Chemokines and matrix metalloproteinases in cerebrospinal fluid of patients with central nervous system complications caused by varicella-zoster virus.

BACKGROUND: Varicella-zoster virus (VZV) is a common viral agent causing central nervous system (CNS) infections including encephalitis, meningitis, and Ramsay Hunt syndrome. Neurological complications occur frequently despite antiviral treatment. Matrix metalloproteinases (MMPs) and cytokines are involved in the neuroinflammatory response during CNS infection. Their role in VZV CNS infections and how they differ between different CNS entities caused by VZV are poorly investigated. METHODS: We analyzed the levels of 30 chemokines and 9 MMPs in cerebrospinal fluid (CSF) and serum from 66 patients with VZV CNS infections diagnosed by detection of VZV DNA in CSF and concomitant neurological symptoms and compared with a control group (n = 24). RESULTS: Levels of CCL19, CXCL8, CXCL9, and CXCL10 were significantly increased and surpassing the levels in serum when analyzing all patients with VZV CNS infections whereas CXCL11 was only increased in CSF of patients with VZV meningitis. MMP-2-levels were highly elevated in CSF of all 66 VZV patients. The patients with encephalitis had the most significantly increased levels of MMPs in CSF, and MMP-3, MMP-8, and MMP-12 were exclusively increased in this group, whereas MMP-9 in CSF was increased in the patients with VZV meningitis. CONCLUSIONS: We show that both chemokines and MMPs are elevated in the CSF of patients with VZV CNS infections. Encephalitis and meningitis patients differed with respect to other chemokines (CXCL11) and MMPs (MMP-3, MMP-8, MMP-9, and MMP-12), indicating that different location of the virus gives rise to qualitative differences in the ensuing inflammatory response. In addition, the pronounced increase of MMPs in CSF of the patients with encephalitis suggests an association to the severity of this manifestation, compared to VZV meningitis and Ramsay Hunt syndrome. The role of MMPs in association to chemokines should be further investigated to evaluate their significance in the neuropathogenesis of VZV CNS infections and as a potential target for new treatment alternatives.

Slowly progressing varicella zoster brainstem encephalitis complicating Ramsay Hunt syndrome in an immunocompetent patient: case report and review of the literature.

A 56-year-old immunocompetent male developed brainstem encephalitis complicating Ramsay Hunt syndrome. The disease had a slowly progressing course of months after the triggering infection, much longer than previously reported. Furthermore, magnetic resonance imaging, physical-chemical, and cell count analyses on cerebrospinal fluid were normal, whereas polymerase chain reaction for varicella zoster virus DNA was positive. The simultaneous negativity of both imaging and basic CSF exams is very rare, although possible event which confirms the irreplaceable role of viral screening on CSF. A systematic review of similar reports with highlights on the unusual aspects of our case is also presented.

Central nervous system infections caused by varicella-zoster virus.

We carried out a clinical and epidemiological study of adult patients with varicella-zoster virus central nervous system infection diagnosed by PCR in cerebrospinal fluid. Twenty-six patients were included. Twelve (46.2 %) patients were diagnosed with meningitis and fourteen (53.8 %) with meningoencephalitis. Twelve (46.2 %) had cranial nerves involvement (mainly the facial (VII) and vestibulocochlear (VIII) nerves), six (23.1 %) had cerebellar involvement, fourteen (53.8 %) had rash, and four (15.4 %) developed Ramsay Hunt syndrome. Three (11.5 %) patients had sequelae. Length of stay was significantly lower in patients diagnosed with meningitis and treatment with acyclovir was more frequent in patients diagnosed with meningoencephalitis. We believe routine detection of varicella-zoster virus, regardless of the presence of rash, is important because the patient may benefit from a different clinical management.

Magnetic Resonance Imaging Evidence of Varicella Zoster Virus Polyneuropathy: Involvement of the Glossopharyngeal and Vagus Nerves Associated With Ramsay Hunt Syndrome.

