Tectorial Research Articles

Prediction and interpretation of rare missense variant in OTOG associated with hearing loss

OTOG encodes for otogelin, a component of the tectorial membrane. This gene is associated with nonprogressive mild-to-moderate hearing loss. However, no studies have yet identified the association between OTOG variation and severe-to-profound hearing loss. Therefore, to address this issue, a family-based whole-exome sequencing strategy (WES) was carried out. Two unrelated Iranian families with non-syndromic hearing loss were identified, and WES was conducted on one selected candidate from each family. As a result, a rare homozygous missense variant, OTOG (c.C2383T:p.R795C), was detected in both of the subjected probands, and segregation analysis confirmed the c.C2383T variant in seven cases of severe-to-profound hearing loss. Additionally, the results from the protein modeling demonstrated that the altered position of a few disulfide bonds in the TIL domain may have a deleterious impact on protein stability and normal functionality. In conclusion, it seems that the homozygosity of the OTOG c.C2383T mutation sheds light on hearing loss pathobiology. Nevertheless, further studies are required to unravel the precise function of OTOG mutation, which is potentially associated with severe-to-profound hearing loss.

Traumatic Retroclival Subdural Hematoma on Top of Stable Bilateral Occipital Condyle Fracture: Impact of Hematoma on Craniocervical Stability and Management Decision

Background and Importance: Bilateral occipital condyle fracture (OCF) is a rare type of injury that occurs at the occipitocervical junction, mostly due to high energy trauma to cranium with axial loading. These fractures are difficult to diagnose based on conventional cervical or cranial radiography and they have non-specific clinical manifestations. However, unstable fractures carry the most risk for morbidity and mortality due to their close relation to important neural and vascular structures. Acute retro-clival subdural hematoma (rcSDH) is a collection of blood dorsal to the tectorial membrane, which is a critical structure for maintaining occipitocervical stability, presence of posttraumatic acute retroclival subdural hematoma in the setting of non-displaced bilateral occipital condyle fractures in traumatic patients is a marker of high energy trauma with fatal course in acute setting due to compression on subarachnoid space by acute hematoma and subsequent increase intracranial pressure and a merely marker of occipitocervical instability due to injury/damage to tectorial membrane. We describe the imaging features and clinical symptoms and signs that led to the diagnosis and classification of stable bilateral OCFs with a quickly resolving rcSDH in a previously healthy man aged 25 years involved in a motor vehicle accident, allowing conservative management. The co-existing of both injuries has not been described in the literature to the best of our knowledge.

"Supradental space sign" on cervical spine CT-a sign of tectorial membrane injury in adults trauma patients.

The supradental space is a small, predominantly fat-filled recess superior to the atlanto-axial joint and inferior to the basion of the clivus that contains a small venous plexus. The posterior boundary of the supradental space is formed by the tectorial membrane, a stabilizing ligament of the craniocervical junction. The purpose of our study was to examine the imaging appearance of the supradental space in patients with tectorial membrane injury. Adult patients with tectorial membrane injury were identified utilizing keyword searches of radiology reports using Nuance mPower software. Age-matched positive and negative control groups were obtained. Two CAQ-certified neuroradiologists evaluated the cervical CT exams of these patients for supradental fat pad effacement from hematoma formation. The integrity of the osteoligamentous structures of the craniocervical junction was recorded on CT and MRI exams along with demographic information, clinical history, surgical management, and global outcome. Statistical analysis was performed. Sixteen adults were diagnosed with tectorial membrane injury on cervical MRI. All patients with a visible supradental space demonstrated fat pad effacement and Hounsfield units consistent with hematoma formation. The positive and negative control groups demonstrated supradental fat pad effacement in 2/16 and 1/16 patients, respectively. A p-value of < 0.001 was obtained. The "supradental space sign," defined as hematoma formation in the supradental space with effacement of the supradental fat pad is associated with tectorial membrane injury in adult trauma patients with sensitivity of 93.75% (95% confidence interval 69.77 to 99.84%) and specificity of 90.62% (95% confidence interval 74.98 to 98.02%).

