Tetsuo Ikezono

Background: Perilymphatic fistula (PLF) after barotrauma has been linked to popping sounds, streaming water-like tinnitus, and fistula signs, but objective evidence is limited. Aims/objectives: To determine whether these features are associated with Cochlin-tomoprotein (CTP)-confirmed PLF after antecedent barotrauma. Materials and methods: We retrospectively analyzed 149 category 2 (external barotrauma) or category 3 (internal pressure-related barotrauma) cases among 736 patients who underwent CTP testing at 80 Japanese institutions. Frequencies of clinical features were compared by CTP status using Fisher’s exact test. Results: CTP positivity was 17% in category 2 and 22% in category 3. In category 2, CTP positivity was higher in patients with a popping sound than in those without it (60% vs. 12%; OR, 10.88; 95% CI, 1.63–68.66; p = 0.035). In category 3, CTP positivity was higher in patients with streaming water-like tinnitus than in those without it (41% vs. 16%; OR, 3.75; 95% CI, 1.30–10.31; p = 0.019) and in patients with nystagmus than in those without it (30% vs. 12%; OR, 3.12; 95% CI, 1.18–8.70; p = 0.033). Fistula signs were not associated with CTP positivity. Conclusions and significance: Symptom profiles differed by barotraumatic mechanism in CTP-confirmed PLF. A popping sound may represent a characteristic clinical clue suggestive of PLF after external barotrauma, whereas streaming water-like tinnitus and nystagmus may better indicate PLF after internal pressure-related events, although the observed associations in this study were exploratory and not adjusted for multiple comparisons. Absence of a fistula sign should not exclude PLF.

Background/Objectives: MYH9 gene variants cause MYH9-related disease (MYH9-RD), which is also known as Epstein syndrome, Fechtner syndrome, May–Hegglin anomaly, and Sebastian syndrome. MYH9-RD is characterized by sensorineural hearing loss, macrothrombocytopenia, thrombocytopenia, hematuria/proteinuria, glomerulonephritis, cataracts purpura, and mucosal bleeding. In addition, the MYH9 gene is also known to be causative of autosomal dominant non-syndromic hearing loss (DFNA17). MYH9-RD is a relatively rare disorder, and the detailed clinical features and mutational spectra remain unclear. Methods: In this study, we performed next-generation sequencing analysis for 15,684 hearing loss patients and identified MYH9-associated hearing loss patients. Detailed clinical information was collected for these patients and summarized. Results: In this study, we identified 24 patients from 18 families with MYH9-associated hearing loss. We clarified the details of hearing deterioration observed in patients based on collected serial audiogram data. Some cases showed rapid hearing deterioration that worsened by about 50 dB within 5 years. Hearing loss is more likely to progress in patients with myosin head domain variants than in patients with myosin tail domain variants, but hearing loss in each set of patients finally deteriorates to bilateral profound hearing loss. Conclusions: In this study, we were able to clarify the detailed characteristics of MYH9-RD- and DFNA17-related hearing loss in a relatively large number of patients, particularly in some cases that showed rapid and asymmetrical hearing deterioration progressing to bilateral profound hearing loss. Our data will be useful for providing more appropriate treatment and follow-up for MYH9-associated hearing loss.

Background: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a common clinical condition. Recent studies indicate that approximately 20% of ISSNHL cases may involve perilymphatic fistula (PLF). The detection of Cochlin-tomoprotein (CTP) in middle-ear lavage samples confirms the diagnosis of PLF.Aims/Objectives: To clarify the clinical characteristics of inner ear–related symptoms in patients with PLF who lacked any antecedent traumatic events prior to symptom onset.Materials and methods: We retrospectively reviewed clinical records and CTP test results in 769 cases from 70 hospitals in Japan.Results: Among these cases, 204 had no history of antecedent events. CTP-positive findings were more frequently observed in patients exhibiting fluctuating and/or progressive hearing loss than in those without these symptoms (p < 0.05, Fisher’s exact test). The odds of a positive CTP test did not differ between patients with and without vestibular symptoms, nystagmus, a fistula sign, a popping sensation, or streaming water–like tinnitus (p > 0.05, Fisher’s exact test). The CTP positivity rate was highest in patients with a high-frequency sloping audiogram.Conclusions and significance: Fluctuating or progressive hearing loss in the middle-to-high frequencies may reasonably suggest PLF in the absence of antecedent traumatic events.

