Cranial
Polyneuritis
and Bell
Palsy
Kedar Karim Adour, MD
\s=b\ In view of the specific nature of the clinical and neurologic findings in Bell palsy and other acute benign cranial neuritides, the neural component of cutaneous herpes simplex, the predilection of the herpesvirus for sensory nerves, and the intrinsic behavior and immunologic interreactions of the herpesvirus within ganglion cells, it is suggested that (1) the entity that has been termed "idiopathic facial paralysis" be recognized as an acute benign cranial polyneuritis; and (2) other acute benign cranial neuritides be recognized as formes frustes of Bell
palsy. (Arch Otolaryngol 102:262-264, 1976)
Idiosy)pathic
facial paralysis (Bell pal¬ cranial polyneuritis1 -"' often involving the trigeminal, glosso¬ pharyngeal, audiovestibular, and contralateral (clinically unaffected) facial nerve. Recent studies have implicated the herpes simplex virus as the causative agent."7 Why, then, when one considers that mucocutaneous herpes simplex is an everyday occurrence, do we not see more cases of cranial polyneuritis? The answer became apparent on review of the Facial Paralysis Research Clinic's file of cases of special interest and from testing consecutive patients who had is
a
herpes labialis, mucocutaneous herpes, both. A sensory cranial neuritis does occur with mucocutaneous herpes simplex," but the facial paralysis occurs in only a small percentage of these patients. Reported here are six representative cases, selected to illusor
n
for publication Jan 13, 1976. From the Facial Paralysis Research Clinic and the Department of Otolaryngology, Kaiser\x=req-\ Permanente Medical Center, Oakland, Calif. Reprint requests to the Department of Otolaryngology, Kaiser-Permanente Medical Center, 280 W MacArthur Blvd, Oakland, CA 94611 (Dr
Accepted
Adour).
trate that the various manifested
signs
and
symptoms associated with mucocutaneous herpes appear to be a forme fruste of the disease that has been called idiopathic facial paraly¬ sis.12 REPORT OF CASES Case 1.—A 56-year-old woman was admitted to the hospital four days after the onset of left occipital headache and pain radiating into the left ear and temporal area, which did not respond to meperidine hydrochloride, acupuncture, a muscle relax¬ ant, a Thomas collar, or heat, but was relieved for short periods by aspirin. One day after admission, she experienced vertigo, nausea, vomiting, and seconddegree nystagmus. The only abnormality found on physical and neurologic examina¬ tion was moderate tenderness to touch over the left occipital area. The erythrocyte sedimentation rate was 26 mm/hr, and the complete blood cell count and blood chemistry studies using an automated multiple analysis system (SMA12) were within normal limits. Findings from the following laboratory tests were normal: two-hour postprandial blood sugar test, VDRL test for syphilis, Coombs test (direct and indirect), antinuclear antibodytest, and latex agglutination test. Serum
protein electrophoresis; urinalysis; cere¬ brospinal fluid analysis; and radioisotopic brain
visual
scan;
field
examination
roentgenographic study of the mastoid area, the skull, and the cervical spine were all within normal limits. Audio-
results; and
a
grams
normal.
were
Drug therapy
was
discontinued. Two
days after its onset, the nystagmus ceased, but headache, vertigo, and nausea per¬ sisted. On the seventh hospital day, all symptoms began to subside; the patient was discharged. Six months later, the left occipital head¬ ache and vertigo recurred and the patient was referred to our otoneurology division. A herpetic vesicle was noted below the left corner of the mouth. There was hypes¬
thesia of the first and third divisions of the left fifth cranial nerve, a 50% decrease in
Downloaded From: http://archotol.jamanetwork.com/ by a New York University User on 05/24/2015
response to caloric stimulation in the left vestibular nerve, and left glossopharyngeal hypesthesia (absence of the afferent arc of the gag reflex; sensory deficit). A white blood cell count and a differential cell count, erythrocyte sedimentation rate, au¬ diogram, and roentgenograms of the inter¬ nal auditory canal were normal. The diag¬ nosis of acute herpes cranial neuritis was made. Treatment was that prescribed at that time for patients with idiopathic facial paralysis: prednisone, 40 mg daily for four days, tapered to zero during four additional days. The headache and vertigo ceased. Hypesthesia of the trigeminal and glossopharyngeal nerves had resolved by the end of two weeks. Case 2.—A 37-year-old woman was admitted to the neurologic service for eval¬ uation of papilledema that was believed to represent pseudotumor cerebri. On the day of admission, herpes labialis developed on the midline of the lower lip. She stated that this was the first day of menstrual flow and that herpes labialis often occurred on her first menstrual day. There was hypes¬ thesia over the distribution of all three divisions of the left fifth cranial nerve and over the left posterior portion of the pharynx (absent afferent arc of the gag reflex). During the hospital stay, numerous laboratory and roentgenographic studies were performed. The vesicles gradually resolved, beginning on the fourth hospital day; by the sixth day, the hypesthesia was no longer detectable. No treatment was given for the herpes. Case 3.—A 35-year-old woman was seen in the otolaryngology clinic for routine evaluation of allergic nasal polyps. A herpes labialis vesicle was noted on the left side of the upper lip. She stated that this commonly occurred in association with the onset of menstruation and that her menses had begun on the day before her clinic visit. She also stated that two days before the onset of menstruation, with associated herpes labialis, she frequently experienced left occipital headache, which she attrib¬ uted to premenstrual tension. Examination revealed hypesthesia of all three branches of the left fifth cranial nerve and absent left gag reflex in the afferent arc; these
