Objective: To report the adverse effects associated with prolonged high-dose prednisone for the treatment of autoimmune inner ear disease (AIED).Study Design: Prospective data collected as part of a multi-center, randomized, controlled trial for the treatment of corticosteroid-responsive AIED with methotrexate.Setting: Tertiary referral centers.Patients: One hundred sixteen patients with rapidly progressive, bilateral sensorineural hearing loss.Intervention: All patients completed a 1-month course of prednisone (60 mg/d). In Phase 2, 67 patients with improvement in hearing underwent a monitored 18-week prednisone taper, resulting in 22 weeks of prednisone therapy at an average dose of 30 mg per day. Thirty-three patients were randomized to receive methotrexate in Phase 2. Thirty-four patients received prednisone and placebo.Main Outcome Measure: Adverse events (AE) in patients treated with prednisone only.Results: Of 116 patients, 7 had to stop prednisone therapy during the 1-month challenge phase due to AE. Of 34 patients, 5 were unable to complete the full 22-week course of prednisone due to AE. The most common AE was hyperglycemia, which occurred in 17.6% of patients participating in Phase 2. Weight gain was also common, with a mean increase in body mass index of 1.6 kg/m(2) (95% confidence interval, 0.77-2.3) during the 22-week steroid course. Patients entering Phase 2 were followed for a mean of 66 weeks. No fractures or osteonecrosis were reported.Conclusion: Although high-dose corticosteroids are associated with known serious side effects, prospective data in the literature are limited. The present study suggests that with appropriate patient selection, monitoring, and patient education, high-dose corticosteroids are a safe and effective treatment of AIED.

OBJECTIVE:Intraosseous cavernous angioma (CA) of the petrous bone is rare and preoperative diagnosis can be challenging, especially when its epicenter is outside the internal auditory canal (IAC) or geniculate ganglion.METHODS:A 45-year-old man presented to our clinic with right-sided hearing loss, tinnitus, and unsteadiness. Neuroimaging revealed a right posterior petrous mass. Aggressive subtotal resection with decompression of the IAC was achieved through a right suboccipital craniotomy. Histopathological findings were consistent with CA.CONCLUSION:As was the case with this patient, we believe that CA should be included in the differential diagnosis of petrous region pathology with bony involvement. Surgery is warranted due to its expansive nature and to decompress the adjacent neural structures.

OBJECTIVE:: To describe nystagmus induced by cranial vibration in a case series of 8 patients with superior semicircular canal dehiscence. DESIGN:: Consecutive case series review. SETTING:: Tertiary vestibular center. PATIENTS:: Eight consecutive patients with computed tomographic confirmed superior semicircular canal dehiscence syndrome observed in the last 24 months. PROCEDURE:: Vertex, bilateral mastoid, and bilateral suboccipital cranial vibration were performed using 100 Hz. Vibration for 10 to 15 seconds on patients in the seated position during office evaluation for vestibular complaints. Nystagmus was monitored by infrared video oculography with digital recording. RESULTS:: All patients demonstrated distinct torsional/vertical vibration-induced nystagmus. Maximal recorded slow-phase velocity was 20 degrees/s. This was observed best with suboccipital vibration on the side of the dehiscence. CONCLUSION:: Vibration-induced torsional/vertical nystagmus, observed best with ipsilateral suboccipital cranial vibration in the seated position, seems to be a sensitive screening test in the office setting for the presence of superior semicircular canal dehiscence.

Autoimmune sensorineural hearing loss (ASNHL) is the most common cause of sudden hearing loss in adults. Although autoimmune etiopathogenic events have long been suspected in ASNHL, inner ear-specific Ags capable of targeting T cell autoreactivity have not been identified in ASNHL. In this study, we show by ELISPOT analysis that compared with normal hearing age- and sex-matched control subjects, ASNHL patients have significantly higher frequencies of circulating T cells producing either IFN-gamma (p = 0.0001) or IL-5 (p = 0.03) in response to recombinant human cochlin, the most abundant inner ear protein. In some patients, cochlin responsiveness involved both CD4(+) and CD8(+) T cells whereas other patients showed cochlin responsiveness confined to CD8(+) T cells. ASNHL patients also showed significantly elevated cochlin-specific serum Ab titers compared with both normal hearing age- and sex-matched control subjects and patients with noise- and/or age-related hearing loss (p < 0.05 at all dilutions tested through 1/2048). Our study is the first to show T cell responsiveness to an inner ear-specific protein in ASNHL patients, and implicates cochlin as a prominent target Ag for mediating autoimmune inner ear inflammation and hearing loss.

