論文

Perrault syndrome is an autosomal recessive condition characterized by hearing loss and ovarian failure. Hearing loss in Perrault syndrome has been reported as sensorineural; however, only two cases in a single report have comprehensively investigated hearing in Perrault syndrome with TWNK variant, and the association between this variant and auditory neuropathy has not been established. The proband presented with hearing difficulties and primary amenorrhea. Hearing tests revealed mild hearing loss. Maximum speech intelligibility score was 95 % with normal otoacoustic emission. However, no auditory brainstem responses were observed, leading to the diagnosis of auditory neuropathy. Genetic tests identified compound heterozygous variants of TWNK (p.Ile253Met and p.Arg391His), which lead to the genetic diagnosis of Perrault syndrome. Electrocochleography suggests a decreased cochlear nerve function. The patient's sister was also subsequently genetically diagnosed with Perrault syndrome upon identification of the same TWNK variant and had auditory neuropathy with low-tone hearing loss on pure-tone audiometry. These cases highlight the importance of detailed hearing tests, including auditory brainstem response and genetic tests in patients with Perrault syndrome, even in cases of mild hearing loss, for accurate diagnosis and appropriate management.

Purpose: The retrolabyrinthine approach is a surgical method designed to preserve hearing after surgery. When paired with intraoperative monitoring and an endoscope, this approach has demonstrated high rates of postoperative hearing preservation. However, the long-term prognosis of hearing preservation after utilizing this approach for vestibular schwannomas remains unexplored. This study aimed to examine the long-term outcomes of preserved hearing, providing insights into the suitability of the retrolabyrinthine approach for hearing preservation surgery. Methods: This study included 34 patients with preserved hearing after vestibular schwannoma surgery using the retrolabyrinthine approach at a single center. Long-term hearing prognosis and requirement for additional interventions were retrospectively examined. Results: Immediate after post-operative hearing preservation rate was 71.7%. Among the 34 patients with preserved hearing post-vestibular schwannoma surgery, four (11.8%) required additional interventions. Other patients experienced a gradual deterioration in their hearing status, with an approximate 10 dB decline during the 5-year follow-up; however, a serviceable hearing level persisted long after the surgery in these individuals. Conclusions: This study indicated the rationale for the retrolabyrinthine approach as a hearing preservation surgery for vestibular schwannomas, emphasizing its long-term hearing prognosis.

Noise-induced hearing loss (NIHL) is a common type of sensorineural hearing loss caused by exposure to high-intensity noise that leads to irreversible cochlear damage. Despite extensive research on cochlear pathophysiology, the precise mechanisms remain unclear, and no established treatment exists. This is due to the challenges in imaging and the inability to perform biopsies in human patients. Consequently, animal models, particularly mice, have been widely used to study NIHL. Clinically, NIHL presents as either a temporary threshold shift, in which hearing recovers, or a permanent threshold shift, which results in an irreversible loss. Histopathological studies have identified the key features of NIHL, including outer hair cell loss, auditory nerve degeneration, and synaptic impairment. Recent findings suggest that oxidative stress and inflammation are major contributors to NIHL, highlighting the potential for therapeutic interventions, such as antioxidants and anti-inflammatory agents. Given the increasing prevalence of NIHL owing to occupational noise exposure and personal audio device use, addressing this issue is a pressing public health challenge. This review summarizes the clinical features, underlying mechanisms, and emerging treatment strategies for NIHL while identifying current knowledge gaps and future research directions.

Objective: Intraoperative systems for monitoring facial nerve function, in which temporal electrical stimulation is applied to the facial nerve through electrodes, are used in many surgeries requiring facial nerve preservation; however, continuous stimulation or quantitative evaluation of facial nerve function is difficult with this approach. We examined the usefulness of a continuous and quantitative facial nerve-monitoring system for temporal bone lesions by using our experience to modify the existing methods used for cases involving vestibular schwannomas. Study design: Retrospective observational study. Setting: Department of Otorhinolaryngology-Head and Neck Surgery at our hospital. Methods: We modified the electrode placement and examined the usefulness of the modified system under several conditions. The study population consisted of patients who were operated on for temporal bone lesions at our department and underwent continuous nerve monitoring using the modified system. Case details, electrode-placement sites, and facial nerve function data before and after the surgery were obtained and retrospectively evaluated. Results: Electrodes were placed safely during surgery in all cases. No obvious deterioration in facial nerve function was observed, except in one case. Conclusion: The advantages of this system include its ability to perform quantitative intraoperative evaluations and prevent unexpected nerve damage in cases where the facial nerve shows complicated pathways. This monitoring system is useful, even in complex temporal bone surgeries.