Inner hair cell stereocilia are embedded in the tectorial membrane

Mammalian hearing depends on sound-evoked displacements of the stereocilia of inner hair cells (IHCs), which cause the endogenous mechanoelectrical transducer channels to conduct inward currents of cations including Ca2+. Due to their presumed lack of contacts with the overlaying tectorial membrane (TM), the putative stimulation mechanism for these stereocilia is by means of the viscous drag of the surrounding endolymph. However, despite numerous efforts to characterize the TM by electron microscopy and other techniques, the exact IHC stereocilia-TM relationship remains elusive. Here we show that Ca2+-rich filamentous structures, that we call Ca2+ ducts, connect the TM to the IHC stereocilia to enable mechanical stimulation by the TM while also ensuring the stereocilia access to TM Ca2+. Our results call for a reassessment of the stimulation mechanism for the IHC stereocilia and the TM role in hearing.

Pediatric Retroclival Epidural Hematoma in the Acute Trauma Setting: A Sign of Tectorial Membrane Stripping Injury.

OBJECTIVE. A traumatic retroclival epidural hematoma is a rare imaging finding of severe cervical flexion-extension injury in the pediatric population. The purpose of our study was to identify pediatric patients with a retroclival epidural hematoma, record the hematoma size and extent, and examine the major craniocervical ligaments for injury. MATERIALS AND METHODS. Pediatric patients who suffered a retroclival epidural hematoma were identified retrospectively using the keywords "clivus," "epidural hematoma," and "retroclival" included in head CT reports between 2012 and 2019. The cervical and brain MRI examinations for these patients were reviewed for craniocervical ligament injury by two certified neuroradiologists. Detailed descriptions of patient injuries were recorded along with demographic information, clinical history, patient management, and outcome. RESULTS. Eleven pediatric patients were identified with an acute posttraumatic retroclival epidural hematoma with a mean anteroposterior dimension of 4.4 mm and craniocaudal dimension of 4.3 cm. All patients with a retroclival epidural hematoma who underwent subsequent cervical MRI had a stripping injury of the tectorial membrane (TM). Disruption of additional major craniocervical ligaments on MRI (alar ligament, transverse ligament, longitudinal ligaments, and ligamentum flavum) was relatively rare with the most common associated ligamentous injuries involving the anterior atlantooccipital membrane, apical ligament, and interspinous ligaments. None of the patients suffered a cervical cord or severe intracranial injury. The majority of the patients were managed conservatively with excellent clinical outcomes. CONCLUSION. A posttraumatic retroclival epidural hematoma in the pediatric population is a rare injury often identified initially by head CT and easily overlooked by the radiologist. We propose that a retroclival epidural hematoma in the pediatric population is a direct result of a significant flexion-extension force, with a subsequent stripping injury of the TM from the posterior clivus. Pediatric patients with a posttraumatic retroclival epidural hematoma on initial head CT should undergo a cervical MRI to evaluate the integrity of the TM and other craniocervical ligaments.

Tectorial Membrane Injury, Frequently Identified in Adult Trauma Patients Who Undergo Occipital-Cervical Fusion for Craniocervical Instability.

BackgroundIn the absence of frank craniocervical dissociation, there is a lack of consensus regarding what patterns of craniocervical junction ligamentous injuries require occipital-cervical fusion. This study was undertaken to examine the integrity of the craniocervical junction ligaments and analyze clinical outcomes in patients who underwent occipital-cervical fusion for craniocervical junction injury.MethodsAdult patients requiring occipital-cervical fusion were identified retrospectively utilizing keyword searches in cervical computed tomography and magnetic resonance imaging reports between 2012 and 2020 using Nuance mPower software (Nuance, Burlington, MA). The cervical magnetic resonance imaging examinations for these patients were reviewed for craniocervical ligamentous injury by two neuroradiologists. Descriptions of craniocervical junction injuries, demographic information, clinical history, surgical management, and global outcomes were recorded.ResultsNine adult patients were identified with an acute, post-traumatic craniocervical junction injury requiring occipital-cervical fusion. All nine patients demonstrated a ligamentous tear in at least one of the four major craniocervical junction ligaments - the occipital condylar-C1 capsular ligaments, alar ligaments, tectorial membrane, and posterior atlantooccipital membrane. The tectorial membrane was the most commonly torn ligament followed by the alar ligament(s), posterior atlantooccipital membrane, and capsular ligament(s). There was wide variability in the number of major craniocervical junction ligaments torn, ranging from one ligament to all four ligaments. Four patients suffered persistent neurologic deficits following surgery.ConclusionCraniocervical injury is best evaluated by cervical magnetic resonance imaging. In the absence of overt craniocervical dissociation, we propose that an injury of the tectorial membrane in the adult population may indicate patients with significant craniocervical instability, possibly necessitating occipital-cervical fusion.

