nucleus.
Further neurologic damage is probably caused by an
autoimmune "allergic" reaction in and around the
ganglion . When the HSV nucleocapsid leaves the
neural cell membrane, it acquires an envelope of lipo-
protein from the plasma membrane of the infected cell
(Fig 3). These alterations in the host cell membrane and
deposition of neural protein in the perineural areas are
central to the hypothesis of virus-induced demyelini-
zation .!' The T-Iymphocytes apparently become sen-
sitized to the neural cell protein.' ! so that each reactiva-
tion of the HSV triggers an autoimmune response and
 HERPES SIMPLEX POLYGANGLIONITIS

Fig 2. -Tr igeminal ganglionic infiltrate in rabbit infected on cornea three days earlier with herpes simplex virus (H.SVI type 1. Ganglion cell shows
typ ical Cowdry type A intranu clear inclusion and is surrounded by largely mononuclear cell mflltrate. Surroundmg ganglion cells appear unal-
fected (hematoxylin-eosin . X 400)

o HERPES VIRAL REPLICATION the poss ibility that the mucocutaneous vesicles repre-
.-__-r81 __
; A" .,. s_. _n'_o.....
r y G ong llo n ! sent an Arthus phenomenon should be considered. No
correlation exists between the degree of mucocutane-
ous involvement and the severity of the neurologic dis-
order. We therefore postulate that because the cranial
motor fibers pass through the sensory ganglia, the
fibers are affected by the demyelinization process
similar to that demonstrated in peripheral motor
neuritis caused by herpes zoster.
In detecting a unilateral superior laryngeal nerve
palsy it must be remembered that only the ipsilateral
cricothyroid muscle is paralyzed. During rest and
respiration , the vocal cords appear normal and are ab-
ducted . Upon phonat ion, both cords adduct; however,
Fig 3.-Schematic representat ion of herpes simplex virus (HSV) the paralysis of the cricothyroid muscle of the involved
repl ication wilhin sensory ganglion cells demonstrating centripetal side produces some subtle, but recogn izable, changes.
and centrifugat m igration and envelopment with port ions of neural cell
protein . The asymmetric tilt of the thyroid upon the cricoid car-

Oto/aryngol Head NecK Surg 88:270-274 (May-june) 1980 273

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 ADOUR ET Al
tilage tenses and lengthens the normal innervated side.
The cord on the paralyzed side remains shorter and at a
different level and may be more hyperemic than the in-
tact tensed cord. An asymmetric lateral shift of the
epiglottis and the anterior larynx toward the intact,
contracting cricothyroid muscle occurs, whereas the
posterior larynx shifts toward the side with the non-
functioning cricothyroid muscle. This rotation of the
larynx can also be verified by careful palpation of the
anterior part of the neck. The superior cornu of the
thyroid cartilage will be more prominent on the af-
fected side.
We are well aware that hypesthesia is a subjective
phenomenon and were careful to ascertain its pres-
ence, especially since none of our patients complained
of numbness. The subjects were appropriately sur-
prised to find that the neurologic wheel appeared shar-
per on the unaffected side of the face. This finding
could be confirmed objectively when the patient was
tested by electromyography. Those who had
hypesthesia of the trigeminal nerve could tolerate a
higher level of nerve stimulation on the affected side
and could also tolerate the needle being inserted into
the face on the affected side but not on the unaffected
side.
The frustration of diagnosing HSV infection using
laboratory aids is well known, but the most common
forms of HSV infection-gingival stomatitis, cold sores,
keratitis, and dermatitis-can be recognized clinically
with almost 100% accuracv.n Because acute pain and
paresthesia with transitory asymptomatic hypesthesia
are requisite in HSV reactivations, we have developed
the adage "if the patient complains of pain or head-
ache, check for hypesthesia." Our findings have been
verified (N. Olson, MD, personal communication, Sep-
tember 1979) and are easily confirmed, since only the
pathophysiologic mechanism of demyelinization re-
quires verification. When similar symptoms and
findings such as those described here occur with or
without mucocutaneous vesicles, it seems plausible to
presume that the disease represents a viral polygan-
glionitis and, therefore, to suspect HSV.
Considering that 80% of our health plan population
have elevated titers to HSV,14 the number of potential
cases of polyganglionitis occurring in anyone year
ranges in the millions. Care must be taken to ascertain
the acute onset, the transitory nature, and the resolu-
274 Otolaryngol Head Neck Surg 88:270-274 (May-june) 1980
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tion of each case. Progressive hypesthesia and motor
paralysis are not signs of polyganglionitis and must
receive appropriate diagnostic evaluation.
ACKNOWLEDGMENTS
This research was supported by the Community Service
Program of Kaiser Foundation Hospitals. Figure 2 was printed
with permission from J. Richard Baringer, MD.
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