Introduction: Cochlin is the most abundant protein in the inner ear. The cleaved N-terminal domain of cochlin, known as LCCL and referred to as CTP (cochlin tomoprotein) in clinical biomarker usage, is a perilymph-specific protein and is widely used as a biomarker to detect perilymph leakage. However, little is known about the secretion or presence of LCCL in the middle ear, even though it can result in false positives when using LCCL as a biomarker for perilymph leakage.Methods: We conducted translational research in humans and mice. A retrospective observational study was conducted on human patients who underwent multiple CTP tests after tympanostomy. In parallel, an experimental study on cochlin and its cleaved product, LCCL, was performed in mice.Results: We found the exceptionally elevated level of CTP within 10 days after tympanostomy in humans regardless of the presence of definite perilymph leakage. In addition, we identified LCCL in the middle ear after tympanostomy in mice. The concentration of LCCL peaked at three days post-tympanic injury. Importantly, the origin of LCCL in the middle ear lavage was not from the inner ear but is secreted from the middle ear space especially the annular ligament, suggesting it functions as an innate immune response in the middle ear.Conclusion: Tympanostomy for the CTP test results in a false positive when the sampling is delayed. While LCCL is a reliable biomarker for clinically detecting perilymph fistula, the timing of its application should be carefully considered to avoid false-positive results.

Several surgical techniques have been documented for approaching and repairing superior semicircular canal dehiscence syndrome (SCDS). These techniques encompass the trans-middle cranial fossa, transmastoid, endoscopic approaches, and round window reinforcement (RWR). RWR entails the placement of connective tissue with or without cartilage and around the round window niche, restricting the round window’s movement to minimize the 3rd window effect and restore the bony labyrinth closer to its normal state. We employed the multilayer RWR technique, resulting in significant postoperative improvement and long-lasting effects for 3.7 years in 2 cases. Here, we present the clinical findings, surgical procedures, and the effectiveness of multilayer RWR. This technique can be the initial choice for surgical treatments of SCDS due to its high effectiveness, longer-lasting effect, and minimal risk of surgical complications.

Purpose: To determine the prevalence of perilymphatic fistula (PLF) in sudden-onset sensorineural hearing loss (SSNHL) patients by employing the Cochlin-tomoprotein (CTP) detection test, a specific diagnostic marker for perilymph. We also analyzed the clinical characteristics associated with hearing outcomes in this cohort. Methods: A total of 74 eligible patients were prospectively enrolled. Following myringotomy, middle ear lavage (MEL) samples underwent the CTP test to identify perilymph leakage. Intratympanic dexamethasone (IT-DEX) therapy was administered, and hearing outcomes were assessed. Control groups comprised patients with chronic otitis media (n = 40) and non-inflammatory middle ears (n = 51) with concurrent MEL sample collection. Results: CTP was positive in 16 (22%) patients. No control samples showed positive results. Multiple regression analysis indicated that age and pre-treatment hearing levels significantly contributed to the CTP value. We found a positive correlation between CTP values, age, and pre-treatment pure-tone averages. Notably, CTP values in SSNHL cases aged 60 and above were significantly higher than in those below 60 years. Patients with positive CTP had significantly worse recovery rates after IT-DEX treatment. Conclusion: This study is the first prospective investigation demonstrating a positive relationship between CTP values, age, and hearing severity in SSNHL, indicating that PLF might be the essential cause of SSNHL, particularly in the elderly. Our findings suggest that IT-DEX may be less effective for PLF-associated SSNHL. Future research could reveal that PLF repair surgery is a viable treatment strategy for SSNHL. This study was registered under the UMIN Clinical Trials Registry (UMIN000010837) on 30/May/2013.

Objective: Vertigo is a quite frequent complication after cochlear implantation. Perilymphatic fistula (PLF) is assumed to be one cause of this problem. Cochlin tomoprotein (CTP) is a newly introduced marker for PLF. The present aim was to evaluate the rate of positive CTP testing in cases of newly occurring vertigo after cochlear implantation. Materials and Methods: Twelve patients with vertigo after cochlear implantation and a revisional electrode-sealing procedure underwent intraoperative rinsing of their middle ear. The sample was evaluated for CTP with monoclonal antibody testing. Sixteen controls from six CI patients were taken. Results: 4 out of 12 (33%) cases showed positive CTP testing, indicating that a PLF could be evaluated. In all of the positive CTP cases, surgery decreased the vertigo symptoms. A relation between the subjective visual assessment of a fistula and a positive CTP value was not observed. Controls confirmed the value of the testing. Discussion: CTP detection objectively shows that PLF can occur in patients with vertigo after CI.