John A. Germiller

Etiology of unilateral neural hearing loss in children

OBJECTIVE Unilateral sensorineural hearing loss (SNHL) can be caused by a variety of lesions of the inner ear and central nervous system. An inner hair cell or neural site of pathology must be suspected when otoacoustic emissions (OAEs) are present, and inconsistent with audiologic data. We reviewed unilateral neural hearing loss (UNHL) in children, to better understand its etiology, clinical and audiologic features. DESIGN Retrospective series. SETTING Tertiary pediatric center. METHODS From a database of 480 children with unilateral SNHL, 148 had OAE data. Patients with a neural pattern (present OAEs in the affected ear) were reviewed. OUTCOME MEASURES Clinical course, audiologic data, imaging findings. RESULTS Of 148 patients with OAE data, 11 (7.4%) had the unilateral neural phenotype. Most had stable, severe-to-profound loss in the affected ear. MRI determined an etiology in all 10 patients who received it. Absent cochlear nerves were remarkably common, being found in eight patients (73%). Tumors, previously unsuspected, were identified in the other two patients who received MRI. CONCLUSIONS Cochlear nerve aplasia appears by far the most common cause of UNHL in children. As in adults, mass lesions must also be considered in children with unilateral SNHL with a neural pattern. As both lesions elude diagnosis on CT, MRI is the better modality for evaluating this condition.

Unilateral Cochlear Nerve Deficiency in Children

Objective Cochlear nerve deficiency (CND) is increasingly diagnosed in children with sensorineural hearing loss (SNHL). We sought to determine the prevalence of CND, its imaging characteristics, and correlations with audiologic phenotype in children with unilateral SNHL. Design Case series with chart review. Setting Tertiary pediatric hospital. Subjects/Methods In 128 consecutive children with unilateral SNHL who underwent high-resolution magnetic resonance imaging, the diameters, area, and signal intensity of the cochlear nerve (CN) were measured and normalized to the ipsilateral facial nerve. Presence of CND was determined by comparison to normative data. Relationships among hearing loss severity, progression, and nerve size were investigated. Results Cochlear nerve deficiency was present in 26% of children with unilateral SNHL. Its prevalence was higher (48%) in severe to profound SNHL, especially when in infants (100%). Width of the bony cochlear nerve canal (BCNC) correlated strongly with relative CN diameter, density, and area (R = 0.5); furthermore, a narrow BCNC (<1.7 mm) strongly predicted CND. Severity of hearing loss modestly correlated with nerve size, although significant variability was observed. Progression never occurred unless there were other inner ear malformations, whereas in the non-CND group, it occurred in 22%. Ophthalmologic abnormalities were very common (67%) in CND children, particularly oculomotor disturbances. Conclusion Cochlear nerve deficiency is a common cause of unilateral SNHL, particularly in congenital unilateral deafness. Width of the BCNC effectively predicts CND, a finding useful when only computed tomography imaging is available. In an ear with CND, hearing can be expected to remain stable over time. Diagnosis should prompt evaluation by an ophthalmologist.

Macrophage migration inhibitory factor acts as a neurotrophin in the developing inner ear

This study is the first to demonstrate that macrophage migration inhibitory factor (MIF), an immune system ‘inflammatory’ cytokine that is released by the developing otocyst, plays a role in regulating early innervation of the mouse and chick inner ear. We demonstrate that MIF is a major bioactive component of the previously uncharacterized otocyst-derived factor, which directs initial neurite outgrowth from the statoacoustic ganglion (SAG) to the developing inner ear. Recombinant MIF acts as a neurotrophin in promoting both SAG directional neurite outgrowth and neuronal survival and is expressed in both the developing and mature inner ear of chick and mouse. A MIF receptor, CD74, is found on both embryonic SAG neurons and adult mouse spiral ganglion neurons. Mif knockout mice are hearing impaired and demonstrate altered innervation to the organ of Corti, as well as fewer sensory hair cells. Furthermore, mouse embryonic stem cells become neuron-like when exposed to picomolar levels of MIF, suggesting the general importance of this cytokine in neural development.

