岡野 高之

The percentage of macrophage subpopulations based on their origins in the adult cochlea remains unclear. This study aimed to elucidate the origins of cochlear macrophages during the onset phase and development of auditory function. We used three types of mice: wildtype ICR mice, colony-stimulating factor 1 receptor (Csf1r)-deficient mice, and Ms4a3Cre-Rosa tdTomato (Ms4a3tdT) transgenic mice. Macrophages were labeled with ionized calcium-binding adapter molecule 1 (Iba1), which is specific to more mature macrophages, and CD11b, which is specific to monocyte lineage. We investigated the spatial and temporal distribution patterns of resident macrophages in the cochlea during the postnatal and early adult stages. During the adult stages, the rate of monocytes recruited from the systemic circulation increased; moreover, Iba1+/CD11b- cochlear macrophages gradually decreased with age. Fate mapping of monocytes using Ms4a3tdT transgenic mice revealed an increased proportion of bone marrow-derived cochlear macrophages in the adult stage. Contrastingly, the proportion of yolk sac- and fetal liver-derived tissue-resident macrophages decreased steadily with age. This heterogeneity could be attributed to differences in environmental niches within the tissue or at the sub-tissue levels. Future studies should investigate the role of cochlear macrophages in homeostasis, inflammation, and other diseases, including infection, autoimmune, and metabolic diseases.

OBJECTIVE: This study aimed to longitudinally evaluate speech perception ability and sound-field thresholds with the first, second, or bilateral cochlear implants (CIs) and MAP parameters of second CI in children. METHODS: Eighteen children who underwent bilateral cochlear implantation at Kyoto University Hospital were included. We evaluated speech perception under quiet and noisy conditions using the first, second, or bilateral CIs, CI-aided sound-field thresholds using the first or second CI, and MAP parameter values (C-levels, T-levels, and dynamic range) of the second CI of more than 5 years after the second implantation. RESULTS: Patients with a second CI after 7 years of age had significantly worse speech perception ability with the second CI even long after the surgery than those with a second CI before 7 years of age. CI-aided sound-field thresholds using the first or second CI were similar, regardless of the second implantation timing. Speech perception in noise with bilateral CIs was enhanced by the addition of a second CI, even after 7 years of age. Patients undergoing second cochlear implantation before 3.5 years of age showed significantly higher C-levels and wider dynamic ranges in the second CI MAP parameters. CONCLUSIONS: When the second implantation was performed after 7 years of age, the second CI effects were limited even with long-term use, which is attributed to unstable MAP parameters. The second CI-aided sound-field threshold contributed to the better outcome of bilateral CIs in noise, even if the second implantation was performed at age of ≥7 years.

OBJECTIVE: This study aimed to evaluate the importance of mobile cone-beam computed tomography in detecting tip fold-over of a slim modiolar electrode within the cochlea during surgery. STUDY DESIGN: Retrospective case review. SETTING: Tertiary medical center. METHODS: From January 2020 to June 2022, 33 ears of 30 patients with normal cochlear morphology underwent cochlear implantation with slim modiolar electrodes and intraoperative mobile cone-beam computed tomography imaging. Furthermore, we retrospectively reviewed the medical records and images. RESULTS: The tip fold-over of the electrodes was detected using mobile cone-beam computed tomography in 3 out of 33 ears (9.1%). We could not identify the tip fold-over by scouting plain X-ray images in 2 out of 3 cases before taking the cone-beam computed tomography images. Electrode removal and reinsertion were performed before wound closure and the successful reinsertion was confirmed by mobile cone-beam computed tomography. The folded electrode tips were located at 238.8°, 152°, and 185.8°. CONCLUSION: Intraoperative mobile cone-beam computed tomography is useful in detecting the tip fold-over of the slim modiolar electrodes during surgery. Therefore, it was possible to reinsert the electrodes in all cases before closing the wound, eliminating the need for revision surgeries. Moreover, the analysis of mobile cone-beam computed tomography images may help to elucidate the mechanisms of electrode tip fold-over.