Objective: To assess pretreatment factors including preoperative vestibular function tests evaluated using cVEMP and caloric tests, which correlate with the development of prolonged dizziness after vestibular schwannoma resection. Study Design: Retrospective cohort study. Setting: Academic tertiary referral centers. Patients: Patients with vestibular schwannoma who underwent surgery and completed preoperative vestibular function tests and questionnaires. Intervention: Diagnostic. Main Outcome Measures: Participants were divided into prolonged dizziness and nonprolonged dizziness groups according to their postoperative DHI scores. The rates of abnormal results of preoperative vestibular function tests (caloric test, cVEMP), including other factors such as preoperative HADS scores, were compared. Furthermore, univariate logistic regression analysis was performed with the DHI score at 3 months as the dependent variable. Results: Of the whole 45 participants, 14 (31%) developed prolonged dizziness postoperatively. The proportion of participants with abnormal cVEMP results was significantly lower in the prolonged dizziness group (7.1%) than in the nonprolonged dizziness group (42%). Other factors did not show any significant differences. Univariate analysis showed that only the cVEMP results correlated with the postoperative DHI score (OR = 9.39, 95% CI [1.56, 181.3], p < 0.05). About 70% of patients with prolonged dizziness continued to exhibit high DHI scores at 6 months after surgery; however, about half of them recovered by 1 year. Conclusion: Vestibular schwannoma patients with normal preoperative cVEMP results tended to develop prolonged dizziness after resection compared to those with abnormal results. Preoperative cVEMP results enable physicians to predict whether vestibular schwannoma patients undergoing resection would likely develop prolonged dizziness postoperatively.

The extent of hearing loss requiring hearing aid (HA) to prevent cognitive decline is unclear; we assessed this post-midlife along with the relationship between hearing thresholds and cognitive function in those who had never used HA (non-users) or used HAs for >3 years (long-term users). This study comprised 117 individuals ≥55 years with an average hearing threshold of ≥25 dB HL in their better ear and 55 of the non-users and 62 of the long-term users. The Mini-Mental State Examination, the Symbol Digit Modalities Test (SDMT), and pure-tone and sound-field audiometry were assessed. Mean ± SD hearing levels of the non-user and long-term user group were 40.83 ± 8.16 and 51.13 ± 14.80 dB HL. Non-users showed a significant association (P = 0.01) between the hearing thresholds and SDMT scores, with a cutoff value of above 38.75 dB HL identified as affecting cognitive function. There were no significant associations for long-term users.

Objective: Febrile neutropenia (FN) is the most serious toxicity in patients with head and neck squamous cell carcinoma (HNSCC) treated with induction chemotherapy (IC). Although it is well-known that sarcopenia is a risk factor for severe toxicity of (chemo)radiotherapy, the data on the association between sarcopenia and FN during IC in HNSCC patients is rare. This study determined the impact of sarcopenia on FN during IC. Methods: IC-treated patients with HNSCC were enrolled in this study. Skeletal muscle mass (SMM) at the C3 vertebral body was used to define sarcopenia from computed tomography (CT) scans. To determine the predictive effect of low SMM on FN, logistic regression analysis was performed. Results: In this study, 71 patients were included, of whom 28 had low SMM and 14 experienced FN. In multivariate analysis, low SMM and high CRP were the independent predictive factors for FN. The combination index of sarcopenia and CRP showed a greater odds ratio than sarcopenia alone suggesting a more significant predicting indicator. Conclusions: Sarcopenia defined by CT imaging is associated with FN in patients with HNSCC treated with IC. The combination of sarcopenia and high CRP is a more significant risk factor, and it helps determine patients at risk of FN during IC.

