**** DISCLAIMER ****

The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at The Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature.

History

Herpes zoster has been known since antiquity. Herpes is derived from the Greek meaning “to creep” and zoster “sword belt or girdle.” The Greeks called it “zona” and for centuries thereafter the disease was thought of as a cutaneous process. By the nineteenth century, physicians had begun to question this understanding.

Bright (1831) and Henley (1840) first suggested that herpes zoster represented a cutaneous manifestation of a nerve disease involving the sensory portion of the spinal nerves. Dr. von Barensprung (1861) demonstrated definitely at autopsy inflammatory lesions at the posterior root ganglion in a patient with herpes zoster.

Numerous observers described cases of herpetic eruption at the cephalic extremity due to herpetic infections involving the various cranial nerve ganglia or the upper cervical spinal root ganglia. Tryde gave the first description of cases of herpes zoster associated with facial palsy in 1872.

Head and Campbell published their landmark study in 1900. By correlating autopsy findings and careful, detailed clinical descriptions, these investigators mapped the sensory dermatomes defined by the dorsal root ganglia. Their work laid the foundation for future work and focused the energy and interest of others in this area.

Koerner, writing in the 1904, coined the term “herpes oticus” designating a syndrome that consists of the triad: blisters at the auricle, facial paralysis, and inner ear disturbances.

In 1907, Dr. Hunt, chief of Neurological Sciences at the Cornell University Medical Center, published his hypothesis regarding the etiology of herpes zoster oticus. Rather than presenting a new theoretic construct for disease, Dr. Hunt’s theory advanced the work begun by Drs. Head and Campbell and accurately classified herpes zoster of the head and neck. His paper represented the capstone of nearly a century of medical research and debate in this area. Hunt felt that herpetic eruption and associated symptoms (a viral prodrome, severe otalgia, facial nerve dysfunction, vesicular eruption involving the pinna, and occasionally vestibulocochlear symptoms), which he was the first to describe together as part of a clinical syndrome, were actually the result of, in his words, geniculate ganglionitis.

Hunt analyzed the sensory innervation of the ear and described the “zoster zone” for the geniculate ganglion as comprising a portion of the tympanic membrane, the external auditory canal, the tragus, antitragus, concha, a part of the helix, and a strip of the lobule. Here the typical herpetic lesions of geniculate zoster are most commonly found. The geniculate zone of the auricle is bounded anteriorly by the gasserian zone and posteriorly by the cervical zone, with some overlapping. Hunt classified herpes zoster at the cephalic extremity according to the sensory ganglion involved and the site of the rash into the following groups: (1) geniculate herpes zoster (herpes oticus), (2) gasserian herpes zoster (herpes facialis), and (3) cervical herpes zoster (herpes occipito-collaris)

Hunt then further classified the herpes zoster oticus syndrome according to severity of symptoms and the degree of extension: (1) herpes zoster auricularis without neurological signs, (2) herpes zoster oticus with facial palsy, (3) herpes zoster oticus with facial palsy and mild acoustic symptoms (diminished hearing and tinnitus), and (4) herpes zoster oticus with facial palsy and Ménière’s syndrome complex (deafness, tinnitus, vertigo, nystagmus, nausea, and vomiting). Ramsay Hunt described not so much a discrete clinical syndrome but rather a spectrum of herpetic disease, involving the ear and cranial nerves VII and VIII.

To support this classification scheme, he postulated that the major site of the pathologic lesion in herpes zoster oticus was the geniculate ganglion of the facial nerve. Increased pressure of the swollen ganglion on the facial nerve resulted in facial palsy. He further postulated that the etiology of the Ménière’s syndrome complex was either the simultaneous infection of the adjacent ganglions of the eighth nerve or the extension of the inflammatory process from the facial to the auditory nerve by means of nerve fibers that communicate between the two. He believed that this clinical syndrome represented “geniculate ganglionitis.” Unfortunately, he was not able to provide evidence for his theory. With histopathologic studies of autopsy speciments, subsequent investigators demonstrated little, if any, ganglion involvement.

Denny-Brown and his colleagues in 1944 were the first to challenge Hunt’s theory. They examined histopathologic specimens from a patient with auricular and occipital herpes zoster and facial palsy. At autopsy, they found no changes in the geniculate ganglion, but were able to demonstrate other significant findings: a necrotizing ganglionitis of the second cervical ganglion and a patchy motor neuritis of the facial nerve. They concluded “the evidence for geniculate ganglionitis in the Ramsay Hunt syndrome is invalid.”