Histological structure of Nannospalax xanthodon cochlea tissue

Because of the growth retardation in the eyes of Nannospalax xanthodon blind mole rat, some genetic and environmental adaptations have occurred in the smelling and hearing systems so that they can communicate efficiently in the galleries underground. This study was aimed to determine the histological and morphometric structure of the unique organization of the cochlea, which plays an important role in hearing in N. xanthodon. After the decalcification process, the cochlear tissue was cut in 5 μm thickness after routine histological procedures. Then these sections stained with Hematoxylin & Eosin and Masson trichrome methods were examined histologically. Besides, the data obtained by taking measurements with the Image J program in the basal, media, and apex regions of the cochlea were evaluated statistically. It was observed that basilar membrane length, tectorial membrane length, stria vascularis thickness, and inner-outer hair cell lengths increased, while Reissner’s membrane length and basilar membrane thickness decreased. These data show that the general histological structure of the blind mole rat cochlea is similar to that of other mammals. By evaluating histomorphological findings, it was concluded that cochlea, which plays a primary role in hearing with the effect of living conditions and genetic structures, develops better in blind mole rats than other living species.

MET currents and otoacoustic emissions from mice with a detached tectorial membrane indicate the extracellular matrix regulates Ca2+ near stereocilia

The aim was to determine whether detachment of the tectorial membrane (TM) from the organ of Corti in Tecta/Tectb-/- mice affects the biophysical properties of cochlear outer hair cells (OHCs). Tecta/Tectb-/- mice have highly elevated hearing thresholds, but OHCs mature normally. Mechanoelectrical transducer (MET) channel resting open probability (Po ) in mature OHC is ∼50% in endolymphatic [Ca2+ ], resulting in a large standing depolarizing MET current that would allow OHCs to act optimally as electromotile cochlear amplifiers. MET channel resting Po in vivo is also high in Tecta/Tectb-/- mice, indicating that the TM is unlikely to statically bias the hair bundles of OHCs. Distortion product otoacoustic emissions (DPOAEs), a readout of active, MET-dependent, non-linear cochlear amplification in OHCs, fail to exhibit long-lasting adaptation to repetitive stimulation in Tecta/Tectb-/- mice. We conclude that during prolonged, sound-induced stimulation of the cochlea the TM may determine the extracellular Ca2+ concentration near the OHC's MET channels. The tectorial membrane (TM) is an acellular structure of the cochlea that is attached to the stereociliary bundles of the outer hair cells (OHCs), electromotile cells that amplify motion of the cochlear partition and sharpen its frequency selectivity. Although the TM is essential for hearing, its role is still not fully understood. In Tecta/Tectb-/- double knockout mice, in which the TM is not coupled to the OHC stereocilia, hearing sensitivity is considerably reduced compared with that of wild-type animals. In vivo, the OHC receptor potentials, assessed using cochlear microphonics, are symmetrical in both wild-type and Tecta/Tectb-/- mice, indicating that the TM does not bias the hair bundle resting position. The functional maturation of hair cells is also unaffected in Tecta/Tectb-/- mice, and the resting open probability of the mechanoelectrical transducer (MET) channel reaches values of ∼50% when the hair bundles of mature OHCs are bathed in an endolymphatic-like Ca2+ concentration (40μM) in vitro. The resultant large MET current depolarizes OHCs to near -40mV, a value that would allow optimal activation of the motor protein prestin and normal cochlear amplification. Although the set point of the OHC receptor potential transfer function in vivo may therefore be determined primarily by endolymphatic Ca2+ concentration, repetitive acoustic stimulation fails to produce adaptation of MET-dependent otoacoustic emissions in vivo in the Tecta/Tectb-/- mice. Therefore, the TM is likely to contribute to the regulation of Ca2+ levels around the stereocilia, and thus adaptation of the OHC MET channel during prolonged sound stimulation.