CHARGE症候群では人工内耳の適応となる重度感音難聴を生じうる。手術困難例で人工内耳電極の挿入に成功しても,内耳・内耳道奇形による術中の電気的誘発複合活動電位の測定困難や,発達遅滞による術後の聴性反応の観察困難により,マッピングの手掛かりが少なく,人工内耳効果が十分ではない場合がある。そこで,本研究では電気刺激に反応する聴神経や中枢の神経核の反応閾値を確定する可能性が高い電気的聴性脳幹反応(EABR)の術中所見と術後経過について検討した。その結果,術前画像評価で問題が認められても術中EABRで反応が検出された例を経験した。また,EABRでパルス幅を変更すると神経反応が検出され,それを元にマッピングに活用した例も経験し,EABRのパルス幅拡大の要否が術後成績と関連している可能性を示唆した。術前の画像評価に加えて術中EABRも施行することにより蝸牛神経の機能を評価することが重要と考えた。(著者抄録)

In contrast to mammals, the avian cochlea, specifically the basilar papilla, can regenerate sensory hair cells, which involves fate conversion of supporting cells to hair cells. To determine the mechanisms for converting supporting cells to hair cells, we used single-cell RNA sequencing during hair cell regeneration in explant cultures of chick basilar papillae. We identified dynamic changes in the gene expression of supporting cells, and the pseudotime trajectory analysis demonstrated the stepwise fate conversion from supporting cells to hair cells. Initially, supporting cell identity was erased and transition to the precursor state occurred. A subsequent gain in hair cell identity progressed together with downregulation of precursor-state genes. Transforming growth factor β receptor 1-mediated signaling was involved in induction of the initial step, and its inhibition resulted in suppression of hair cell regeneration. Our data provide new insights for understanding fate conversion from supporting cells to hair cells in avian basilar papillae.

医療器具の消毒に関しては,クリティカル・セミクリティカル・ノンクリティカル器具に分けて考えられ,軟性内視鏡はセミクリティカル器具に分類されるため高水準消毒が必要となる.高水準消毒に用いられる高水準消毒薬の代表としてグルタラールがあるが,種々の問題から使用制限傾向であり,代替物質・代替法が求められている.消化器内視鏡は軟性内視鏡のパイオニアであり,1950年代に胃カメラが開発されて以降,改良が加えられ臨床現場で広く用いられている.消化器内視鏡の歴史において感染事故が報告されているが,これを防ぐために洗浄・消毒に関するガイドラインが策定され,改良されている.そのような状況下において,強酸性電解水を用いた消毒が注目されている.強酸性電解水は広い抗微生物スペクトルと高い安全性を併せ持つ消毒薬であるが,有効塩素濃度が高いと金属腐食性を持ち,有効塩素濃度が低いと十分な消毒効果が得られないため,適切な使用が必須であり,現在では強酸性電解水のpH,酸化還元電位,有効塩素濃度の3物性を常時モニタリングすることが可能な自動洗浄消毒器が実用化されている.一方,耳鼻咽喉科・頭頸部外科診療においても軟性内視鏡は汎用されており,消化器内視鏡と比べて,よりさまざまな施設で鎮静なしで用いられ,1日あたりの使用回数も多く,感染性微生物を含んだ粘膜に触れる頻度が高いと考えられる.このような状況下で「耳鼻咽喉科内視鏡の感染制御に関する手引き」が出版され,洗浄・消毒に関する標準化の第一歩となった.さらに近年の新型コロナウイルス感染症(COVID-19)のアウトブレイクに際し,耳鼻咽喉科・頭頸部外科の内視鏡診療における感染対策が大きく見直されようとしている.(著者抄録)