In time, virology research further clarified these questions. Tissue culture studies published by Drs. Weller and Coons in 1954 confirmed the theory that the virus that causes varicella and herpes zoster is one in the same. In 1965, Hope-Simpson’s novel hypothesis unified thinking on herpes zoster and has laid the foundation for our current understanding. He suggested that the varicella virus lies dormant in the sensory ganglion after the initial infection. In a patient with low circulating antibodies, the virus would reactivate and infection would then manifest itself as herpes zoster, anywhere along the distribution supplied by that particular ganglion. Indeed, the facial nerve may be affected at any site from the brainstem to the periphery by the herpes virus. What is still not known is what activates the virus after it has lain dormant for so long.

In 1967, Blackley presented histologic evidence to support this emerging notion. He found extensive lymphocytic infiltration along the course of the facial nerve, as well as divisions of the VIII cranial nerve including vestibular and cochlear ganglia. Massive lymphocytic infiltration of the right facial nerve was seen. In addition, there was collapse and disruption of Reissner’s membrane, an increase of round cells in the stria vascularis, and destruction of the organ of Corti near the apical turn. Broad perivascular cuffing of several vessels is seen and marked atrophy of spiral neurones.

Epidemiology

A Mayo clinic study estimated the annual incidence of herpes zoster, regardless of site, as 130 cases per 100,000. The attack rate increased dramatically over the age of 60, and 10% this population had identifiable risk factors for decreased cell-mediated immunity including carcinoma, trauma, radiation therapy, or chemotherapy. The increased incidence in the elderly population is explained by a decrease in cellular immune response to varicella-zoster virus with age.

Adour reported the incidence as 5 per 100,000 a year, or one case every 52 minutes. These age-adjusted incidence figures for VZV cranial neuritis with facial paralysis parallel those Hope-Simpson estimated for VZV in the general population in 1965. These figures compare with those for Bell’s palsy: 20 per 100,000 per year. Few studies outside J.R. Hunt’s own assess the incidence of herpes zoster oticus in the population.

Microbiology: The Herpesvirus family

Members of the family herpesviridae are found in a wide range of host systems. To date, at least seven different species are known to infect man, including herpes simplex virus (HSV); cytomegalovirus (CMV), Epstein Barr virus (EBV), and varicella zoster (VZV).

Nomenclature is critical. It is important to distinguish VZV as a member of the greater family of herpes viruses. But it is distinct from herpes simplex. This is a common point of confusion.

The varicella-zoster virus (VZV) belongs to the herpes family. It is a double-stranded DNA virus that causes chicken pox (varicella) and zoster infections. Again what distinguishes Varicella from Zoster is the time of presentation. Reactivation of virus stored in sensory ganglia from previous varicella infection results in zoster.

Herpes viruses have an envelope surrounding an icosahedral capsid, approximately 100nm in diameter, which contains the dsDNA genome. When the envelope breaks and collapses away from the capsid, negatively stained virions have a typical "fried-egg" appearance.

Work Up and Evaluation

A thorough history and physical examination, a fundamental axiom in medicine, is the most crucial element of the work-up. Diagnosis still hinges on the clinical findings described in Hunt's classification scheme.

Clinical Presentation

Frequently, the first symptom is a deep, burning pain in the region of the ear. This is shortly followed in 1 to 4 days by a vesicular eruption of the EAC and concha, or, less frequently, of the face, neck, trunk, palate or fauces. The distribution of the vesicles depends on which sensory afferent fibers are involved by the viral eruption, but all the fibers may be involved, including cranial nerves V, IX, X and the cervical plexus arising from cervical roots II, III, IV. Cranial nerves VII and VIII are almost always both involved. During the acute illness, a varicelliform rash often accompanies the painful vesicular eruption. Facial nerve paralysis, vertigo, and hearing loss are commonly seen.

