C. Eduardo Corrales

Differential Distribution of Stem Cells in the Auditory and Vestibular Organs of the Inner Ear

The adult mammalian cochlea lacks regenerative capacity, which is the main reason for the permanence of hearing loss. Vestibular organs, in contrast, replace a small number of lost hair cells. The reason for this difference is unknown. In this work we show isolation of sphere-forming stem cells from the early postnatal organ of Corti, vestibular sensory epithelia, the spiral ganglion, and the stria vascularis. Organ of Corti and vestibular sensory epithelial stem cells give rise to cells that express multiple hair cell markers and express functional ion channels reminiscent of nascent hair cells. Spiral ganglion stem cells display features of neural stem cells and can give rise to neurons and glial cell types. We found that the ability for sphere formation in the mouse cochlea decreases about 100-fold during the second and third postnatal weeks; this decrease is substantially faster than the reduction of stem cells in vestibular organs, which maintain their stem cell population also at older ages. Coincidentally, the relative expression of developmental and progenitor cell markers in the cochlea decreases during the first 3 postnatal weeks, which is in sharp contrast to the vestibular system, where expression of progenitor cell markers remains constant or even increases during this period. Our findings indicate that the lack of regenerative capacity in the adult mammalian cochlea is either a result of an early postnatal loss of stem cells or diminishment of stem cell features of maturing cochlear cells.

Correlation of expression of the actin filament-bundling protein espin with stereociliary bundle formation in the developing inner ear

The vertebrate hair cell is named for its stereociliary bundle or hair bundle that protrudes from the cells apical surface. Hair bundles mediate mechanosensitivity, and their highly organized structure plays a critical role in mechanoelectrical transduction and amplification. The prototypical hair bundle is composed of individual stereocilia, 50–300 in number, depending on the animal species and on the type of hair cell. The assembly of stereocilia, in particular, the formation during development of individual rows of stereocilia with descending length, has been analyzed in great morphological detail. Electron microscopic studies have demonstrated that stereocilia are filled with actin filaments that are rigidly cross‐linked. The growth of individual rows of stereocilia is associated with the addition of actin filaments and with progressively increasing numbers of cross‐bridges between actin filaments. Recently, a mutation in the actin filament‐bundling protein espin has been shown to underlie hair bundle degeneration in the deaf jerker mouse, subsequently leading to deafness. Our study was undertaken to investigate the appearance and developmental expression of espin in chicken inner ear sensory epithelia. We found that the onset of espin expression correlates with the initiation and growth of stereocilia bundles in vestibular and cochlear hair cells. Intense espin immunolabeling of stereocilia was colocalized with actin filament staining in all types of hair cells at all developmental stages and in adult animals. Our analysis of espin as a molecular marker for actin filament cross‐links in stereocilia is in full accordance with previous morphological studies and implicates espin as an important structural component of hair bundles from initiation of bundle assembly to mature chicken hair cells. J. Comp. Neurol. 468:125–134, 2004.

Differentiation of neurons from neural precursors generated in floating spheres from embryonic stem cells

BackgroundNeural differentiation of embryonic stem (ES) cells is usually achieved by induction of ectoderm in embryoid bodies followed by the enrichment of neuronal progenitors using a variety of factors. Obtaining reproducible percentages of neural cells is difficult and the methods are time consuming.ResultsNeural progenitors were produced from murine ES cells by a combination of nonadherent conditions and serum starvation. Conversion to neural progenitors was accompanied by downregulation of Oct4 and NANOG and increased expression of nestin. ES cells containing a GFP gene under the control of the Sox1 regulatory regions became fluorescent upon differentiation to neural progenitors, and ES cells with a tau-GFP fusion protein became fluorescent upon further differentiation to neurons. Neurons produced from these cells upregulated mature neuronal markers, or differentiated to glial and oligodendrocyte fates. The neurons gave rise to action potentials that could be recorded after application of fixed currents.ConclusionNeural progenitors were produced from murine ES cells by a novel method that induced neuroectoderm cells by a combination of nonadherent conditions and serum starvation, in contrast to the embryoid body method in which neuroectoderm cells must be selected after formation of all three germ layers.

Pediatric Semicircular Canal Dehiscence: Radiographic and Histologic Prevalence, With Clinical Correlation.