Real-time intraoperative computed tomography to assist cochlear implant placement in the malformed inner ear.

Objective: Cochlear implantation is increasingly being performed in children with inner ear malformations. In severe cochleovestibular anomalies, such as severe partitioning defects and common cavity dysplasia, positioning of the electrode array can be hazardous, with inadvertent placement into the internal auditory canal (IAC) or carotid canal being well known. We describe a case in which real-time intraoperative computed tomographic scanning was used to help achieve proper electrode positioning in a child with a severe malformation. Patient: Child with common cavity malformations undergoing cochlear implantation. Intervention: Intraoperative computed tomography used during implantation procedure. Main Outcome Measure Use of technique in determining electrode position. Results: A 10-year-old patient with bilateral common cavity malformations presented with declining performance in a functioning implant placed 7 years earlier. The family elected implantation of the contralateral ear. Via a posterior labyrinthotomy approach, a straight array was placed into the common cavity. Intraoperative computed tomographic scanning was immediately performed on the operating room table, showing that the array was in the IAC. A second attempt with a different insertion angle also resulted in IAC placement. In a third attempt, the electrode was advanced as a loop, grasping the tip through an adjacent second labyrinthotomy. Computed tomography confirmed good position against the outer wall of the cavity. Conclusion: Real-time intraoperative computed tomography is a new technology with many potential applications in surgery. In our patient, it allowed rapid and accurate determination of electrode position and helped achieve ideal placement in a severely malformed inner ear.

Chronic Pseudomonas infections of cochlear implants.

Objective: To discuss chronic, refractory Pseudomonas infections of cochlear implants and their management. Design: Retrospective case series. Setting: Two university-based cochlear implant programs. Patients: Twenty-eight-year-old (Case 1) and 4-year-old (Case 2), different devices. Interventions: Medical and surgical management. Main Outcome Measures: Clinical course. Results: Both patients had delayed presentations, 4 months and 3 years postimplantation, respectively, with fluctuating scalp edema and pain resistant to multiple courses of oral antibiotics. Infections began as localized granulation and progressed to complete encasement of both devices with rubbery, poorly vascularized tissue. In each case, two different strains of multiresistant Pseudomonas aeruginosa were cultured. Infections progressed despite local debridement and targeted antipseudomonal antibiotic coverage, and sensitive organisms continued to appear in cultures of refractory granulation tissue. Both patients underwent partial explantation, with the electrode array left in the cochlea, then received 2 to 3 more months of further medical therapy and observation and then were reimplanted successfully with new devices. Both have shown excellent performance and no sign of recurrent infection. Conclusions: Infections of cochlear implants are uncommon, and cases of successful conservative management without device explantation have been reported. However, our experience and the implanted device literature suggest that chronic Pseudomonas infections may represent a distinct clinical entity, likely to fail protracted therapy and ultimately require device removal. Fortunately, successful reimplantation is possible.

Molecular Characterization of Conditionally Immortalized Cell Lines Derived From Mouse Early Embryonic Inner Ear

Inner ear sensory hair cells (HCs), supporting cells (SCs), and sensory neurons (SNs) are hypothesized to develop from common progenitors in the early embryonic otocyst. Because little is known about the molecular signals that control this lineage specification, we derived a model system of early otic development: conditionally immortalized otocyst (IMO) cell lines from the embryonic day 9.5 Immortomouse. This age is the earliest stage at which the otocyst can easily be separated from surrounding mesenchymal, nervous system, and epithelial cells. At 9.5 days post coitum, there are still pluripotent cells in the otocyst, allowing for the eventual identification of both SN and HC precursors—and possibly an elusive inner ear stem cell. Cell lines derived from primitive precursor cells can also be used as blank canvases for transfections of genes that can affect lineage decisions as the cells differentiate. It is important, therefore, to characterize the “baseline state” of these cell lines in as much detail as possible. We characterized seven representative “precursor‐like” IMO cell populations and the uncloned IMO cells, before cell sorting, at the molecular level by polymerase chain reaction (PCR) and immunocytochemistry (IHC), and one line (IMO‐2B1) in detail by real‐time quantitative PCR and IHC. Many of the phenotypic markers characteristic of differentiated HCs or SCs were detected in IMO‐2B1 proliferating cells, as well as during differentiation for up to 30 days in culture. These IMO cell lines represent a unique model system for studying early stages of inner ear development and determining the consequences of affecting key molecular events in their differentiation. Developmental Dynamics 231:815–827, 2004.