Natural History

The natural history of herpes zoster oticus differs from that of Bell’s palsy in several ways, perhaps reflecting the difference in the behavior of herpes simplex type I and VZV. Bell’s palsy recurs in 10% -12% of cases, but herpes zoster oticus rarely recurs. In addition, the acute phase of the infection, as measured by electrical response and progression, peaks in 5 to 10 days with Bell’s palsy, whereas herpes zoster oticus peaks in days 10 to 14. Finally, 84% of individuals with Bell’s palsy have a satisfactory recovery of function, but only 60% of patients with herpes zoster oticus recover function.

Crabtree (1968) was among the first to suggest that complete facial nerve recovery is less likely following herpes zoster oticus than in other cases of idiopathic facial palsy—despite treatment with high-dose steroids. Ten percent of patients with total facial nerve paralysis and 66 percent of those with partial paralysis recover completely. Recovery is better in those cases in which vesicles appear prior to nerve paralysis. Two percent of patients over age 50 will have severe, while nine percent will have moderate, post herpetic neuralgia.

The timing of the appearance of the vesicular eruption may have prognostic significance. In most cases, eruption and paralysis occur simultaneously. In approximately 25% of cases, the eruption precedes the paralysis, and the likelihood of recovery is higher in this group (Devriese and Moesker, 1988).

Diagnosis

The Tzanck prep, which is useful with herpes zoster, located on the truck in more peripheral nerve distribution areas, required toluidine blue staining a scraping from the blister. Occasionally, these blisters are located medially in the ear canal, andl are quite small. So, often it is difficult to obtain adequate specimens for the prep. A positive prep demonstrates multinucleated giant cells. Vesicular fluid, when present, can be cultured with human diploid fibroblasts and after 3-5 days multinucleated giant cells within the fibroblast population can confirm clinical diagnosis. These studies, however, require five days or more to produce results. Laboratory confirmation of the diagnosis is based on increasing antibody titers in repeated complement fixation tests. Immunofluorescence of varicella antigen obtained from exfoliated cells from lesions can provide a more expedient verification of clinical suspicion. Often, diagnosis rests alone on the clinical criteria, defined by Dr. Hunt

Diagnosis: Immunological Evaluation

Clinical diagnosis can be confirmed by either viral culture or fluorescence antibody testing using VZV identification reagent (Fluorescein isothiocyanate-conjugated monoclonal anti-VZV; Ortho Diagnostic Systems).

Hadar and colleagues from the Tel-Aviv University Medical Centers designed and tested VZV-specific IgG and IgA antibody titers in serial serum samples of 23 patients with Ramsay Hunt using immunoperoxidase assay. They demonstrated that all patients had VZV-specific IgG antibodies, but IgA can be a useful marker in confirming early diagnosis of the disease.

The mechanism of reactivation of VZV in herpes zoster oticus has not been clarified. Although the mechanism involved in general herpes zoster is also unclear, deterioration of cell-mediated immunity is thought to play a specific role as the “trigger” in reactivating the virus. The term "cellular immunity" colloquially refers to the T cell system. In fact, cell-mediated immunity is initiated by lymphokines produced by activated CD4+ T cells, activate macrophages and the precursors of CD8+ cytotoxic T cells. These effector cells then cause cell-mediated immune responses such as delayed- types hypersensitivity and cell-mediated cytotoxicity.

Nucleic acid hybridization and more recently polymerase chain reaction technology have confirmed VZV latency in human sensory dorsal root ganglia.

Diagnosis: Audiological Evaluation

In 1976, Byl and Adour were the first to thoroughly review the auditory symptoms and audiological data associated with herpes zoster oticus. They compared auditory symptoms in patient’s with Bell’s palsy and herpes zoster oticus. of 1080 patients with idiopathic facial paralysis, 29% of patients had auditory symptoms, while 37% of 172 patients with HZO had these symptoms. In their series of 1252 patients, 377 patients with facial paralysis had auditory symptoms. However, in only 11 of these 377 patients were abnormal cause-related sensorineural hearing loss documented with audiological testing. All of these patients had been diagnosed with HZO. These authors were the first to recommend a diagnosis in patients with idiopathic facial nerve paralysis and hearing loss—even when the characteristic vesicular eruption was absent. In their series, when recovery of auditory function occurs, a high-frequency sensorineural loss may persist, except in younger patients. Factors that appeared favorable for the recovery of hearing include not being older than 64 years, a mild initial hearing loss, a cochlear pattern of hearing loss, and absence of vertigo.