findings were confirmed by a neurologist. The vesicle resolved in six days. Sensation in the fifth cranial nerve and the gag reflex returned by the eighth day. Case 4.—A 46-year-old woman under¬ went a left stapedectomy for otosclerosis. One week later, at routine postoperative examination herpes labialis was noted on the right side of the lower lip. There was hypesthesia of the second and third divi¬ sions of the right fifth cranial nerve and absent right gag reflex in the afferent arc. When she was seen one week later, the vesicle and the sensory deficits had re¬ solved. Case 5.—A 25-year-old woman was admitted to the hospital after sudden onset of severe vertigo and nausea without auditory symptoms. Examination revealed
third-degree right beating spontaneous a positive Rhomberg test, and herpetic vesicles on the left side of the posterior pharyngeal wall. The trigeminal a
nystagmus,
intact, but the gag reflex was absent on the right side. Chest and skull x-ray films and laboratory test results were normal. She was given 40 mg of methylprednisolone sodium succinate in¬ travenously. Within four hours, she was able to sit in bed and the nystagmus had subsided to first-degree level. The next day, an audiogram and ENG revealed normal hearing and absent response to caloric stimulation on the right (vestibular neuronitis). While in the hospital, she was given prednisone orally, 60 mg daily to be tapered to 0 during ten days (our current treatment for Bell palsy). The vertigo and palatal vesicle resolved in 48 hours and the patient was discharged. She did not take the prednisone as directed, and was read¬ mitted to the hospital within 12 hours with recurrent vertigo and third-degree nystag¬ mus. She was again given 40 mg of methyl¬ prednisolone intravenously with resultant reduction of vertigo. Oral administration of 60 mg of prednisone daily was again started and she was discharged one day later with minimal vertigo and no nystagmus. The prednisone was taken as directed. She had no vertigo and the gag reflex was present when she was seen seven days later. Case 6.—A 39-year-old woman who suffered from left-sided headaches that
nerve was
were
thought possibly to represent tempo¬
ral arteritis was given phenylbutazone. The headaches ceased in two days. Five days later, she had a sore throat, with swelling of both submandibular glands. The examining physician noted that the appearance of the left tonsil was "rather unusual." No organisms grew on throat culture. On the following day, the throat was more sore and she had dysphagia.
She
was
referred to the
otolaryngology
clinic, where examination revealed bilat¬ eral submandibular node enlargement, inflammation of the oropharynx with multiple punctate and coalescent herpetic lesions, hypesthesia of the first division of the trigeminal nerve on the left side, and decreased gag reflex (sensory deficit) on the left side. A white blood cell count was 11,200/cu mm, with 74% polymorphonuclear leukocytes, 18% lymphocytes, 2% monocytes, and 3% eosinophils. A diagnosis of herpetic stomatitis was made, and treat¬ ment was begun with prednisone, 40 mg daily, to be tapered to 5 mg daily at the end of eight days. (The use of steroids in primary herpes¬ virus infection has been thought to be contraindicated because of the theoretical possibility of ensuing "systemic viremia." In giving prednisone to healthy adults with severe herpetic stomatitis, I have seen no indication of viremia; in fact, the dramatic relief of symptoms has encouraged me to consider this drug as the treatment of choice in such cases. A report of experience with the use of steroids in herpes zoster and in several patients with acute herpes simplex is in preparation.) On the following day, the nodular swelling was greatly reduced, the herpetic stomatitis had decreased in intensity, and the associated pain had almost completely ceased. The patient then reported that she had also experienced vertigo, which she had not reported previously because she had been preoccupied by the severe pain of the stomatitis. A cold water caloric stimu¬ lation test revealed absence of response on the left side. Viral studies were performed: the first serum specimen was taken on the first day of observation in the otolaryngol¬ ogy clinic; three weeks later, a specimen was taken during convalescence. The herpes simplex titer of the first specimen was less than 1:8, and that of the specimen taken during convalescence was 1:32,
suggesting
a
primary herpes simplex
infection. The varicella titer was less than 1:8. When the prednisone dosage had been reduced to 20 mg daily, the vertiginous symptoms recurred and the dosage was increased to 40 mg daily, maintained there for another four days, then tapered to zero during four more days. One month after the acute episode, there was no hypesthesia of the trigeminal nerve and the gag reflex had returned.
