Immune-mediated Inner Ear Disease Research Articles

Cochlear implant in immune mediated inner ear diseases: Impedance variations and clinical outcomes

OBJECTIVE Immune-mediated inner ear disease (IMIED) might cause severe/profound hearing loss and these patients are considered ideal candidates to cochlear implant (CI) surgery. The aim of the study was to evaluate impedance changes over time. METHOD The Study Group (SG) was composed of CI IMIED patients (31 ears) and a Control Group (CG) of CI patients with hearing loss not related to their immune system (31 ears). Audiological performance and impedance values were measured and compared amongst groups at 3, 6, 12 and 18 months following the fitting sessions. RESULTS Speech perception was significantly better for SG in word and sentence recognition in quiet. Impedance values were, on average, significantly higher for apical and middle electrode segments in SG compared to CG at the 3- month follow-up and were maintained over time. Additionally, a subset of SG patients (active patients) experienced significantly greater impedance fluctuation corresponding to clinical symptom reactivation. CONCLUSION IMIED patients achieve good audiological performance. However, the relapsing inflammation could change the inner ear environment, causing impedance fluctuations and, consequently, more frequent CI fittings. Additionally, impedance evaluation could be utilized as an early warning sign of IMIED recurrence and as an aid to therapeutic decision-making.

Advances in diagnosis and therapies of immune-mediated inner ear diseases

Immune-Mediated Inner Ear Diseases（IMIED） is one of the curable sensorineural hearing loss caused by abnormal immune response, which may be primary inner ear diseases or associated with systemic autoimmune diseases. Since the complex differential diagnosis and no reliable diagnostic tests, the early identification of IMIED was extremely tricky. The treatment still mainly depends on glucocorticoid, but as researchs move along, directing at different pathogenesis, more and more therapies have been proposed. This article reviews the diagnosis and different treatment methods of IMIED.

Intratympanic gadolinium magnetic resonance imaging supports the role of endolymphatic hydrops in the pathogenesis of immune-mediated inner-ear disease.

To evaluate the presence of endolymphatic hydrops in patients with immune-mediated inner-ear disease. The presence of endolymphatic hydrops was prospectively evaluated in 17 patients clinically diagnosed with secondary (n = 5) or primary (n = 12) immune-mediated inner-ear disease, who attended the ENT department of a tertiary care centre for evaluation or treatment over the previous year. All patients underwent magnetic resonance imaging of the temporal bone. Intratympanic gadolinium three-dimensional magnetic resonance imaging diagnosed hydrops in 11 of 12 patients with primary immune-mediated inner-ear disease (92 per cent). Of these, seven patients (64 per cent) presented only cochlear (n = 5) or predominantly cochlear (n = 2) hydrops. A positive magnetic resonance imaging result was observed in only one of five patients with secondary immune-mediated inner-ear disease (20 per cent). This study confirms the presence of endolymphatic hydrops in immune-mediated inner-ear disease patients. The virtual absence of hydrops in patients with secondary immune-mediated inner-ear disease is remarkable, although firm conclusions cannot be drawn; this should be explored in a multicentre study with a larger sample of patients. A different immune reaction without development of endolymphatic hydrops should not be ruled out in secondary immune-mediated inner-ear disease patients.

Can positron emission tomography support the characterization of immune-mediated inner ear disease?

IntroductionTo evaluate the utility of positron emission tomography-computed tomography (PET/CT) as an imaging tool for the characterization of immune-mediated inner ear disease (IMIED), providing measurements of the inner ear region activity as well as detecting possible involvement of other organs. Material and methodsThe study included 28 patients with IMIED and 4 sex-matched and age-matched control subjects with no history of ear disease.Eighteen patients were considered to be suffering from primary IMIED and 10 patients from secondary. PET/CT scans with 18F-FDG were performed to assess systemic involvement as well as inner ear region activity.Interpretation of PET/CT scans was performed independently by two nuclear medicine physicians blinded to clinical history. In order to assess inter-rater agreement before performing the analysis of the inner ear, different Bland & Altman plots and the intraclass correlation coefficients were estimated. ResultsDifferent metabolically active foci findings were reported in 13 patients. Four patients diagnosed as primary IMIED showed thyroid and aorta activity. Regarding the inner-ear semiquantitative analysis, the inter-rater agreement was not sufficiently high. Comparisons between groups, performed using Mann–Whitney test or Kruskal–Wallis tests, showed no differences. ConclusionsThe study showed 18F-FDG PET/CT could be an important tool in the evaluation of IMIED as it can support the characterization of this entity providing the diagnosis of unknown or underestimated secondary IMIED. Nevertheless, we consider PET is not an adequate tool to approach the inner ear because of the small size and volume of the cochlea which makes the assessment very difficult.

