Sulfoglucuronosyl glycolipids as putative antigens for autoimmune inner ear disease.

Autoimmune inner ear disease is diagnosed based on clinical history of fluctuating but progressive sensorineural hearing loss (SNHL) with or without vestibular symptoms occurring over weeks to months. An initial response to steroids or immunosuppressive drugs usually reverses the hearing loss. In search of specific diagnostic and therapeutic markers for autoimmune inner ear diseases, we investigated serum anti-glycolipid antibody activities in these patients by two different methods, HPTLC-immunoblotting and ELISA. We found that 37 out of 74 patients of clinically diagnosed autoimmune inner ear disease (30 of sensorineural hearing loss (SNHL) (group I), 14 of vestibular symptoms only (group II), 30 of Menieres symptoms (with both hearing loss and vestibular symptoms) (group III)) showed positive anti-sulfoglucuronosyl lactosaminyl paragloboside (SGLPG) antibody titers (p < 0.001). On the other hand, anti-sulfoglucuronosyl paragloboside (SGPG) titers were not elevated in these conditions. In contrast, only 3 out of 56 pathological control and 2 out of 28 healthy volunteers had measurable anti-SGLPG antibody titers. We further analyzed the localization of SGLPG in the auditory pathway and found that the antigens existed exclusively in inner ear and the eighth nerve, but not in pons, cerebellum, nor cerebrum. We conclude that the anti-SGLPG antibody represents a novel diagnostic marker for autoimmune inner ear disease and may participate in the pathogenesis of this disease.

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.

[An experimental herpes simplex virus infection in the vestibular nerve].

The author succeeded in producing vestibular ganglionitis by inoculating herpes simplex virus type 1 (HSV-1) into the back of the auricle of a new-born mouse. Postural deviation to the inoculated side was observed in 14 of 275 mice (5.1%) 6 to 10 days after the inoculation. In 6 of the 14 mice (42.9%) with postural deviation, HSV antigens were demonstrated immunohistochemically in the vestibular ganglion cells of the inoculated side. No antigens were identified in the animals with normal posture or in controls. Vestibular functions were evaluated in 5 animals suffering from postural deviation by the following test procedures. 1. behavior in an open field, 2. righting reflex, 3. transversing a narrow path, 4. ascending a rope, 5. negative geotaxis, 6. grasping a rod, 7. swimming. None could perform these tasks due to impairment of vestibular function. Histopathological and immunohistochemical examinations showed degeneration of the vestibular ganglion cells in 4 of the 5 mice, while HSV-1 antigens were recognized in 2 of them. The results of the present study show that inoculation of HSV into the back of the auricle of a new-born mouse can cause infection of the vestibular ganglion resulting in symptoms similar to those of vestibular neuritis, though the incidence is low compared to that of facial paralysis.

[T-lymphocyte subpopulation and HLA-DR antigens in hearing loss of vestibular neuropathy, Ménière's diseases and Bell's palsy]. / T-Lymphozytensubpopulationen und HLA-DR-Antigene beim Hörsturz, der Neuropathia vestibularis, dem Morbus Ménière und der Bellschen Parese.

In patients with various otoneurological diseases like hearing loss, neuronitis vestibularis, Ménière's disease and Bell's palsy, analyses concerning the immunoregulation and immunogenetics were done. For analysing the immunoregulation the T-helper (CD4) T-suppressor (CD8) ratio was determined. In contrast to patients with hearing loss caused by otobasal fractures and a healty control group, this ratio was elevated in 50% of the patients suffering from hearing loss. The elevation of the CD4/CD8 ratio was mainly caused by a reduction of CD8 positive cytotoxic-suppressor T-lymphocytes. The CD4/CD8 ratio may be of prognostic value, since an elevated ratio was found more often in patients with relapse of hearing loss, fluctuations, persistence of tinnitus or vestibular symptoms. An elevated ratio could also be detected in 48% of the patients with neuronitis vestibularis, in 50% of the patients with Ménière's disease and in 39% of the patients with Bell's palsy. A normal value was found in paralysis of the facial nerve of known origin like a state after trauma or after herpes zoster oticus paralysis. Immunogenetics was tested by HLA-DR typing. In patients with hearing loss HLA-DR4 antigen was distinctly increased, the relative risk was 2.8. The presence of the HLA-DR4 antigen proved to be an unfavourable sign, since in 44% of the patients presenting these antigens we found no improvement of the hearing. In patients with neuronitis vestibularis we found a relative risk of 3.12 and in patients with Ménière's disease a relative risk of 3.64, both for HLA-DR4.(ABSTRACT TRUNCATED AT 250 WORDS)

[Possible viral etiology of inner ear diseases (author's transl)]. / Mögliche virale Genese von Innenohrerkrankungen.

After a short review of the possible viral etiology of inner ear diseases viral titers of 20 patients with inner ear problems are given. In the history of nearly all patients a viral infection was found. Inspite of some positive results in the titrations no significance was seen. Therefore we refute a relation between viral infection and inner ear troubles; for a practical point of view virological diagnostics is not indicated.

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.

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.

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.