COMMENT
Clinical evidence has long indicated that recurrent cutaneous herpes sim¬ plex has a neural accompaniment,""' so that the entity should be desig-
Downloaded From: http://archotol.jamanetwork.com/ by a New York University User on 05/24/2015
nated "neurocutaneous herpes sim¬ plex."' It is also known that the herpesvirus has a predilection for sensory nerves.141" Baringer and Swoveland, in routine autopsies, have isolated herpesvirus type I from the trigeminal ganglion,17 and herpes¬ virus type II from the sacral gan¬ glion," and have suggested that the virus could probably be isolated from other cranial nerve ganglia as well.1" The glossopharyngeal ganglion would appear to be a likely site, since the second most common locus for herpet¬ ic vesicles is the palate and the pharyngeal wall; further, herpes sim¬ plex virus has been isolated from the nasal pharynx of many asymptomatic
persons."
It has been suggested that the virus remains latent within the ganglion cells, and that when activated, it repli¬ cates within the cell, where it is protected from the circulating anti¬ bodies.1" The virus then migrates within the axon, where it is again protected from the circulating anti¬ bodies until it reaches the mucocuta¬ neous area, at which point it rekindles the vesicular eruption. The virus may induce recurrent mucocutaneous erup¬
tions without causing neural symp¬ toms; conversely, it may cause recur¬ rent neurologic disorders without mu¬ cocutaneous manifestations." Activa¬ tion of the herpes simplex virus involves not only intrinsic viral behav¬ ior, but also complex immunologie interreactions related to the acquisi¬ tion of a protein envelope by the virus capsids as they break through the nerve cell membrane.1" The first manifestations of acute benign cranial neuritis may be pain,
hypesthesia, vertigo, hearing loss,
decreased autonomie function, or mus¬ cle paralysis.-" Such cranial nerve dysfunction may bring fear to the patient and consternation to the physician. That even neurologists and neurosurgeons, when confronted with such manifestations, may feel driven into a series of futile and expensive investigations is clearly documented in case 1 of this report. Involvement of the afferent (sen¬ sory) arc of the gag reflex is repre¬ sented clinically by hypesthesia of the area supplied by the glossopharyngeal
nerve; involvement of the efferent
arc
is manifested as paresis or paralysis of the palatal muscles innervated by the vagus nerve. The presence or absence of a gag reflex is too often misjudged on the basis of the efferent response, without regard for the sepa¬ rate innervation of the two sides of the pharynx. To perform this test properly, both hands should be free in order that one may depress the tongue while applying an applicator only to the posterior pharyngeal wall, first on one then on the other side, assiduously avoiding contact with the tonsillar pillars or tongue. When this is prop¬ erly done, more cases of unilateral hypesthesia of the glossopharyngeal nerve will be found. The contradictory finding of hypes¬ thesia of one or more branches of the trigeminal nerve in patients whose most prominent initial symptom is pain is a frequent one in mucocuta¬ neous herpes simplex. It parallels the decreased response of the vestibular system to cold water caloric testing when vertigo is the initial symptom. Naufal and Sehuknecht-1 have demon¬ strated a decreased number of cells in the Scarpa ganglion in a patient with recurrent vestibular neuronitis, ad¬ ding support to the concept that repli¬ cation of the virus probably takes place in the sensory ganglion, and may induce neural cell death. An unanswered question remains: What is the mode of entry of the virus into
the acoustic-vestibular system? The suggestion that idiopathic fa¬ cial paralysis is a variant of acute cranial neuritis is not new. Antoniain 1919, on the basis of clinical find¬ ings in five cases of polyneuritis with facial paralysis and no zoster vesicles, offered the term, "acute infectious polyneuritis cerebralis acusticofacialis," interpreting the disease as infec¬ tious neuritis localized to the proximal parts of the nerve, with predilection for the spinal ganglion. He also ques¬ tioned whether ordinary facial paral¬ ysis did not belong in this category. Friedman- has recently made a simi¬ lar proposal. Recognition that these cranial neu¬ ritides are variants of a single entity has been delayed, apparently by frag¬ mentation of care due to the variety of the symptoms. Since herpes simplex has classically been thought to involve only the mucocutaneous areas, it has come to the attention of dermatolo¬ gists, and the asymptomatic involve¬ ment of the vestibular system went unobserved. Treatment for vertigo was sought from the otolaryngologist, who ignored the glossopharyngeal nerve. When bizarre or unexplained manifestations occurred, the neurol¬ ogist became involved and made such exotic diagnoses as monoplegia masti¬
catoria,^' glossopharyngeal neuralgia,
Sluder syndrome, to name a few. It has been demonstrated that the epidemiology and clinical course of
or
herpes simplex cranialis are identical with those of Bell palsy.7 Examples sustaining this observation are cases 2 and 3 of this article, in which the
manifestations had their onset with the start of menstruation. When the relation between Bell palsy and the menstrual cycle was analyzed, the facial paralysis was found to occur most often at its onset or within the first 14 days.-' In acute idiopathic facial paralysis, which I believe to be a herpes simplex cranial polyneuritis, the trigeminal nerve is involved in 25% of the cases; in 3% there is decreased function of the masseter muscle; in 40% there is evidence of abnormal response in the vestibular system; and in 35% the afferent arc of the gag reflex is absent or decreased. It has also been demonstrated that conduction veloci¬ ties may be decreased in the opposite facial nerve in as many as 50% to 75% of the patients,-4 - although it appears clinically to be uninvolved, indicating that the disease is often bilateral. These observations appear to sup¬ port the conclusion that the cases of cranial neuritis described here, which appeared with a primary herpesvirus infection or reappeared concurrently with mucocutaneous herpes simplex, represent variants (formes frustes) of Bell palsy. The benign nature of the cranial neuritis is established by acuteness of onset, transient duration, and clinical resolution. '
References 1. Adour KK, Doty HE: Electronystagmographic comparison of acute idiopathic and herpes zoster facial paralysis. Laryngoscope
83:2029-2034, 1973.