Three-dimensional tonotopic mapping of the human cochlea based on synchrotron radiation phase-contrast imaging

The human cochlea transforms sound waves into electrical signals in the acoustic nerve fibers with high acuity. This transformation occurs via vibrating anisotropic membranes (basilar and tectorial membranes) and frequency-specific hair cell receptors. Frequency-positions can be mapped within the cochlea to create a tonotopic chart which fits an almost-exponential function with lowest frequencies positioned apically and highest frequencies positioned at the cochlear base (Bekesy 1960, Greenwood 1961). To date, models of frequency positions have been based on a two-dimensional analysis with inaccurate representations of the cochlear hook region. In the present study, the first three-dimensional frequency analysis of the cochlea using dendritic mapping to obtain accurate tonotopic maps of the human basilar membrane/organ of Corti and the spiral ganglion was performed. A novel imaging technique, synchrotron radiation phase-contrast imaging, was used and a spiral ganglion frequency function was estimated by nonlinear least squares fitting a Greenwood-like function (F = A (10ax − K)) to the data. The three-dimensional tonotopic data presented herein has large implications for validating electrode position and creating customized frequency maps for cochlear implant recipients.

An Analytical Mechanical Model of Corti in the Cochlea

The organ of Corti (OC) in the cochlea is a significant structure for feeling sound. The components of OC and the interaction of the part with the surroundings contribute to the fact that the passive tuning of the cochlear macrostructure is unclear. Based on the interaction between the basilar membrane (BM), tectorial membrane (TM), reticular lamina (RL), and various parts of OC, a mechanical model of the cochlea is established to study the motion patterns of each part under the action of a certain pressure. The variational principle is applied to the calculation of the analytical expression of the displacement of the BM. The results of the analytical solution differ little from the experimental value, and the variation trend is consistent, which presents the correctness of the model. The parameter sensitivity analysis is carried out for obtaining the interaction principle and the primary and secondary roles of each component in the process of the sense of sound. The results show that the absence of the TM and the decrease in the stiffness of the outer hair cells (OHCs) and OHC bundles will shift vibratory response patterns to lower frequencies, in which the lack of TM will result in the greatest reduction of CF. The absence of RL exerts a negative influence on the CF as well as the amplitude of BM and thereby loss of hearing. Therefore, both TM and RL are essential structures during the process of the sense of sound. At the same time, the resonance frequency at the base of the BM is concentrated on the high-frequency segment, while the apex of the BM is mainly in the low frequency. Different points of BM correspond to different CF, which demonstrates the frequency selectivity of the BM.

Comparing spontaneous and stimulus frequency otoacoustic emissions in mice with tectorial membrane defects

The global standing-wave model for generation of spontaneous otoacoustic emissions (SOAEs) suggests that they are amplitude-stabilized standing waves and that the spacing between SOAEs corresponds to the interval over which the phase changes by one cycle as determined from the phase-gradient delays of stimulus frequency otoacoustic emissions (SFOAEs). Because data characterizing the relationship between spontaneous and evoked emissions in nonhuman mammals are limited, we examined SOAEs and SFOAEs in tectorial membrane (TM) mutants and their controls. Computations indicate that the spacing between adjacent SOAEs is predicted by the SFOAE phase-gradient delays for TM mutants lacking Ceacam16, where SOAE frequencies are greater than ~20 kHz and the mutants retain near-normal hearing when young. Mice with a missense mutation in Tecta (TectaY1870C/+), as well as mice lacking Otoancorin (Otoa−/−), were also examined. Although these mutants exhibit hearing loss, they generate SOAEs with average frequencies of 11 kHz in TectaY1870C/+ and 6 kHz in Otoa−/−. In these animals, the spacing between adjacent SOAEs is larger than predicted by the SFOAE phase delays. It is also demonstrated that mice do not exhibit the strong frequency-dependence in signal coding that characterizes species with good low-frequency hearing. In fact, a transition occurs near the apical end of the mouse cochlea rather than at the mid-point along the cochlear partition. Hence, disagreements with the standing-wave model are not easily explained by a transition in tuning ratios between apical and basal regions of the cochlea, especially for SOAEs generated in TectaY1870C/+mice.

Investigation on coupling between tectorial membrane mode and basilar membrane mode along cochlea.

