Basal Turn Research Articles

GJB2 and GJB6 gene transcripts in the human cochlea: A study using RNAscope, confocal, and super-resolution structured illumination microscopy.

BackgroundGap junction (GJ) proteins, connexin26 and 30, are highly prevalent in the human cochlea (HC), where they are involved in transcellular signaling, metabolic supply, and fluid homeostasis. Their genes, GJB2 and GJB6, are both located at the DFNB1 locus on chromosome 13q12. Mutations in GJB2 may cause mild to profound non-syndromic deafness. Here, we analyzed for the first time the various expressions of GJB2 and GJB6 gene transcripts in the different cell networks in the HC using the RNAscope technique.Materials and methodsArchival paraformaldehyde-fixed sections of surgically obtained HC were used to label single mRNA oligonucleotides using the sensitive multiplex RNAscope® technique with fluorescent-tagged probes. Positive and negative controls also included the localization of ATP1A1, ATP1A2, and KCNJ10 gene transcripts in order to validate the specificity of labeling.ResultsConfocal and super-resolution structured illumination microscopy (SR-SIM) detected single gene transcripts as brightly stained puncta. The GJB2 and GJB6 gene transcripts were distributed in the epithelial and connective tissue systems in all three cochlear turns. The largest number of GJB2 and GJB6 gene transcripts was in the outer sulcus, spiral ligament, and stria vascularis (SV). Oligonucleotides were present in the supporting cells of the organ of Corti (OC), spiral limbus fibrocytes, and the floor of the scala vestibuli. Multiplex gene data suggest that cells in the cochlear lateral wall contain either GJB2 or GJB6 gene transcripts or both. The GJB6, but not GJB2, gene transcripts were found in the intermediate cells but none were found in the marginal cells. There were no GJB2 or GJB6 gene transcripts found in the hair cells and only a few in the spiral ganglion cells.ConclusionBoth GJB2 and GJB6 mRNA gene transcripts were localized in cells in the adult HC using RNAscope® in situ hybridization (ISH) and high resolution microscopy. Generally, GJB6 dominated over GJB2, except in the basal cells. Results suggest that cells may contain either GJB2 or GJB6 gene transcripts or both. This may be consistent with specialized GJ plaques having separate channel permeability and gating properties. A reduction in the number of GJB2 gene transcripts was found in the basal turn. Such information may be useful for future gene therapy.

Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss

BackgroundChronic suppurative otitis media (CSOM) is the most common cause of permanent hearing loss in children in the developing world. A large component of the permanent hearing loss is sensory in nature and our understanding of the mechanism of this has so far been limited to post-mortem human specimens or acute infection models that are not representative of human CSOM. In this report, we assess cochlear injury in a validated Pseudomonas aeruginosa (PA) CSOM mouse model.MethodsWe generated persisters (PCs) and inoculated them into the mouse middle ear cavity. We tracked infection with IVIS and detected PA using RT-PCR. We assessed cochlear damage and innate immunity by Immunohistochemistry. Finally, we evaluated cytokines with multiplex assay and quantitative real-time PCR.ResultsWe observed outer hair cell (OHC) loss predominantly in the basal turn of the cochlear at 14 days after bacterial inoculation. Macrophages, not neutrophils are the major immune cells in the cochlea in CSOM displaying increased numbers and a distribution correlated with the observed cochlear injury. The progression of the morphological changes suggests a transition from monocytes into tissue macrophages following infection. We also show that PA do not enter the cochlea and live bacteria are required for cochlear injury. We characterized cytokine activity in the CSOM cochlea.ConclusionsTaken together, this data shows a critical role for macrophages in CSOM-mediated sensorineural hearing loss (SNHL).

Morphology of the internal auditory canal: Deriving parameters from computer tomography scans. An observational STROBE-MR study.

