Differential effects of AAV.BDNF and AAV.Ntf3 in the deafened adult guinea pig ear.

Cochlear hair cell loss results in secondary regression of peripheral auditory fibers (PAFs) and loss of spiral ganglion neurons (SGNs). The performance of cochlear implants (CI) in rehabilitating hearing depends on survival of SGNs. Here we compare the effects of adeno-associated virus vectors with neurotrophin gene inserts, AAV.BDNF and AAV.Ntf3, on guinea pig ears deafened systemically (kanamycin and furosemide) or locally (neomycin). AAV.BDNF or AAV.Ntf3 was delivered to the guinea pig cochlea one week following deafening and ears were assessed morphologically 3 months later. At that time, neurotrophins levels were not significantly elevated in the cochlear fluids, even though in vitro and shorter term in vivo experiments demonstrate robust elevation of neurotrophins with these viral vectors. Nevertheless, animals receiving these vectors exhibited considerable re-growth of PAFs in the basilar membrane area. In systemically deafened animals there was a negative correlation between the presence of differentiated supporting cells and PAFs, suggesting that supporting cells influence the outcome of neurotrophin over-expression aimed at enhancing the cochlear neural substrate. Counts of SGN in Rosenthal's canal indicate that BDNF was more effective than NT-3 in preserving SGNs. The results demonstrate that a transient elevation in neurotrophin levels can sustain the cochlear neural substrate in the long term.

Importance of cochlear health for implant function.

Amazing progress has been made in providing useful hearing to hearing-impaired individuals using cochlear implants, but challenges remain. One such challenge is understanding the effects of partial degeneration of the auditory nerve, the target of cochlear implant stimulation. Here we review studies from our human and animal laboratories aimed at characterizing the health of the implanted cochlea and the auditory nerve. We use the data on cochlear and neural health to guide rehabilitation strategies. The data also motivate the development of tissue-engineering procedures to preserve or build a healthy cochlea and improve performance obtained by cochlear implant recipients or eventually replace the need for a cochlear implant. This article is part of a Special Issue entitled .

Speech and language outcomes of cochlear implantation in children with isolated auditory neuropathy versus cochlear hearing loss.

OBJECTIVE: Children with auditory neuropathy (AN) have variable hearing on pure tone testing, and the presence of speech and language delays often play a major role in the decision to offer cochlear implantation (CI) in this population. Despite this fact, the speech and language outcomes in this group after CI are not well described. This study compares speech and language outcomes after CI in a subset of the pediatric AN population that does not have a confounding cognitive disorder with those of their peers with cochlear hearing loss (CoHL). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Seventeen pediatric patients with AN who received a CI and a group of children with CoHL who received a CI were the subjects of this study. The 2 groups demonstrated similar ages at implant. Children with cognitive delays were excluded from each group. INTERVENTION: Cochlear implantation. MAIN OUTCOME MEASURES: All subjects were evaluated preoperatively and postoperatively with standardized age appropriate speech and language measures, including the Expressive Vocabulary Test (EVT), Peabody Picture Vocabulary Test (PPVT), and Preschool Language Scale (PLS). RESULTS: There was no significant difference between the groups on age of activation of the CI. Children with a diagnosis of AN had a significantly lower unaided pure tone average preoperatively as compared with children with cochlear hearing loss; however, there was no significant difference between the groups on either their preimplantation or postimplantation speech and language scores. CONCLUSION: Children with a diagnosis of AN without associated cognitive or developmental disorders have speech and language outcomes comparable to other children who received a CI.

Outcomes of cochlear implantation in children with isolated auditory neuropathy versus cochlear hearing loss.

OBJECTIVE: Auditory neuropathy (AN) is a heterogeneous clinical entity for which the optimal method of auditory rehabilitation has been a matter of some debate. Such patients often do not receive sufficient benefit from hearing aids. Previous studies have shown that select AN patients may benefit from cochlear implantation (CI), but reported outcomes are variable and likely are a reflection of the heterogeneous patient population included under the umbrella diagnosis of AN. This study compares CI outcomes in a subset of the pediatric AN population who do not have a confounding cognitive disorder with their cochlear hearing loss peers. Additionally, it examines the impact of a confounding cognitive or developmental disorder on CI outcomes within the AN population. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Twenty-six pediatric patients with AN who received a CI were the subjects of this study. Seventeen of these children had a diagnosis of AN alone, and their CI outcomes were compared with those of a similar group of children with cochlear hearing loss. The remaining 9 children had a diagnosis of AN in association with a confounding cognitive or developmental disorder, and their CI outcomes were compared with those of children with isolated AN. INTERVENTION: Cochlear implantation. MAIN OUTCOME MEASURES: All subjects were evaluated preoperatively and postoperatively with age-appropriate speech perception testing. RESULTS: Children with a diagnosis of AN alone performed comparably to their peers with cochlear hearing loss. The presence of a confounding cognitive or developmental disorder within the AN population was correlated with significantly poorer CI outcomes as compared with those of children with isolated AN. CONCLUSION: Children with a diagnosis of AN without associated cognitive or developmental disorders perform at a level comparable to other children requiring a CI. Children with a diagnosis of AN associated with other developmental anomalies derive some benefit from CI but are significantly more likely to continue to rely on nonoral/aural methods of communication after implantation.