Wayman et al in 1990 retrospectively reviewed the audiological manifestations of herpes zoster oticus in 186 patients. In their study, active herpes zoster infection was confirmed by a four-fold increase between acute and convalescent complement fixation serum titres of VZV. Audiograms were performed on 152 patients, 82%, not all of whom had auditory symptoms at the time. Seven of these underwent more extensive evaluation to determine a cochlear or retrocochlear pattern of hearing loss. Patients with a demonstrated cause-related hearing loss were treated with oral prednisone, 60mg/day for six days, then gradually tapered. Of the 152 initial audiograms, 93 or 61% were normal, 29 or 19% were cause-related abnormal, and 30 or 20% were unrelated abnormal examinations. This final group was excluded from their analysis. Vertigo was documented in 8 of 29 of the cause-related hearing loss patients and in only 5 of 93 (5%) of normal hearing patients [p=0.002]. Vertigo was more likely with increased severity of hearing loss in the isolated high-frequency hearing loss group. Of the seven patients who underwent more extensive audiological work-up, six had findings consistent with cochlear pathology: elevated SISI, ABLB recruitment pattern, type II Bekesy tracing, with no evidence of tone delay. The seventh patient had severe speech-frequency hearing loss with a speech discrimination score of 18%, type IV Bekesy tracing, evidence of tone delay, and grossly abnormal brainstem evoked response with marked delay or wave V latency, all suggestive of retrocochlear hearing loss. No correlation was demonstrated between severity of facial paralysis and presence of any hearing loss. The incidence of incomplete paralysis was 68% in the normal hearing and 62% in the cause-related abnormal hearing group. Extrapolating their clinical data to the previous histopathologic findings, especially of Blackley et al., these investigators suggested that a cochlear pattern represents inflammation confined to the cochlea while the retrocochlear pattern represents a more profound change involving the entire nerve.

Diagnosis: Radiological Evaluation

Magnetic resonance imaging has added a new dimension to the research of herpes zoster oticus and confirmed the histopathologic findings of early investigators. Images are taken with and without the paramagnetic agent Gadolinium as a contrast medium. Gadolinium does not normally cross the blood-brain barrier but this barrier is broken down in the presence of inflammation or edema. This results in increased signal density and enhancement in these areas. Another reason suggested for abnormal enhancement in these situations is venous congestion in the epineurium and perineurium. There is little dispute that the facial nerve enhances on MRI in the majority of patients with acute facial palsy, but the role of MRI in differential diagnosis and prognostic determination is not entirely clear. The majority of published studies refer to MRI of the facial nerve in idiopathic Bell’s facial palsy. It has been shown that even the normal facial nerve shows some mild to moderate enhancement of the geniculate ganglion and the tympanic-mastoid segment. Nearly twenty studies of the use of MRI in evaluation have been published. All the papers reported enhancement of the facial nerve on MRI scanning in the majority of patients with facial palsy but only three papers suggested that the degree of enhancement or the anatomical level of the facial nerve enhancement had any prognostic significance. Brugel et al (1993) concluded that moderate enhancement in the geniculate ganglion as well as in the labyrinthine segment correlated with a good prognosis with respect to restoration of facial movement while an increased enhancement correlated with poor prognosis. Yanagida et al in 1993 noted that in subjects with Ramsay Hunt syndrome who experience internal auditory symptoms such as vertigo and tinnitus, enhancement was not only in the facial nerve but also in the vestibular and cochlear nerves.

Treatment: Medical Management

Introduced in 1977, the antiviral agent acyclovir has dramatically improved the treatment of herpesviridae infections. In the treatment of herpes zoster oticus, acyclovir therapy can be expected to produce House-Brackmann grade I-III recovery in most cases. Consequently, the success of antiviral therapy has greatly diminished enthusiasm for surgical decompression in cases of herpes zoster oticus with facial nerve paralysis.