The objective of this study is to identify and define landmarks to adequately describe the internal auditory canal for inclusion in three-dimensional computational models of the cochlea and its surrounding structures. Computer tomography scans of live human cochleae were collected in the retrospective period. Descriptive and comparative statistics were used to describe the data obtained from the scans. The mean anterior-posterior (AP) diameter at the base of the basal turn, the diameter of the AP at the midpoint of the IAC, and the anterior and posterior length of the internal acoustic canal were measured. 57.14% of the internal acoustic canals observed presented with a cylindrical, 40.48% was funnel-shaped and 2.38 % were bud-shaped. A statistically significant differences were found between the diameters of male and female internal acoustic meatus. This paper serves as a reference that provides a set of references for the description of the internal acoustic canal for inclusion in three-dimensional computational reconstruction of the cochlea and surrounding structures.

Lead exposure induces nitrative stress and disrupts ribbon synapses in the cochlea.

Environmental exposure to heavy metal lead, a public health hazard in many post-industrial cities, causes hearing impairment upon long-term exposure. Lead-induced cochlear and vestibular dysfunction is well-documented in animal models. Although short-term exposure to lead at concentrations relevant to environmental settings does not cause significant shifts in hearing thresholds in adults, moderate- to low-level lead exposures induce neuronal damage and synaptic dysfunction. We reported that lead exposure induces oxidative stress in the mouse cochlea. However, lead-induced nitrative stress and potential damage to cochlear ribbon synapses are yet to be fully understood. Therefore, this study has evaluated cochlear synaptopathy and nitrative stress in young-adult mice exposed to 2 mM lead acetate for 28 days. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated that this exposure significantly increased the blood lead levels. Assessment of hair cell loss by immunohistochemistry analysis and outer hair cell (OHC) activity by recording distortion product otoacoustic emissions (DPOAEs) indicated that the structure and function of the hair cells were not affected by lead exposure. However, this exposure significantly decreased the expression of C-terminal-binding protein-2 (CtBP2) and GluA2, pre- and post-synaptic protein markers in the inner hair cell synapses, particularly in the basal turn of the organ of Corti, suggesting lead-induced disruption of ribbon synapses. In addition, lead exposure significantly increased the nitrotyrosine levels in spiral ganglion cells, suggesting lead-induced nitrative stress in the cochlea. Collectively, these findings suggest that lead exposure even at levels that do not affect the OHCs induces cochlear nitrative stress and causes cochlear synaptopathy.

Typical and Atypical Symptoms of Petrous Apex Cholesterol Granuloma: Association with Radiological Findings.

Objective: Petrous apex cholesterol granuloma (PACG) is a lesion that can give rise to different symptoms, and correlations with etiopathology are ambiguous. The aim of this study is to analyze the association between PACG symptoms and radiological findings at presentation, in order to establish a reproduceable pre-operative radiological evaluation and guide the surgical indication. Methods: PACG patients were collected in two tertiary care hospitals. All cases underwent CT/MRI to evaluate the cyst localization and erosion of surrounding structures. Typical and atypical symptoms were then analyzed and compared to radiologic findings established in accordance with the literature. Results: Twenty-nine patients were recruited; the most common symptoms were headache (69%), diplopia (20.7%) and fainting (24.1%), an atypical clinical manifestation related to jugular tubercle involvement. Significant associations between symptoms and radiologic findings were noted in terms of headache and temporal lobe compression (p = 0.04), fainting and jugular tubercle erosion (p < 0.001), vestibular symptoms and internal auditory canal erosion (p = 0.02), facial paresthesia and Meckel’s cave compression (p = 0.03), diplopia and Dorello canal involvement (p = 0.001), and tinnitus and cochlear basal turn erosion (p < 0.001). All patients were treated via an endoscopic–endonasal approach, in which extension was tailored to each case. At a median follow-up of 46 months, 93.1% of patients experienced resolution of symptoms. Conclusions: This clinico-radiological series demonstrates associations between symptoms and anatomical subsites involved with PACG. Hence, it may guide the surgeon at the time of surgical decision, since it asserts that typical and atypical symptoms are actually related to PACG.