OBJECTIVE:We analyzed pure-tone and speech audiometric results from a prospective trial of anti-inflammatory treatment of subjects with active autoimmune inner ear disease (AIED). We sought to characterize the pattern and size of the treatment effect as reflected in clinical audiometry and to identify audiometric predictors of response to steroid treatment of AIED.SUBJECTS:Adult participants demonstrated clinically established criteria for AIED (n = 116). Eligibility required audiometric evidence of active AIED as indicated by idiopathic sensorineural hearing loss with threshold elevations within 3 months of enrollment.METHODS:We evaluated audiometric changes after 4 weeks of treatment with pharmacologic doses (60 mg/day) of prednisone. We examined the relationship between audiometric pure-tone thresholds at baseline and changes in word intelligibility score (WIS) using parametric and nonparametric analyses. Magnitudes of change were assessed using independent or paired t-tests. Separate analyses were performed on subgroups that did or did not show improved WIS score with steroid treatment.RESULTS:Overall mean pure-tone averages improved from baseline to closeout of prednisone treatment in better hearing ears from 52.4 to 48.3 dB (p < .0001). Mean WIS improved in the better ear from 71.4% to 78.1% (p < .0001). Of pure-tone measures, only the six-tone average showed significant correlation with both the absolute improvements in WIS and with the percentage change in WIS after treatment. Individual frequencies at baseline showed no significant relationship with changes in WIS score after treatment. In 69 (59.5%) of 116 subjects, WIS improved (range, 2-80%) in the better ear. In these subjects, the baseline pure-tone thresholds and pure-tone averages correlated significantly and positively with improvement in WIS.CONCLUSIONS:Steroid treatment in AIED-mediated hearing loss produce variable but significant hearing gains. Neither a focal, cochleotopic region of greatest vulnerability to AIED nor frequency-specific amenability to treatment were evident. We did observe that analysis of predictors and the degree of treatment effect vary with different approaches to measuring change in the WIS. Depending on the approach adopted, the size of the treatment effect may be greatest across intermediate hearing levels at baseline. These observations offer an audiometric database that may enable greater precision in judging clinically meaningful parameters for future studies of AIED treatment and other interventions for sensorineural hearing loss.

Problem: We have shown that SWXJ mice develop hearing loss when immunized with the p131–150 peptide of Coch-5B2 or following transfer of activated T cells specific for the Coch 131–150 peptide. Further studies to establish associated histopathology in the cochleas of these mice were pursued in this paper.

Objective: To review published literature regarding the use of intratympanic steroids in the treatment of Ménière's disease and sudden sensorineural hearing loss and to make recommendations regarding their use based on the literature review. Data Sources: Literature review from 1996 to 2003, PubMed, Medline Plus, and Web of Science. Study Selection: Retrospective case series and uncontrolled prospective cohort studies were the only types of studies available for review. Conclusion: On the basis of the available literature, a weak recommendation is made to use intratympanic steroid treatment of sudden hearing loss if oral steroid therapy fails or is con-traindicated. The available studies regarding intratympanic steroid treatment of Ménière's disease and tinnitus are inadequate to answer the question of the efficacy of this treatment for these conditions. Higher quality studies are needed.