The involvement of lower cranial nerve palsies is less frequent in Ramsay Hunt syndrome caused by varicella zoster virus (VZV). The authors report 1 of extremely rare patients of radiologically proven polyneuropathy of VZV infection with magnetic resonance imaging findings of VII, IX, and X cranial nerve involvement is a 62-year-old female patient, who initially presented with Ramsay Hunt syndrome. Varicella zoster virus infection should be considered even in patients who show unilateral palsy of the lower cranial nerves associated with laryngeal paralysis. Thin-section T2W and T1W images with a contrast agent should be added to the imaging protocol to show the subtle involvement.

Mandibular osteonecrosis and Ramsay Hunt syndrome following a case of herpes zoster.

Varicella zoster virus (VZV) is the agent that causes chicken pox, a common childhood infection that characteristically presents as vesicular rashes affecting the trunk and head. After the primary infection has resolved, VZV lies dormant in the spinal dorsal root ganglia or extramedullary cranial nerve ganglia until reactivation results in herpes zoster (shingles). The sensory nerves of the trunk, as in classic shingles, and the fifth cranial nerve, as in trigeminal zoster, are the most frequently affected. Shingles is an acute viral infection characterized by the appearance of painful unilateral vesicular rash usually restricted to a dermatomal distribution of a sensory nerve. The rash of shingles is usually preceded by pain and paresthesia. A rare, severe complication of the reactivation of VZV in the geniculate ganglion of the facial nerve is Ramsay Hunt syndrome (RHS). RHS is characterized by otalgia, vesicles in the auditory canal, and ipsilateral facial paralysis. An even rarer complication of VZV infection includes post-zoster osteonecrosis. This report documents a case of severe mandibular osteonecrosis and RHS after an outbreak of herpes zoster and treatment strategies.

Ramsay Hunt syndrome revisited.

Varicella-zoster infections commonly are seen in clinical practice; however, Ramsay Hunt syndrome caused by reactivation of latent varicella-zoster virus in the geniculate ganglion is rare. We report the case of a 30-year-old woman who developed Ramsay Hunt syndrome and also review the characteristic features of this disease.

[Case of atypical Ramsay-Hunt syndrome who presented with severe vertigo and vomiting].

We herein present a case of 6-year-old female demonstrating atypical Ramsay-Hunt syndrome. She presented with an earache, severe vertigo, and vomiting at onset, and thereafter, herpes zoster oticus appeared. No facial nerve palsy was seen. She was vaccinated for varicella and had no past history of apparent varicella infection. The patient showed positive IgG and negative IgM serum antibodies for varicella-zoster virus (VZV). An analysis of VZV-DNA from the patient's ear lesion using alleric discrimination real-time PCR identified a wild-type strain of VZV. We diagnosed her to have atypical Ramsay-Hunt syndrome caused by reactivation of the VZV. Aciclovir and prednisolone were administered, and she recovered completely. This case indicates that Ramsay-Hunt syndrome could be caused by a VZV infection after vaccination, even though its frequency is low. Ramsay-Hunt syndrome may thus be considered as one of causes of sudden onset vertigo in children.

Neurological disease produced by varicella zoster virus reactivation without rash.

Reactivation of varicella zoster virus (VZV) from latently infected human ganglia usually produces herpes zoster (shingles), characterized by dermatomal distribution pain and rash. Zoster is often followed by chronic pain (postherpetic neuralgia or PHN) as well as meningitis or meningoencephalitis, cerebellitis, isolated cranial nerve palsies that produce ophthalmoplegia or the Ramsay Hunt syndrome, multiple cranial nerve palsies (polyneuritis cranialis), vasculopathy, myelopathy, and various inflammatory disorders of the eye. Importantly, VZV reactivation can produce chronic radicular pain without rash (zoster sine herpete), as well as all the neurological disorders listed above without rash. The protean neurological and ocular disorders produced by VZV in the absence of rash are a challenge to the practicing clinician. The presentation of these conditions varies from acute to subacute to chronic. Virological confirmation requires the demonstration of amplifiable VZV DNA in cerebrospinal fluid (CSF) or in blood mononuclear cells, or the presence of anti-VZV IgG antibody in CSF or of anti-VZV IgM antibody in CSF or serum.