CHARGE症候群では側頭骨奇形を伴い、人工内耳植込術の際に、乳突削開、後鼓室開放、蝸牛開窓や電極挿入に影響を与える。このような場合、手術用ナビゲーションシステム(Image-guided surgery system:IGSS)が有用であるが、通常のIGSSでは側頭骨手術に必要な精度は得られない。また精度向上のため骨に基準マーカーを埋め込む手法があるが、従来法では術前のCT撮影前に小手術が必要であった。今回、CHARGE症候群に対する人工内耳植込症例2例に対し、手術室で利用可能な移動式コーンビームCTを用いて手術開始後に設置した骨埋め込み型基準マーカーを含むレジストレーション用画像を作成し、IGSSを使用した。2例とも合併症なく蝸牛内に電極を挿入可能であった。電極挿入困難が予測されるような側頭骨奇形の合併症例の手術の場合は安全かつ正確な手術施行の為、IGSSの使用は有用な選択肢の一つであると考える。(著者抄録)

OBJECTIVE: Cleft palate (CP) in children is frequently complicated by otitis media with effusion (OME) due to Eustachian tube dysfunction. Although tympanostomy tube (TT) placement can be beneficial in the treatment of OME to prevent short-term hearing loss, there is no consensus regarding the indications for and timing of TT insertion. The present study was performed to define the safety and effectiveness of simultaneous TT placement with palatoplasty during the language-acquisition period. METHODS: We retrospectively reviewed the medical charts of pediatric patients who underwent palatoplasty for CP in a tertiary medical center, Kyoto University Hospital, from June 2010 to October 2018. The TT retention time was estimated using the Kaplan-Meier method. The incidence of OME recurrence was compared among four Veau classification groups based on the patients' sex, type of CP, median TT retention time, and type of fluid. RESULTS: Seventy-six subjects (150 ears) were enrolled in the study. The median follow-up duration was 48.7 months (range, 18.2-108.0 months) after the first TT placement. A first TT retention time of <20.1 months was a significant risk factor for OME recurrence. Subjects with maxillofacial anomaly complex and subjects with cleft lip and palate and an alveolar cleft showed a significantly higher OME recurrence rate than subjects with clefts only in the hard and/or soft palate. There was no significant difference in the occurrence of sequelae between subjects with only a single TT placement and subjects with more than one TT placement. CONCLUSIONS: Based on the findings of the present study, it is reasonable to perform TT insertion at the same time as palatoplasty on patients who meet the indications. This technique may reduce the number of times the patient requires general anesthesia and maintain good middle ear condition during the period of language acquisition between 1 and 3 years of age.

Glutaraldehyde, a germicide for reprocessing endoscopes that is important for hygiene in the clinic, might be hazardous to humans. Electrolyzed acid water (EAW) has a broad anti-microbial spectrum and safety profile and might be a glutaraldehyde alternative. We sought to assess EAW disinfection of flexible endoscopes in clinical otorhinolaryngological settings and its in vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and bacteria commonly isolated in otorhinolaryngology. Ninety endoscopes were tested for bacterial contamination before and after endoscope disinfection with EAW. The species and strains of bacteria were studied. The in vitro inactivation of bacteria and SARS-CoV-2 by EAW was investigated to determine the efficacy of endoscope disinfection. More than 20 colony-forming units of bacteria at one or more sampling sites were detected in 75/90 microbiological cultures of samples from clinically used endoscopes (83.3%). The most common genus detected was Staphylococcus followed by Cutibacterium and Corynebacterium at all sites including the ears, noses, and throats. In the in vitro study, more than 107 CFU/mL of all bacterial species examined were reduced to below the detection limit (<10 CFU/mL) within 30 s after contact with EAW. When SARS-CoV-2 was treated with a 99-fold volume of EAW, the initial viral titer (> 105 PFU) was decreased to less than 5 PFU. Effective inactivation of SARS-CoV-2 was also observed with a 19:1 ratio of EAW to the virus. EAW effectively reprocessed flexible endoscopes contributing to infection control in medical institutions in the era of the coronavirus disease 2019 pandemic.