＜文献概要＞はじめに　耳鳴再訓練法(tinnitus retraining therapy:TRT)とは1980年後半にPawel Jastreboffによって提唱された音響療法と教育カウンセリングで成り立っている治療法である。TRTは耳鳴を消失させることが目的ではなく脳に順応を起こすことで耳鳴の苦痛を減少させる治療である。耳鳴治療器(tinnitus control instrument):サウンドジェネレーター(sound generator:SG)の作用機序は,静寂を避け,耳に雑音を与えることにより大脳皮質における耳鳴の信号のコントラストを減弱させ耳鳴に対する過敏性を減らすように働きかけ,耳鳴に対する順応を起こすとされている。また補聴器の作用機序は,補聴器による外界音の入力によって(1)耳鳴を紛らわせること,(2)蝸牛障害による末梢入力低下により上昇した聴覚中枢での神経活性を抑制することとされている。Jastreboffが提唱するプロトコールでは難聴の自覚のない耳鳴症例ではSGを,難聴の自覚のある耳鳴症例では補聴器を推奨している(表1)。本邦においては2001年の松田による報告以来,TRTを行う施設は増加した。筆者が2004年4月～2022年3月の18年間でTRTを施行し購入された治療器は,SG,補聴器,SG付き補聴器,一側性難聴に対するCROS補聴器であった。本稿では購入された治療器の個数の推移について報告する。

Carcinoma of the external auditory canal is a rare tumor, accounting for about 1% of all head and neck cancers. Although no treatment method has been established yet, surgical treatment is the primary treatment method in cases where resection is possible. At our institution, we adopt surgical treatment, mainly lateral temporal bone resection （LTBR）, for cases with T1―T3 disease, and chemoradiation therapy（CCRT）for cases with T4 disease, as the treatment of first choice. We have adopted cartilage conduction hearing aids（CC―HAs）in some cases following LTBR. We examined the short―term outcomes, at two years, in the patients treated at our department. This study was a retrospective case review of 22 ears with carcinoma of the external auditory canal in 21 patients who underwent initial treatment at our institution between January 2012 and June 2018. The observation period was 2 to 81 months（median 26 months）. The tumors were analyzed using the modified Pittsburgh tumor staging system. The tumor T stage was T1 in four ears, T2 in nine ears, T3 in six ears, and T4 in three ears. CCRT was performed in three ears with T4 disease and one ear with T2 disease, heavy ion radiotherapy was performed in one ear with T2 disease, and surgery（LTBR in 16 ears and partial external auditory meatus resection in one ear）was performed for all the other cases. The surgical margin after LTBR was positive in three out of six cases with T3 disease and negative in all of the cases with T1 and T2 disease. The positive surgical margin was mainly found in the medial wall of the tympanic cavity or cartilaginous portion of the external acoustic meatus. The overall 2―year survival rate was 87.4%; the rate was 100% in the T1 cases, 87.5% in the T2 cases, 75.0% in the T3 cases, and 100% in the T4 cases. Four out of five patients who tried CC―HAs continued to use them after the LTBR. The indication for LTBR should be carefully judged in cases with T3 disease. The appropriate indication for LTBR in cases with T3 disease are: 1）a small amount of soft tissue shadow beyond the tympanum in the preoperative CT, and/ or 2）a clear boundary between the tumor and the soft tissue around the external acoustic meatus in the preoperative enhanced MRI. In cases with T3 disease not fulfilling these criteria, CCRT should be selected as the treatment of first choice. However, considering the side effects after CCRT, including sensorineural hearing loss and persistent otorrhea in some cases, LTBR with postoperative CC―HAs is one of the optimal treatment options that would allow the remaining hearing ability to be utilized.

Purpose: To achieve the challenging goal of simultaneously improving aesthetics and auditory function in the treatment of microtia, we developed an auricular prosthesis incorporating a cartilage conduction hearing aid (APiCHA), which covers a cartilage conduction hearing aid (CC-HA). We evaluated the acoustic characteristics generated by the method of combining these two components using an artificial mastoid and investigated the possibility of clinical translation. Methods: The first step in creating an APiCHA is to take molds of both the affected and normal auricles and invert the 3D data of the normal auricle to create data for the auricular prostheses. Grooves were then made inside the prosthetic data to fit the affected ear and a CC-HA, and the APiCHA was made of silicone. The acoustic characteristics were measured using an artificial mastoid, and the results were compared between CC-HA alone and with APiCHA. Results: Compared with CC-HA alone, the gain was approximately 2 dB lower at high frequencies from 1 k Hz and higher, and approximately 2 dB higher at approximately 900 Hz when CC-HA was used with APiCHA. For the other frequencies, the acoustic characteristics were almost the same. Conclusion: The changes in acoustic characteristics caused by the combined use of APiCHA and CC-HA were minimal and did not pose a clinical problem. The combined use of APiCHA and CC-HA can be considered as a non-invasive and clinically applicable treatment option to achieve both aesthetic and auditory improvements for microtia.