Unusual presentation of Ramsay Hunt syndrome in renal transplant patients: case report and literature review.

Ramsay Hunt syndrome (RHS) is a rare manifestation of varicella zoster virus (VZV) infection that accounts for around 12% of all cases of facial paralysis. Although it is more common in immunosuppressed individuals, it has not been yet reported in kidney transplant recipients. We describe the case of a 41-year-old man with a history of renal transplant for whom the diagnosis and treatment of RHS were delayed owing to an unusual presentation. We also review the literature on VZV infection in renal transplant patients.

Ramsay Hunt syndrome in patients infected with human immunodeficiency virus.

Ramsay Hunt syndrome (RHS) is defined as herpes zoster infection of the head and neck that involves the facial nerve. Immunocompromised people, such as those infected with human immunodeficiency virus (HIV), are predisposed to herpes zoster. However, reports of RHS in patients with HIV are rare. We report two cases of RHS in patients with HIV at our hospital, located in southern Brazil. We hope this report will increase the awareness of this condition among doctors caring for patients with HIV.

Ramsay Hunt syndrome: a rare complication of herpes zoster infection in a lung cancer patient.

Objectives: Ramsay Hunt syndrome (RHS) is a rare complication of varicella zoster virus (VZV) reactivation with high morbidity, requiring swift and specific treatment. Methods: We discuss the epidemiology, diagnosis and treatment of RHS using a case report of a cancer patient who presented with disseminated VZV reactivation, including RHS. Results: A 68-year old man with stage IV lung adenocarcinoma, for which he received pemetrexed maintenance chemotherapy, presented to the emergency department with a progressive skin rash despite broad spectrum antibiotics, vertigo, and diminished hearing. Valacyclovir was started for a varicella zoster virus (VZV) reactivation. Despite antiviral therapy, his symptoms progressed with late appearance of vesicles in the external ear canal, leading to a diagnosis of Ramsay Hunt syndrome (RHS). Conclusion: RHS is a rare complication of VZV reactivation and can lead to peripheral facial nerve palsy, hearing loss, vestibular problems, and vesicles in the dermatome of the cranial nerve. Timely initiation of steroids and antiviral therapy lead to recovery of the facial nerve in >75% of cases, although the optimal therapy is still unclear.

Facial palsy after dental procedures - Is viral reactivation responsible?

OBJECTIVES: Herpes labialis viral reactivation has been reported following dental procedures, but the incidence, characteristics and outcomes of delayed peripheral facial nerve palsy following dental work is poorly understood. Herein we describe the unique features of delayed facial paresis following dental procedures. MATERIALS AND METHODS: An institutional retrospective review was performed to identify patients diagnosed with delayed facial nerve palsy within 30 days of dental manipulation. Demographics, prodromal signs and symptoms, initial medical treatment and outcomes were assessed. RESULTS: Of 2471 patients with facial palsy, 16 (0.7%) had delayed facial paresis following ipsilateral dental procedures. Average age at presentation was 44 yrs and 56% (9/16) were female. Clinical evaluation was consistent with Bell's palsy in 14 (88%) and Ramsay-Hunt syndrome in 2 patients (12%). Patients developed facial paresis an average of 3.9 days after the dental procedure, with all individuals developing a flaccid paralysis (House Brackmann (HB) grade VI) during the acute stage. 50% of patients developed persistent facial palsy in the form of non-flaccid facial paralysis (HBIII-IV). CONCLUSION: Facial palsy, like herpes labialis, can occur in the days following dental procedures and may also be related to viral reactivation. In this small cohort, long-term facial outcomes appear worse than for spontaneous Bell's palsy.

A case study of Ramsay Hunt Syndrome in conjunction with cranial polyneuritis.

