Disrupted harmony of the skull skeleton: Middle ear resonance in acromegaly.

OBJECTIVES: This study aims to investigate whether the middle ear resonance frequency (RF) is affected in acromegaly, which causes growth in the skull bone. METHODS: Thirty acromegaly patients and 38 volunteers were included in the study. Pure tone average scores and middle ear RF values of the groups that underwent pure tone audiometry, tympanometry, and multifrequency tympanometry tests were compared. RESULTS: The pure tone mean was 14.95 ± 12.13 in acromegaly patients and 5.70 ± 8.52 in the control group (p:0.18). Sensorineural hearing loss(SNHL) was observed in 16.6% of the patients. The average middle ear RF was calculated as 815 ± 179.05 Hz in patients with acromegaly and 773 ± 127.15 in the control group. (p = 0.0001). CONCLUSION: This study is the first to evaluate middle-ear RF in acromegaly patients. Acromegaly-induced changes in soft tissues and bone structures impact middle ear functions. In this patient group, we found an increase in middle ear RF without conductive-type hearing loss and a 16.6% rate of SNHL.

The A2ml1-Knockout mouse as an animal model for non-syndromic otitis media.

BACKGROUND: Inflammation and infection of the middle ear, known as otitis media (OM), is a leading cause of hearing loss and the most frequently diagnosed disease in children worldwide. Traditionally, mouse models for OM rely on inducing acute infection through inoculation of the middle ear, e.g. with the human otopathogen non-typeable Haemophilus influenzae (NTHi), and with very few genetic models with spontaneous or chronic OM. A2ML1 variants, including loss-of-function variants, were associated with susceptibility to OM in humans, but no animal model has been reported for A2ml1-related OM. Here, we report our middle ear findings in a mouse line with a CRISPR-induced knockout (KO) of A2ml1. METHODS: Mice were X-rayed prior to harvest to determine if there are craniofacial or skeletal abnormalities. Tissue from mouse middle ears, as well as other upper respiratory mucosal tissues, were harvested. The harvested middle ear bullae were examined under microscope and submitted for histologic preparation to study phenotypic indications of OM. RNA samples isolated from middle ear tissue were assayed for expression of genes correlated with A2ML1 expression in humans. RESULTS: Data from a total of 119 mice (35 wildtype, 40 heterozygous, 44 homozygous) are presented here, with each analyses being performed on subsets of these mice. There were no significant craniofacial differences by genotype (n = 22). Findings in mice with the A2ml1-KO indicated an increased incidence of OM (n=29; odds ratio = 11; CI: 1.1, 573.6; Fisher exact two-sided p = 0.02) with tympanic membrane perforations or thickening, as well as cases of middle ear effusion, inflammatory cells, or fluid from histologic sections. Dsp was upregulated in the middle ear tissues of homozygous mice (Wilcoxon test p = 0.001). CONCLUSION: Thus far, our results in this A2ml1-KO mouse line indicate spontaneous occurrence of OM and dysregulation of Dsp in the middle ear as a potential disease mechanism for A2ml1-related OM.

Diagnostic and Imaging Findings in Inflammatory Opacifications of the Middle Ear: A Review of the Literature.

Opacification in the middle ear and mastoid region can stem from a wide range of factors. In terms of diagnostic imaging, CT is the primary tool due to its exceptional spatial resolution, particularly for examining the temporal bone and ossicles. MRI complements this by offering detailed soft tissue lesion characterization and assessing involvement in the inner ear and cranial nerves. This study focuses on inflammatory causes of opacification in the middle ear and mastoid, with an emphasis on the utility of CT and MRI. This comprehensive review aimed to provide a practical framework for considering potential differential diagnoses.

Middle Ear Tophi: A Case Series of Two Unusual Lesions and a Report of Facial Weakness and Review of the Literature.