Objectives To determine the prevalence of radiographic and histologic superior semicircular canal dehiscence (SSCD) and posterior semicircular canal dehiscence (PSCD) and associated changes in temporal bone thickness in children aged 0 to 7 years. Study Design Retrospective chart review and histopathologic review of cadaveric bone specimens. Setting Two tertiary referral centers. Patients Children younger than 7 years who underwent high-resolution computed tomography scan including the temporal bones between 1998 and 2013 and temporal bones harvested from children younger than 7 years. Intervention(s) Two hundred twenty-eight computed tomography studies and 58 temporal bone specimens were reviewed. Available patient demographics were tabulated. Main Outcome Measure(s) Prevalence of SSCD and PSCD and bone thickness over semicircular canals, with comparison across age groups. Clinical data were extracted for patients with radiographic dehiscence. Results Prevalence by ear of SSCD was 11.9%, 4.9%, 2.8%, and 0% and of PSCD was 16.7%, 2.4%, 1.4%, and 0% in children aged less than 6 months, 6 to 11 months, 12 to 35 months, and 3 to 7 years, respectively. SSCD was statistically more common before 1 year of age and PSCD before 6 months of age. Bone thickness overlying both the SSC and the PSC increased with age. Radiographic PSC bone was significantly thicker than SSC bone in patients older than 12 months. No dehiscences were found in the histologic specimens. Conclusion Radiographic dehiscence of the canals is common in the first 6 months of life, with thin bone seen histologically. Prevalence decreases with increasing age as the bone overlying the canals increases in thickness.

Cochlear Implant Considerations in Children with Additional Disabilities

Early identification and management of disabilities in children are essential to reduce long-term developmental sequelae. Many of the causes of hearing loss also produce cognitive delays resulting in a large number of children with both deafness and developmental disabilities. Children who have hearing loss and additional disabilities require complex, individualized therapy to maximize their long-term quality of life. Hearing loss is often detected early because of widespread newborn hearing screening programs and the decision for cochlear implantation in children presenting with multiple medical and developmental disorders is still evolving. This article will review the literature regarding cochlear implant considerations in children with additional developmental disabilities in areas of family perception, speech and language development, cognitive development including adaptive behavior and intelligence, communication and functional skills, auditory outcomes, quality of life outcomes, predictors of outcomes and realistic expectations after cochlear implantation.

Dizziness and death: An imbalance in mortality

To determine if dizziness is an independent risk factor for mortality among adults in the United States.

Transient, afferent input-dependent, postnatal niche for neural progenitor cells in the cochlear nucleus

Significance The cochlear nucleus is the first central relay station for auditory signals from the cochlea. Like many other central relays for sensory systems, the cochlear nucleus features a period in newborn animals during which neuron survival and the number of synaptic contacts depends on afferent innervation from the periphery. This study extends this concept of postnatal plasticity toward neurogenesis. We identified neural progenitor cells in the cochlear nucleus whose proliferative capacity is controlled by interplay of several signaling pathways. When the cochlea was removed, the proliferating cell population diminished, suggesting that signals from the periphery are required to maintain this plasticity. In the cochlear nucleus (CN), the first central relay of the auditory pathway, the survival of neurons during the first weeks after birth depends on afferent innervation from the cochlea. Although input-dependent neuron survival has been extensively studied in the CN, neurogenesis has not been evaluated as a possible mechanism of postnatal plasticity. Here we show that new neurons are born in the CN during the critical period of postnatal plasticity. Coincidently, we found a population of neural progenitor cells that are controlled by a complex interplay of Wnt, Notch, and TGFβ/BMP signaling, in which low levels of TGFβ/BMP signaling are permissive for progenitor proliferation that is promoted by Wnt and Notch activation. We further show that cells with activated Wnt signaling reside in the CN and that these cells have high propensity for neurosphere formation. Cochlear ablation resulted in diminishment of progenitors and Wnt/β-catenin-active cells, suggesting that the neonatal CN maintains an afferent innervation-dependent population of progenitor cells that display active canonical Wnt signaling.

Imaging Innovations in Temporal Bone Disorders

The development of new imaging techniques coupled with new treatment algorithms has created new possibilities in treating temporal bone diseases. This article provides an overview of recent imaging innovations that can be applied to temporal bone diseases. Topics covered include the role of magnetic resonance (MR) diffusion-weighted imaging in cholesteatomas and skull base epidermoids, whole-body molecular imaging in paragangliomas of the jugular foramen, and MR arterial spin labeling perfusion for dural arteriovenous fistulas and arteriovenous malformations.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on Surgical Resection for the Treatment of Patients With Vestibular Schwannomas

