Angela G. Shoup

Etanercept Treatment for Autoimmune Inner Ear Disease: Results of a Pilot Placebo-controlled Study

Purpose: Autoimmune Inner Ear Disease (AIED) is an idiopathic progressive, often bilateral, sensironeural hearing loss that occurs over weeks to months, generally resulting in significant auditory disability. Response to treatment with immunomodulators other than corticosteroids has been poor. Data from a guinea pig model of AIED and a recent open label trial of etanercept suggested potential treatment benefit. Based on these preliminary results, we conducted a pilot placebo controlled trial of etanercept in AIED patients. Methods: Twenty AIED patients were enrolled in a 12-week blinded placebo (PLA) controlled randomized clinical trial of etanercept (ETA) with 25 mg SC twice weekly. Patients received treatment for 8 weeks with a 4-week follow-up off-treatment. The primary study endpoint was an improvement in pure tone threshold (PTA) of 10Db in two consecutive frequencies and/or improvement in speech discrimination of >12% at week 8. Results: Patient demographics were similar for the ETA and PLA patients. Seventeen subjects (8 ETA, 9 PLA) completed the trial. The 3 dropouts were due to lack of efficacy. One ETA and 2 PLA subjects achieved the primary endpoint (p > 0.999). One ETA and 1 PLA pt demonstrated improved in hearing loss and vertigo severity by VAS and hearing disability. No safety issues were observed. Conclusion: The results of this pilot trial demonstrate that etanercept 25 mg twice weekly for 8 weeks was no better than placebo for treatment of AIED in this patient population.

Newborn Hearing Screening and Detection of Congenital Cytomegalovirus Infection

OBJECTIVES. The objectives were to determine the frequency of congenital cytomegalovirus infection among newborns who did not pass hearing screening tests or had confirmed hearing loss and to determine how often abnormal hearing screening results were the only manifestation of congenital cytomegalovirus infection. METHODS. Retrospective chart review was performed for newborns who had abnormal hearing screening results and positive urine cytomegalovirus culture results at Parkland Memorial Hospital between September 1, 1999, and August 31, 2004. RESULTS. During the 5-year study period, 572 of 79047 newborns (7 of 1000 live births) did not pass hearing screening tests. Cytomegalovirus infection was identified in 24 (5%) of 483 tested infants and 16 (6%) of the 256 infants with subsequently confirmed hearing impairment. Of those 16 infants, 12 (75%) were identified as having congenital cytomegalovirus infection only because of failure to pass newborn hearing screening tests. CONCLUSIONS. Congenital cytomegalovirus infection was present for 6% of newborns with confirmed hearing impairment, and the majority of those infants were identified on the basis of abnormal newborn hearing screening results.

Verification of Improved Patient Outcomes With a Partially Implantable Hearing Aid, The SOUNDTEC Direct Hearing System†

Introduction Partially implantable hearing devices have been developed to address some of the user‐perceived shortcomings of standard amplification systems. Partially implantable devices are purported to provide improved sound quality as a result of decreased occlusion, decreased feedback, and enhanced clarity resulting from increased high‐frequency gain. Such improvements may result in greater user satisfaction. To justify selection of a partially implantable device and undergoing a minor surgical procedure, verification techniques must be used to document user improvement or increased satisfaction over conventional amplification.

Vestibular Dysfunction in Gulf War Syndrome

METHODS: Vestibular complaints of Gulf War veterans were characterized by a nested case-control study of 23 veterans with 3 different Gulf War syndromes and 20 matched control subjects. All subjects completed a standardized symptom questionnaire and underwent standard audiovestibular tests administered by audiologists blinded to group identities. RESULTS: The prevalence of reported dizzy spells was higher in veterans with Gulf War syndromes 1 (100%), 2 (85%), and 3 (100%) than in controls (25%, P < 0.0001). Dizzy spells were more frequent, lasted longer, and involved a wider variety of accompanying symptoms in veterans with syndrome 2 than in those with syndromes 1 and 3. Audiovestibular testing showed greater interocular asymmetry of nystagmic velocity on sinusoidal harmonic acceleration in syndromes 1 (P = 0.015) and 2 (P = 0.002), greater asymmetry of saccadic velocity in syndrome 2 (P = 0.4), diminished nystagmic velocity after caloric stimulation bilaterally in syndrome 3 (P = 0.02 to 0.04), more subjects with pathologic nystagmus (P = 0.09), and greater interside asymmetry of wave I to III interpeak latency on auditory brain stem response in syndromes 1 (P = 0.005) and 2 (P = 0.07). Asymmetry of gain on sinusoidal harmonic acceleration and pathologic nystagmus were most strongly associated with symptoms of paroxysmal vertigo (P = 0.002 and 0.07, respectively); asymmetry of saccadic velocity, with the severity of vertigo (P = 0.004); and abnormal caloric response, with chronic dysequilibrium (P = 0.006). CONCLUSIONS: The findings are compatible with a subtle neurologic injury from organophosphate-induced delayed neurotoxicity.