OBJECTIVE: Tophaceous lesions of the middle ear from calcium pyrophosphate deposition disease (CPPD, or pseudogout) and gout are infrequently reported. Recognizing its characteristic findings will allow clinicians to accurately narrow the differential diagnosis of bony-appearing middle ear lesions and improve management. PATIENTS: Two consecutive cases of tophaceous middle ear lesions presenting to a tertiary care center between January 2021 and December 2021. Neither with previous rheumatologic history. INTERVENTIONS: Surgical excision of tophaceous middle ear lesions. MAIN OUTCOME MEASURE: Improvements in facial weakness and conductive hearing loss. RESULTS: The first case was a 66-year-old gentleman with progressive conductive loss, ipsilateral progressive facial weakness over years, and an opaque, irregular-appearing tympanic membrane anterior to the malleus found to have CPPD on surgical pathology, with immediate postoperative improvement of facial function. The second was a 75-year-old gentleman with progressive conductive loss and similar appearing tympanic membrane as case 1, previously diagnosed with tympanosclerosis, found to have gout on surgical pathology. In both cases, the CT showed a heterogenous, bony-appearing lesion in the middle ear, and both tophaceous lesions were a of gritty, chalky consistency intraoperatively. CONCLUSION: Tophaceous lesions of the middle ear are rare but have similar findings. Notably, the tympanic membrane can appear opaque and irregular, and the CT demonstrates a radiopaque, heterogeneous appearance. Facial weakness is an unusual finding. Specimens of suspected tophi must be sent to pathology without formalin for accurate diagnosis.

Blue laser for the exclusive endoscopic transcanal approach to middle ear paraganglioma.

BACKGROUND: The management of glomus tympanicum tumours can be challenging. Blue laser coagulation may improve bleeding control thus facilitating an endoscopic transcanal excision. The objective of this presentation is to illustrate the authors' experience using this novel tool. METHODS: Case report of a patient that underwent exclusive endoscopic transcanal blue laser surgery of a class A2 glomus tympanicum tumour in a tertiary referral center. CONCLUSION: The present study provides evidence of the safety and efficacy of endoscopic blue laser surgery, for the minimally invasive treatment of early-stage glomus tympanicum tumours.

[Specialist consensus on endoscopic surgery of the middle ear mastoid].

This article discusses otoscopic middle ear mastoid surgery from multiple perspectives. Firstly, it discusses the indications and contraindications for surgery from the nature of the lesion and the imaging manifestations; secondly, it recommends the applicable equipment and describes the surgical approach in detail; finally, it summarizes the principles of the management of the operative cavity of the mastoid process in the middle ear from the perspectives of function and reconstruction. The purpose of this article is to illustrate otoscopic middle ear mastoid surgery with the aim of providing reference or guidance for performing related surgeries.

Oral and middle ear delivery of otitis media standard of care antibiotics, but not biofilm-targeted antibodies, alter chinchilla nasopharyngeal and fecal microbiomes.

Otitis media (OM) is one of the most globally pervasive pediatric conditions. Translocation of nasopharynx-resident opportunistic pathogens like nontypeable Haemophilus influenzae (NTHi) assimilates into polymicrobial middle ear biofilms, which promote OM pathogenesis and substantially diminish antibiotic efficacy. Oral or tympanostomy tube (TT)-delivered antibiotics remain the standard of care (SOC) despite consequences including secondary infection, dysbiosis, and antimicrobial resistance. Monoclonal antibodies (mAb) against two biofilm-associated structural proteins, NTHi-specific type IV pilus PilA (anti-rsPilA) and protective tip-region epitopes of NTHi integration host factor (anti-tip-chimer), were previously shown to disrupt biofilms and restore antibiotic sensitivity in vitro. However, the additional criterion for clinical relevance includes the absence of consequential microbiome alterations. Here, nine chinchilla cohorts (n = 3/cohort) without disease were established to evaluate whether TT delivery of mAbs disrupted nasopharyngeal or fecal microbiomes relative to SOC-OM antibiotics. Cohort treatments included a 7d regimen of oral amoxicillin-clavulanate (AC) or 2d regimen of TT-delivered mAb, AC, Trimethoprim-sulfamethoxazole (TS), ofloxacin, or saline. Fecal and nasopharyngeal lavage (NPL) samples were collected before and several days post treatment (DPT) for 16S sequencing. While antibiotic-treated cohorts displayed beta-diversity shifts (PERMANOVA, P < 0.05) and reductions in alpha diversity (q < 0.20) relative to baseline, mAb antibodies failed to affect diversity, indicating maintenance of a eubiotic state. Taxonomic and longitudinal analyses showed blooms in opportunistic pathogens (ANCOM) and greater magnitudes of compositional change (P < 0.05) following broad-spectrum antibiotic but not mAb treatments. Collectively, results showed broad-spectrum antibiotics induced significant fecal and nasopharyngeal microbiome disruption regardless of delivery route. Excitingly, biofilm-targeting antibodies had little effect on fecal and nasopharyngeal microbiomes.