OBJECTIVE: Bone conduction hearing aids are the only non-surgical devices used for conductive hearing loss. However, they are impractical for lifelong use since they require close contact of the transducer with the head skin, causing skin erosion and discomfort. Bone conduction hearing implants and active middle ear implants do not present these issues; however, they require surgery and can sometimes cause issues in the skin surrounding the devices. This study aimed to develop a new bone conduction hearing device that does not exert pressure on the skin or require surgery. METHODS: Our device modified a piezoelectric element by using the skin of a pinna as one of the two electrodes of a conventional piezoelectric device. We compared the sound transmission of a speaker, a conventional piezoelectric device, or the new device to the guinea pig cochlea, a physiological sound transducer to the auditory nerve, in normal and air-conductive hearing loss conditions. RESULTS: The novel device transmitted sound to the cochlea even after causing air-conductive hearing loss. Its bone conduction was more efficient than the speaker and the conventional piezoelectric device. CONCLUSION: We developed a novel type of bone conduction device that efficiently transmits sound to the cochlea by skipping the external auditory canal, tympanic membrane, and middle ear ossicles. This device does not exert pressure on the skin that can result in skin damage, an adverse effect of a conventional bone conduction hearing aid. SIGNIFICANCE: Our novel hearing device can be used as a substitute for current bone-conduction hearing devices.

Macrophages play important roles in tissue homeostasis and inflammation. Recent studies have revealed that macrophages are dispersed in the inner ear and may play essential roles in eliciting an immune response. Autoinflammatory diseases comprise a family of immune-mediated diseases, some of which involve sensorineural hearing loss, indicating that similar mechanisms may underlie the pathogenesis of immune-mediated hearing loss. Autoimmune inner ear disease (AIED) is an idiopathic disorder characterized by unexpected hearing loss. Tissue macrophages in the inner ear represent a potential target for modulation of the local immune response in patients with AIED/autoinflammatory diseases. In this review, we describe the relationship between cochlear macrophages and the pathophysiology of AIED/autoinflammatory disease.

OBJECTIVE: To evaluate the efficacy and safety of regenerative treatment for tympanic membrane perforation (TMP) using gelatin sponge, basic fibroblast growth factor (bFGF), and fibrin glue. METHODS: This was a multicenter, non-randomized, single-arm study conducted at tertiary referral centers. Twenty patients with chronic TMP (age 23-78 years, 6 males, 14 females) were registered from three institutions. All treated patients were included in the safety analysis population. The edges of the TMP were disrupted mechanically by myringotomy and several pieces of gelatin sponge immersed in bFGF were placed and fixed with fibrin glue to cover the perforation. The TMP was examined 4 ± 1 weeks later. The protocol was repeated up to four times until closure was complete. The main outcome measures were closure or a decrease in size of the TMP, hearing improvement, and air-bone gap evaluated 16 weeks after the final regenerative procedure (FRP). Adverse events (AEs) were monitored throughout the study. RESULTS: Total closure of the TMP at 16 weeks was achieved in 15 out of 20 patients (75.0%, 95% confidence interval [CI]: 50.9%-91.3%) and the mean decrease in size was 92.2% (95%CI: 82.9%-100.0%). The ratio of hearing improvement and the air-bone gap at 16 weeks after FRP were 100% (20/20; 95%CI: 83.2%-100%) and 5.3 ± 4.2 dB (p <0.0001), respectively. Thirteen out of 20 patients (65.0%) experienced at least one AE, but no serious AEs occurred. CONCLUSION: The results indicate that the current regenerative treatment for TMP using gelatin sponge, bFGF, and fibrin glue is safe and effective.

世界的に流行が広がったCOVID-19によって我々も、それ以前とは異なった診療体制を余儀なくされた。当施設において実践したオンラインシステムを用いた遠隔遺伝カウンセリングの体制について報告する。2020年2月〜9月の間に257セッションのオンラインあるいはオンサイトの遺伝カウンセリングが行われた。そのうち19セッション(7.4%)ではCL側が病院を訪れない形であり、124セッション(48.2%)は完全オンサイトであり、残りの114セッション(44.4%)は両者のハイブリッドであった。すなわち全ての遺伝カウンセリングのうち半数以上が何らかの形で遠隔診療として行われた。オンサイトとオンラインの遺伝カウンセリングにはそれぞれメリット・デメリットがあったが、十分遺伝カウンセリングとして成立しており、今後は感染防止だけでなくCOVID-19の収束後も医療資源の不十分な地域における遺伝カウンセリングを始め多くの場面で遠隔遺伝カウンセリングは重要となると考えられた。(著者抄録)