The use of neurotrophin therapy in the inner ear to augment cochlear implantation outcomes.

Severe to profound deafness is most often secondary to a loss of or injury to cochlear mechanosensory cells, and there is often an associated loss of the peripheral auditory neural structures, specifically the spiral ganglion neurons and peripheral auditory fibers. Cochlear implantation is currently our best hearing rehabilitation strategy for severe to profound deafness. These implants work by directly electrically stimulating the remnant auditory neural structures within the deafened cochlea. When administered to the deafened cochlea in animal models, neurotrophins, specifically brain derived neurotrophic factor and neurotrophin-3, have been shown to dramatically improve spiral ganglion neuron survival and stimulate peripheral auditory fiber regrowth. In animal models, neurotrophins administered in combination with cochlear implantation has resulted in significant improvements in the electrophysiological and psychophysical measures of outcome. While further research must be done before these therapies can be applied clinically, neurotrophin therapies for the inner ear show great promise in enhancing CI outcomes and the treatment of hearing loss.

Nerve maintenance and regeneration in the damaged cochlea.

Following the onset of sensorineural hearing loss, degeneration of mechanosensitive hair cells and spiral ganglion cells (SGCs) in humans and animals occurs to variable degrees, with a trend for greater neural degeneration with greater duration of deafness. Emergence of the cochlear implant prosthesis has provided much needed aid to many hearing impaired patients and has become a well-recognized therapy worldwide. However, ongoing peripheral nerve fiber regression and subsequent degeneration of SGC bodies can reduce the neural targets of cochlear implant stimulation and diminish its function. There is increasing interest in bio-engineering approaches that aim to enhance cochlear implant efficacy by preventing SGC body degeneration and/or regenerating peripheral nerve fibers into the deaf sensory epithelium. We review the advancements in maintaining and regenerating nerves in damaged animal cochleae, with an emphasis on the therapeutic capacity of neurotrophic factors delivered to the inner ear after an insult. Additionally, we summarize the histological process of neuronal degeneration in the inner ear and describe different animal models that have been employed to study this mechanism. Research on enhancing the biological infrastructure of the deafened cochlea in order to improve cochlear implant efficacy is of immediate clinical importance.

The effects of cochlear implantation on speech perception in older adults.

OBJECTIVES: To determine whether significant differences in cochlear implant (CI) performance exist between older and younger CI recipients. DESIGN: Retrospective comparison of audiometric data. SETTING: University hospital center. PARTICIPANTS: Sixty participants who received CIs at age 70 and older and 48 younger adults implanted between age 18 and 69. MEASUREMENTS: Speech outcome scores (Consonant-Nucleus-Consonant words and phonemes and City University of New York Sentence test in quiet and noise). RESULTS: Older participants show significant improvement in speech perception scores after implantation. Although on average they do not perform as well as younger adults, this difference correlates with duration of deafness rather than age. In contrast to younger adults, significant differences in CI performance are seen in older recipients depending on the side of implantation, with those implanted on the right performing better than those implanted on the left. CONCLUSION: Postlingually deafened older adults obtained significant speech perception benefits from CIs, although differences in speech outcomes were seen between younger recipients and those implanted after age 70. In older adults considering CIs, hearing benefits appear greater if they are implanted in the right ear.

Actinomycosis of the temporal bone and brain: case report and review of the literature.

OBJECTIVES: Actinomycosis is a rare disease with a typically indolent course in the head and neck. During the modern era, only 12 cases within the ear and temporal bone and 75 intracranial cases have been reported. We present a case of actinomycosis of the petrous apex that led to meningitis and encephalitis. METHODS: The patient was a 12-year-old girl who presented with mental status changes. After 48 hours of treatment with empiric antibiotics for meningitis without improvement, imaging revealed an enhancing mass in the right petrous apex, destruction of the cochlea, meningeal enhancement, and left temporoparietal encephalitis. RESULTS: The initial therapy included broad-spectrum antibiotic, antifungal, and antiviral agents, as well as myringotomy and tympanostomy tube placement. When the patient's clinical status worsened, she underwent subtotal petrosectomy with drainage of the petrous apex. The final pathologic findings were consistent with actinomycosis. CONCLUSIONS: Actinomycosis is a rare infection in the temporal bone and central nervous system that can have a high mortality risk if not treated appropriately. Often, these bacteria do not grow well in culture, and diagnosis must be made on the basis of histopathologic features. Good clinical outcomes can be obtained with surgical debridement followed by long-term antibiotic treatment.

