Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c.

Because there are currently no biological treatments for hearing loss, we sought to advance gene therapy approaches to treat genetic deafness. We focused on Usher syndrome, a devastating genetic disorder that causes blindness, balance disorders and profound deafness, and studied a knock-in mouse model, Ush1c c.216G>A, for Usher syndrome type IC (USH1C). As restoration of complex auditory and balance function is likely to require gene delivery systems that target auditory and vestibular sensory cells with high efficiency, we delivered wild-type Ush1c into the inner ear of Ush1c c.216G>A mice using a synthetic adeno-associated viral vector, Anc80L65, shown to transduce 80-90% of sensory hair cells. We demonstrate recovery of gene and protein expression, restoration of sensory cell function, rescue of complex auditory function and recovery of hearing and balance behavior to near wild-type levels. The data represent unprecedented recovery of inner ear function and suggest that biological therapies to treat deafness may be suitable for translation to humans with genetic inner ear disorders.

Surgical techniques and outcomes of cochlear implantation in patients with radiographic findings consistent with X-linked deafness.

OBJECTIVES: X-linked deafness is a potential etiology of sensorineural hearing loss characterized by bulbous dilatation of the fundus of the internal auditory canal (IAC) and the absence of the bony plates separating the basal turn of the cochlea and IAC. These malformations predispose patients to IAC insertion during cochlear implantation (CI). Our objective is to describe the surgical technique, audiometric and speech performance outcomes in a group of patients with this unique cochlear malformation. METHODS: A retrospective chart review was performed of all patients at a tertiary care facility who underwent CI between January 2006 and July 2011. RESULTS: A total of five patients were identified with radiographic findings characteristic of X-linked deafness, specifically a deficient modiolous, absent lamina cribrosa and bulbous IAC. A modified cochleostomy was utilized to ensure electrode insertion within the scala tympani avoiding the IAC. In each case, fluoroscopy was utilized to visual electrode progression during insertion and complete insertion was accomplished. All patients demonstrated improved speech performance following implantation. CONCLUSIONS: Utilizing the techniques described, patients with these unique radiographic findings consistent with X-linked deafness may successfully undergo CI with excellent potential for auditory rehabilitation.

Reduced Cochlear Implant Performance After the Use of Growth Hormone With Regain of Function After Cessation of Growth Hormone Therapy.

OBJECTIVE: To assess whether recombinant growth factor (hGH) therapy has an effect on cochlear implant (CI) performance. PATIENTS: Two pediatric CI recipients (S1, S2) who underwent treatment with hGH for short stature were identified for review. S1 has bilateral labyrinthine dysplasia and received implants at ages 10 months (right) and 4 years 3 months (left). S2 was diagnosed with severe to progressive sensorineural hearing loss bilaterally and received a CI at age 9 years 10 months (left). INTERVENTION(S): Case series. MAIN OUTCOME MEASURE(S): Cochlear implant, hGH, and speech perception data were collected. Phonetically Balanced Kindergarten (PBK) and Consonant Nucleus Consonant (CNC) word recognition scores were reviewed to assess auditory perception. Electrode impedances, threshold levels, and comfort levels were also reviewed. RESULTS: After 4 months of hGH, word recognition scores for S1 were observed to decrease from 90 to 72% (right) and were stable at 40% (left). Despite troubleshooting, performance continued to decline bilaterally to 52% (right) and 28% (left), and the decision was made to discontinue hGH. One month after cessation of hGH, word recognition scores began improving to 74% (right) and 68% (left). Word recognition scores for S2 were observed to have decreased from 92% the previous year to 82% after taking hGH for 2 months. Given both our previous experience with S1 and discussions with S2's parents, hGH was discontinued after 10 months of therapy. Two months after cessation of hGH, S2's word recognition had improved to 86% (left). CONCLUSIONS: Our case studies illustrate that implanted children undergoing treatment with hGH may experience a decrease in speech perception, which recovers after the cessation of treatment. Since hGH use has become more prevalent in recent years, it is important to inquire whether children undergoing, or who have undergone, implantation are receiving hGH so that they may be appropriately monitored.