Difference in cochlear length between male and female patients

Objective: To compare cochlear duct length (CDL) between male and female patients by evaluating the diameter of the basal turn (distance A) on CT scans. Method: All temporal bone CT scans performed between 2014 and 2020 were reviewed in our medical center. Using multiplanar reconstructions, the length A, which is the greatest distance of the basal turn was measured on both sides. We performed an analysis of variance considering two factors: sex and side. Two different physicians carried out the measurements, an otolaryngologist and a neuroradiologist. The patients who had several CT scans allowed us to evaluate the reliability of our procedure. Results: Among the 888 CT scans reviewed, 8 were excluded because of cochlear malformations. The inter-sex difference of length A was found to be 0.29 millimeters(mm) 95% IC [0.26-0.34] and was longer in the male group (p < 0.0001). Using Alexiades' equation, we found that CDL was 34.5mm [34.37-34.61] in the male group and 33.3mm [33.13-33.38] in the female group. When one side was compared to the other, there was no significant difference (p = 0.226). An intra-class correlation found a good absolute agreement between the two screeners of 0.79. Conclusion: Males have a statistically significant longer CDL than females.

Frequency Mapping of a Precurved Electrode Array in the Internal Auditory Canal for a Pediatric Cochlear Implant Recipient.

Review the effectiveness of an alternative mapping procedure of a precurved electrode array in the internal auditory canal (IAC). A 7-year-old bilateral cochlear implant (CI) recipient of precurved arrays transferred to the study site and demonstrated no speech recognition with the left CI. Imaging revealed bilateral incomplete partition type III malformations. For the left CI, four contacts were observed in the basal cochlear turn and 18 contacts were coiled in the IAC. The family decided against revision surgery. Pitch ranking was completed to map the contacts in the IAC that were perceptually discrete and tonotopically organized. For the left CI, PB-K word recognition improved from no recognition to 32% after 1 month and to 52% after 3 months. In the bilateral CI condition, performance improved from 56 to 72% after 1 month and 80% after 3 months. A precurved array in the IAC creates difficult management decisions. Direct stimulation of the auditory nerve resulted in better monaural and bilateral speech recognition, likely due to better spectral representation of the speech signal. Individualizing the map using imaging and behavioral findings may improve performance for malpositioned arrays when revision surgery is not pursued.

Efficient Delivery of Adeno-Associated Virus into Inner Ear In Vivo Through Trans-Stapes Route in Adult Guinea Pig.

Adeno-associated virus (AAV) are potent vectors to achieve treatment against hearing loss resulting from genetic defects. However, the effects of delivery routes and the corresponding transduction efficiencies for clinical applications remain elusive. In this study, we screened AAV vectors of three serotypes (AAV 8 and 9 and Anc80L65) into the inner ears of adult normal guinea pigs through trans-stapes (oval window) and trans-round window delivery routes in vivo. Trans-stapes route is akin to stape surgeries in humans. Then, auditory brainstem response (ABR) measurements were conducted to evaluate postoperative hearing, and inner ear tissues were harvested for transduction efficiency analysis. Results showed that AAV8 targeted partial inner hair cells (IHCs) in cochlear basal turn; AAV9 targeted IHCs in cochlear basal and second turn, also a part of vestibular hair cells (VHCs). In contrast, Anc80L65 contributed to green fluorescent proteins (GFP) signals of 80 - 95% IHCs and 67 - 91% outer hair cells (OHCs), as well as 69% VHCs through the trans-round window route, with 15-20 decibel (dB) ABR threshold shifts. And, through the trans-stapes (oval window) route, there were 71 - 90% IHCs and 42 - 81% OHCs, along with 64% VHCs demonstrating GFP positive, and the ABR threshold shifts were within 10 dB. This study revealed AAV could be efficiently delivered into mammalian inner ear cells in vivo through the trans-stapes (oval window) route with postoperative hearing preservation, and both delivery routes showed promise of virus-based clinical translation of hearing impairment treatment.