Effect of cochlear implant technology in sequentially bilaterally implanted adults.

OBJECTIVE: Bilateral sequential cochlear implantation outcomes are dependent on many different factors. Newer technology in the second implanted ear may also contribute to outcome. This study examines the effect of cochlear implant technology on speech recognition outcomes in a population of adult patients who have undergone bilateral sequential implantation using different technologies in each ear. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Twenty adults who underwent bilateral sequential cochlear implantation with different technologies and processing strategies in each ear were patients for this study. Control Group A included patients (n = 8) who were simultaneously implanted, and Control Group B (n = 3) were patients who were sequentially implanted with the same technology. INTERVENTION: Bilateral sequential cochlear implantation. OUTCOME MEASURES: The outcome measure was the Consonant-Nucleus-Consonant monosyllabic word test administered in each implanted ear and in the binaural condition before and 1 year after operation. A multivariate analysis was performed to account for factors including duration of deafness, length of device usage, and severity of deafness. RESULTS: There was significant improvement from before to 1 year after the operation in word scores for the individual ears and in the binaural condition for all groups. All patients were consistent users of both devices, and the use of different technology in the second implanted ear did not affect the patients' ability to benefit from bilateral implantation despite the use of different devices and processing strategies. CONCLUSION: Bilateral sequential implantation with newer and/or differing technology in the second implanted ear did not reduce the benefits of bilateral stimulation and should not be considered a deterrent to second-sided implantation.

Revision cochlear implantation.

PURPOSE OF REVIEW: Cochlear implantation is a well tolerated and effective procedure in the rehabilitation of profoundly and severely hearing-impaired individuals. Cochlear reimplantation may be necessary for a variety of reasons. The recent literature regarding the indications, surgical considerations, and outcomes in revision cochlear implant (RCI) surgery is reviewed here. RECENT FINDINGS: A small but significant percentage (3-8%) of all cochlear implant procedures requires RCI surgery. The most common indication for RCI is hard failure (40-80%), but other common indications include soft failures, wound complications, infection, improper initial placement, and electrode extrusions. There is a high rate of surgical success in RCI with preservation or improvement of preoperative performance in the majority of patients, in addition to the alleviation of prereimplantation symptoms. Both children and adults benefit from RCI when indicated and experience similar auditory successes following RCI. SUMMARY: The need for RCI is uncommon, but the potential for restoration or improvement in speech perception and alleviation of symptoms exists. Regardless of indication, RCI surgery is well tolerated, and, with thoughtful preparation, individualized patient counseling, and proper surgical technique, most patients can expect successful outcomes.

Predictability of cochlear implant outcome in families.

OBJECTIVES: The purpose of this study is to determine if the performance of the first implanted member of a family predicts the performance of subsequently implanted family members. STUDY DESIGN: Retrospective chart review. METHODS: Seventy-one cochlear implant recipients, each belonging to a family with two or more implanted members, were the subjects of this study. Routine audiometric measurements and age-appropriate speech perception tests were performed pre- and postoperatively. In addition, length of deafness, age at implantation, etiology, and length of device usage were correlated to outcome. RESULTS: All implant recipients within a family showed improvement postimplantation, and the predictive component between family members was strong. Presence of GJB2 mutations and greater age at implantation were predictive of poorer rehabilitative outcome, while length of device usage was associated with improved speech perception scores. CONCLUSIONS: On average, if the first implanted family member performs well with a cochlear implant, those following will do well; however, GJB2-related deafness and increased age at implantation are associated with poorer outcome. These findings have important implications for members of families considering cochlear implantation.

Hairy polyp of the pharynx obscured on physical examination by endotracheal tube, but diagnosed on brain imaging.

We report a case of hairy polyp of the pharynx diagnosed on brain MRI in order to stress the need to examine carefully all tissues included on an imaging study, even those outside the clinically stated region of interest, and to remind practitioners to consider unusual as well as common etiologies for neonatal respiratory distress. Our case is unique in that thorough examination of a brain MRI, ordered in the evaluation of presumed central apnea, led to the correct diagnosis.