Review of the Biological Agents Used for Immune-Mediated Inner Ear Disease

Introduction and objectives: Immune-mediated inner ear disease (IMIED) is one of the few reversible forms of sensorineural hearing loss. Treatment is based on high-dose corticosteroids, although long-term therapy is associated with serious adverse effects; this has led to the use of other agents or different routes of administration such as transtympanic delivery. This study analyses the role of biological agents in IMIED management. Material and methods: We searched PUBMED for studies that examined the response to treatment with different biological agents in patients with IMIED. The following data were extracted from the selected studies and entered into a standardised database: exclusion and inclusion criteria, characteristics of the patients studied, treatment, outcome measures and response rates achieved. Results: Thirteen studies were included in this review. A TNF alpha inhibitor (etanercept, infliximab, adalimumab) was used in 8 studies, an IL-1 antagonist (anakinra) was used in 3 studies and rituximab, and an antibody directed against the CD20 surface antigen on B lymphocytes was evaluated in 2 studies. Most studies achieved a hearing improvement or stabilisation in more than 70% of treated patients. Conclusions: Biological agents can play a role in the management of patients with IMIED, at least in those patients who do not respond to conventional therapy or whose hearing is not stabilised. However, specially designed randomised controlled clinical trials are needed to assess their effectiveness.

Spectrum of immune‐mediated inner ear disease and cochlear implant results

To characterize the progression of hearing loss in patients with immune-mediated inner ear disease (IMIED), and to identify disease- and patient-specific factors associated with cochlear implant (CI) performance. Retrospective cohort study. Subjects consisted of CI patients suspected to have lost their hearing due to IMIED. The primary dependent variable for functional decline was time to deafness, whereas for CI benefit it was post-CI speech perception scores. Independent variables included presence or absence of systemic autoimmune disease, age at CI, and insertion depth of the cochlear electrode. A transient favorable response to immunosuppressive therapy was reported in 16 of 26 patients (66.67%). The time to deafness differed between an organ (ear)-specific immune-mediated group, a systemic immune-mediated group including Cogan syndrome and relapsing polychondritis (subgroup A), and a systemic immune-mediated group associated with other autoimmune diseases (subgroup B; P = .001). Disease group (-15.52; P = .04), insertion depth of the CI electrode (40.71; P = .01), and the age at CI (-0.48, P = .05) were associated with speech perception results. Triaging IMIED cases based on presence and type of systemic autoimmune disease may aid in selecting a management strategy. Knowledge about the predictors of CI outcome will help clinicians select appropriate patients for CIs. In the setting of significant and irreversible hearing deficit, the restoration of hearing using a cochlear prosthesis may be appropriate earlier rather than later.

Etiology of 26 Cases with Progressive Bilateral Sensorineural Hearing Loss

Objective: To reveal the causes of rapidly progressive bilateral sensorineural hearing loss (SNHL), too fast to be age-related degeneration, and too slow to be sudden sensorineural hearing loss. Method: We retrospectively evaluated 26 patients with bilateral progressive HL who visited our hospital from 2007 to 2011. We excluded the patients with bilateral Ménière’ss disease and acute low-tone SNHL from our study. Results: We diagnosed 5 cases with immune-mediated inner ear disease (IMIED) such as vasculitis, 5 with functional HL, 4 with intracranial diseases including nonbacterial meningitis, lymphoma, and siderosis, and 1 with drug-induced HL. We could not identify causes in the remaining 11 cases. HL was one of the first symptoms in 10 of 11 cases with IMIED and intracranial diseases. Treatments including steroid administration achieved significant hearing recovery in 4 cases, including 3 with IMIED and 1 with lymphoma. Conclusion: We revealed that the bilateral progressive HL was often the first symptom of systemic or intracranial diseases. Screening for systemic and intracranial diseases is, thus, important for adequate treatment at early stage of disease.