Autoimmune sensorineural. hearing loss (ASNHL) is characterized typically by bilateral, rapidly progressive hearing loss that responds therapeutically to corticosteroid treatment. Despite its name, data implicating autoimmunity in the etiopathogenesis of ASNHL have been limited, and targeted self-antigens have not been identified. In the current study we show that the inner ear-specific proteins cochlin and beta-tectorin are capable of targeting experimental autoimmune hearing loss (EAHL) in mice. Five weeks after immunization of SWXJ mice with either Coch 131-150 or beta-tectorin 71-90, auditory brainstem responses (ABR) showed significant hearing loss at all frequencies tested. Flow cytometry analysis showed that each peptide selectively activated CD4(+) T cells with a proinflammatory Th1-like phenotype. T cell mediation of EAHL was determined by showing significantly increased ABR thresholds 6 weeks after adoptive transfer of peptide-activated CD4(+) T cells into naive SWXJ recipients. Immunocytochemical analysis showed that leukocytic infiltration of inner ear tissues coincided with onset of hearing loss. Our study provides a contemporary mouse model for clarifying our understanding of ASNHL and facilitating the development of novel effective treatments for this clinical entity. Moreover, our data provide experimental confirmation that ASNHL may be a T cell-mediated organ-specific autoimmune disorder of the inner ear.

Rationale Autoimmune sensorineural hearing loss (ASNHL) is diagnosed by excluding ototoxicity, systemic immunologic disease, infections or tumors, and by a therapeutic response to corticosteroids. The relative prominence of B or T cells in ASNHL remains controversial. Methods We tested our hypothesis that Th1-like effector T cells have a pivotal role in ASNHL in an inner ear-specific mouse model system. We searched for immunogenic peptides within inner ear proteins using our binding motif for IA s and IA q MHC class II molecules. ELISA was used to characterize the T cell cytokine profile. Disease induction was achieved by active immunization with the peptide and adoptive transfer of peptide-activated T cells. Results β-Tectorin 71-90 and Coch protein 131-150 induced a Th1-like effector immune responses in primed mice. Mice immunized with either β-tectorin 71-90 or Coch protein 131-150 showed increased hearing thresholds when compared to non-treated age- and sex- matched controls (p=0.010 and 0.024) and ovalbumin treated controls (p=0.012 and 0.017). Furthermore, increased hearing thresholds were observed in SWXJ mice after adoptive transfer of β-tectorin 71-90 or Coch protein 131-150 activated T cells (p=0.002 and 0.018). Conclusion β-Tectorin 71-90 and Coch protein 131-150 peptides induce Th1-like effector T cell immune responses in SWXJ mice. Active and passive immunization with these peptides induce hearing loss, which leads to the establishment of an inner ear-specific mouse model for ASNHL. These data show that Th1-like effector T cells may have a pivotal role in the etiopathogenesis of ASNHL.

Contexte Un certain nombre de traitements ont été proposés dans la prise en charge au long cours des pertes auditives bilatérales neuro-sensorielles, rapidement progressives, répondant à la corticothérapie (atteinte auto-immune de l'oreille interne [AIED]). Le méthotrexate émerge comme le traitement de choix, mais il n'a pas été évalué rigoureusement chez les patients atteintes de AIED.

CONTEXTA number of therapies have been proposed for the long-term management of corticosteroid-responsive, rapidly progressive, bilateral sensorineural hearing loss (autoimmune inner ear disease [AIED]). Methotrexate has emerged as the benchmark agent but has not been rigorously evaluated for hearing improvement in patients with AIED.OBJECTIVETo assess the efficacy of long-term methotrexate in maintaining hearing improvements achieved with glucocorticoid (prednisone) therapy in patients with AIED.DESIGN, SETTING, AND PARTICIPANTSA randomized, double-blind, placebo-controlled trial conducted from February 3, 1998, to November 5, 2001, of 67 patients with rapidly progressive, bilateral sensorineural hearing loss at 10 tertiary care centers in the United States.INTERVENTIONRandomization to either oral methotrexate (15 to 20 mg/wk; n = 33) or placebo (n = 34), in combination with an 18-week prednisone taper. Follow-up examinations, including audiometric evaluation, were performed at 4, 8, 12, 24, 36, 48, and 52 weeks, or until hearing loss was documented.MAIN OUTCOME MEASUREMaintenance of hearing improvement achieved from prednisone treatment.RESULTSSixty-seven patients (57.8%) enrolled in the prednisone challenge experienced hearing improvement. Twenty-five patients (37%) experienced hearing improvements in both ears. Of the individuals who reached study end points, 24 (80%) of 30 end points were because of measured hearing loss in the methotrexate group and 29 (93.5%) of 31 end points were because of measured hearing loss in the placebo group (P =.15). Methotrexate was no more effective than placebo in maintaining the hearing improvement achieved with prednisone treatment (hazard ratio, 1.31; 95% confidence interval, 0.79-2.17; P =.30).CONCLUSIONMethotrexate does not appear to be effective in maintaining the hearing improvement achieved with prednisone therapy in patients with AIED.

