Is vestibular neuritis an immune related vestibular neuropathy inducing vertigo?

OBJECTIVES: To review the current knowledge of the aetiology of vestibular neuritis including viral infections, vascular occlusion, and immunomediated mechanisms and to discuss the pathogenesis with relevance to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY: Relevant publications on the aetiology and treatment of vestibular neuritis from 1909 to 2013 were analysed. RESULTS AND CONCLUSIONS: Vestibular neuritis is the second most common cause of peripheral vestibular vertigo and is due to a sudden unilateral loss of vestibular function. Vestibular neuronitis is a disorder thought to represent the vestibular-nerve equivalent of sudden sensorineural hearing loss. Histopathological studies of patients who died from unrelated clinical problems have demonstrated degeneration of the superior vestibular nerve. The characteristic signs and symptoms include sudden and prolonged vertigo, the absence of auditory symptoms, and the absence of other neurological symptoms. The aetiology and pathogenesis of the condition remain unknown. Proposed theories of causation include viral infections, vascular occlusion, and immunomediated mechanisms. The management of vestibular neuritis involves symptomatic treatment with antivertiginous drugs, causal treatment with corticosteroids, and physical therapy. Antiviral agents did not improve the outcomes.

Latency of herpes simplex virus type-1 in human geniculate and vestibular ganglia is associated with infiltration of CD8+ T cells.

Herpes simplex virus type-1 latency and CD8+ T-cell occurrence were investigated in the trigeminal, geniculate, and vestibular ganglia from seven deceased humans. The HSV-1 "latency-associated transcript" was assessed by in situ hybridization and quantitative RT-PCR. Infiltration of CD8+ T cell was detected by immunohistochemistry and quantitative RT-PCR. The data show that HSV-1 latency and CD8+ T-cell infiltration are not solely confined to the trigeminal ganglia but can also occur in other cranial ganglia along the neuroaxis. However, the HSV-1 latency transcripts in the geniculate and vestibular ganglia were expressed at a very low level. The difference in CD8 transcript levels among HSV-1 latently infected trigeminal ganglia, geniculate, and vestibular ganglia was less conspicuous. Colocalization of latent HSV-1 and CD8+ T cells in geniculate and vestibular ganglia supports further the hypothesis that HSV-1 reactivation is possible in these ganglia and is the cause of Bell's palsy and vestibular neuritis.

Growth of postoperative remnants of unilateral vestibular nerve schwannoma: role of the vestibular ganglion.

Histopathological examination of seven temporal bones from patients who underwent a removal of vestibular nerve schwannomas by the translabyrithine or middle fossa approaches has demonstrated small tumor remnants that failed to grow as long as 25 years after surgery. In spite of the high incidence of residual tumors, the clinical recurrence rate of tumors operated at our institution by the translabyrinthine or middle fossa approaches is low (0.3%). Immunohistochemical labeling of dividing cells demonstrated that segments of tumor adjacent to the vestibular nerve and ganglion contained more dividing cells than were present in areas of the tumor at a distance from them.

Lipopolysaccharide-induced expression of nitric oxide synthase II in the guinea pig vestibular end organ.

The purpose of the investigation was to ascertain whether inoculation of bacterial lipopolysaccharide (LPS) into the vestibular organ of the guinea pig might induce formation of nitric oxide synthase (NOS) II. Forty-eight hours after the animals were injected with 1 mg transtympanic LPS, varying degrees of impaired caloric responses were observed with similar degeneration of vestibular hair cells. These effects could be blocked with N-nitro-L-arginine methylester, a competitive inhibitor of NOS. Findings suggested that NOS II, which was not normally detectable in the guinea pig vestibular organ but was present following inoculation of LPS, produced the nitric oxide as the toxic factor causing cell damage. If true, LPS may represent a reproducible method for studying the vestibular pathogenesis of inner ear disease.

[Immunohistochemical study on temporal bone of autopsy cases with Mycobacterium leprae infection].