Acyclovir remains the most widely prescribed and clinically effective antiviral drug available. It is 9-(2-hydroxy-methyl) guanine and a selective inhibitor of the replication of varicella-zoster and both herpes simplex types 1 and 2. It is converted by virus-encoded thymidine kinase to its monophosphate derivative, an event that does not occur to any substantial extent in uninfected cells. Subsequent disphosphorylation and triphosphorylation are then catalyzed by cellular enzymes resulting in acyclovir triphosphate concentrations that are 40 to 100 times higher in VZV-infected cells than uninfected cells. Acyclovir triphosphate inhibits viral DNA synthesis by competing with deoxyguanosine triphosphate as a substrate for viral DNA polymerase. Because acyclovir triphosphate lacks the 3’-hydroxyl group required to elongate the DNA chain, the synthesis of viral DNA is terminated. Furthermore, the viral DNA polymerase is tightly associated with the terminated DNA chain and is functionally inactivated. Viral polymerase has greater affinity for acyclovir triphosphate than does cellular DNA polymerase, resulting in little incorporation of acyclovir into cellular DNA. In vitro, acyclovir is most active against HSV-1, HSV-2, and VZV (average median effective concentrations 0.04, 0.10, and 0.50 µg per mL respectively.) Higher concentrations are required to inhibit replication of the Epstein Barr virus. Cytomegalovirus, which lacks a virus-specific thymidine kinase, is resistant.

Absorption from the GI tract is only 15% - 25% of the ingested dose. In addition, the blood-brain barrier results in a 50% reduction of circulating acyclovir into cerebrospinal fluid. Thymidine kinase found in VZV has diminished affinity for acyclovir than TK found in HSV. For these reasons, the oral dose is more substantial than the recommended dose for herpes simplex.

A recent randomized prospective clinical study in the NEJM compared 7-day treatment of acyclovir to two other treatment arms: 21-day course of acyclovir with and without prednisone. Neither additional treatment reduced the frequency of post-herpetic neuralgia.

HSV can develop resistance to acyclovir through mutations in the viral gene encoding thymidine kinase, through the generation of thymidine-kinase deficient mutants or through the selection of mutants possessing a thymidine kinase that is unable to phosphorylate acyclovir.

Acyclovir-resistant isolates of VZV have been identified much less frequently than acyclovir-resistant HSV, but they have recently been recovered from bone-marrow transplant patients and AIDS patients. The acyclovir-resistant isolates all had altered or absent thymidine kinase function but remained susceptible to vidarabine and foscarnet. Acyclovir therapy has been associated with very few adverse effects. Renal dysfunction has been reported, especially in patients given large doses of acyclovir by rapid intravenous infusion. This appears to be an uncommon finding and usually reversible. Administering the drug in a slow infusion and ensuring adequate hydration can minimize the risk of administering acyclovir. On the other hand, oral acyclovir even at doses of 800mg five times daily has not been associated with renal dysfunction.

Several limited retrospective studies have been done to examine specifically the role of acyclovir in herpes zoster oticus.

Hall and Kerr from the Royal Victoria Hospital in Belfast reported in a 1985 edition of the Lancet the first use of acyclovir for herpes zoster oticus. They treated seven patients with HZO with a parenteral dose of 5 mg/kg three times per day. Within 3 days these investigators noted a striking improvement in the toxemia associated with this condition. Of the six patients who had total facial paralysis, four recovered completely, one partially recovered, and one patient had no recovery.

Stafford and Welch reported a year later from Newcastle upon Tyne another small series of only 5 patients. Each patient received intravenous administration of acyclovir (5mg/kg) TID for a minimum of three days, followed by a two-week course of oral acyclovir. High-dose oral steroids (20mg PO QID in four cases; 10mg IVSS dexamethasone QID x 3 days) were prescribed for 5 days in full dosage, tapered gradually over another week. Each patient made a “satisfactory” recovery (4 patients with complete recovery by six months; one with partial recovery).

Dickens et al published their results in 1988. All patients received intravenous acyclovir 10mg/kg every 8 hours over a 7-day hospitalization period. Five of seven patients showed some return of facial function at the time of discharge. Their study suggests that prognosis depends on immediate initiation of therapy, and that multiple cranial nerve involvement did not appear to be a negative prognostic indicator.

Newer antiviral agents are available now for the treatment of herpes zoster. Valaciclovir and Famciclovir are both available in oral preparations and in more convenient thrice-daily dosing regimen.

Valaciclovir is the l-valine ester of acyclovir and essentially an acyclovir prodrug. It is rapidly and almost completely converted to acyclovir in vivo. Valaciclovir requires less frequent dosing than acyclovir due to its superior bioavailability over acyclovir. Acyclovir bioavailability is 3—5 times greater when administered as valaciclovir compared to 800 mg oral doses of acyclovir. Major adverse reactions include nausea (16%-19%), headache (11%-14%), vomiting (4%-9%), diarrhea (4%-6%).