Prevalence of middle ear effusion in French bulldogs without clinical signs of otic disease: A retrospective study of magnetic resonance imaging (2017-2022).

BACKGROUND: Canine middle ear effusion (MEE) is usually asymptomatic, being an incidental finding when computed tomography or magnetic resonance imaging (MRI) of the head is performed for other reasons unrelated to otic disease. The clinical relevance of the presence of material in the tympanic bulla (TB) remains uncertain, and more detail about its prevalence and appearance in MRI are required. OBJECTIVE: To assess the prevalence of presence of material within the TB of French bulldogs (FB) with no clinical signs suggestive of otitis (externa, media or interna) that underwent high-field MRI for other medical reasons. ANIMALS: Two hundred fifty-two TB of 126 FB were included in this study. MATERIALS AND METHODS: Nonexperimental retrospective study in which MRI images were evaluated by a board-certified veterinary radiologist. RESULTS: Fifty-eight per cent of the dogs had material in the TB lumen (46% of the TB) and 59% were bilaterally affected. The signal intensity of this material related to the grey matter was variable on T1w and mainly hyperintense on T2w sequences. CONCLUSION AND CLINICAL RELEVANCE: FB are predisposed to MEE. This is important when assessing imaging studies of TB of FB with chronic otitis externa, as high percentage of cases may have concurrent MEE. MRI findings in FB with MEE are characterised by a hyperintense signal to the grey matter on T2w in most cases and variable on T1w sequences.

Middle Ear Ossicular Joint Changes in Type 2 Diabetes Mellitus: A Histopathological Study.

OBJECTIVES: Although previous research has indicated inner ear changes in diabetes mellitus (DM) patients, no prior study has explored the middle ear, particularly the ossicles and their joints, in DM patients. This study aimed to investigate whether type 2 DM is associated with middle ear changes, specifically affecting the ossicular chain and joints. METHODS: This study included 47 ears from 25 patients with DM (male = 13, female = 12, age: 51.0 ± 20.5) and age- and sex-matched controls (male = 10, female = 10, age: 54.8 ± 15.9) (sex; p = 1.000, Age; p = 0.991). Otopathological evaluations of the auditory ossicles and incudomalleolar joint (IMJ) were performed using light microscopy. RESULTS: In the IMJ of DM cases, malleus hyalinized cartilage (Malleus hC) and incus hyalinized cartilage (Incus hC) were significantly increased compared with control cases (Malleus hC; DM, 34.17 ± 9.71 µm vs. control 21.96 ± 4.16 µm, p < 0.001) (Incus hC; DM 35.11 ± 10.12 µm vs. control 22.42 ± 4.368 µm, p < 0.001). In addition, bone-line distance was significantly longer than in DM cases than control cases (DM 266.72 ± 59.11 µm vs. control 239.81 ± 35.56 µm p = 0.040). On the other hand, joint discus distance was longer in the control group than in DM cases (DM 96.84 ± 36.80 µm vs. Control 113.63 ± 23.81 µm, p = 0.001). CONCLUSIONS: This study reveals a notable increase in the hyalinized cartilage layer and bone-line distance accompanied by reducing joint discus distance within the IMJ in DM cases. These findings suggest that DM may influence microjoints, such as the IMJ, and potentially impact auditory function. EVIDENCE LEVEL: N/A Laryngoscope, 134:2871-2878, 2024.