Clival fibrous dysplasia: Case series and review of the literature.

Slightly more than 30 cases of fibrous dysplasia involving the clivus have been reported in the international literature, primarily in the neurosurgery and radiology literature. In this article we present a series of 4 cases involving patients with clival fibrous dysplasia. In a retrospective chart review, 4 patients presenting to tertiary care centers from January 1, 2006, to January 31, 2008, were identified and their presenting symptoms and radiologic findings reviewed. Based on our literature review, we describe the presenting symptoms of patients with clival fibrous dysplasia and characterize the findings of imaging studies associated with this disorder. All patients in this series had a presenting complaint of headache or cranial nerve deficits, which is consistent with previous reports found in our literature review. Additional presenting symptoms that have been reported include dysphagia and a nontender occipital mass; there was also an incidental asymptomatic finding. Magnetic resonance imaging findings are consistent with those associated with fibrous dysplasia at other sites of the body. We conclude that clival involvement in monostotic fibrous dysplasia may not be as rare as previously perceived.

Otologic outcomes after blast injury: the Boston Marathon experience.

OBJECTIVE: Otologic trauma was the most common physical injury sustained after the April 15, 2013, Boston Marathon bombings. The goal of this study is to describe the resultant otologic morbidity and to report on early outcomes. STUDY DESIGN: Multi-institutional prospective cohort study. METHODS: Children and adults seen for otologic complaints related to the Boston Marathon bombings comprised the study population. Participants completed symptom assessments, quality-of-life questionnaires, and audiograms at initial and 6-month visits. Otologic evaluation and treatment, including tympanoplasty results, were reviewed. RESULTS: More than 100 patients from eight medical campuses have been evaluated for blast-related otologic injuries; 94 have enrolled. Only 7% had any otologic symptoms before the blasts. Ninety percent of hospitalized patients sustained tympanic membrane perforation. Proximity to blast (RR = 2.7, p < 0.01) and significant nonotologic injury (RR = 2.7, p < 0.01) were positive predictors of perforation. Spontaneous healing occurred in 38% of patients, and tympanoplasty success was 86%. After oral steroid therapy in eight patients, improvement in hearing at 2 and 4 kHz was seen, although changes did not reach statistical significance. Hearing loss, tinnitus, hyperacusis, and difficulty hearing in noise remain persistent and, in some cases, progressive complaints for patients. Otologic-specific quality of life was impaired in this population. CONCLUSION: Blast-related otologic injuries constitute a major source of ongoing morbidity after the Boston Marathon bombings. Continued follow-up and care of this patient population are warranted.

Revision cochlear implantation following internal auditory canal insertion.

OBJECTIVES/HYPOTHESIS: In pediatric patients with congenital malformations of the inner ear, anomalies within the anatomy may facilitate unintentional insertion of the cochlear implant electrode into the internal auditory canal. Revision procedures for removal and replacement of cochlear implant electrodes following internal auditory canal insertion are fraught with potential danger, including the theoretical risk of injury to vasculature within the internal auditory canal, repeat insertion within the internal auditory canal, and cerebrospinal fluid leak. The objective of this presentation is to describe a technique for revision cochlear implantation following internal auditory canal insertion to minimize the potential associated risks. STUDY DESIGN: Case series. METHODS: A retrospective chart review was performed on all patients at a tertiary care facility who underwent revision cochlear implantation for internal auditory canal insertion between January 1999 and July 2011. RESULTS: A total of four patients referred from outside institutions have undergone revision cochlear implantation for internal auditory canal insertion. The records from these patients were reviewed. Electrodes were safely removed in all cases without injury to the anterior inferior cerebellar artery or its branches (i.e., labyrinthine artery). Complete insertion was accomplished on reimplantation. Neural response telemetry was performed in all cases, and responses were noted. Fluoroscopy was utilized to visualize electrode progression during insertion. A detailed description of the operative technique is provided. CONCLUSIONS: This case series describes a technique for revision cochlear implantation that appears to be safe and effective in preventing potential associated complications.