A Pilot Study of Rituximab in Immune-Mediated Inner Ear Disease

Immune-mediated inner ear disease (IMED) is a cause of rapidly progressive auditory dysfunction. Patients are often responsive to high-dose corticosteroids and the disease is believed to be mediated by an antibody to inner ear proteins. To date, no therapies have proven effective as corticosteroid-sparing agents. Rituximab is a monoclonal antibody that depletes B cells, resulting in a reduction in autoantibody production. For that reason, rituximab was evaluated in a small pilot study in patients with IMED to see if there was a signal suggesting benefit. In all, 5/7 patients met the primary endpoint of an improvement in pure tone average (500–3000 Hz) by 10 dB in at least one ear, or an improvement in word identification score by at least 12% at 24 weeks, both relative to screening precorticosteroid values after 1 course of treatment. No significant adverse events were reported. The results of this study suggest further evaluation of rituximab as a treatment for IMED is indicated.

Alternatives to systemic steroid therapy for refractory immune-mediated inner ear disease: a physiopathologic approach

Immune-mediated inner ear disease (IMIED) is one of the few forms of reversible sensorineural hearing loss. Corticosteroids-responsive patients are usually associated with hearing improvement. Due to the long clinical course of IMIED that frequently present recurrences (hearing loss and vertigo), alternatives to corticosteroids such as methotrexate and recently TNF-alpha blockers have been proposed. Likewise new procedures for delivering corticosteroids to the inner ear have been developed. The aim of this article is to assess the efficacy of methotrexate and transtympanic 6-methylprednisolone in refractory IMIED. From a database of 200 patients affected by IMIED, 16 selected patients with refractory disease were included in the present study. Five patients were treated with methotrexate and 11 by means of transtympanic injection of 6-methylprednisolone. All patients treated with methotrexate had an improvement in their vestibular symptoms. However, hearing loss did not improve. Most patients treated with local 6-methylprednisolone (68.75%) showed an improvement in hearing loss and vestibular symptoms. Methotrexate has been shown to be ineffective in maintaining long-term remissions of hearing relapses although patients presented an improvement in vestibular symptoms. However, transtympanic 6-methylprednisolone has been shown to be a safe, easy and useful therapy in refractory IMIED and it may actually become the first-line treatment for these patients based on the existence of glucocorticoid receptors and the possible targets of immune-mediated damage within the inner ear.

Immune-mediated inner-ear disorders in neuro-otology

Immune-mediated inner-ear disorders may present to different medical disciplines and new research findings emerge rapidly. The purpose of this review is to draw the different strands together to produce an overview describing the clinical presentation of immune-mediated inner-ear disorders and to discuss useful diagnostic criteria with a focus on tissue-specific and tissue-non-specific antibodies. The importance of diagnosing an immune-mediated inner-ear disorder is highlighted in the context of it being one of few forms of treatable inner-ear disorder with a good response to immunosuppressive therapy. Due to a lack of reliable tests, the criteria upon which the diagnosis of immune-mediated inner-ear disease is based are often arbitrary. Previous and current research focuses mainly on the investigation of the aetiology of immune-mediated disorders, studying the presence of autoantibodies and the antigens responsible for their production. The prognostic and therapeutic values of inner-ear-specific antibodies are still unclear. Various antigens have been suggested. However, most antigens identified have been ubiquitous proteins not specific to the inner ear and therefore lack logical association with localized inner-ear pathology. Early diagnosis of immune-mediated inner-ear disorders with prompt treatment may prevent irreversible damage to inner-ear structures. Accordingly, it is important to include immune-mediated inner-ear disorders in the differential diagnosis of patients presenting with 'idiopathic' audiovestibular dysfunction. To enable early diagnosis, we recommend that the current available routine immunological laboratory tests (antinuclear, antineutrophil cytoplasmic, antiendothelial cell, antiphospholipid/anticardiolipin and antithyroid antibodies) are used when assessing a patient with suspected immune-mediated inner-ear disorder.