Background: Usher syndrome (USH) typically leads to deaf-blindness, requiring the provision of extensive education and rehabilitation services. Therefore, investigating the prevalence is crucial to requests for proper government support for USH patients. Objective: The aim was to perform a nationwide epidemiologic survey of USH in Japan to estimate the prevalence of USH and reveal the relative frequency and characteristics of the three USH subtypes. Methods: To estimate the number of USH patients visiting hospitals over a 1-year period, 1,628 hospitals were randomly selected from all Departments of Otorhinolaryngology and Ophthalmology in Japan. Subsequently, we collected data regarding the clinical characteristics of each patient treated and the results of genetic testing, if performed. Results: We found that the prevalence of USH was at least 0.4 per 100,000 population. The frequency of clinical subtypes and causal genes for USH were consistent with previous reports. Also, we demonstrated the feasibility of genetic counseling for USH patients based on the results of genetic testing. Conclusion: USH is a rare disease, but requires social support due to the severity of symptoms. To minimize these issues, understanding the clinical characteristics and performing comprehensive genetic testing could allow early and accurate diagnosis as well as medical intervention.

Sensorineural hearing loss is a common disability often caused by the loss of sensory hair cells in the cochlea. Hair cell (HCs) regeneration has long been the main target for the development of novel therapeutics for sensorineural hearing loss. In the mammalian cochlea, hair cell regeneration is limited, but the auditory epithelia of non-mammalian organisms retain the capacity for hair cell regeneration. In the avian basilar papilla (BP), supporting cells (SCs), which give rise to regenerated hair cells, are usually quiescent. Hair cell loss induces both direct transdifferentiation and mitotic division of supporting cells. Here, we established an explant culture model for hair cell regeneration in chick basilar papillae and validated it for investigating the initial phase of hair cell regeneration. The histological assessment demonstrated hair cell regeneration via direct transdifferentiation of supporting cells. Labeling with 5-ethynyl-2'-deoxyuridine (EdU) revealed the occurrence of mitotic division in the supporting cells at specific locations in the basilar papillae, while no EdU labeling was observed in newly generated hair cells. RNA sequencing indicated alterations in known signaling pathways associated with hair cell regeneration, consistent with previous findings. Also, unbiased analyses of RNA sequencing data revealed novel genes and signaling pathways that may be related to the induction of supporting cell activation in the chick basilar papillae. These results indicate the advantages of our explant culture model of the chick basilar papillae for exploring the molecular mechanisms of hair cell regeneration.

BACKGROUND: Early detection of cognitive decline allows timely intervention to delay progression of dementia. However, current cognitive evaluation tools often include items delivered via verbal forms of instruction, which can cause poor performance in patients with hearing loss. OBJECTIVE: To develop and validate a cognitive screening battery, the Reading Cognitive Test Kyoto (ReaCT Kyoto), comprising test items given through non-verbal instruction. METHODS: A cross-sectional and multi-center study was conducted in the three medical institutes. ReaCT Kyoto was designed to evaluate domains of "registration," "repetition," "delayed recall," "visuospatial recognition," "orientation in time and place," and "executive function." The Japanese version of the Mini-Mental State Examination Test (MMSE-J) and ReaCT Kyoto were applied by experienced psychotherapists. Concurrent validity was evaluated between the ReaCT Kyoto Test and MMSE-J and between the ReaCT Kyoto Test and physician-diagnosed dementia. RESULTS: ReaCT Kyoto was validated in a sample of 115 participants. The mean age of subjects was 81.0±6.4 years, and the sample comprised 53.0% females. The area under the receiver operating curves was 0.95 for detecting physician-diagnosed dementia. When classifying patients in accordance with presence or absence of hearing loss, the AUCs were 0.93 and 0.97 for those with and without hearing loss, respectively. With a cut-off score of < 29 points for suspected dementia, ReaCT Kyoto correctly classified 90.4% of the subjects as belonging to the group with or without physician-diagnosed dementia. CONCLUSION: ReaCT Kyoto provides an appropriate solution for detection of cognitive impairment in persons with or without hearing loss.