RATIONALE: Ramsay Hunt syndrome in conjunction with cranial polyneuritis is not extensively documented, and is very easily misdiagnosed. PATIENT CONCERNS: A case of a 53-year-old male with Ramsay Hunt syndrome in conjunction with cranial polyneuritis is presented with early symptoms of vertigo, cephalalgia, and facial palsy, followed by zoster oticus 10 days later. DIAGNOSES: Diagnosis was challenging as this condition presents with multiple neuropathies, and attempting to diagnose based on clinical symptoms was often misleading. Polymerase chain reaction can be used to test for presence of the virus in the cerebrospinal fluid, followed by targeted drug therapy. INTERVENTIONS: Acupuncture, in conjunction with fire cupping, bloodletting around the afflicted region on the face, as well as oral consumption of herbal medicine and vitamins for nerve nourishment was given to treat this disease. OUTCOMES: Due to misdiagnosis resulting in delayed treatment, peripheral facial paralysis was left as the main sequelae, while other symptoms responded quickly to treatment. After a 6-month follow-up, facial palsy was still present. LESSONS: Considering that targeted antiviral therapy can be used to increase the effectiveness of treatment, early diagnosis, and timely use of medication is critical.

Varicella-zoster virus load and cochleovestibular symptoms in Ramsay Hunt syndrome.

OBJECTIVES: The mechanism by which varicella-zoster virus (VZV) reactivation causes cochleovestibular symptoms (CVSs) in patients with Ramsay Hunt syndrome (RHS) remains to be elucidated. The present study analyzed the relationship between VZV load and the onset of CVSs in RHS. METHODS: The subjects consisted of 56 patients with RHS; 29 exhibited CVSs and facial paralysis (FP; group 1), and 27 exhibited FP without CVSs (group 2). The VZV DNA copy number in the saliva was measured with a quantitative polymerase chain reaction. Anti-VZV antibodies were assayed by an enzyme-linked immunosorbent assay with paired sera. RESULTS: There was no significant difference in maximum viral copy number between the two groups. In group 1, CVSs occurred at various times between the early phase and the regression phase of VZV reactivation. In some patients, CVSs occurred in the early phase of VZV reactivation, before the onset of zoster lesions and FP. CONCLUSIONS: There are various different patterns in the development of eighth cranial nerve dysfunction, which is caused by progression of neuritis or labyrinthitis following VZV reactivation. Our data suggest that CVSs in RHS may also be caused by reactivation of VZV in the spiral and/or vestibular ganglia.

Inner ear and facial nerve complications of acute otitis media with focus on bacteriology and virology.