Famciclovir is an oral prodrug for penciclovir and acts through a mechanism that is similar to that of acyclovir. Recommended dose for herpes zoster is 500mg PO TID for 7 days. It also is reported to diminish post-herpetic neuralgias.

Oral steroids have been used in zoster infections since the early 1950's. Some studies advocate the use of steroids along with acyclovir to reduce the incidence of post herpetic neuralgia and to enhance facial nerve recovery. Recovery of labyrinthine dysfunction after pharmacological therapy is not delineated in the current literature.

A 62-year-old white male presented for consultation to the VAMC Otolaryngology—Head and Neck Surgery service. The patient reported a 3-day history of left facial weakness, left otalgia, and left hearing loss. There was no vertigo, nausea or vomiting, no recent otologic infection, and no recent trauma to the head and neck. On physical examination, a vesicular eruption was noted over the left concha and extending into the left external auditory canal. Grade IV House-Brackmann facial nerve weakness was noted. There was numbness and vesicular eruption along the V2 trigeminal nerve distribution. No nystagmus was elicited. Cranial nerves I-VI, IX, X, XI, XII were grossly intact. A diagnosis of herpes zoster oticus was made. Treatment was begun with oral regimen of acyclovir 800mg five doses per day. Oral prednisone (20mg PO TID) for 5 days was begun and gradually tapered over the next week. The patient was instructed in the use of artificial tears, lacrilube, and nightly application of a left eyepatch. At 3-month follow-up, the vesicular eruption had completely resolved and facial nerve function had returned to normal (House-Brackmann Grade I). There was no post-herpetic neuralgia.

Aleksic SN, Budzilovich GN, Lieberman AN. Herpes zoster oticus and facial paralysis (Ramsay Hunt Syndrome). J Neurol Sci 1973;20:149-159.

Anderson RE, Laskoff JM. Ramsay Hunt syndrome mimicking intracanalicular acoustic neuroma on contrast-enhanced MR. Am J Neuroradiol 1990;11:409.

Aono T, Murakami S, Yanagihara N, Yamanishi K. Detection of human alpha-herpesvirus DNA using consensus primers and specific probes. Acta Otolaryngol Suppl 1994;514:132-134.

Berg R, Forsgren M, Schiratzki H. Acute facial palsy. Acta Otolaryngol 1976;81:462-467.

Brandle P, Satoretti-Schefer S, Bohmer A, Wichmann W, Fisch U. Correlation of MRI, clinical, and electroneuronographic findings in acute facial nerve palsy. Am J Otol 1996;17:154-161.

Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother 1995;39:1546-1553.

Blackley B, Friedmann I, Wright I. Herpes zoster auris associated with facial nerve palsy and auditory nerve symptoms: a case report with histopathological findings. Acta Otolaryngol 1967;63:533-550.

Burgoon CF, Burgoon JS, Baldridge GD. The natural history of herpes zoster. JAMA 1957;164:265-268.

Byl FM, Adour KK. Auditory symptoms associated with herpes zoster or idiopathic facial paralysis. Laryngoscope 1977;87:372-379.

Carroll SM, Mastaglia FL. Optic neuropathy and ophthalmoplegia in herpes zoster oticus. Neurol 1979;29:726-729. Crabtree JA. Herpes zoster oticus. Laryngoscope 1968;78:1853-1878.

Crabtree JA. Herpes zoster and facial paralysis. Otolaryngol Clin North Am 1974;7:369-373.

Crumpacker C . The pharmacological profile of famciclovir. Sem Dermatol 1996;15(Suppl 1):14-26, 1996. Daniels DL, Czervionke LF, Millen SJ. MR findings in the Ramsay Hunt syndrome. Am J Neuroradiol 1988;9:609.

Denny-Brown D, Adams RD, Fitzgerald PJ. Pathologic features of herpes zoster. Arch Neurol Psychiatr 1944;51:216.

Devriese PP, Moesker WH. The natural history of facial paralysis in herpes zoster. Clin Otolaryngol 1988;13:289-298.