Paraganglioma presenting as cholesterol granuloma of the petrous apex.

We report the unique finding of a petrous apex cholesterol granuloma associated with a paraganglioma, also known as a glomus jugulare tumor, in a 52-year-old woman who presented to our department with pulsatile tinnitus, hearing loss, aural fullness, and disequilibrium. She had been treated for a petrous apex cholesterol granuloma 20 years earlier, at which time she had undergone drainage of the granuloma via subtotal petrous apicectomy. When she came to our facility approximately 20 years later, she had signs and symptoms consistent with a jugular paraganglioma, which was likely to have been present at the time of her initial presentation for the cholesterol granuloma. In fact, microscopic bleeding from the paraganglioma might have led to the formation of the cholesterol granuloma. The metachronous presentation of these two entities, which to our knowledge has not been reported previously in the literature, indicates the potential association of paragangliomas with the formation of cholesterol granulomas of the petrous apex.

The effects of residual hearing in traditional cochlear implant candidates after implantation with a conventional electrode.

OBJECTIVE: To analyze the effects of residual hearing on postoperative speech performance in traditional cochlear implant (CI) patients implanted with a conventional electrode. STUDY DESIGN: Retrospective review. SETTING: Academic tertiary referral center. PATIENTS: A total of 129 adults implanted by a single surgeon at a tertiary care facility between June 2005 and November 2010 with measurable preoperative pure tone thresholds at any frequency were included. INTERVENTION: Cochlear implantation with a conventional electrode via an anterior inferior cochleostomy. MAIN OUTCOME MEASURE: Speech perception using monosyllabic word scores in quiet and sentences in quiet and noise in the electric (CI-only) condition of the implanted ear. Preservation of hearing was defined as complete for postoperative thresholds within 10 dB of preimplant values and partial if greater than 11 dB. Pure tone audiometry and speech perception testing were performed preoperatively and at regular intervals postoperatively, with the 1-year evaluation being the final outcome period. RESULTS: Preservation at any frequency or level was not a factor in speech perception outcome, although preservation was more common in low frequencies. Hearing preservation was correlated with younger age at implantation, but was not related to length of hearing loss, cause of deafness, device type, sex, preoperative speech performance, or low-frequency pure-tone average. CONCLUSION: Hearing can be preserved in traditional CI patients implanted with a conventional electrode. Although preservation of hearing may have implications for future technology, it is not currently correlated with speech performance in the CI-only condition.

Management of surgical complications and failures in acoustic neuroma surgery.

Acoustic neuromas (ANs) are the most common tumors of the cerebellopontine angle. Although numerous advances have occurred in the operative management of AN and perioperative care leading to a significant decrease in associated morbidity and mortality, there are several characteristic complications that accompany microsurgical resection of AN. Understanding the types and rates of complications in association with the various approaches is essential in patient counseling, establishing patient expectations, and ensuring the best patient outcome. In this article, the justification for incomplete surgical resection is discussed. Also, the most common complications of AN microsurgery and the associated management are reviewed.

Pediatric cochlear implantation: candidacy evaluation, medical and surgical considerations, and expanding criteria.

Since the first cochlear implant approved by the US Food and Drug Administration in the early 1980s, great advances have occurred in cochlear implant technology. With these advances, patient selection, preoperative evaluation, and rehabilitation consideration continue to evolve. This article describes the current practice in pediatric candidacy evaluation, reviews the medical and surgical considerations in pediatric cochlear implantation, and explores the expanding criteria for cochlear implantation within the pediatric population.

Sudden sensorineural hearing loss: a review of diagnosis, treatment, and prognosis.