Three temporal bones were obtained en bloc from autopsy cases with lepromatous leprosy from the middle cranial fossa side after removing the brain. After fixation with 10% formalin followed by sufficient decalcification, the specimens were embedded in paraffin en bloc and cut serially to stain every 10th section with hematoxylin and eosin (H&E) for anatomical orientation. An immunohistochemical study with anti-neurofilament, anti-MBP (myelin basic protein), anti-BCG (Bacillus Calmette-Gue'rin) and anti-PGL (Mycobacterium leprae-specific antiphenolic glycolipid-I) antibodies were performed to vestibular, cochlear and facial nerves, respectively, on the basis of anatomical orientation of the adjacent H&E sections. In one of three cases, positive staining by anti-PGL antibodies was recognized only in the facial nerve both in its internal auditory meatal and tympanic portions. However, even in this case, no neural damage was observed either by anti-neurofilament nor anti-MBP stainings. This finding supports the possibility of central neural infection by Mycobacterium leprae.

Serum viral antibody titer in vestibular neuronitis.

Fifty-seven cases of vestibular neuronitis were evaluated for viral infection by means of serum antibody titer. The viruses tested were herpes simplex virus, varicella-zoster virus, cytomegalovirus, EB virus, adenovirus, influenza virus A, influenza virus B, parainfluenza virus 3, mumps virus, rubella virus and measles virus. Paired sera were examined in 49 cases among 57 cases, 26 cases showed significant change (four-fold or greater change) in viral antibody titer. Only one case (53-year old female) showed high HSV 1 IgM antibody level by ELISA method, so the vestibular neuronitis in this case was assumed to have a close relation to viral infection.

Experimental vestibular neuritis induced by herpes simplex virus.

An animal model of vestibular neuritis was developed by inoculating herpes simplex virus type 1 (HSV-1) in the auricle of a mouse. Deviation of the body was observed in 4 of 30 mice 6 days after inoculation. These animals were sacrificed 6 to 10 days after inoculation and the vestibular nerve was examined histopathologically and immunohistochemically. The HSV-1 antigens were recognized exclusively in Scarpa's ganglion of the vestibular nerve in 2 of 4 mice in which signs of vestibular involvement were manifested.

Experimental reactivation of HSV-I in rat vestibular ganglia.

Rats with no clinical symptoms after inoculation were administered with cyclophosphamide in order to reactivate HSV-I in the vestibular ganglia. After this immunosuppression, the vestibular ganglia, trigeminal ganglia, cerebrum, cerebellum and brainstem were examined immunohistologically in order to detect HSV-I. HSV-I antigen could not be detected by using indirect immunofluorescence or the ABC method, however, it could be detected by using the PCR method. In this study, latent infection of HSV-I was shown but reactivation could not be established. We need further investigations to determine the reactivation of HSV-I in the vestibular ganglia, to obtain an animal model of vestibular neuronitis.

Viruses and vestibular neuritis: review of human and animal studies.

There is increasing evidence in man and animals that several human viruses can damage the vestibular labyrinth. Clinical and serologic studies of patients with vestibular neuritis suggest that the viruses may play a role in the pathogenesis of this disease. Temporal bone studies of patients dying after vestibular neuritis have found maximal damage in the distal branches of the vestibular nerve. These changes are felt to be consistent with a viral etiology. No satisfactory animal viral model of vestibular neuritis currently exists. However, animal studies have demonstrated that several human viruses including rubeola, herpes simplex, reovirus, mouse and guinea pig cytomegalovirus, and neurotropic strains of influenza A and mumps virus, can infect the vestibular nerve and the vestibular membranous labyrinth.

[Immunohistochemistry of the Scarpa's ganglion and the crista ampullaris of patients with Menière disease]. / Immunohistochemie am Ganglion scarpae und an der Crista ampullaris von Menière-Patienten.

In certain long-lasting cases of Menière's disease with recurrent attacks, despite of saccotomy, the removal of the vestibular ganglion is the only procedure that relieves vertigo. During ganglionectomy of this group of patients all fresh tissues gotten and gathered from operation are frozen immediately and preserved for immunohistochemical assay with direct and indirect incubations. The positive findings such as ASMA+, AEA+ and ANA+ in tissues of patient's own as well as in control tissues further confirmed the results previously reported by us. The immune-complex mediated arteriolar and capillary vasculitis on the basis of an autoimmune disorder as a secondary autoimmune marker might play a dominant role in this patients group. The demyelination of vestibular neurons in the Ganglion Scarpae might be the cause of the Menière symptoms. To confirming the hypothesis, the research plan must be continuously carried out.