Dickins JRE, Smith JT, Graham SS. Herpes zoster oticus: treatment with intravenous acyclovir. Laryngoscope 1988;98:776-779.

Downie AC, Howlett DC, Koefman RJ, Banerjee AK, Tonge KA . Case report: prolonged contrast enhancement of the inner ear on magnetic resonance imaging in Ramsay Hunt syndrome. Br J Radiol 1994;67:819-821.

Djupesland G, Degre M, Stien R, Skrede S. Acute peripheral facial palsy. Arch Otolaryngol 1977;103:641-644.

Fisch U. Surgery for Bell's palsy. Arch Otolaryngol 1981;107:1-11.

Gelfand ML. Treatment of herpes zoster with cortisone. JAMA 1954;154:911-912.

Goldsmith P, Zammit-Maempel I, Meikle D. Ramsay Hunt syndrome mimicking acoustic neuroma on MRI. J Laryngol Otol 1995;109:1013-1015.

Hall SJ, Kerr AG. Acyclovir in herpes zoster oticus. Lancet 1985;1(8437):1103.

Harner SG, Heiny BA, Newell RC. Herpes zoster. Arch Otolaryngol 1970;92:632-635.

Head H, Campbell AW. The pathology of herpes zoster: a long-term study and a new hypothesis. Brain 1900;23:353.

Hope-Simpson RE. The nature of herpes zoster: a long-term study and a new hypothesis. Proc Royal Soc Med 1965;58:9-20.

House JW, Brackmann DE. Facial nerve grading system. Otolaryngol Head Neck Surg 1985;93:146-147.

Huff JC, Bean B, Balfour HH Jr, Laskin OL, Connor JD, Corey L, et al. Therapy of herpes zoster with oral acyclovir. Am J Med 1988;85:84-89.

Hunt JR. Herpetic inflammations of the geniculate ganglion. A new syndrome and its complications. J Nerv Ment Dis 1907;34:73-96.

Ikeda M, Hiroshige K, Abiko Y, Onoda K. Impaired specific cellular immunity to the varicella-zoster virus in patients with herpes zoster oticus. J Laryngol Otol 1996;110:918-921.

Inamura H, Aoyagi M, Tojima H, Koike Y. Viral infection in acute peripheral facial palsy: investigation in Yamagata prefecture. Acta Otolaryngol Suppl 1988;446:23-26.

Johnson L, Zonderman B. Herpes zoster oticus (“Ramsay Hunt Syndrome”): a report of a case. Arch Otolaryngol 1948;48:1-8.

Jonsson L, Tien R, Engstrom M, Thuomas KA. Gd-DPTA enhanced MRI in Bell's palsy and herpes zoster oticus: an overview and implications for future studies. Acta Otolaryngol 1995;115:577-584.

Kanzaki J. Electrodiagnostic findings in the early stages of Bell's palsy and Ramsay-Hunt's syndrome. Acta Otolaryngol Suppl 1985;446:42-46.

Keane JR. Delayed trochlear nerve palsy in a case of zoster oticus. Arch Ophthalmol 1975;93:382-383.

Korzec K, Sobol SM, Kubal W, Mester SJ, Winzelberg G, May M. Gadolinium-enhanced magnetic resonance imaging of the facial nerve in herpes zoster oticus and Bell's palsy: clinical implications. Am J Otol 1991;12:163-168.

Kukimoto N, Ikeda M, Yamada K, Tanaka M, Tsurumachi M. Tomita H. Viral infections in acute peripheral facial paralysis: nationwide analysis centering on CF. Acta Otolaryngol Suppl 1988;446:17-22.

Kuo MJ, Drago PC, Proops DW, Chavda SV. Early diagnosis and treatment of Ramsay Hunt syndrome: the role of magnetic resonance imaging. J Laryngol Otol 1995;109:777-780.

LaBagnara J, Jahn AF, Habif DV, Solomon EM. MRI findings in two cases of acute facial paralysis. Otolaryngol Head Neck Surg 1989;101:562-565.

Lee D, Belmont M, Lucente FE. Pathologic quiz case 2. Bilateral herpes zoster oticus. Arch Otolaryngol Head Neck Surg 1996;122:195,197-198.

May M, Schlaepfer WW. Bell's palsy and the chorda tympani nerve: a clinical and electron microscopic study. Laryngoscope 1975;85:1957-1975.