Otolaryngology–Head and Neck SurgeryVolume 129, Issue 2 p. P156-P157 Research Posters R015: Induction of Autoimmune Hearing Loss in SWXJ Mice by Th1-like Effector T Cells Clementino Arturo Solares presenter MD, Clementino Arturo Solares presenter MD Cleveland, OHSearch for more papers by this authorAndrea E Edling PhD, Andrea E Edling PhD Cleveland, OHSearch for more papers by this authorKeiko Hirose MD, Keiko Hirose MD Shaker Heights, OHSearch for more papers by this authorGordon B Hughes MD, Gordon B Hughes MD Cleveland, OHSearch for more papers by this authorVincent Kuohy PhD, Vincent Kuohy PhD Cleveland, OHSearch for more papers by this author Clementino Arturo Solares presenter MD, Clementino Arturo Solares presenter MD Cleveland, OHSearch for more papers by this authorAndrea E Edling PhD, Andrea E Edling PhD Cleveland, OHSearch for more papers by this authorKeiko Hirose MD, Keiko Hirose MD Shaker Heights, OHSearch for more papers by this authorGordon B Hughes MD, Gordon B Hughes MD Cleveland, OHSearch for more papers by this authorVincent Kuohy PhD, Vincent Kuohy PhD Cleveland, OHSearch for more papers by this author First published: 17 May 2016 https://doi.org/10.1016/S0194-59980300759-9Read the full textAboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume129, Issue2August 2003Pages P156-P157 RelatedInformation

Autoimmune sensorineural hearing loss (ASNHL) typically produces a bilateral rapidly progressive loss of hearing that may occur suddenly. The diagnosis is made by excluding ototoxicity, systemic disease, and other factors that mimic ASNHL and by showing a therapeutic response to corticosteroid treatment. Although autoantibodies and autoreactive T cells have been implicated in the etiopathogenesis of ASNHL, several central issues remain unresolved, including the relative prominence of B cell or T cell autoimmunity in the initiation and progression of ASNHL, the identity of the putative inner ear self-antigen(s) that target ASNHL, and the development and application of immunosuppressive therapies for preventing the progressive hearing loss which may be profound and require cochlear implantation. In this review, we will examine the seminal human and animal studies that have led to our current views regarding the autoimmune etiopathogenesis of ASNHL. In addition, we will address the need for developing an inner ear-specific mouse model for ASNHL that may define the stages leading to the development of ASNHL and may also provide new diagnostic markers and help develop novel and effective treatments for preventing progressive hearing loss in ASNHL.

Autoimmune sensorineural hearing loss (ASNHL) typically produces bilateral rapidly progressive loss of hearing over a few days or weeks, but may also produce sudden loss over a few hours. The diagnosis is made by excluding ototoxicity, systemic disease, and other factors that mimic ASNHL and by showing a therapeutic response to corticosteroid treatment. Antibody production and T-cell proliferative responses to inner ear antigens have been implicated in the etiopathogenesis of ASNHL. In the current study, we have extended these autoimmune investigations by determining the frequencies of inner ear specific IFN-gamma producing T cells in peripheral blood mononuclear cells (PBMC) from ASNHL patients and from age- and sex-matched control subjects. ELISPOT analysis showed that 25% of ASNHL patients have significant increased frequencies of inner ear specific IFN-gamma producing T cells in their PBMC. All control subjects were relatively unresponsive. Our results implicate inner ear specific IFN-gamma producing proinflammatory T cells in the pathogenesis of ASNHL.

Educational objectives: To better understand the various etiologies and pathophysical mechanisms of pulsatile tinnitus and to perform a thorough and cost‐effective workup and effectively treat most of these patients.

Educational objectives: To diagnose and treat immune inner ear disease.