We analyzed the dispersion relations of the tectorial membrane mode and the basilar membrane mode of the cochlea. We focused on the coupling between these two modes. We estimated the coupling points of the modes from the intersection points where the dispersion curves of both modes cross. We investigated the relationship between the frequency and the location of the intersection points and compared the result with the frequency map obtained from Greenwood function.

A role for tectorial membrane mechanics in activating the cochlear amplifier

The mechanical and electrical responses of the mammalian cochlea to acoustic stimuli are nonlinear and highly tuned in frequency. This is due to the electromechanical properties of cochlear outer hair cells (OHCs). At each location along the cochlear spiral, the OHCs mediate an active process in which the sensory tissue motion is enhanced at frequencies close to the most sensitive frequency (called the characteristic frequency, CF). Previous experimental results showed an approximate 0.3 cycle phase shift in the OHC-generated extracellular voltage relative the basilar membrane displacement, which was initiated at a frequency approximately one-half octave lower than the CF. Findings in the present paper reinforce that result. This shift is significant because it brings the phase of the OHC-derived electromotile force near to that of the basilar membrane velocity at frequencies above the shift, thereby enabling the transfer of electrical to mechanical power at the basilar membrane. In order to seek a candidate physical mechanism for this phenomenon, we used a comprehensive electromechanical mathematical model of the cochlear response to sound. The model predicts the phase shift in the extracellular voltage referenced to the basilar membrane at a frequency approximately one-half octave below CF, in accordance with the experimental data. In the model, this feature arises from a minimum in the radial impedance of the tectorial membrane and its limbal attachment. These experimental and theoretical results are consistent with the hypothesis that a tectorial membrane resonance introduces the correct phasing between mechanical and electrical responses for power generation, effectively turning on the cochlear amplifier.

Positional Audiometry in Patients with Light Cupula: A Preliminary Study

Objectives: Light cupula is characterized by persistent geotropic direction-changing positional nystagmus in a supine head-roll test. The purpose of this study is to investigate if hearing level is influenced by the change of head position in light cupula under the assumption that relative density difference similarly occurs between the tectorial membrane and endolymph. Methods: Twelve patients with unilateral light cupula who underwent positional audiometry were included in this study. Pure tone thresholds were compared among three head positions. Results: Hearing threshold in pure tone audiometry (PTA) of the affected ear was not different from that of the healthy ear. PTA thresholds of the affected side were not significantly different in three head positions; upright seating, cochlear apex-up, and cochlear apex-down positions. Conclusions: Although positional change of nystagmus direction is the most significant clinical feature of light cupula, positional change of hearing level was not observed in those patients. The lack of positional influence on hearing may be explained as follows: (1) the heavier endolymph phenomenon occurs only in the vestibular end organ without involving the cochlea; (2) the light cupula phenomenon is more likely to occur due to light debris mechanism rather than heavier endolymph or lighter cupula mechanism; and (3) the effects of light cupula could be modified by outer hair cells, which work for tuning in the cochlea, even though light tectorial membrane or heavy endolymph occurs. Keywords: Light cupula; Positional audiometry; Vertigo; Nystagmus; Hearing loss 중심 단어: 가벼운팽대부마루, ì²´ìœ„ì„±ì²­ë ¥ê²€ì‚¬, 현훈, 안진, 난청

Atlanto-occipital distraction injuries in survivors: craniometrics and associated ligamentous, spinal cord, and blunt cerebrovascular injury.

Newer classification systems for upper cervical spine trauma now include ligamentous injury in addition to fracture and dislocation patterns. Assessment of associated ligamentous injury, spinal cord injury (SCI), and blunt cerebrovascular injuries (BCVI) in patients with atlanto-occipital distraction injuries (AODI) are critical for management. We aim to determine the incidence of ligamentous injury, SCI, and BCVI in patients with AODI and assess how craniometrics perform in diagnosis of AODI. We performed an IRB-approved retrospective analysis of 35 cases of diagnosed AODI over a period of 8 years. Imaging was analyzed by two experienced neuroradiologists for craniometric measurements, ligamentous injury, SCI, and BCVI. Craniometric measurements were compared to 35 age-matched controls with normal atlanto-occipital joint. Out of 35 patients diagnosed with AODI, 27 were adults and 8 belonged to pediatric age group. The mean age of presentation was 29.4 years with a male/female ratio of 22:13. The basion-dental interval (70.4%) and the combined condylar sum (74.1%) were the most sensitive craniometric measurements for diagnosis of AODI. Alar ligament (83%) and the tectorial membrane (89%) injuries were most commonly injured ligaments. Three adult patients sustained SCI and 10 patients had BCVI. Majority of BCVI involved the internal carotid artery followed by the vertebral artery. The combination of craniometric indices with assessment of ligamentous injuries provides higher diagnostic accuracy for AODI. Alar ligament and tectorial membrane injuries have high association with AODI. There is high association of SCI and BCVI in AODI survivors.