Highly accurate real-time cochlear nerve monitoring to preserve cochlear nerve function is essential for simultaneous cochlear implantation and ipsilateral vestibular schwannoma resection. In the present study, we developed a novel real-time monitoring system that combines dorsal cochlear nucleus action potential monitoring with intracochlear stimulating electrodes (Auditory Nerve Test System, ANTS). We used this system for a case with vestibular schwannoma resection via the translabyrinthine approach. The monitoring system developed in this study detected highly reliable evoked potentials from the cochlear nerve every two seconds continuously during tumor resection. Near-total tumor resection was achieved, and cochlear implantation was performed successfully after confirming the preservation of cochlear nerve function in a case. The patient’s hearing was well compensated by cochlear implantation after surgery. Our novel method continuously achieved real-time monitoring of the cochlear nerve every two seconds during vestibular schwannoma resection. The usefulness of this monitoring system for simultaneous tumor resection and cochlear implantation was demonstrated in the present case. The system developed in this study is compatible with continuous facial nerve monitoring. This highly accurate and novel monitoring method will broaden the number of candidates for this type of surgery in the future.

Thrombosis is a characteristic symptom of coronavirus disease 2019 (COVID-19). Here, we present a case of external ear stenosis caused by arterial thrombosis after COVID-19 infection. To the best of our knowledge, this is the first report of external ear stenosis related to COVID-19. A 62-year-old man presented with left hearing loss. The patient had a history of hospitalization for COVID-19 treatment 11 months prior to visiting our hospital. He had been experiencing ear fullness and tinnitus after COVID-19 treatment. Physical examination revealed severe left external ear canal stenosis with a subcutaneous mass. Surgical removal of the subcutaneous mass was performed. Histopathological analysis revealed that a subcutaneous thrombosis caused the external ear canal stenosis. This case describes an unusual case of external ear canal stenosis after COVID-19. Clinical and pathological findings indicate that COVID-19 affected the external ear canal. In addition, histopathological results confirmed the formation of arterial thrombosis in the temporal bone region after COVID-19 treatment. This case shows the broad range of body sites that can be involved with thrombotic events with COVID including the subcutaneous tissue around the outer ear. This observation would be helpful in investigating or explaining the various otological symptoms of COVID-19.

Otof, which encodes otoferlin, knockout mice are considered model mice for auditory neuropathy spectrum disorder, which is characterized by an absent auditory brainstem response (ABR) despite preserved distortion product otoacoustic emission (DPOAE). Although otoferlin-deficient mice lack neurotransmitter release at the inner hair cell (IHC) synapse, it remains unclear how the Otof mutation affects spiral ganglions. Thus, we used Otof-mutant mice carrying the Otoftm1a(KOMP)Wtsi allele (Otoftm1a) and analyzed spiral ganglion neurons (SGNs) in Otoftm1a/tm1a mice by immunolabeling type Ⅰ SGNs (SGN-Ⅰ) and type II SGNs (SGN-II). We also examined apoptotic cells in SGNs. Four-week-old Otoftm1a/tm1a mice had an absent ABR but normal DPOAEs. The number of SGNs was significantly lower in Otoftm1a/tm1a mice on postnatal day 7 (P7), P14, and P28 compared with that of wild-type mice. Moreover, significantly more apoptotic SGNs were observed in Otoftm1a/tm1a mice than in wild-type mice on P7, P14, and P28. SGN-IIs were not significantly reduced in Otoftm1a/tm1a mice on P7, P14, and P28. No apoptotic SGN-IIs were observed under our experimental conditions. In summary, Otoftm1a/tm1a mice showed a reduction in SGNs accompanied by apoptosis of SGN-Ⅰs even before the onset of hearing. We speculate that the reduction in SGNs with apoptosis is a secondary defect caused by a lack of otoferlin in IHCs. Appropriate glutamatergic synaptic inputs may be important for the survival of SGNs.