Resection of Intracochlear Schwannomas With Immediate Cochlear Implantation.

Intralabyrinthine schwannomas, including the intracochlear variety, are rare benign tumors. They can cause a number of symptoms and have the potential to grow to involve other critical structures of the inner ear and skull base. While surgical resection is feasible, there is typically permanent hearing dysfunction as a result of resection and subsequent fibrosis. Here, we present 2 cases of intracochlear schwannomas (ICS) that were successfully resected with simultaneous cochlear implant placement. Patient 1 presented with an intravestibulocochlear schwannoma. This patient underwent a translabyrinthine approach. Endoscopic assistance was used to dissect the tumor from the vestibule and basal turn of the cochlea, through an enlarged round window approach. A cochlear implant was placed via a round window cochleostomy. Patient 2 presented with an intracochlear schwannoma involving the basal and middle turns of the cochlea. The patient underwent a trans-otic approach for resection. A large portion of the cochlear promontory required unroofing for complete exposure of the tumor. A cochlear implant was then placed via a round window cochleostomy. Upon cochlear implant activation, Patient 1's sound field thresholds using the implant were near the normal range of hearing, ranging from 25 to 50 dB HL from 250 to 6000 Hz. Patient 2's 6-month post-operative cochlear implant sound field testing ranged from 20 to 30 dB HL from 250 to 6000 Hz and speech recognition testing revealed 59% on AZ Bio sentences compared to 0% pre-operatively. Simultaneous cochlear implantation after resection of intracochlear schwannomas is safe and successful in restoring hearing. Attention to adequate exposure and endoscopic assistance, when required, allow for gross total resection while minimizing trauma to cochlear structures. In such cases, immediate cochlear implantation allows for hearing rehabilitation before likely cochlear fibrosis can occur.

Symptoms: Sudden Hearing Loss and Vertigo

Symptoms: Sudden Hearing Loss and Vertigo

Robot-assisted cochlear implant surgery in a patient with partial ossification of the basal cochlear turn: A technical note.

Robotic cochlear implant surgery is a new and safe technique. A system for robotic cochlear implant surgery has become available in Europe. Robotic cochlear implant surgery can be successfully performed in partially-ossified basal cochlear turns. Adaption of the planning procedure by increasing the milling depth enables robotic cochlear implant surgery in ossified basal cochlear turns. By adaption of the planning procedure, more complex anatomical variations will become implantable in the future.

Two Cases of Cochlear Implantation in Patients With Unilateral Profound Hearing Loss Due to Intralabyrinthine Schwannoma

When vestibular schwannoma originates from the segment within the labyrinth of the vestibulocochlear nerve, it is termed intralabyrinthine schwannoma (ILS). As most of the cases are presented with profound sensorineural hearing loss on the affected side, for auditory rehabilitation, cochlear implantation can be considered simultaneously as the tumor removal. Successful results of cochlear implantation were reported in patients with ILS even after partial resection of the mass. In this study, we report the cases of two patients with ILS with unilateral deafness. In one patient, a mass found in the basal turn of cochlea was removed totally and a cochlear implantation electrode was fully inserted. In the other patient, a mass found in the basal turn and vestibule was partially removed and an electrode was inserted. Postoperatively, hearing was improved and tinnitus was reduced.

Injected 3T-3D-FLAIR-MRI labyrinthine patterns match with the severity and tonotopic alteration in sudden sensorineural hearing loss.