Injuries of the upper cervical spine-how can instability be identified?

The diagnosis of instability of the injured upper cervical spine remains controversial, due to its complicated anatomical configuration and biomechanical property. Since identifying unstable injuries of the upper cervical spine is essential for immediate stabilizing therapy, this article reviews the current classification systems of upper cervical spine injuries and their statements towards instability. A systematic review of literature concerning upper cervical spine injuries was performed on the PubMed database from inception to December 2019. An English literature search was conducted using various combinations of keyword terms. Numerous separate classification systems for each specific injury of the upper cervical spine were obtained. The early classifications are based primarily on injury morphology and mechanism. The recent classifications pay more attention to the investigation of ligamentous status. Various instability criteria were established as well. The determinants involve translation, vertical distraction, angulation, rotation, obliquity of fracture line, comminution, and ligamentous disruption. The status of crucial ligaments plays a key role in determining instability of upper cervical spine injuries. CT scan is more sensitive and reliable than X-ray in detecting misalignment of the upper cervical spine. Only a few classification systems support decision-making concerning instability leading to early operative treatment. The ligamentous integrity is the key element of impacting the stability of the upper cervical spine injuries. The transverse ligament serves as the most crucial element in determining the stability of occipital condyle fractures and atlas fractures as well as atlanto-axial injury. The integrity of anterior longitudinal ligament, disc, and facet joint attributes to the stability of axis fractures. The integrity of tectorial membrane and alar ligaments determines the stability of atlanto-occipital dislocation. The development of a newly classification system concerning ligamentous instability with a high clinical and scientific impact is recommended.

Integrity of the tectorial membrane is a favorable prognostic factor in atlanto-occipital dislocation

Objective: Atlanto-occipital dislocation is usually considered to be a fatal injury or one that leaves the victim with serious neurological deficits. The aim of this study is to illustrate a novel positive prognostic factor for atlanto-occipital dislocation, based on cervical MRI studies of patients who suffered this injury.Methods: Over the course of the past year, the authors have treated three consecutive patients with atlanto-occipital dislocation who attained an excellent clinical outcome. We retrospectively evaluated clinical, surgical and radiographic parameters in search of a common denominator to explain the excellent outcome of these patients.Results: All patients presented with severe polytrauma that required urgent surgical intervention including two laparotomies and a thoracotomy. The patients were subsequently treated with an occipitocervical fusion. No patient developed neurological deficits on long-term follow-up. The cervical MRI studies of all patients were notable for a having a preserved tectorial membrane, while other primary stabilizers of the craniocervical junction such as the apical, alar and cruciate ligaments were shown to be severely disrupted. We consider this anatomical distinction to account for their benign clinical course.Conclusion: A preserved tectorial membrane appears to be an important favorable prognostic factor in atlanto-occipital dislocation and may serve to mitigate neurological outcome in such injuries. To determine the integrity of the ligament and consequently affect clinical management, expeditious MRI of the cranio-cervical junction should be considered routinely in such injuries in addition to cervical CT scans.

Distinct roles of stereociliary links in the nonlinear sound processing and noise resistance of cochlear outer hair cells