Sudden sensorineural hearing loss (SSNHL) is commonly encountered in audiologic and otolaryngologic practice. SSNHL is most commonly defined as sensorineural hearing loss of 30 dB or greater over at least three contiguous audiometric frequencies occurring within a 72-hr period. Although the differential for SSNHL is vast, for the majority of patients an etiologic factor is not identified. Treatment for SSNHL of known etiology is directed toward that agent, with poor hearing outcomes characteristic for discoverable etiologies that cause inner ear hair cell loss. Steroid therapy is the current mainstay of treatment of idiopathic SSNHL in the United States. The prognosis for hearing recovery for idiopathic SSNHL is dependent on a number of factors including the severity of hearing loss, age, presence of vertigo, and shape of the audiogram.

Severe nasal frostbite injury from nasal cannula supplemental oxygen malfunction.

We describe the presentation and management of a patient who presented to our institution with severe nasal frostbite from nasal cannula supplemental oxygen malfunction. This rare complication has not previously been reported in the English Literature. We describe the physical properties of compressed oxygen release that may contribute to these malfunctions and the role of the otolaryngologist in the management of the resulting injuries.

Asymmetric sudden sensorineural hearing loss: is all this testing necessary?

OBJECTIVE: A number of factors have been identified that contribute to the presentation of asymmetric sudden sensorineural hearing loss (ASSNHL). Routinely, patients presenting with ASSNHL undergo a battery of serologic testing and imaging in an attempt to determine a cause. The objective of this study was to assess the utility of this diagnostic evaluation in elucidating a cause of an ASSNHL and to assess the average cost associated with this battery of testing. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care facility. SUBJECTS AND METHODS: Charts from patients presenting to the otolaryngology clinic of a tertiary care facility between December 1, 2002, and November 30, 2007, with ASSNHL confirmed by audiometric evaluation were reviewed. Diagnostic tests included in the workup of ASSNHL and test results were recorded. The percentage of positive tests was determined and compared to national data. Cost analysis of the diagnostic battery was performed. RESULTS: The battery of testing performed for sudden sensorineural hearing loss included antineutrophil antibody, cholesterol, creatinine, anti-DNA antibody, erythrocyte sedimentation rate, blood glucose, Lyme titer, rheumatoid factor, rapid plasmin reagent, triiodothyronine, thyroid-stimulating hormone, and magnetic resonance imaging with gadolinium. The average cost associated with the full diagnostic evaluation is greater than $2000. The diagnostic impact of these tests is extremely low. CONCLUSIONS: The utility of the comprehensive ASSNHL evaluation should be reconsidered. The choice of diagnostic evaluation should be directed by patient risk factors and exposures.

A combination antioxidant therapy prevents age-related hearing loss in C57BL/6 mice.

OBJECTIVE: Age-related hearing loss (ARHL) is characterized by gradual, progressive sensorineural hearing loss, which impairs communication, lending to clinical depression and social withdrawal. There are currently no effective treatments for ARHL. The purpose of this study is to evaluate the potential of a combination antioxidant therapy in preventing ARHL. STUDY DESIGN: Randomized controlled trial. SETTING: Animal study. SUBJECTS AND METHODS: C57BL/6 mice, a recognized animal model of ARHL, were assigned to one of three groups: early treatment (n = 12), late treatment (n = 9), or control group (n = 9). Treatment groups of mice were fed with a combination agent comprising six antioxidant agents that target four sites within the oxidative pathway: L-cysteine-glutathione mixed disulfide, ribose-cysteine, NW-nitro-L-arginine methyl ester, vitamin B12, folate, and ascorbic acid. Auditory brainstem response (ABR) thresholds were recorded at baseline and every three months following initiation of treatment. RESULTS: Threshold shifts from baseline were decreased in the treatment groups when compared to the control group at all tested frequencies (P < 0.001). The ABR threshold shift at 12 months of age for the control group was 34.7 dB with a 95% confidence interval (CI) of +/-1.6. The mean threshold shifts for the early and late treatment groups were 7.5 dB (+/-0.87, 95% CI) and 9.2 dB (+/-1.6, 95% CI). CONCLUSION: Combination antioxidant therapy effectively decreased threshold shifts on ABR within an animal model of ARHL. Combination antioxidant therapy, with further research and investigation, may provide a safe and cost-effective method of preventing presbycusis in the growing elderly population.