Abstract Please see the full‐text version of this guideline (https://www.cns.org/guidelines/guidelines‐management‐patients‐vestibular‐schwannoma/chapter_8) for the target population of each recommendation listed below. QUESTION 1 What surgical approaches for vestibular schwannomas (VS) are best for complete resection and facial nerve (FN) preservation when serviceable hearing is present? RECOMMENDATION There is insufficient evidence to support the superiority of either the middle fossa (MF) or the retrosigmoid (RS) approach for complete VS resection and FN preservation when serviceable hearing is present. QUESTION 2 Which surgical approach (RS or translabyrinthine [TL]) for VS is best for complete resection and FN preservation when serviceable hearing is not present? RECOMMENDATION There is insufficient evidence to support the superiority of either the RS or the TL approach for complete VS resection and FN preservation when serviceable hearing is not present. QUESTION 3 Does VS size matter for facial and vestibulocochlear nerve preservation with surgical resection? RECOMMENDATION Level 3: Patients with larger VS tumor size should be counseled about the greater than average risk of loss of serviceable hearing. QUESTION 4 Should small intracanalicular tumors (<1.5 cm) be surgically resected? RECOMMENDATION There are insufficient data to support a firm recommendation that surgery be the primary treatment for this subclass of VSs. QUESTION 5 Is hearing preservation routinely possible with VS surgical resection when serviceable hearing is present? RECOMMENDATION Level 3: Hearing preservation surgery via the MF or the RS approach may be attempted in patients with small tumor size (<1.5 cm) and good preoperative hearing. QUESTION 6 When should surgical resection be the initial treatment in patients with neurofibromatosis type 2 (NF2)? RECOMMENDATION There is insufficient evidence that surgical resection should be the initial treatment in patients with NF2. QUESTION 7 Does a multidisciplinary team, consisting of neurosurgery and neurotology, provides the best outcomes of complete resection and facial/vestibulocochlear nerve preservation for patients undergoing resection of VSs? RECOMMENDATION There is insufficient evidence to support stating that a multidisciplinary team, usually consisting of a neurosurgeon and a neurotologist, provides superior outcomes compared to either subspecialist working alone. QUESTION 8 Does a subtotal surgical resection of a VS followed by stereotactic radiosurgery (SRS) to the residual tumor provide comparable hearing and FN preservation to patients who undergo a complete surgical resection? RECOMMENDATION There is insufficient evidence to support subtotal resection (STR) followed by SRS provides comparable hearing and FN preservation to patients who undergo a complete surgical resection. QUESTION 9 Does surgical resection of VS treat preoperative balance problems more effectively than SRS? RECOMMENDATION There is insufficient evidence to support either surgical resection or SRS for treatment of preoperative balance problems. QUESTION 10 Does surgical resection of VS treat preoperative trigeminal neuralgia more effectively than SRS? RECOMMENDATION Level 3: Surgical resection of VSs may be used to better relieve symptoms of trigeminal neuralgia than SRS. QUESTION 11 Is surgical resection of VSs more difficult (associated with higher facial neuropathies and STR rates) after initial treatment with SRS? RECOMMENDATION Level 3: If microsurgical resection is necessary after SRS, it is recommended that patients be counseled that there is an increased likelihood of a STR and decreased FN function. The full guideline can be found at: https://www.cns.org/guidelines/guidelines‐management‐patients‐vestibular‐schwannoma/chapter_8.

Perpetuation of errors in illustrations of cranial nerve anatomy.

For more than 230 years, anatomical illustrations have faithfully reproduced the German medical student Thomas Soemmerrings cranial nerve (CN) arrangement. Virtually all contemporary atlases show the abducens, facial, and vestibulocochlear nerves (CNs VI-VIII) all emerging from the pontomedullary groove, as originally depicted by Soemmerring in 1778. Direct observation at microsurgery of the cerebellopontine angle reveals that CN VII emerges caudal to the CN VIII root from the lower lateral pons rather than the pontomedullary groove. Additionally, the CN VI root lies in the pontomedullary groove caudal to both CN VII and VIII in the vast majority of cases. In this high-resolution 3D MRI study, the exit location of CN VI was caudal to the CN VII/VIII complex in 93% of the cases. Clearly, Soemmerrings rostrocaudal numbering system of CN VI-VII-VIII (abducens-facial-vestibulocochlear CNs) should instead be VIII-VII-VI (vestibulocochlear-facial-abducens CNs). While the inaccuracy of the CN numbering system is of note, what is remarkable is that generations of authors have almost universally chosen to perpetuate this ancient error. No doubt some did this through faithful copying of their predecessors. Others, it could be speculated, chose to depict the CN relationships incorrectly rather than run contrary to long-established dogma. This study is not advocating that a universally recognized numbering scheme be revised, as this would certainly create confusion. The authors do advocate that future depictions of the anatomical arrangements of the brainstem roots of CNs VI, VII, and VIII ought to reflect actual anatomy, rather than be contorted to conform with the classical CN numbering system.