Outer hair cells (OHCs) play an essential role in hearing by acting as a nonlinear amplifier which helps the cochlea detect sounds with high sensitivity and accuracy. This nonlinear sound processing generates distortion products, which can be measured as distortion-product otoacoustic emissions (DPOAEs). The OHC stereocilia that respond to sound vibrations are connected by three kinds of extracellular links: tip links that connect the taller stereocilia to shorter ones and convey force to the mechanoelectrical transduction channels, tectorial membrane-attachment crowns (TM-ACs) that connect the tallest stereocilia to one another and to the overlying TM, and horizontal top connectors (HTCs) that link adjacent stereocilia. While the tip links have been extensively studied, the roles that the other two types of links play in hearing are much less clear, largely because of a lack of suitable animal models. Here, while analyzing genetic combinations of tubby mice, we encountered models missing both HTCs and TM-ACs or HTCs alone. We found that the tubby mutation causes loss of both HTCs and TM-ACs due to a mislocalization of stereocilin, which results in OHC dysfunction leading to severe hearing loss. Intriguingly, the addition of the modifier allele modifier of tubby hearing 1 in tubby mice selectively rescues the TM-ACs but not the HTCs. Hearing is significantly rescued in these mice with robust DPOAE production, indicating an essential role of the TM-ACs but not the HTCs in normal OHC function. In contrast, the HTCs are required for the resistance of hearing to damage caused by noise stress.

C1 Hemilaminectomy for Resection of Foramen Magnum Meningioma: 2-Dimensional Operative Video.

We present a case of a sizeable foramen magnum meningioma that was resected through a C1 hemilaminectomy in prone (concorde) position. The patient is a 51-year-old woman with a 3-month history of progressive paresthesia of the upper and lower extremities, followed by gait disturbance, and hand apraxia. There was no complaint of nuchal pain.On magnetic resonance imaging (MRI) a briskly enhancing extra-axial, intradural craniospinal lesion, extending from the basion of the lower clivus, over the tectorial membrane to the middle of the axis' body was discovered. There was significant transposition and compression of the medulla and corresponding focal hyperintensity on T2-weighted imaging.On physical examination, the patient was ambulatory independently, notwithstanding a pronounced spinal ataxia. There were deficits in sensation and proprioception, as well as urinary retention, but preserved function of the lower cranial nerves.In view of the profound transposition of the medulla, utilization of the corridor created by the tumor seemed feasible and we felt that a limited C1 hemilaminectomy would provide sufficient microsurgical access thus obviating a more extensive and invasive approach to the craniocervical junction.A gross-total resection was achieved; histopathology confirmed a World Health Organization (WHO) grade I angiomatous meningioma with a low-proliferation index. The patient was discharged home 3 days after surgery and her spinal ataxia resolved completely within 3 months of out-patient rehabilitation. At 3-year follow-up, there was no indication of residual or recurrence. The link to the video can be found at: https://youtu.be/WyShbfr-xi0 .

Calcium signaling in interdental cells during the critical developmental period of the mouse cochlea

The tectorial membrane (TM), a complex acellular structure that covers part of the organ of Corti and excites outer hair cells, is required for normal hearing. It consists of collagen fibrils and various glycoproteins, which are synthesized in embryonic and postnatal development by different cochlear cell types including the interdental cells (IDCs). At its modiolar side, the TM is fixed to the apical surfaces of IDCs, which form the covering epithelium of the spiral limbus.We performed confocal membrane imaging and Ca2+ imaging in IDCs of the developing mouse cochlea from birth to postnatal day 18 (P18). Using the fluorescent membrane markers FM 4–64 and CellMask™ Deep Red on explanted whole-mount cochlear epithelium, we identified the morphology of IDCs at different z-levels of the spiral limbus.Ca2+ imaging of Fluo-8 AM-loaded cochlear epithelia revealed spontaneous intracellular Ca2+ transients in IDCs at P0/1, P4/5, and P18. Their relative frequency was lowest on P0/1, increased by a factor of 12.5 on P4/5 and decreased to twice the initial value on P18. At all three ages, stimulation of IDCs with the trinucleotides ATP and UTP at 1 and 10 μM elicited Ca2+ transients of varying amplitude and shape. Before the onset of hearing, IDCs responded with robust Ca2+ oscillations. At P18, after the onset of hearing, ATP stimulation either caused Ca2+ oscillations or an initial Ca2+ peak followed by a plateau while the UTP response was unchanged from that at pre-hearing stage. Parameters of spontaneous and nucleotide-evoked Ca2+ transients such as amplitude, decay time and duration were markedly reduced during cochlear development, whereas the kinetics of the Ca2+ rise did not show relevant changes. Whether low-frequency spontaneous Ca2+ transients are necessary for the formation and maintenance of the tectorial membrane e.g. by regulating gene transcription needs to be elucidated in further studies.