2. Friedman SR: Neuropathy: mono- or poly-? N Engl J Med 282:632, 1970. 3. Ch'ien LT, Halsey JH Jr: Trigeminal sensory neuropathy and Bell's palsy. N Engl J Med 282:224-225, 1970. 4. Spector RH, Schwartzman RJ: Benign trigeminal and facial neuropathy. Arch Intern Med 135:992-993, 1975. 5. McGovern FH: Trigeminal sensory neuropathy and Bell's palsy. Arch Otolaryngol 94:466\x=req-\ 470, 1971. 6. McCormick DP: Herpes-simplex virus as cause of Bell's palsy. Lancet 1:937-939, 1972. 7. Adour KK, Bell DN, Hilsinger RL Jr: Herpes simplex virus in idiopathic facial paralysis (Bell palsy). JAMA 233:527-530, 1975. 8. Selmanowitz VJ: Neurocutaneous herpes simplex. Int J Dermatol 10:227-232, 1971. 9. Slavin HB, Ferguson JJ Jr: Zoster-like eruptions caused by the virus of herpes simplex. Am J Med 8:456-467, 1950.
10. Baringer JR: Herpetic manifestations. N Engl J Med 289:159, 1973. 11. Kirby WMM: Herpetic manifestations. N Engl J Med 289:158-159, 1973. 12. Adour KK: Bell's Palsy: A complete expression of acute benign cranial polyneuritis, in Ahlvin RC, Blanchard LB, Brown DC, et al (eds): Primary Care. Philadelphia, WB Saunders Co,
1975, vol 2, pp 717-733.
Cushing, cited by Baringer JR, Swoveland Recovery of herpes simplex virus from human trigeminal ganglions. N Engl J Med 288:648-650, 13.
P:
1973.
14. Paine TF Jr: Latent herpes simplex infection in man. Bacteriol Rev 28:472-479, 1964. 15. Ellison SA, Carton CA, Rose HM: Studies of recurrent herpes simplex infections following section of the trigeminal nerve. J Infect Dis 105:161-167, 1959. 16. Goodpasture EW: Herpetic infection, with especial reference to involvement of the nervous system (DeLamar Lecture). Medicine 8:223-243, 1929. 17. Baringer JR, Swoveland P: Recovery of herpes-simplex virus from human trigeminal
Downloaded From: http://archotol.jamanetwork.com/ by a New York University User on 05/24/2015
ganglions. N Engl J Med 288:648-650, 1973. 18. Baringer JR: Recovery of herpes simplex virus from human sacral ganglions. N Engl J Med 291:828-830, 1974. 19. Nahmias AJ, Roizman B: Infection with herpes-simplex viruses 1 and 2. N Engl J Med 289:667-674, 1973. 20. Foley JM: The cranial mononeuropathies. N Engl J Med 281:905-906, 1969. 21. Naufal PM, Schuknecht HF: Vestibular, facial, and oculomotor neuropathy in diabetes mellitus. Arch Otolaryngol 96:468-474, 1972. 22. Antoni, cited by M\l=o"\llerF: Critical viewpoints on the pathogenesis in Bell's palsy. Acta
Neurol Scand 43:228-238, 1967. 23. Hilsinger RL Jr, Adour KK, Doty HE: Idiopathic facial palsy, pregnancy, and the menstrual cycle. Ann Otol Rhinol Laryngol 84:433-442, 1975. 24. Safman BL: Bilateral pathology in Bell's palsy. Arch Otolaryngol 93:55-57, 1971. 25. Chaco J: Subclinical peripheral nerve involvement in unilateral Bell's palsy. Am J Phys Med 52:195-197, 1973.