The aim of the study was to assess a correlation between MRI labyrinthine changes detected with IV-gadolinium optimized high-resolution 3D-FLAIR sequences 4h after injection (OPT4-3DFLAIR) and the type of SSNHL, in terms of frequency alteration and severity. This was a prospective monocentric study achieved from July 2019 to December 2020. The inclusion criterion was acute hearing loss of at least 30dB over three contiguous frequencies occurring within a 72-h period, documented by a pure-tone audiometry (PTA). The primary endpoint was the visual assessment of hyperintensity in labyrinthine structures on OPT4-3DFLAIR performed on 3T MRI. Thirty-six affected ears were included (20 men, 15 women; mean age: 54.5 ± 16.3years) with 69.4% full-spectrum hearing loss. The median hearing loss, expressed as median and interquartile range [IQR] was 91dB [74-120], with 47.2% of concomitant acute vestibular syndrome. Pathological signal was found in 26 out of 36 ears (72.2%). Basal turn enhancement was found in all abnormal MRIs, with 73.1% of apical turn enhancement and 50% of vestibular enhancement. Seventeen on 19 cases (89.5%) with apical involvement on MRI had low-frequency hearing loss. Vestibular involvement on MRI was significantly associated with a wider frequency range of hearing loss (p = 0.0002) and the severity of SSNHL (84.5 [71.7-92.5] dB versus 120 [85.8-120] dB, p = 0.0158). This report shows that in pathological MRI in SSNHL, a pathologic cochlear base signal is always detected, a cochlear apical turn enhancement matches with low-tone impairment, and a pathological signal within the posterior labyrinth is associated with an impairment of all frequencies and the severity of SSNHL.

Failure Of Hearing Acquisition in Mice With Reduced Expression of Connexin 26 Correlates With the Abnormal Phasing of Apoptosis Relative to Autophagy and Defective ATP-Dependent Ca2+ Signaling in Kölliker's Organ.

Mutations in the GJB2 gene that encodes connexin 26 (Cx26) are the predominant cause of prelingual hereditary deafness, and the most frequently encountered variants cause complete loss of protein function. To investigate how Cx26 deficiency induces deafness, we examined the levels of apoptosis and autophagy in Gjb2loxP/loxP; ROSA26CreER mice injected with tamoxifen on the day of birth. After weaning, these mice exhibited severe hearing impairment and reduced Cx26 expression in the cochlear duct. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells were observed in apical, middle, and basal turns of Kölliker’s organ at postnatal (P) day 1 (P1), associated with increased expression levels of cleaved caspase 3, but decreased levels of autophagy-related proteins LC3-II, P62, and Beclin1. In Kölliker’s organ cells with decreased Cx26 expression, we also found significantly reduced levels of intracellular ATP and hampered Ca2+ responses evoked by extracellular ATP application. These results offer novel insight into the mechanisms that prevent hearing acquisition in mouse models of non-syndromic hearing impairment due to Cx26 loss of function.

Cochlear Implant Electrode Misplacement: A Case Series and Contemporary Review.

To determine root causes leading to misplaced cochlear implant (CI) electrode arrays and discuss their management using a case series and contemporary literature review. Retrospective case review and contemporary literature review. Single tertiary-referral center. Adult and pediatric patients who were diagnosed with a misplaced CI electrode array, excluding tip-foldover. Literature review was performed via a MEDLINE database PubMed query. All articles that described at least one case of extracochlear electrode array misplacement were included; partial insertions and extrusions were excluded. Extracochlear misplacement. A total of 61 cases were reviewed, including 4 new cases and 57 cases from 29 previously published articles. We discuss management of CI arrays in the carotid canal, the vestibule, and the modiolus. The rate of CI misplacement is estimated to be 0.49%. The most frequent location of misplacement CI was the vestibular system (50.8%) followed by the internal carotid canal (11.5%). Normal cochlear anatomy was noted on preoperative computer tomography (CT) in 59.0% of patients; abnormalities were noted in 27.9%. The most common technical issue was misidentification or poor visualization of the round window. CI electrode misplacement is rare but can cause postoperative complications and may result in permanently diminished CI performance and hearing outcomes, even after revision surgery. Failure to identify the round window is the most common reason for CI misplacement, despite most patients having normal cochlear anatomy. Surgical strategies to localize the round window and basal turn are imperative for proper electrode placement. 4.