Non-rigid point cloud registration for middle ear diagnostics with endoscopic optical coherence tomography.

PURPOSE: Middle ear infection is the most prevalent inflammatory disease, especially among the pediatric population. Current diagnostic methods are subjective and depend on visual cues from an otoscope, which is limited for otologists to identify pathology. To address this shortcoming, endoscopic optical coherence tomography (OCT) provides both morphological and functional in vivo measurements of the middle ear. However, due to the shadow of prior structures, interpretation of OCT images is challenging and time-consuming. To facilitate fast diagnosis and measurement, improvement in the readability of OCT data is achieved by merging morphological knowledge from ex vivo middle ear models with OCT volumetric data, so that OCT applications can be further promoted in daily clinical settings. METHODS: We propose C2P-Net: a two-staged non-rigid registration pipeline for complete to partial point clouds, which are sampled from ex vivo and in vivo OCT models, respectively. To overcome the lack of labeled training data, a fast and effective generation pipeline in Blender3D is designed to simulate middle ear shapes and extract in vivo noisy and partial point clouds. RESULTS: We evaluate the performance of C2P-Net through experiments on both synthetic and real OCT datasets. The results demonstrate that C2P-Net is generalized to unseen middle ear point clouds and capable of handling realistic noise and incompleteness in synthetic and real OCT data. CONCLUSIONS: In this work, we aim to enable diagnosis of middle ear structures with the assistance of OCT images. We propose C2P-Net: a two-staged non-rigid registration pipeline for point clouds to support the interpretation of in vivo noisy and partial OCT images for the first time. Code is available at: https://gitlab.com/nct_tso_public/c2p-net.

Isolated embryonal rhabdomyosarcoma of the anterior petrous bone in a young child: Focusing on the intra-operative diagnosis and differentials.

OBJECTIVE: Rhabdomyosarcoma is a common soft tissue tumor, but isolated involvement of anterior portion of petrous bone is exceedingly rare. Here, we present a case of embryonal rhabdomyosarcoma involving the anterior petrous without involvement of the mastoid and middle ear. PATIENT: A 6-year-old boy presented with a progressive right side lower motor neuron facial paresis for 1-month duration along with headache and recurrent vomiting episodes. Radiology showed a contrast-enhancing lesion involving the right petrous apex. He underwent craniotomy and excision of the lesion. Based on the frozen section, a diagnosis of rhabdomyosarcoma was rendered, and gross total resection could be achieved. Postoperative course was uneventful. CONCLUSION: Isolated petrous bone involvement of embryonal rhabdomyosarcoma is a rare presentation. Intra-operative frozen section plays a key role in decision making regarding the extent of excision. Hence, a prompt and accurate diagnosis is essential in managing these cases.

Mucosa-associated Lymphoid Tissue Misdiagnosis as Glomus Tympanicum.

Middle ear tumors are diverse, but relatively uncommon. The most frequent tumor in the middle ear is glomus tumor, followed by others such as schwannoma and cholesteatoma. We experienced a case of Mucosa-associated lymphoid tissue hyperplasia as a middle ear tumor. The mass behind tympanic membrane appeared a hypervascular tumor, mimicking a glomus tumor, but the form of multiple separate masses in middle ear and mastoid cavity was the distinguishing feature that set it apart from a glomus tumor. Additionally, another characteristic was its tendency to easily shrink under pressure. This characteristic should be considered when encounter a hypervascular looking middle ear mass. Laryngoscope, 134:1894-1896, 2024.

Experience in the management of sigmoid sinus thrombophlebitis secondary to middle ear cholesteatoma.