Polyneuritis
and Bell
Palsy
Kedar Karim Adour, MD
\s=b\ In view of the specific nature of the clinical and neurologic findings in Bell palsy and other acute benign cranial neuritides, the neural component of cutaneous herpes simplex, the predilection of the herpesvirus for sensory nerves, and the intrinsic behavior and immunologic interreactions of the herpesvirus within ganglion cells, it is suggested that (1) the entity that has been termed "idiopathic facial paralysis" be recognized as an acute benign cranial polyneuritis; and (2) other acute benign cranial neuritides be recognized as formes frustes of Bell
palsy. (Arch Otolaryngol 102:262-264, 1976)
Idiosy)pathic
facial paralysis (Bell pal¬ cranial polyneuritis1 -"' often involving the trigeminal, glosso¬ pharyngeal, audiovestibular, and contralateral (clinically unaffected) facial nerve. Recent studies have implicated the herpes simplex virus as the causative agent."7 Why, then, when one considers that mucocutaneous herpes simplex is an everyday occurrence, do we not see more cases of cranial polyneuritis? The answer became apparent on review of the Facial Paralysis Research Clinic's file of cases of special interest and from testing consecutive patients who had is
a
herpes labialis, mucocutaneous herpes, both. A sensory cranial neuritis does occur with mucocutaneous herpes simplex," but the facial paralysis occurs in only a small percentage of these patients. Reported here are six representative cases, selected to illusor
n
for publication Jan 13, 1976. From the Facial Paralysis Research Clinic and the Department of Otolaryngology, Kaiser\x=req-\ Permanente Medical Center, Oakland, Calif. Reprint requests to the Department of Otolaryngology, Kaiser-Permanente Medical Center, 280 W MacArthur Blvd, Oakland, CA 94611 (Dr
Accepted
Adour).
trate that the various manifested
signs
and
symptoms associated with mucocutaneous herpes appear to be a forme fruste of the disease that has been called idiopathic facial paraly¬ sis.12 REPORT OF CASES Case 1.—A 56-year-old woman was admitted to the hospital four days after the onset of left occipital headache and pain radiating into the left ear and temporal area, which did not respond to meperidine hydrochloride, acupuncture, a muscle relax¬ ant, a Thomas collar, or heat, but was relieved for short periods by aspirin. One day after admission, she experienced vertigo, nausea, vomiting, and seconddegree nystagmus. The only abnormality found on physical and neurologic examina¬ tion was moderate tenderness to touch over the left occipital area. The erythrocyte sedimentation rate was 26 mm/hr, and the complete blood cell count and blood chemistry studies using an automated multiple analysis system (SMA12) were within normal limits. Findings from the following laboratory tests were normal: two-hour postprandial blood sugar test, VDRL test for syphilis, Coombs test (direct and indirect), antinuclear antibodytest, and latex agglutination test. Serum
protein electrophoresis; urinalysis; cere¬ brospinal fluid analysis; and radioisotopic brain
visual
scan;
field
examination
roentgenographic study of the mastoid area, the skull, and the cervical spine were all within normal limits. Audio-
results; and
a
grams
normal.
were
Drug therapy
was
discontinued. Two
days after its onset, the nystagmus ceased, but headache, vertigo, and nausea per¬ sisted. On the seventh hospital day, all symptoms began to subside; the patient was discharged. Six months later, the left occipital head¬ ache and vertigo recurred and the patient was referred to our otoneurology division. A herpetic vesicle was noted below the left corner of the mouth. There was hypes¬
thesia of the first and third divisions of the left fifth cranial nerve, a 50% decrease in
Downloaded From: http://archotol.jamanetwork.com/ by a New York University User on 05/24/2015
response to caloric stimulation in the left vestibular nerve, and left glossopharyngeal hypesthesia (absence of the afferent arc of the gag reflex; sensory deficit). A white blood cell count and a differential cell count, erythrocyte sedimentation rate, au¬ diogram, and roentgenograms of the inter¬ nal auditory canal were normal. The diag¬ nosis of acute herpes cranial neuritis was made. Treatment was that prescribed at that time for patients with idiopathic facial paralysis: prednisone, 40 mg daily for four days, tapered to zero during four additional days. The headache and vertigo ceased. Hypesthesia of the trigeminal and glossopharyngeal nerves had resolved by the end of two weeks. Case 2.—A 37-year-old woman was admitted to the neurologic service for eval¬ uation of papilledema that was believed to represent pseudotumor cerebri. On the day of admission, herpes labialis developed on the midline of the lower lip. She stated that this was the first day of menstrual flow and that herpes labialis often occurred on her first menstrual day. There was hypes¬ thesia over the distribution of all three divisions of the left fifth cranial nerve and over the left posterior portion of the pharynx (absent afferent arc of the gag reflex). During the hospital stay, numerous laboratory and roentgenographic studies were performed. The vesicles gradually resolved, beginning on the fourth hospital day; by the sixth day, the hypesthesia was no longer detectable. No treatment was given for the herpes. Case 3.—A 35-year-old woman was seen in the otolaryngology clinic for routine evaluation of allergic nasal polyps. A herpes labialis vesicle was noted on the left side of the upper lip. She stated that this commonly occurred in association with the onset of menstruation and that her menses had begun on the day before her clinic visit. She also stated that two days before the onset of menstruation, with associated herpes labialis, she frequently experienced left occipital headache, which she attrib¬ uted to premenstrual tension. Examination revealed hypesthesia of all three branches of the left fifth cranial nerve and absent left gag reflex in the afferent arc; these