A Case of Cochlear Implantation in a Patient With Intracochlear Schwannoma

Intralabyrinthine schwannomas are rare benign tumors, which arise from neural portions within the labyrinth. These are subclassified into seven groups according to the affected inner ear structures. Intracochlear schwannomas (ICS) are tumors confined to the cochlea, and these can cause progressive unilateral sensorineural hearing loss, tinnitus, vertigo and aural fullness. Here, we report a 49-year-old female patient with left sudden sensorineural hearing loss. There was no improvement of hearing despite steroid and hyperbaric oxygen therapy. Space occupying lesion in the basal turn of the left cochlea was identified in MRI with enhancement. She underwent tumor removal through an extended round window approach, and cochlear implantation was performed successfully. This is the first case report of cochlear implantation after tumor removal in a patient with ICS in Korea, and we discuss management options with a review of the literature.

Human vestibular schwannoma reduces density of auditory nerve fibers in the osseous spiral lamina

Hearing loss in patients with vestibular schwannoma (VS) is commonly attributed to mechanical compression of the auditory nerve, though recent studies suggest that this retrocochlear pathology may be augmented by cochlear damage. Although VS-associated loss of inner hair cells, outer hair cells, and spiral ganglion cells has been reported, it is unclear to what extent auditory-nerve peripheral axons are damaged in VS patients. Understanding the degree of damage VSs cause to auditory nerve fibers (ANFs) is important for accurately modeling clinical outcomes of cochlear implantation, which is a therapeutic option to rehabilitate hearing in VS-affected ears. A retrospective analysis of human temporal-bone histopathology was performed on archival specimens from the Massachusetts Eye and Ear collection. Seven patients met our inclusion criteria based on the presence of sporadic, unilateral, untreated VS. Tangential sections of five cochlear regions were stained with hematoxylin and eosin, and adjacent sections were stained to visualize myelinated ANFs and efferent fibers. Following confocal microscopy, peripheral axons of ANFs within the osseous spiral lamina were quantified manually, where feasible, and with a “pixel counting” method, applicable to all sections. ANF density was substantially reduced on the VS side compared to the unaffected contralateral side. In the upper basal turn, a significant difference between the VS side and unaffected contralateral side was found using both counting methods, corresponding to the region tuned to 2000 Hz. Even spiral ganglion cells (SGCs) contralateral to VS were affected by the tumor as the majority of contralateral SGC counts were below average for age. This observation provides histological insight into the clinical observation that unilateral vestibular schwannomas pose a long-term risk of progression of hearing loss in the contralateral ear as well. Our pixel counting method for ANF quantification in the osseous spiral lamina is applicable to other pathologies involving sensorineural hearing loss. Future research is needed to classify ANFs into morphological categories, accurately predict their electrical properties, and use this knowledge to inform optimal cochlear implant programming strategies.

Intracochlear New Fibro-Ossification and Neuronal Degeneration Following Cochlear Implant Electrode Translocation: Long-Term Histopathological Findings in Humans.

We aim to assess the histopathology of human temporal bones (TBs) with evidence of cochlear implantation (CI) electrode scalar translocation. Otopathology study. Otopathology laboratory. TBs from patients who had a history of CI and histopathological evidence of interscalar translocation. Specimens with electrode placed entirely within the ST served as controls. Histopathological assessment of human TBs. TBs from each patient were harvested postmortem and histologically analyzed for intracochlear changes in the context of CI electrode translocation and compared to controls. Intracochlear new fibro-ossification, and spiral ganglion neuron (SGN) counts were assessed. Postoperative word recognition scores (WRS) were also compared. Nineteen human TBs with electrode translocation and eight controls were identified. The most common site of translocation was the ascending limb of the basal turn (n = 14 TBs). The average angle of insertion at the point of translocation was 159° ± 79°. Eighteen translocated cases presented moderate fibroosseous changes in the basal region of the cochlea, extending to the translocation point and/or throughout the electrode track in 42%. Lower SGN counts were more pronounced in translocated cases compared to controls, with a significant difference for segment II (p = 0.019). Although final postoperative hearing outcomes were similar between groups, translocated cases had slower rate of improvement in WRS (p = 0.021). Cochlear implant electrode translocation was associated with greater fibroosseous formation and lower SGN population. Our findings suggest that scalar translocations may slow the rate of improvement in WRS overtime as compared to atraumatic electrode insertions.Level of evidence: IV.