CONCLUSION: Among 20 patients with inner ear complications and/or peripheral facial palsy secondary to acute otitis media (AOM) a proven or probable bacteriological cause was found in 13 (65%). In seven patients (35%), a proven or probable viral cause was found. Only two of the patients (10%), with a proven bacterial AOM and a clinical picture of a purulent labyrinthitis in both, together with a facial palsy in one, had a substantial degree of dysfunction. Although the number of patients in this study is relatively low our findings show that inner ear complications and facial palsy due to AOM can be of both bacterial and viral origin. Severe sequelae were found only where a bacterial origin was proven. OBJECTIVES: Inner ear complications and/or peripheral facial palsy secondary to AOM are rare. The general understanding is that they are due to bacterial infections. However, in some of these patients there are no clinical or laboratory signs of bacterial infections and they have negative bacterial cultures. During recent years different viruses have been isolated from the middle ear or serologically proven in AOM patients and are thought to play a pathogenetic role. We suggest that in some cases of AOM complications from the inner ear and the facial nerve can be caused by viruses. The purpose of our study was to analyze infectious agents present in patients with inner ear complications and/or facial palsy arising from AOM. PATIENTS AND METHODS: The medical records of 20 patients who had inner ear complications and/or facial palsy following AOM ( unilateral in 18, bilateral in 2) between January 1989 and March 2003 were evaluated. Bacterial cultures were carried out for all patients. Sera from 12 of the patients were stored and tested for a battery of specific viral antibodies. In three patients, investigated between November 2002 and March 2003, viral cultures were also performed on samples from the middle ear and nasopharynx. RESULTS: Nineteen patients had inner ear symptoms. Eight of them had a unilateral sensorineural hearing loss and vertigo, three had vertigo as an isolated symptom and one, with bilateral AOM, had bilateral sensorineural hearing loss. Seven patients had a combination of facial palsy and inner ear symptoms (unilateral sensorineural hearing loss in three, unilateral sensorineural hearing loss and vertigo in two, bilateral sensorineural hearing loss and vertigo in one, with bilateral AOM, and vertigo alone in one). One patient had an isolated facial palsy. Healing was complete in 11 of the 20 patients. In seven patients a minor defect remained at follow-up (a sensorineural hearing loss at higher frequencies in all). Only two patients had obvious defects (a pronounced hearing loss in combination with a moderate to severe facial palsy (House-Brackman grade 4) in one, distinct vestibular symptoms and a total caloric loss in combination with a high-frequency loss in the other. Eight patients had positive bacteriological cultures from middle ear contents: Streptococcus pneumoniae in two, beta-hemolytic Streptococcus group A in two, beta-hemolytic Streptococcus group A together with Staphylococcus aureus in one, Staph. aureus alone in one and coagulase-negative staphylococci (interpreted as pathogens) in two. In the 12 patients with negative cultures, there was a probable bacteriological cause due to the outcome in SR/CRP and leukocyte count in five. In four patients serological testing showed a concomitant viral infection that was interpreted to be the cause (varicella zoster virus in two, herpes simplex virus in one and adenovirus in one.) In three there was a probable viral cause despite negative viral antibody test due to normal outcome in SR/CRP, normal leukocyte count, serous fluid at myringotomy and a relatively short pre-complication antibiotic treatment period.

Varicella-zoster virus-specific cell-mediated immunity in Ramsay Hunt syndrome.

OBJECTIVES/HYPOTHESIS: The etiology of Ramsay Hunt syndrome (Hunt syndrome) is reactivation of latent varicella-zoster virus (VZV) in the geniculate ganglion of the facial nerve, leading to neuritis. Although the mechanism of the VZV reactivation is unclear, one possibility is that the reactivation involves a low level of VZV-specific cell-mediated immunity (CMI). The aim of this study was to clarify the characteristics of the VZV-specific CMI in Hunt syndrome compared to that in Bell's palsy, and to obtain clues to its role in the development of Hunt syndrome. STUDY DESIGN: Prospective study. METHODS: We determined the median spot numbers and examined VZV-specific CMI in patients with Hunt syndrome and with Bell's palsy using interferon-γ enzyme-linked immunospot (ELISPOT) assays. We analyzed the relationship between the value of VZV-specific CMI and days from disease onset. RESULTS: The median spot number in Hunt syndrome (87.3 spot-forming cells [SFCs]/4 × 10(5) peripheral blood mononuclear cells [PBMCs]) was higher than that in Bell's palsy (62.3 SFCs/4 × 10(5) PBMCs). Hunt syndrome showed a strong relationship between the ELISPOT count and days from onset (r = 0.65). Within the first 5 days from onset, no ELISPOT counts higher than 80 SFCs/4 × 10(5) PBMCs were observed. On the other hand, no correlation was observed between the ELISPOT count and days from onset in patients with Bell's palsy (r = -0.19). CONCLUSIONS: These results suggest that VZV-specific CMI in Hunt syndrome is low at disease onset and increases rapidly thereafter. Consequently, reduced VZV-specific CMI may play an important role in the reactivation of VZV in the facial nerve, leading to Hunt syndrome.

A case of Ramsay Hunt-like syndrome caused by herpes simplex virus type 2.

We report an immunocompetent patient with recurrent auricular and facial vesicles associated with painful paresthesias and facial paralysis, consistent with Ramsay Hunt syndrome, due to herpes simplex virus (HSV) type 2. Clinical and laboratory-proven acyclovir resistance developed during therapy. Immunologic assays revealed normal reactivity to HSV-2.