findings were confirmed by a neurologist. The vesicle resolved in six days. Sensation in the fifth cranial nerve and the gag reflex returned by the eighth day. Case 4.—A 46-year-old woman under¬ went a left stapedectomy for otosclerosis. One week later, at routine postoperative examination herpes labialis was noted on the right side of the lower lip. There was hypesthesia of the second and third divi¬ sions of the right fifth cranial nerve and absent right gag reflex in the afferent arc. When she was seen one week later, the vesicle and the sensory deficits had re¬ solved. Case 5.—A 25-year-old woman was admitted to the hospital after sudden onset of severe vertigo and nausea without auditory symptoms. Examination revealed
third-degree right beating spontaneous a positive Rhomberg test, and herpetic vesicles on the left side of the posterior pharyngeal wall. The trigeminal a
nystagmus,
intact, but the gag reflex was absent on the right side. Chest and skull x-ray films and laboratory test results were normal. She was given 40 mg of methylprednisolone sodium succinate in¬ travenously. Within four hours, she was able to sit in bed and the nystagmus had subsided to first-degree level. The next day, an audiogram and ENG revealed normal hearing and absent response to caloric stimulation on the right (vestibular neuronitis). While in the hospital, she was given prednisone orally, 60 mg daily to be tapered to 0 during ten days (our current treatment for Bell palsy). The vertigo and palatal vesicle resolved in 48 hours and the patient was discharged. She did not take the prednisone as directed, and was read¬ mitted to the hospital within 12 hours with recurrent vertigo and third-degree nystag¬ mus. She was again given 40 mg of methyl¬ prednisolone intravenously with resultant reduction of vertigo. Oral administration of 60 mg of prednisone daily was again started and she was discharged one day later with minimal vertigo and no nystagmus. The prednisone was taken as directed. She had no vertigo and the gag reflex was present when she was seen seven days later. Case 6.—A 39-year-old woman who suffered from left-sided headaches that
nerve was
were
thought possibly to represent tempo¬
ral arteritis was given phenylbutazone. The headaches ceased in two days. Five days later, she had a sore throat, with swelling of both submandibular glands. The examining physician noted that the appearance of the left tonsil was "rather unusual." No organisms grew on throat culture. On the following day, the throat was more sore and she had dysphagia.
She
was
referred to the
otolaryngology
clinic, where examination revealed bilat¬ eral submandibular node enlargement, inflammation of the oropharynx with multiple punctate and coalescent herpetic lesions, hypesthesia of the first division of the trigeminal nerve on the left side, and decreased gag reflex (sensory deficit) on the left side. A white blood cell count was 11,200/cu mm, with 74% polymorphonuclear leukocytes, 18% lymphocytes, 2% monocytes, and 3% eosinophils. A diagnosis of herpetic stomatitis was made, and treat¬ ment was begun with prednisone, 40 mg daily, to be tapered to 5 mg daily at the end of eight days. (The use of steroids in primary herpes¬ virus infection has been thought to be contraindicated because of the theoretical possibility of ensuing "systemic viremia." In giving prednisone to healthy adults with severe herpetic stomatitis, I have seen no indication of viremia; in fact, the dramatic relief of symptoms has encouraged me to consider this drug as the treatment of choice in such cases. A report of experience with the use of steroids in herpes zoster and in several patients with acute herpes simplex is in preparation.) On the following day, the nodular swelling was greatly reduced, the herpetic stomatitis had decreased in intensity, and the associated pain had almost completely ceased. The patient then reported that she had also experienced vertigo, which she had not reported previously because she had been preoccupied by the severe pain of the stomatitis. A cold water caloric stimu¬ lation test revealed absence of response on the left side. Viral studies were performed: the first serum specimen was taken on the first day of observation in the otolaryngol¬ ogy clinic; three weeks later, a specimen was taken during convalescence. The herpes simplex titer of the first specimen was less than 1:8, and that of the specimen taken during convalescence was 1:32,
suggesting
a
primary herpes simplex
infection. The varicella titer was less than 1:8. When the prednisone dosage had been reduced to 20 mg daily, the vertiginous symptoms recurred and the dosage was increased to 40 mg daily, maintained there for another four days, then tapered to zero during four more days. One month after the acute episode, there was no hypesthesia of the trigeminal nerve and the gag reflex had returned.