Immunologic work-up study for inner ear disorders: Looking for a rational strategy

Conclusions. For the evaluation of a patient with suspected immune-mediated inner ear disease (IMIED), an exhaustive immunologic work-up study is not recommended if financial resources are limited. Analysis of antinuclear antibodies (ANA) and the immunophenotype of peripheral blood lymphocytes (PBL) proved to be the most useful tests in our population to support the clinical diagnosis of IMIED. Objective. Owing to the lack of specific serological markers for the diagnosis of IMIED, an exhaustive immunologic work-up study for patients with suspected IMIED is usually performed. The aim of this study was to estimate the use of resources and the costs involved in the routine laboratory tests used for the diagnosis of IMIED. Material and methods. This was a comparative study of two groups of patients with a high suspicion of diverse clinical forms of IMIED who were subjected to different serologic test designs. The cost of the classical immunologic work-up study used for the diagnosis of IMIED (n=125) was estimated in comparison with that of a more restricted examination, based on a recently reported high-risk profile, involving the analysis of ANA and PBL (n=57). Results. The diagnostic efficiency of the two protocols was similar. The cost of a complete immunologic work-up study was €241.77 and that of the limited analysis was €53.12.

Sudden presentation of immune-mediated inner ear disease: characterization and acceptance of a cochleovestibular dysfunction.

Since the McCabe report, growing indirect evidence has accumulated to indicate the implication of immune mechanisms in the pathogenesis of immune-mediated inner-ear disease (IMIED). A clinical study of a group of patients affected by this condition was performed in order to characterize the immune group, based on a recently reported profile, and compared with the vascular, viral and idiopathic aetiologies of sudden deafness. Patients affected by immune-mediated inner-ear disease had the best and the earliest recovery rate of hearing (p = 0.0028 and p = 0.017, respectively). However, this group of patients also had the higher rate of recurrence (p = 0.034), supporting the typical clinical course of the autoimmune disorders. On the basis of the results the criteria used in the diagnosis of the sudden presentation of the immune-mediated inner ear disease could be accepted leading to the characterization of this condition. Likewise, the role of the supporting cells in the pathogenesis of the IMIED is discussed.

Immune response and immunopathology of the inner ear: an update.

Immune-mediated inner-ear disease includes clinical conditions associated with unilateral or bilateral rapidly progressive forms of sensorineural hearing loss. A systemic autoimmune disorder can be present in less than one-third of cases. Because of the lack of well defined detection methods to identify immune-mediated processes within the inner ear, and the fact that the human inner ear is not amenable to diagnostic biopsy, there has been great interest in developing animal models. Experimental models of sterile and virus-induced labyrinthitis support the participation of the immune system in the aetiopathogenesis of inner-ear disorders: interleukin-2 emanates from the endolymphatic sac and assists in changing the spiral modiolar vein, as in the expression of intercellular adhesion molecule 1, which allows the egrees of immune cells from the circulation. The formation of a fibro-osseous matrix ultimately results in degeneration of the inner ear. These investigations have allowed us to alter the immune response for the purpose of regulating its intensity and the subsequent damage to patients.

Immune-mediated inner ear disease.

Immune-mediated inner ear disease (IMIED) is a syndrome that includes the subacute onset of sensorineural hearing loss, often accompanied by vertigo and tinnitus. This constellation of symptoms may occur as a primary disorder in which no other organ involvement is evident, or it may complicate certain systemic conditions, including Wegener's granulomatosis, Cogan's syndrome, polyarteritis nodosa, and systemic lupus erythematosus. The precise disease mechanisms remain undefined, largely because of the difficulty obtaining relevant tissue specimens in untreated patients. However, if treated promptly with aggressive immunosuppression, the devastating sequelae of IMIED may be avoided. In this article, we review the pathophysiology, clinical evaluation, diagnostic testing, and therapy of IMIED.