Postoperative Ramsay-Hunt syndrome after acoustic neuroma resection. Viral reactivation.

The aim of this paper is to present a patient suffering from acoustic neuroma and operated on with immediate postoperative hearing and facial function preservation who developed delayed Ramsay-Hunt syndrome. To our knowledge, this is the first case in whom a postoperative delayed facial palsy and hearing loss occurred. The patient gave an history of previously diagnosed herpes zoster reactivation limited to chest one-year before. This is undoubtdetly a predisposing factor for development of delayed facial palsy. It must not be underestimated and it obliges to consider a prophylaxis. Theoretically, the prophylactic antiviral therapy might prevent the evolution towards the herpes zoster oticus or reduce the severity of the symptoms allowing the preservation of the hearing function. It would be pointed out that the delayed facial plasy has favourable prognosis, while the hearing impairment may recover with a greater difficulty even after an antiviral treatment as in our case.

Molecular temporal bone pathology: II. Ramsay Hunt syndrome (herpes zoster oticus).

In 1907 J. Ramsay Hunt suggested that herpes zoster oticus resulted from a geniculate ganglionitis; however, many contemporary authors believe that this disorder represents a neuritis or polycranial neuropathy. Herpes varicella-zoster viral (VZV) DNA was identified, using the polymerase chain reaction, in archival celloidin-embedded temporal bone sections from two patients who clinically had Ramsay Hunt syndrome (herpes zoster oticus). The presence of VZV was confirmed by sequencing the PCR products. These experiments demonstrated that VZV genomic DNA was present in the geniculate ganglion of the side with facial paralysis and cutaneous recrudescence in both patients and in the clinically unaffected side in patient 1. In addition, patient 2 had a sudden hearing loss and was found to have VZV genomic DNA in sections from the affected side containing the spiral ganglion, Scarpa's ganglion, organ of Corti, and macula of the saccule. No VZV genomic DNA was identified in temporal bone sections from five patients with Bell's palsy and ten patients without evidence of otologic disease. In this study, the histopathology of these two cases yielded complementary information regarding the role of VZV in herpes zoster oticus. These data suggest that in patients with Ramsay Hunt syndrome, latent VZV is located in the geniculate ganglia and may be present in the auditory and vestibular primary afferent ganglia in some patients.

Detection of varicella zoster virus DNA in tear fluid and saliva of patients with Ramsay Hunt syndrome.

OBJECTIVE: To clarify the dynamics of the reactivation of the varicella zoster virus in Ramsay Hunt syndrome. SUBJECTS AND METHODS: Varicella zoster virus DNA in the tear fluid, submandibular gland saliva, and parotid gland saliva of 15 patients with Ramsay Hunt syndrome was studied. The presence of varicella zoster virus DNA was detected quantitatively by the use of polymerase chain reaction and a microplate hybridization method. RESULTS: Of 102 specimens of the tear fluid and saliva collected from 15 patients, varicella zoster virus DNA was detected in 40 specimens (39%) from 12 patients (80%). The detection rate was 72% in the submandibular saliva, 57% in the parotid saliva, and 27% in the tear fluid. Varicella zoster virus DNA was detected not only in specimens from the affected side but also in specimens from the unaffected side at the same rate of detection, and at nearly the same number of DNA copies. Regarding the parotid saliva, varicella zoster virus DNA was detected in samples collected at an early stage of the disease. In the tear fluid and submandibular saliva, however, the detection rate was high in samples collected 2 weeks after the onset of disease or later. CONCLUSIONS: Secretion of varicella zoster virus DNA into the tear fluid and saliva was confirmed in the patient with Ramsay Hunt syndrome. The increase and decrease in the detection rate and the number of varicella zoster virus DNA copies detected in samples collected at different times was considered to substantiate varicella zoster virus reactivation in Ramsay Hunt syndrome. Varicella zoster virus reactivation was thought to occur in the unaffected side at the same level as in the affected side, and some of the secreted varicella zoster virus DNA was suspected to be derived from the ganglion trigeminale.