COMMENT
Clinical evidence has long indicated that recurrent cutaneous herpes sim¬ plex has a neural accompaniment,""' so that the entity should be desig-
Downloaded From: http://archotol.jamanetwork.com/ by a New York University User on 05/24/2015
nated "neurocutaneous herpes sim¬ plex."' It is also known that the herpesvirus has a predilection for sensory nerves.141" Baringer and Swoveland, in routine autopsies, have isolated herpesvirus type I from the trigeminal ganglion,17 and herpes¬ virus type II from the sacral gan¬ glion," and have suggested that the virus could probably be isolated from other cranial nerve ganglia as well.1" The glossopharyngeal ganglion would appear to be a likely site, since the second most common locus for herpet¬ ic vesicles is the palate and the pharyngeal wall; further, herpes sim¬ plex virus has been isolated from the nasal pharynx of many asymptomatic
persons."
It has been suggested that the virus remains latent within the ganglion cells, and that when activated, it repli¬ cates within the cell, where it is protected from the circulating anti¬ bodies.1" The virus then migrates within the axon, where it is again protected from the circulating anti¬ bodies until it reaches the mucocuta¬ neous area, at which point it rekindles the vesicular eruption. The virus may induce recurrent mucocutaneous erup¬
tions without causing neural symp¬ toms; conversely, it may cause recur¬ rent neurologic disorders without mu¬ cocutaneous manifestations." Activa¬ tion of the herpes simplex virus involves not only intrinsic viral behav¬ ior, but also complex immunologie interreactions related to the acquisi¬ tion of a protein envelope by the virus capsids as they break through the nerve cell membrane.1" The first manifestations of acute benign cranial neuritis may be pain,
hypesthesia, vertigo, hearing loss,
decreased autonomie function, or mus¬ cle paralysis.-" Such cranial nerve dysfunction may bring fear to the patient and consternation to the physician. That even neurologists and neurosurgeons, when confronted with such manifestations, may feel driven into a series of futile and expensive investigations is clearly documented in case 1 of this report. Involvement of the afferent (sen¬ sory) arc of the gag reflex is repre¬ sented clinically by hypesthesia of the area supplied by the glossopharyngeal
nerve; involvement of the efferent
arc
is manifested as paresis or paralysis of the palatal muscles innervated by the vagus nerve. The presence or absence of a gag reflex is too often misjudged on the basis of the efferent response, without regard for the sepa¬ rate innervation of the two sides of the pharynx. To perform this test properly, both hands should be free in order that one may depress the tongue while applying an applicator only to the posterior pharyngeal wall, first on one then on the other side, assiduously avoiding contact with the tonsillar pillars or tongue. When this is prop¬ erly done, more cases of unilateral hypesthesia of the glossopharyngeal nerve will be found. The contradictory finding of hypes¬ thesia of one or more branches of the trigeminal nerve in patients whose most prominent initial symptom is pain is a frequent one in mucocuta¬ neous herpes simplex. It parallels the decreased response of the vestibular system to cold water caloric testing when vertigo is the initial symptom. Naufal and Sehuknecht-1 have demon¬ strated a decreased number of cells in the Scarpa ganglion in a patient with recurrent vestibular neuronitis, ad¬ ding support to the concept that repli¬ cation of the virus probably takes place in the sensory ganglion, and may induce neural cell death. An unanswered question remains: What is the mode of entry of the virus into
the acoustic-vestibular system? The suggestion that idiopathic fa¬ cial paralysis is a variant of acute cranial neuritis is not new. Antoniain 1919, on the basis of clinical find¬ ings in five cases of polyneuritis with facial paralysis and no zoster vesicles, offered the term, "acute infectious polyneuritis cerebralis acusticofacialis," interpreting the disease as infec¬ tious neuritis localized to the proximal parts of the nerve, with predilection for the spinal ganglion. He also ques¬ tioned whether ordinary facial paral¬ ysis did not belong in this category. Friedman- has recently made a simi¬ lar proposal. Recognition that these cranial neu¬ ritides are variants of a single entity has been delayed, apparently by frag¬ mentation of care due to the variety of the symptoms. Since herpes simplex has classically been thought to involve only the mucocutaneous areas, it has come to the attention of dermatolo¬ gists, and the asymptomatic involve¬ ment of the vestibular system went unobserved. Treatment for vertigo was sought from the otolaryngologist, who ignored the glossopharyngeal nerve. When bizarre or unexplained manifestations occurred, the neurol¬ ogist became involved and made such exotic diagnoses as monoplegia masti¬
catoria,^' glossopharyngeal neuralgia,
Sluder syndrome, to name a few. It has been demonstrated that the epidemiology and clinical course of
or
herpes simplex cranialis are identical with those of Bell palsy.7 Examples sustaining this observation are cases 2 and 3 of this article, in which the
manifestations had their onset with the start of menstruation. When the relation between Bell palsy and the menstrual cycle was analyzed, the facial paralysis was found to occur most often at its onset or within the first 14 days.-' In acute idiopathic facial paralysis, which I believe to be a herpes simplex cranial polyneuritis, the trigeminal nerve is involved in 25% of the cases; in 3% there is decreased function of the masseter muscle; in 40% there is evidence of abnormal response in the vestibular system; and in 35% the afferent arc of the gag reflex is absent or decreased. It has also been demonstrated that conduction veloci¬ ties may be decreased in the opposite facial nerve in as many as 50% to 75% of the patients,-4 - although it appears clinically to be uninvolved, indicating that the disease is often bilateral. These observations appear to sup¬ port the conclusion that the cases of cranial neuritis described here, which appeared with a primary herpesvirus infection or reappeared concurrently with mucocutaneous herpes simplex, represent variants (formes frustes) of Bell palsy. The benign nature of the cranial neuritis is established by acuteness of onset, transient duration, and clinical resolution. '
References 1. Adour KK, Doty HE: Electronystagmographic comparison of acute idiopathic and herpes zoster facial paralysis. Laryngoscope
83:2029-2034, 1973.
