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.

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.

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.

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.

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.

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.

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.

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.

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.

An unexpected case of Ramsay Hunt syndrome: case report and literature review.

BACKGROUND: Ramsay Hunt Syndrome (RHS) is a rare, severe complication of varicella zoster virus (VZV) reactivation in the geniculate ganglion. Facial paralysis is one of the features and without treatment, it fully recovers in as little as 20% of cases; this is much improved if treatment is started within 72 hours. This case is noteworthy in that coexistence of facial palsy with cervical dermatome involvement by VZV is not typical of RHS. Yet, it has been reported before. CASE PRESENTATION: A 54 year old Caucasian woman presented with right ear discomfort, difficulty hearing and a vesicular rash along the pinnae, 8 days after the eruption of a similar rash in the right C2-C4 dermatomes. 2 days later, she awoke with a partial right-sided facial paralysis, which improved with treatment (valacyclovir and prednisone). CONCLUSIONS: This case is most pertinent to Family Practice, Otolaryngology and Neurology. It highlights the possible co-existence of RHS with cervical VZV reactivation and encourages physicians to monitor for this complication even before geniculate ganglion reactivation occurs. RHS is a rare disease that can present with vague symptoms. A high index of suspicion and close follow up are essential. Early intervention with antivirals and corticosteroids has shown significantly improved outcomes in these patients.

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.

Vestibular and cochlear neuritis in patients with Ramsay Hunt syndrome: a Gd-enhanced MRI study.

CONCLUSION: It is suggested that vertigo in patients with Ramsay Hunt syndrome is mostly induced by superior vestibular neuritis consecutive to the reactivation of varicella-zoster virus (VZV) infection from the geniculate ganglion through the faciovestibular anastomosis. Refractory hearing loss in patients with Ramsay Hunt syndrome may be due to cochlear neuritis following the spread of VZV. OBJECTIVES: An attempt was made to selectively identify vestibulocochlear nerves in the internal auditory canal (IAC) on gadolinium (Gd)-enhanced MRI in patients with Ramsay Hunt syndrome. METHODS: Fourteen patients with Ramsay Hunt syndrome presenting with facial palsy, herpes zoster oticus, vertigo, and/or sensorineural hearing loss were scanned on 1.5 T MRI enhanced with Gd. Perpendicular section images of the IAC were reconstructed to identify the facial, superior, and inferior vestibular nerves and the cochlear nerves separately. RESULTS: All except one of the patients with Ramsay Hunt syndrome with vertigo showed both canal paresis on the caloric test and Gd enhancement of the superior vestibular nerve in the IAC on MRI. Among 10 patients with hearing loss, 3 patients with severe to moderate sensorineural hearing loss showed Gd enhancement of the cochlear nerve in the IAC on MRI.

Herpes zoster oticus: a clinical model for a transynaptic, reflex pathways, viral transmission hypotheses.

Reactivation of the varicella-zoster virus (VZV) along the sensory nerves innervating the ear, including the geniculate ganglion, is responsible for herpes zoster oticus (HZO). In some cases, HZO is associated with polyneuropathy of the cranial nerves, although the mechanism of this involvement is not known. To explain this phenomenon and based on some clinical considerations, the present authors hypothesize an intersynaptic spread of VZV along the reflex pathways of the brainstem.

Successful response of non-recovering Ramsay Hunt syndrome to intravenous high dose methylprednisolone.

Ramsay Hunt syndrome (RHS) is a frequent cause of facial palsy. It is a consequence of the infection of geniculate ganglion by herpes zoster or herpes simplex virus. In the lack of randomized controlled trials, RHS is empirically treated by a combination therapy of antiviral agents and steroids given orally. However, RHS has, per se, a poorer prognosis than idiopathic facial palsy (Bell's palsy). We describe a case series of two patients with RHS unsuccessfully treated with antiviral drugs and oral corticosteroids, showing an almost complete recovery after late administration of intravenous (i.v.) high dose methylprednisolone. Both patients had all recognized negative prognostic factors including age of onset, a high grade facial weakness, absence of R1 and R2 response at blink reflex test, and in the first case, the involvement of greater superficial petrosal nerve. We propose that i.v. high dose methylprednisolone should be considered, even as a late treatment option, in patients with RHS non recovering after standard antiviral and oral steroid therapy as well as presenting clinical features suggestive of a poor prognosis.

A case of Ramsay Hunt syndrome in living-kidney transplant recipient.

A 36-year-old woman underwent ABO-incompatible living-donor kidney transplantation. Immunosuppression was achieved by quadruple therapy with tacrolimus, basiliximab, mycophenolate mofetil (MMF), and prednisone. Desensitization and removal of anti-ABO antibody was achieved by administration of MMF for 4 weeks before transplantation followed by intravenous administration of rituximab, double-filtered plasmapheresis, and plasma exchange. At 1 month after transplantation, she complained of left ear pain without vesicle rash, tinnitus, and vertigo. Physical examination revealed left facial paralysis and nystagmus. T2 fluid-attenuated inversion recovery magnetic resonance imaging (MRI) visualized swelling of the left facial nerve. Real-time polymerase chain reaction showed the existence of varicella zoster virus DNA in the patient's tears and saliva. The final diagnosis was Ramsay Hunt syndrome without vesicle rash, which is called zoster sine herpete. The patient was treated by intravenous administration of acyclovir (3 mg/kg, 3 times per day) in addition to the reduction of the MMF dose. For facial nerve palsy, prednisolone was prescribed for 3 days and then gradually tapered. These treatments improved the symptoms of tinnitus and vertigo after a month; the facial nerve palsy completely disappeared after 10 months. This case demonstrated MRI to be a useful modality for the early diagnosis of Ramsay Hunt syndrome without vesicle eruption.