OBJECTIVE: To discuss the management of sigmoid sinus thrombophlebitis secondary to middle ear cholesteatoma. METHODS: We retrospectively analyzed all cases of sigmoid sinus thrombophlebitis caused by middle ear cholesteatoma over a period of 7 years. 7 male and 2 female patients, ranging in age from 9 to 66 years, were diagnosed with sigmoid sinus thrombophlebitis by clinical presentation and radiological examination. By executing a modified mastoidectomy and tympanoplasty (canal wall-down tympanoplasty) to entirely remove the cholesteatoma-like mastoid epithelium, all patients were effectively treated surgically without opening the sigmoid sinus. All patients were treated with broad-spectrum antibiotics, but no anticoagulants were used. RESULTS: 9 patients had otogenic symptoms such as ear pus, tympanic membrane perforation, and hearing loss. In the initial stage of the surgery, modified mastoidectomy and tympanoplasty were performed on 8 of the 9 patients. 1 patient with a brain abscess underwent puncturing (drainage of the abscess) to relieve cranial pressure, and 4 months later, a modified mastoidectomy and tympanoplasty were carried out. Following surgery and medication, the clinical symptoms of every patient improved. After the follow-up of 6 months to 7 years, 3 patients were re-examined for MRV and showed partial sigmoid sinus recovery with recanalization. 4 months following middle ear surgery, the extent of a patient's brain abscess lesions was significantly reduced. 1 patient experienced facial paralysis after surgery and recovered in 3 months. None of the patients had a secondary illness, an infection, or an abscess in a distant organ. CONCLUSION: The key to a better prognosis is an adequate course of perioperative antibiotic medication coupled with surgical treatment. A stable sigmoid sinus thrombus can remain for a long time after middle ear lesions have been removed, and it is less likely to cause infection and abscesses in the distant organs. The restoration of middle ear ventilation is facilitated by tympanoplasty. It is important to work more closely with multidisciplinary teams such as neurology and neurosurgery when deciding whether to perform lateral sinusotomies to remove thrombus or whether to administer anticoagulation.

[FGF23 tumor induced osteomalacia with localization of neoplasm in the tympanic cavity]. / FRF23-indutsirovannaya osteomalyatsiya opukholevogo geneza s lokalizatsiei novoobrazovaniya v barabannoi polosti.

Tumor induced osteomalacia is a rare paraneoplastic syndrome caused by mesenchymal tumors that secrete fibroblast growth factor 23 (FGF23). Patients complain of progressive bone pain, muscle weakness and brittle fractures. Delayed diagnosis of osteomalacia caused by a tumor is often found in clinical practice. When verifying the exact localization of the neoplasm, radical removal within healthy tissues is recommended. The article considers a clinical example of FGF23 tumor induced osteomalacia with localization of neoplasm in the tympanic cavity.

Proto-oncogene mutations in middle ear cholesteatoma contribute to its pathogenesis.

BACKGROUND: Chronic inflammation causes bone destruction in middle ear cholesteatomas (MECs). However, the causes of their neoplastic features remain unknown. The present study demonstrated for the first time that neoplastic features of MEC are based on proto-oncogene mutations. RESULTS: DNA was extracted from MEC and blood samples of five patients to detect somatic mutations using depth-depth exome sequencing. Exons with somatic variants were analyzed using an additional 17 MEC/blood test pairs. Variants detected in MECs but not in blood were considered pathogenic variant candidates. We analyzed the correlation between proto-oncogene (NOTCH1 and MYC) variants and the presence of bone destruction and granulation tissue formation. MYC and NOTCH1 variants were detected in two and five of the 22 samples, respectively. Two of the NOTCH1 variants were located in its specific functional domain, one was truncating and the other was a splice donor site variant. Mutations of the two genes in attic cholesteatomas (n = 14) were significantly related with bone destruction (p = 0.0148) but not with granulation tissue formation (p = 0.399). CONCLUSIONS: This is the first study to demonstrate a relationship between neoplastic features of MEC and proto-oncogene mutations.

Expression of MMP-14 and its role in bone destruction in middle ear cholesteatoma: A prospective observational study.