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.

A targeted approach for congenital cytomegalovirus screening within newborn hearing screening

BACKGROUND AND OBJECTIVE: Congenital cytomegalovirus (cCMV) infection remains a leading cause of childhood hearing loss. Currently universal CMV screening at birth does not exist in the United States. An alternative approach could be testing infants who do not pass their newborn hearing screening (NHS) for cCMV. This study was undertaken to evaluate whether a targeted approach will identify infants with CMV-related sensorineural hearing loss (SNHL). METHODS: Infants born at 7 US medical centers received NHS and were also screened for cCMV while in the newborn nursery. Infants who tested positive for CMV received further diagnostic audiologic evaluations to identify or confirm hearing loss. RESULTS: Between 2007 and 2012, 99 945 newborns were screened for both hearing impairment and cCMV. Overall, 7.0% of CMV-positive infants did not pass NHS compared with 0.9% of CMV-negative infants (P < .0001). Among the cCMV infants who failed NHS, diagnostic testing confirmed that 65% had SNHL. In addition, 3.6% of CMV-infected infants who passed their NHS had SNHL confirmed by further evaluation during early infancy. NHS in this cohort identified 57% of all CMV-related SNHL that occurred in the neonatal period. CONCLUSIONS: A targeted CMV approach that tests newborns who fail their NHS identified the majority of infants with CMV-related SNHL at birth. However, 43% of the infants with CMV-related SNHL in the neonatal period and cCMV infants who are at risk for late onset SNHL were not identified by NHS.

Electrocochleographic changes after intranasal allergen challenge: A possible diagnostic tool in patients with Meniere's disease

Numerous observers have suggested a relationship between allergy and Menieres disease, but objective proof has heretofore been limited. Using standard criteria, we studied a group of 7 patients with previously diagnosed Menieres disease in whom significant allergy to 1 or more inhalants had also been diagnosed. Patients underwent a baseline electrocochleographic study followed by intranasal challenge with a carefully quantified amount of the allergen to which they were most sensitive. This was followed by a second electrocochleogram. Four of the 7 patients demonstrated at least a 15% increase in the summating potential/action potential ratio in 1 ear, associated with the production of subjective inner ear symptoms. We present this protocol as a potentially useful tool to further study whether inhalant allergy may be a causative factor in patients with Menieres disease.

Hearing loss and vestibular dysfunction among children with cancer after receiving aminoglycosides

Children undergoing cancer therapy often receive aminoglycosides to treat febrile neutropenia or gram‐negative infections. The magnitude of the risk of developing aminoglycoside‐induced ototoxicity and the dose threshold at which that risk significantly increases are unknown.

Inhalant Allergy and Meniere's Disease: Use of Electrocochleography and Intranasal Allergen Challenge as Investigational Tools:

INTRODUCTION: In an earlier study, we demonstrated the feasibility of using electrocochleography (ECoG) to document changes in inner ear function objectively after intranasal challenge of patients with inhalant allergy (with no prior immunotherapy) and Menieres disease, using the antigen to which they were most sensitive. OBJECTIVE: We expand on this earlier study and continue to investigate the feasibility of this model in a subset of patients with inhalant allergy and Menieres disease after immunotherapy. STUDY DESIGN: Prospective study of 11 patients identified with both Menieres disease and inhalant allergy in the practices of 2 neurotologists at our institution. Patients underwent a baseline ECoG, followed by intranasal challenge with the allergen to which they were most sensitive. This was followed by a second ECoG. RESULTS: Six of 11 patients had at least 1 year of immunotherapy (group 1), and 5 of 11 had had 0 to 6 months of immunotherapy (group 2). Four of 6 group 1 patients had a >15% increase in SP/AP ratio after immunotherapy. In group 2, 2 patients increased the SP/AP in at least 1 ear. No patient with a normal ECoG experienced vestibular symptoms after allergen challenge, whereas 2 of group 1 and 2 of group 2 had vestibular symptoms with abnormal ECoGs. CONCLUSION: This protocol is a useful tool for investigating the relationship of inhalant allergy and Menieres disease, but needs a larger group of patients and further study to draw valid statistical conclusions.

Should infants who fail their newborn hearing screen undergo cytomegalovirus testing

BACKGROUND Congenital cytomegalovirus (cCMV) is the leading infectious cause of pediatric sensorineural hearing loss (SNHL) with significant public health costs on par with those from otitis media. Polymerase chain reaction (PCR)–based assays have been tested in a large number of children and have demonstrated high sensitivity and specificity. Despite these findings and recent studies showing efficacy, feasibility, and cost effectiveness, there is a paucity of evidence-based reviews evaluating the role of cytomegalovirus (CMV) testing, specifically for infants who fail their newborn hearing screening.