May M, Shambaugh GE Jr. Facial nerve paralysis. In: Paparella MM, Shumrick DA, Gluckman JL, Meyerhoff WL, editors. Otolaryngology, 3rd ed. Philadelphia: Saunders; 1991. pp.1123-1124.

Neely JG, Joaquin AH, Kohn LA, Cheung JY. Quantitative assessment of the variation within grades of facial paralysis. Laryngoscope 1996;106:438-442.

Obituary: JR Hunt. J Nerv Disorders Ment Dis 1938;87:394-402.

Osumi A, Tien RD. MR findings in a patient with Ramsay-Hunt syndrome. J CompAssist Tomogr 1990;14:991-993

Peterslund NA, Seyer-Hansen K, Ipsen J, Esmann V, Schonheyder H, Juhl H. Acyclovir in herpes zoster. Lancet 1981;2(8251):827-830.

Proctor L, Lindsay J, Perlman H, Matz G. Acute vestibular paralysis in herpes zoster oticus. Ann Otol Rhinol Laryngol 1979;88:303-309.

Ragozzino MW, Melton LJ 3d, Kurland LT, Chu CP, Perry HO. Population-based study of herpes zoster and its sequelae. Medicine 1982;61:310-316.

Rathore MH, Friedman AD, Barton LL, Dunkle LM. Herpes zoster oticus. Am J Dis Child 1991;45:722-723.

Robillard RB, Hilsinger RL, Adour KK. Ramsay Hunt facial paralysis: clinical analyses of 185 patients. Otolaryngol Head Neck Surg 1986;95:292-297.

Sartoretti-Schefer S, Wichmann W, Valavanis A. Idiopathic, herpetic, and HIV-associated facial nerve palsies: abnormal MR enhancement patterns. Am J Neuroradiol 1994;15:479-485.

Schuknecht HF. Pathology of the Ear, 2nd ed. Boston: Harvard University Press; 1993. pp. 236-237.

Stafford FW, Welch AR. The use of acyclovir in Ramsay Hunt syndrome. J Laryngol Otol 1986;100:337-340.

Tien R, Dillon WP, Jackler RK. Contrast-enhanced MR imaging of the facial nerve in 11 patients with Bell's palsy. Am J Neuroradiol 1990;11:735-741.

Tschiassny K. The site of facial nerve lesion in cases of Ramsay Hunt’s syndrome. Ann Otol Rhinol Laryngol 1946;55:152-174.

Uri N, Meyer W, Greenberg E, Kitzes-Cohen R. Herpes zoster oticus: treatment with Acyclovir. Ann Otol Rhinol Laryngol 1992;101:161-162.

Wayman DM, Pham HN, Byl FM, Adour KK. Audiological manifestations of Ramsay Hunt syndrome. J Laryngol Otol 1990;104:104-108.

Weller S, Blum MR, Doucette M, Burnette T, Cederberg DM, de Miranda P, et al. Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single- and multiple-dose administration to normal volunteers. Clin Pharmacol Therap 1993;54:595-605.

Weller TH.,Coons AH. Fluorescent antibody studies with agents of varicella and herpes zoster propagated in vitro. Proc Soc Exper Biol 1954;86:789.

Wilson WR. The relationship of herpesvirus family to sudden hearing loss: a prospective clinical study and literature review. Laryngoscope 1986;96:870-877.

Whitley RJ, Gnann JW Jr. Acyclovir: a decade later. N Engl J Med 1992;327:782-789.

Wood MJ, Johnson RW, McKendrick MW, Taylor J, Mandal BK, Crooks J. A randomized trial of acyclovir for 7 days or 21 days with and without prednisone for treatment of acute herpes zoster. N Engl J Med 1994;330:896-900.

Yanagida M, Ushiro K, Yamashita T, Kumazaqa T, Katoh T. Enhanced MRI in patients with Ramsay Hunt’s Syndrome. Acta Otolaryngol Suppl 1993;500:58-61.

Zajtchuk JT, Matz GJ, Lindsay JR. Temporal bone pathology in herpes oticus. Ann Otol Rhinol Laryngol 1972;81:331-338.

Zammit-Maempel I, Campbell RSD. Prolonged contrast enhancement of the inner ear on MRI in Ramsay Hunt syndrome. Br J Radiol 1995;68:334-335