Relapsing polychondritis (RP) is a rare chronic inflammatory disease characterized by recurrent inflammation of cartilages throughout the body, with treatment-resistant dizziness and hearing loss in 40%-50% of patients with RP. Although rare, severe binaural hearing loss in RP is an indication for cochlear implantation (CI). Therefore, there are only a few reports on CI insertion in cases of RP. This report describes a 68-year-old woman who developed binaural hearing loss due to RP. She was treated with steroids and immunosuppressive drugs; however, her hearing did not improve significantly, and she relied on written communication for conversation. Subsequently, the patient underwent CI in the right ear. The patient showed improvement in speech perception; at 14 months postoperatively, she was able to speak with lipreading, and at 2 years postoperatively, she was able to speak without lipreading. Previous case reports on CI in patients with RP have shown varying degrees of postoperative hearing improvement. Our case demonstrates the effectiveness of CI in improving hearing and speech recognition in patients with RP having semicircular canal calcification. However, previous reports have shown that speech recognition declines 13 years after CI for RP. Therefore, continuous long-term follow-up is necessary.

Cartilage conduction hearing aids (CC-HA), bone anchored hearing aids (Baha), and ADHEAR are good choices to improve hearing in patients who cannot use air conduction hearing aids because of aural atresia or continuous otorrhea. As there are many overlaps in the characteristics of these devices, we conducted a comparative trial of CC-HA, Baha, and ADHEAR. We provided patients with the opportunity to select their devices. The data of 6 patients who underwent comparative trials in our department between October 2021 and August 2022 were retrospectively examined. The gains of Baha and CC-HA outweighed those of ADHEAR. Regarding the sound localization test, there was no significant tendency for any of the hearing devices. Regarding the Glasgow Benefit Inventory, there was no clear tendency among the three devices in the quality of life evaluation. The most satisfactory model was the one subjectively chosen by the patient, regardless of the gain and score of the sound source localization test. Therefore, we believe that it is necessary to provide an opportunity for comparative trials and a consultation with each patient in the process of selecting a device.

Type I spiral ganglion neurons are peripheral neurons essential for hearing perception. While they can be subdivided in mice based on characteristic gene expression patterns, detailed examinations of these subtypes in primates and humans are lacking. In this study, we investigated the developmental subtypes of spiral ganglion neurons in the common marmoset (Callithrix jacchus). We confirmed that Type I spiral ganglion can be divided based on the characteristic gene expression patterns of several marker genes. However, some combinations of these genes differ from those in rodents, suggesting common marmoset's suitability for advancing our understanding of human cochlear development. Additionally, identifying the essential time points for subtype specifications and subsequent maturation will aid in studying the primate-specific developmental biology of the inner ear. This could lead to new treatment strategies for hearing loss in humans and be valuable for studying age-related hearing loss, as well as designing regenerative therapies.

Facial nerve paralysis caused by a vestibular schwannoma is a rare but critical symptom; however, few reports have focused on preoperative facial nerve palsy from the viewpoint of treatment. In addition, its mechanism is not fully understood. We report a rare case of preoperative facial nerve palsy that improved after the surgical resection of a small vestibular schwannoma with hearing preservation. A small vestibular schwannoma within the internal auditory canal caused acute deafness and facial paralysis in a 51-year-old woman. Conservative treatment was initially administered, but severe hearing loss and facial paralysis persisted for 3 months after onset. Subsequently, we performed tumor resection using the retrolabyrinthine approach. The tumor, which compressed the cochlear and facial nerves, was almost completely removed under continuous intraoperative monitoring to preserve the facial nerve function. “Wait and scan” is generally recommended for vestibular schwannomas within the internal auditory canal. However, this case suggests that early successful surgery, at least in selected cases, can improve paralysis without hearing deterioration and maintain the patient's quality of life.

A vestibular schwannoma is a benign tumor; however, the schwannoma itself and interventions can cause sensorineural hearing loss. Most vestibular schwannomas are unilateral tumors that affect hearing only on one side. Attention has focused on improving the quality of life for patients with unilateral hearing loss and therapeutic interventions to address this issue have been emphasized. Herein, we encountered a patient who was a candidate for hearing preservation surgery based on preoperative findings and had nonserviceable hearing after the surgery, according to the Gardner–Robertson classification. Postoperatively, the patient had decreased listening comprehension and ability to localize sound sources. He was fitted with bilateral hearing aids, and his ability to localize sound sources improved. Although the patient had postoperative nonserviceable hearing on the affected side and age-related hearing loss on the unaffected side, hearing aids in both ears were useful for his daily life. Therefore, the patient was able to maintain a binaural hearing effect and the ability to localize the sound source improved. This report emphasizes the importance of hearing preservation with vestibular schwannomas, and the demand for hearing loss rehabilitation as a postoperative complication can increase, even if hearing loss is nonserviceable.