Cholesteatoma is a noncancerous cystic lesion caused by an abnormal growth of keratinizing squamous epithelium which is invasive and capable of destroying structures. A prospective study on the expression of membrane type1-matrix metalloproteinases (MMP-14) and its related influencing factors in middle ear cholesteatoma was conducted to fully understand the pathogenesis of cholesteatoma in the molecular level. We examined the expression of MMP-14 by immunohistochemical staining 39 middle ear cholesteatoma specimens and 10 external auditory meatus epithelial cell specimens. The cholesteatoma specimens were divided into 4 groups according to the degree of destruction of the ossicles during surgery. The associated factors affecting MMP-14 expression were analyzed using statistical methods; The positive expression of MMP-14 in the epithelium of the external auditory canal was significantly different between middle ear cholesteatoma and normal patients (P < .05); Gender, age, and the degree of hearing loss had no statistically significant effect on MMP-14 expression (P > .05); The expression of MMP-14 was positively correlated with the severity of bone destruction (R = 0.535, P < .05); MMP-14 plays an important role in the pathological development of the epithelium of cholesteatoma; MMP-14 expression in middle ear cholesteatoma tissue was not strongly correlated with the level of hearing loss, age or gender, but was positively correlated with the degree of middle ear bone destruction.

Diagnosis and management of bilateral lipoma of the middle ear.

INTRODUCTION: Middle ear lipomas are rare, accounting for less than 1% of all middle ear tumours. To our knowledge there have been only 16 reported patients with middle ear lipoma. Only one of these had bilateral congenital middle ear lipomas. The aim of this review is to comprehensive overview the diagnosis and management of congenital lipomas of the middle ear. METHODS: A literature review was performed searching multiple data bases, using the key words "middle ear", AND "lipoma", AND "congenital". A total of 116 articles were identified. One hundred were excluded on various criteria, leaving 16 articles for detailed review. Additionally, we report the second case of bilateral congenital middle ear lipoma. RESULTS: Based on this case report and literature review, the incidence of middle ear lipomas is greater in paediatric patients than in adult patients. Middle ear lipomas are distributed evenly between males and females. Three patients had recognised genetic syndromes, while five had prior ventilation tube placement. Clinically patients present with conductive hearing loss and middle ear effusions. In some cases, presence of a white or yellow mass behind the anterior aspect of the tympanic membrane is recognised. The most common location of the masses is in the anterosuperior quadrant of the middle ear, the site of predilection for small congenital cholesteatomas. An MRI scan is most useful in distinguishing between lipoma and cholesteatoma. All cases reported surgical excision of the middle ear lipoma. There was no evidence of recurrence noted up to 4 years follow up. CONCLUSION: Though rare, congenital lipomas of the middle ear should be a differential diagnosis of a middle ear masses. Early identification can allow surgical lipoma resection with minimal disruption to the ossicular chain. Though there is currently no consensus regarding management, surgical removal and appropriate reconstruction of the ossicular chain if needed, is appropriate.

Congenital Retrosigmoid Cholesteatoma: Case Series and Literature Review.

BACKGROUND: This study aimed to discuss 3 cases of congenital cholesteatoma located posterior to the sigmoid sinus, with no/minimal involvement of mastoid, and compare them with cases presented in the literature to better define this rare entity. METHODS: Retrospective chart analysis of 3 congenital cholesteatomas located posterior to the sigmoid sinus treated surgically in 2 skull-base centers and literature review. Though congenital cholesteatoma can arise outside the middle ear, only a few cases presenting in the retrosigmoid occipital bone have been described earlier. RESULTS: In all 3 patients, there was a delay in the presentation, as symptoms were nonspecific or lacking, leading in 1 case to severe complications. Computed tomography and magnetic resonance imaging, especially diffusion-weighted imaging scans, allowed accurate diagnosis and surgical planning. Surgery happened to be challenging due to the tight adherence of the cholesteatoma to the thinned dural surface. Complete excision was achieved in all the cases. CONCLUSION: Congenital cholesteatoma located posterior to the sigmoid sinus is a rare entity and is even more exceptional after a critical review of the literature. Complete excision is quintessential to prevent intradural extension or infection. The most important surgical issue is the management of the posterior fossa dura and the sigmoid sinus. We recommend meticulous dissection with slow peeling of the epithelial lining from the dura. Bipolar coagulation of the dura may help in avoiding recidivism. Moreover, cerebrospinal fluid (CSF) leak during dissection has to be avoided as long as possible, because the loss of tension of the already thinned dura makes its peeling particularly difficult.