Rapamycin ameliorates age-related hearing loss in C57BL/6J mice by enhancing autophagy in the SGNs

Autophagy plays a pathogenic role in neurodegenerative disease. However, the involvement of autophagy in the pathogenesis of age-related hearing loss (ARHL) remains obscure. Naturally aged C57BL/6J mice were used to identify the role of autophagy in ARHL, and rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, was administered for 34 weeks to explore the potential therapeutic effect of rapamycin in ARHL. We found that the number of autophagosomes and the expression of microtubule-associated protein 1 light chain 3B (LC3B) decreased as the mice aged. The expression of autophagy-related (Atg) proteins, including Beclin1 and Atg5, and the ratio of LC3-II/I was reduced in aged mice, while mTOR activity in aged mice gradually increased. Rapamycin improved the auditory brainstem response (ABR) threshold (at 8, 12, and 24 kHz). Further exploration demonstrated that spiral ganglion neuron (SGN) density was enhanced in response to administration of rapamycin. The rate of apoptosis in the basal turn SGNs was decreased, whereas autophagy activity was increased in the experimental group. Meanwhile, mTOR activity in the experimental group was decreased. Our findings indicate that age-related deficiency in autophagy may lead to increased apoptosis of aged SGNs. Rapamycin enhances autophagy of SGNs by inhibiting mTOR activation, resulting in amelioration of ARHL. Therapeutic strategy targeting autophagy may provide a potential approach for treating ARHL.

Insights into Presbycusis From the First Temporal Bone Laboratory Within the United States.

The Johns Hopkins Otologic Research Laboratory was founded in 1924 as the first human temporal bone laboratory within the United States. To better understand the contributions of the Johns Hopkins Otologic Research Laboratory to our understanding of presbycusis, we consulted with a medical librarian and archivist to search the Alan Mason Chesney Medical Archives, PubMed, JSTOR, and Johns Hopkins Bulletin for published and unpublished works from the lab. Between 1924 and 1938, Samuel J. Crowe, the Chairman of Otolaryngology, and anatomist Stacy R. Guild amassed a collection of ∼1,800 temporal bones. This collection allowed for an unprecedented period of discovery related to otologic disease. They combined hearing thresholds measured by the recently invented audiometer with new techniques for temporal bone decalcification, sectioning, and staining, and a method for the graphic reconstruction of the cochlea. Crowe and Guild used this unique opportunity to correlate otopathology with hearing and to make the first detailed descriptions of the otopathology of presbycusis. In 1931 and 1934, they observed spiral ganglion neuron and outer hair cell loss in the basal turn of the cochlea in individuals with high-frequency hearing loss. These were the first studies to reveal that stria vascularis degeneration and middle ear pathology were not the most common causes for high-frequency hearing loss. Aside from revealing the primary driving factors of presbycusis, this work provided insight into the tonotopic organization of the cochlea. After initially being recruited to help raise money for the laboratory, medical illustrator Max Brödel used the vertical histologic cross-sections of the cochlea to produce illustrations of the ear. The decision to produce histologic sections in the plane of the superior semicircular canal likely influenced Brödel's illustrations that share a similar orientation and would later become widely circulated. Significant contributions from the Otologic Research Laboratory were also made by Mary Hardy, D.Sc., a woman who has previously received little recognition for her work. The sectioning of temporal bones was stopped in 1938 due to World War II, but much of Crowe's and Guild's work continued into the 1940s until a rift between the two resulted in the temporary closure of the laboratory in 1949. Nearly 100 years after its founding, discoveries from the Johns Hopkins Otologic Research Laboratory remain relevant and emphasize the importance of continued human temporal bone research to improve our understanding and treatment of otologic disease.