Quinton Gopen

Anatomy of the normal human cochlear aqueduct with functional implications

There is great variation in published descriptions of the shape, size, and patency of the human cochlear aqueduct. The first part of this paper describes the anatomy of the normal human cochlear aqueduct as determined from a study of 101 temporal bones. Nineteen bones aged 0-1 years and approximately 10 bones per decade of life until age 100 years were examined. The aqueduct was found to have a funnel shaped aperture at the cranial end with a dural sheath extending into it for a varying distance. The rest of the aqueduct was filled with a meshwork of loose connective tissue, often with a central lumen within it. Four types of patencies were noted: central lumen patent throughout length of aqueduct (34%), lumen filled with loose connective tissue (59%), lumen occluded by bone (4%), and obliteration of the aqueduct (3%). The mean value (+/- SD) of the narrowest portion was 138 (+/- 58) microns which occurred 200-300 microns from the cochlear end of the aqueduct. There was no correlation between age and narrowest diameter, or between age and category of patency. In the second part of this paper, we propose quantitative models of aqueduct function, based on measurements of ductal dimensions and known acoustical properties of the inner ear. Our model analyses suggest that in normal ears, the aqueduct (1) cannot support fluid flows large enough to explain stapedectomy gushers, (2) does filter out cardiac- and respiration-induced pulses in CSF and prevents them from affecting cochlear function, and (3) has little effect on normal ossicular transmission of sound for frequencies above 20 Hz. In pathological ears, such as those with ossicular disruption or after a type IV tympanoplasty, a patent aqueduct might affect hearing for frequencies below 150 Hz.

The molecular genetics and tumor pathogenesis of meningiomas and the future directions of meningioma treatments

Meningiomas are mostly benign, slow-growing tumors of the CNS that originate from arachnoidal cap cells. While monosomy 22 is the most frequent genetic abnormality found in meningiomas, a multitude of other aberrant chromosomal alterations, signaling pathways, and growth factors have been implicated in its pathogenesis. Losses on 22q12.2, a region encoding the tumor suppressor gene merlin, represent the most common genetic alterations in early meningioma formation. Malignant meningioma progression, however, is associated with more complex karyotypes and greater genetic instability. Cytogenetic studies of atypical and anaplastic meningiomas revealed gains and losses on chromosomes 9, 10, 14, and 18, with amplifications on chromosome 17. However, the specific gene targets in a majority of these chromosomal abnormalities remain elusive. Studies have also implicated a myriad of aberrant signaling pathways involved with meningioma tumorigenesis, including those involved with proliferation, angiogenesis, and autocrine loops. Understanding these disrupted pathways will aid in deciphering the relationship between various genetic changes and their downstream effects on meningioma pathogenesis. Despite advancements in our understanding of meningioma pathogenesis, the conventional treatments, including surgery, radiotherapy, and stereotactic radiosurgery, have remained largely stagnant. Surgery and radiation therapy are curative in the majority of lesions, yet treatment remains challenging for meningiomas that are recurrent, aggressive, or refractory to conventional treatments. Future therapies will include combinations of targeted molecular agents as a result of continued progress in the understanding of genetic and biological changes associated with meningiomas.

Posterior semicircular canal dehiscence: first reported case series.

Objective: To identify clinical, audiological, and vestibular characteristics of posterior semicircular canal dehiscence. Study Design: Retrospective case review. Setting: Tertiary referral center. Patients: Twelve patients aged 2 to 67 years identified with posterior semicircular canal dehiscence. Interventions: Patients identified by suspicious clinical history and examination, confirmed by high-resolution computed tomography. Audiological evaluation included air and bone audiometry, tympanometry, acoustic reflexes, and vestibular evoked myogenic potential testing. Results: Hearing loss was mixed in 9 patients, conductive in 2 patients, and sensorineural in 1 patient, with downward-sloping configuration being the most common. Imaging revealed that 7 of 12 patients had dehiscence into a high-riding jugular bulb and 1 patient had an enlarged vestibular aqueduct with a Mondini malformation. One patient had Apert syndrome and another patient had microtia/atresia. Vestibular symptoms were more common in the adult patients than in the pediatric patients, with chronic disequilibrium the most common complaint. Vestibular evoked myogenic potential testing confirmed dehiscence with the characteristic response of reduced threshold and higher amplitude compared with healthy patients. Conclusion: This is the first reported series of adult and pediatric patients with symptomatic posterior semicircular canal dehiscence. Posterior semicircular canal dehiscence represents a third-window lesion manifesting as hearing loss with vestibular dysfunction. Computed tomography findings of a dehiscent posterior canal can be verified with increased vestibular evoked myogenic potential responses as in other third-window lesions. Patients found to have a high-riding jugular bulb and hearing loss should have specific inspection of the posterior canal to ensure it is not dehiscent.

Enlarged vestibular aqueduct: Review of controversial aspects†‡

To review the controversial aspects of the enlarged vestibular aqueduct syndrome.

The molecular biology and novel treatments of vestibular schwannomas.