2. Friedman SR: Neuropathy: mono- or poly-? N Engl J Med 282:632, 1970. 3. Ch'ien LT, Halsey JH Jr: Trigeminal sensory neuropathy and Bell's palsy. N Engl J Med 282:224-225, 1970. 4. Spector RH, Schwartzman RJ: Benign trigeminal and facial neuropathy. Arch Intern Med 135:992-993, 1975. 5. McGovern FH: Trigeminal sensory neuropathy and Bell's palsy. Arch Otolaryngol 94:466\x=req-\ 470, 1971. 6. McCormick DP: Herpes-simplex virus as cause of Bell's palsy. Lancet 1:937-939, 1972. 7. Adour KK, Bell DN, Hilsinger RL Jr: Herpes simplex virus in idiopathic facial paralysis (Bell palsy). JAMA 233:527-530, 1975. 8. Selmanowitz VJ: Neurocutaneous herpes simplex. Int J Dermatol 10:227-232, 1971. 9. Slavin HB, Ferguson JJ Jr: Zoster-like eruptions caused by the virus of herpes simplex. Am J Med 8:456-467, 1950.
10. Baringer JR: Herpetic manifestations. N Engl J Med 289:159, 1973. 11. Kirby WMM: Herpetic manifestations. N Engl J Med 289:158-159, 1973. 12. Adour KK: Bell's Palsy: A complete expression of acute benign cranial polyneuritis, in Ahlvin RC, Blanchard LB, Brown DC, et al (eds): Primary Care. Philadelphia, WB Saunders Co,
1975, vol 2, pp 717-733.
Cushing, cited by Baringer JR, Swoveland Recovery of herpes simplex virus from human trigeminal ganglions. N Engl J Med 288:648-650, 13.
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14. Paine TF Jr: Latent herpes simplex infection in man. Bacteriol Rev 28:472-479, 1964. 15. Ellison SA, Carton CA, Rose HM: Studies of recurrent herpes simplex infections following section of the trigeminal nerve. J Infect Dis 105:161-167, 1959. 16. Goodpasture EW: Herpetic infection, with especial reference to involvement of the nervous system (DeLamar Lecture). Medicine 8:223-243, 1929. 17. Baringer JR, Swoveland P: Recovery of herpes-simplex virus from human trigeminal
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ganglions. N Engl J Med 288:648-650, 1973. 18. Baringer JR: Recovery of herpes simplex virus from human sacral ganglions. N Engl J Med 291:828-830, 1974. 19. Nahmias AJ, Roizman B: Infection with herpes-simplex viruses 1 and 2. N Engl J Med 289:667-674, 1973. 20. Foley JM: The cranial mononeuropathies. N Engl J Med 281:905-906, 1969. 21. Naufal PM, Schuknecht HF: Vestibular, facial, and oculomotor neuropathy in diabetes mellitus. Arch Otolaryngol 96:468-474, 1972. 22. Antoni, cited by M\l=o"\llerF: Critical viewpoints on the pathogenesis in Bell's palsy. Acta
Neurol Scand 43:228-238, 1967. 23. Hilsinger RL Jr, Adour KK, Doty HE: Idiopathic facial palsy, pregnancy, and the menstrual cycle. Ann Otol Rhinol Laryngol 84:433-442, 1975. 24. Safman BL: Bilateral pathology in Bell's palsy. Arch Otolaryngol 93:55-57, 1971. 25. Chaco J: Subclinical peripheral nerve involvement in unilateral Bell's palsy. Am J Phys Med 52:195-197, 1973.