Immunohistochemical localization of vimentin and S-100 antigen in small acoustic tumors and adjacent cochlear nerves.

To clarify the involvement of cochlear nerves in small acoustic tumors, we used immunoperoxidase techniques to determine the presence and distribution of vimentin and S-100 antigens in two acoustic tumor specimens and a transected vestibular nerve. Schwann cells and acoustic tumor cells failed to react positively with monoclonal antibody to vimentin. Reaction was observed in mesenchymal-appearing cells within both the normal nerve and the acoustic tumors, predominantly in association with blood vessels. Normal schwann cells and acoustic tumor cells reacted with polyclonal antibody to S-100 antigen with a similar, uniform distribution. Mesenchymal-appearing cells did not react with antibody to S-100. Immunostaining of a vestibular nerve from a Meniere's disease patient, used as a control, did not differ significantly from nerves adjacent to acoustic tumors. Because tumor cells and normal schwann cells stained similarly with antibody to S-100, it was not possible to establish with certainty if tumor cells invaded adjacent nerves.

Immunohistochemical findings in the vestibular ganglion from a patient with Menière's disease.

Immunofluorescent staining techniques were performed on a series of cryostat sections of the vestibular ganglion taken during ganglionectomy from a patient with Menière's disease. The direct technique using FITC-labelled antiserum proved the presence of immunoglobulins in the patient's blood vessels and endoneural connective tissue. Preincubation with unlabelled antiserum blocked this reaction. An additional positive reaction of ganglion cells was demonstrated by incubating tissue with the patient's serum. These findings prove antibodies in the patient's serum against the autologous ganglion cells. The vestibular ganglion from a patient with dizziness following a skull base fracture served as a control specimen. No autoimmune reaction was found in the ganglion cells when incubation was carried out with the patient's serum. A positive reaction in the blood vessels and connective tissue was less pronounced. The findings of the present study underline the occurrence of immunological reactions in the vestibular ganglion of patients with Menière's disease. A subsequent degeneration of ganglion cells could provoke clinical Menière's attacks.

Serovirological study of vestibular neuronitis.

A serovirological study to clarify the pathogenesis of vestibular neuronitis was made on 44 patients. The diagnosis of vestibular neuronitis was made under the diagnostic criteria. Sera from all 44 cases were collected twice or more at defined intervals. Of these, 36 cases were treated as paired sera. Seventeen out of 36 paired cases showed significant change in serum viral antibody titer (HSV, 2 cases; CMV, 1 case; EBV, 7 cases; rubella, 2 cases; adeno., 2 cases; influ. A, 1 case; influ. B, 2 cases). It was assumed that infection caused by these detected viruses played an important role in the onset of vertigo in each case.

Vestibular neuronitis--serum and CSF virus antibody titer.

The cerebrospinal fluid (CSF) findings of patients with vestibular neuronitis were virologically evaluated and discussed in contrast to those of herpes zoster. CSF samples obtained from seven patients with vestibular neuronitis, aged 28 to 55 years, were examined. The results were as follows: The CSF protein level in the vestibular neuronitis showed the peculiar change; i.e. its level was normal at the onset period of vertigo, but it rose to abnormal levels mostly in the period of two weeks, while the cell count remained normal throughout all phases of our study. Herpes simplex virus (HSV) type 1 IgG antibody titers measured by indirect immunofluorescent antibody technique (IF) in paired sera rose in one of the seven cases of vestibular neuronitis, but the antibody titers of the same virus in the CSF were not detected. HSV type 1 IgG antibody titers measured by IF in the CSF were detected in two of seven cases of vestibular neuronitis, but not significant. The ratio of EB virus (EBV) capsid antigen IgG antibody titers in CSF to that in serum ranged from 1:160 to 1:80 in vestibular neuronitis. There was no direct available evidence that vestibular neuronitis caused a break in blood-CSF barrier, an increase in IgG synthesis in the central nervous system or active infection with HSV, varicella zoster virus (VZV), or EBV. In this paper, we summarized the recent information on studies of the CSF and a latent herpes virus infection in order to give perspective to the pathogenesis of vestibular neuronitis.