Venous malformations of the temporal bone are a common feature in CHARGE syndrome

CHARGE (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital and/or urinary abnormalities, and Ear abnormalities and/or deafness) syndrome is a genetic disorder with prominent otolaryngologic features including choanal atresia and inner ear malformations. Recent experience with venous malformations during cochlear implant surgery prompted this study to define the spectrum of venous abnormalities in CHARGE and their surgical implications in otology.

Pseudoaneurysm of the proximal facial artery presenting as oropharyngeal hemorrhage.

Penetrating trauma to the neck traversing zones II and III may cause considerable damage to soft tissues and neurovascular structures. Delayed sequelae of vascular injuries, such as pseudoaneurysm (PA), may present weeks to months after the initial injury.

Early Prediction of Postmeningitic Hearing Loss in Children Using Magnetic Resonance Imaging

OBJECTIVE To determine whether early gadolinium-enhanced magnetic resonance imaging (GdMRI) can reliably detect meningitic labyrinthitis and thereby predict which children are at high risk for hearing loss. Permanent sensorineural hearing loss (SNHL) remains a common sequela of bacterial meningitis, and early diagnosis of the associated suppurative labyrinthitis can be difficult, especially in critically ill, sedated patients and young children. DESIGN Retrospective cohort study. SETTING Tertiary pediatric hospital. PARTICIPANTS Twenty-three survivors of bacterial meningitis (median age, 15 months [range, 3 months-14 years]) who had undergone brain GdMRI during the acute disease and had subsequent ear-specific audiometric data. MAIN OUTCOME MEASURE Blinded to disease and outcome, a neuroradiologist rated the relative enhancement of each cochlea on T1-weighted images using a 4-point scale. Scores were then correlated with the degree of hearing loss on subsequent testing. RESULTS Sensorineural hearing loss occurred in 15 of 46 ears (8 of 23 patients). Enhancement on GdMRI was detected in 13 of the 15 ears that later developed SNHL but was absent in all 31 unaffected ears. Thus, GdMRI was 87% sensitive and 100% specific for predicting which ears would develop permanent SNHL. In the subgroup with pneumococcal meningitis (n = 15), GdMRI was 100% sensitive and 100% specific. Labyrinthine enhancement was detectable as early as 1 day after diagnosis. CONCLUSION Gadolinium-enhanced MRI detected meningitic labyrinthitis at early stages and accurately predicted which patients would later develop hearing loss.

Muscle and tendon size relationships in a paralyzed chick embryo model of clubfoot

Clubfoot is a birth defect that may be related to muscle weakness or imbalance. The purpose of this study was to examine the relationships among muscle and tendon size and embryonic motility in a paralyzed chick embryo model of clubfoot and arthrogryposis. Decamethonium bromide, a neuromuscular blocking agent, was administered to a series of embryos in five dosage groups, producing a cohort of embryos with various degrees of paralysis and atrophy of tendons and muscle. Embryonic movement frequency was monitored, and after death in late gestation, the cross-sectional areas of the calf musculature and the gastrocnemius tendon proximal to the ankle were measured histologically. Significant correlations were found between embryonic motility and both muscle (r2 = 0.52) and tendon (r2 = 0.77) areas. In addition, a significant correlation (r2 = 0.74) was found between muscle and tendon areas, suggesting that a measurement of one may be used to predict the other.