Vestibular schwannomas are histopathologically benign tumors arising from the Schwann cell sheath surrounding the vestibular branch of cranial nerve VIII and are related to the NF2 gene and its product merlin. Merlin acts as a tumor suppressor and as a mediator of contact inhibition. Thus, deficiencies in both NF2 genes lead to vestibular schwannoma development. Recently, there have been major advances in our knowledge of the molecular biology of vestibular schwannomas as well as the development of novel therapies for its treatment. In this article the authors comprehensively review the recent advances in the molecular biology and characterization of vestibular schwannomas as well as the development of modern treatments for vestibular schwannoma. For instance, merlin is involved with a number of receptors including the CD44 receptor, EGFR, and signaling pathways, such as the Ras/raf pathway and the canonical Wnt pathway. Recently, merlin was also shown to interact in the nucleus with E3 ubiquitin ligase CRL4(DCAF1). A greater understanding of the molecular mechanisms behind vestibular schwannoma tumorigenesis has begun to yield novel therapies. Some authors have shown that Avastin induces regression of progressive schwannomas by over 40% and improves hearing. An inhibitor of VEGF synthesis, PTC299, is currently in Phase II trials as a potential agent to treat vestibular schwannoma. Furthermore, in vitro studies have shown that trastuzumab (an ERBB2 inhibitor) reduces vestibular schwannoma cell proliferation. With further research it may be possible to significantly reduce morbidity and mortality rates by decreasing tumor burden, tumor volume, hearing loss, and cranial nerve deficits seen in vestibular schwannomas.

Clinical characteristics and diagnostic imaging of epidermoid tumors

Epidermoid tumors are rare, benign congenital lesions which typically present between the third and fifth decades of life. They are thought to originate from ectodermal cells misplaced during neural tube formation and separation. While epidermoids may present anywhere in the cranial vault, they are characteristically located intradurally and in a paramedian position within the cerebellopontine angle and parasellar regions. Although imaging results may vary depending upon cystic content, CT scanning generally reveals a well-circumscribed, nonenhancing, lobulated, hypodense mass. They are hypointense on T1-weighted MRI, and hyperintense on T2-weighted MRI, diffusion-weighted imaging and fluid-attenuated inversion recovery sequences. The use of appropriate neuroimaging should be utilized to differentiate epidermoids from other intracranial lesions. While gross total resection of these tumors is the definitive treatment to prevent recurrence and aseptic meningitis, a subtotal resection may be necessary to preserve neurological function.

Delineating the hearing loss in children with enlarged vestibular aqueduct.

Objective/Hypothesis: To explore the clinical characteristics and audiologic outcomes in children with enlarged vestibular aqueduct (EVA).

Facial Nerve Palsy in the Pediatric Population

Paralysis of the seventh cranial nerve (CN VII), the facial nerve, is a relatively uncommon condition in the pediatric population. Although it appears 2 to 4 times less frequently in children than in adults, the dramatic appearance of the affected child is often of great immediate concern to the child and parents. Regardless of the cause, the result is weakness of the facial musculature, affecting facial expression, oral competence, verbal communication, social interaction, taste, and potentially vision. Sir Charles Bell first discovered in 1821 that the facial nerve is responsible for facial muscle movement. Whereas idiopathic facial nerve palsy, also termed Bell’s palsy, accounts for the majority of adult cases of facial weakness, secondary causes are more often identified in children with facial nerve palsy. This makes early recognition, diagnosis, and treatment increasingly important in the pediatric population. In this article, we provide a review of the relevant anatomy and a discussion of the clinical presentation and current management of this condition.

Clinical experience in diagnosis and management of superior semicircular canal dehiscence in children.

To identify clinical characteristics of pediatric superior semicircular canal dehiscence (SSCD) and explore suitable options of management.

Inner ear anomalies and conductive hearing loss in children with Apert syndrome: an overlooked otologic aspect.

Objective: To identify the occurrence of inner ear structural anomalies and conductive hearing loss (CHL) in children with Apert syndrome. Study Design: Retrospective review. Setting: Pediatric tertiary referral center. Patients: Twenty pediatric patients with Apert syndrome were found; all patients (38/40 ears) had inner ear anomalies. Intervention(s): Computerized tomography of the head/temporal bone, pure-tone (including air and bone conduction) audiometry, and tympanometry. Main Outcome Measure(s): Imaging demonstrating inner ear anomalies, including malformations of the cochlea, dilated vestibule, and/or semicircular canal; audiologic findings of air-bone gap(s). Results: Hearing loss was found in 90% of the patients with Apert syndrome, and 80% of them had CHL. Air-bone gaps were found at all frequencies, with larger gaps at low frequencies. Fifty percent (20/40) of the ears had better than 0 dB hearing level bone conduction thresholds at 250 and/or 500 Hz. Normal middle ear pressure and mobility were found in all ears with intact eardrum. Inner ear anomalies were found in all patients, and 90% of them had bilateral involvement. Most frequently observed inner ear anomalies were dilated vestibule, malformed lateral semicircular canal, and cochlear dysplasia. Conclusion: Children with Apert syndrome may present with significant CHL that cannot be explained by minor middle ear pathologies alone. This conductive loss may be, at least partially, attributed to the inner ear anomalies; however, these structural anomalies are usually not recognized in these patients. Failure to close air-bone gap after surgical intervention may raise the suspicion of inner ear anomalies, and computed tomographic scan of the temporal bone can provide definitive proof.