OBJECTIVE: This study aims to evaluate the speech perception with first, second, or bilateral cochlear implants (CI) and to reveal the effects of wearing bilateral CI in children. METHODS: After reviewing the medical records, a total of 19 children who underwent bilateral cochlear implantation serially between 2012 and 2015 at Kyoto University Hospital (tertiary referral center) were included in this study. All patients had no delay in language development. The study group comprised nine boys and ten girls, and their age ranged from 3 years 8 months to 12 years 5 months when they underwent the tests in this study. The mean and median ages were 8 years 6 months and 9 years 2 months, respectively. We measured the appropriate signal/noise ratio (SNR) to test speech perception of Japanese language in noise by testing the hearing ability of unilateral CI patients with or without noise and by surveying the sound environment in a classroom of a mainstream elementary school. Speech perception in quiet and noise and the left-right localization ability were examined using first, second, or bilateral cochlear implants in all patients. RESULTS: Considering the results of hearing ability tests with noise and the SNR of the elementary school classrooms, we decided to use SNR of +10 dB to evaluate the speech perception ability in noise. The speech perception ability using the second CI was significantly worse in patients undergoing second cochlear implantation after 7 years old than in those who underwent surgery before 3.5 years old. Moreover, patients undergoing second cochlear implantation before 7 years old showed significantly better left-right localization of high-frequency sound. CONCLUSIONS: Second cochlear implantation before 7 years old is a critical factor in acquiring beneficial speech perception ability with the second CI and sound localization ability with the bilateral CI.

The development of asymmetric patterns along biologically relevant axes is a hallmark of many vertebrate organs or structures. One example is the sensory epithelium of the mammalian auditory system. Two distinct types of mechanosensory hair cells (inner and outer) and at least six types of associated supporting cells are precisely and asymmetrically arrayed along the radial (medial-lateral) axis of the cochlear spiral. Immunolabeling of developing cochleae indicates differential expression of Glycogen synthase kinase 3β (GSK3β) along the same axis. To determine whether GSK3β plays a role in specification of cell fates along the medial-lateral axis, GSK3 activity was blocked pharmacologically in cochlear explants. Results indicate significant changes in both the number of hair cells and in the specification of hair cell phenotypes. The overall number of inner hair cells increased as a result of both a shift in the medial boundary between sensory and non-sensory regions of the cochlea and a change in the specification of inner and outer hair cell phenotypes. Previous studies have inhibited GSK3 as a method to examine effects of canonical Wnt signaling. However, quantification of changes in Wnt pathway target genes in GSK3-inhibited cochleae, and treatment with more specific Wnt agonists, indicated that the Wnt pathway is not activated. Instead, expression of Bmp4 in a population of GSK3β-expressing cells was shown to be down-regulated. Finally, addition of BMP4 to GSK3-inhibited cochleae achieved a partial rescue of the hair cell phenotype. These results demonstrate a role for GSK3β in the specification of cellular identities along the medial-lateral axis of the cochlea and provide evidence for a positive role for GSK3β in the expression of Bmp4.

OBJECTIVE: To evaluate the electrode status during cochlear implantation (CI) using mobile cone-beam CT (mCBCT). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral hospital. PATIENTS: Fifty-seven patients (7 bilateral surgeries, 64 ears) who underwent CI and who received intraoperative mCBCT imaging. INTERVENTION: CI and CBCT during surgery. MAIN OUTCOME MEASURE: Electrode location and angular insertion depth determined by intraoperative mCBCT images. RESULTS: There were six cases with cochlear malformation where intraoperative mCBCT was useful to confirm electrode location. Of 58 ears with a normal cochlear morphology, perimodiolar, straight, and mid-scalar electrodes were used in 30 (cochleostomy; 14 advance off-stylet technique cases), 27 (26 round window [RW] insertion, 1 extended round window [ERW] insertion), and 1 (RW insertion) ears, respectively. Complete scala-tympani (ST) insertion was achieved in 35 ears (14 cochleostomy, 21 RW or ERW insertion). The complete ST-insertion rate was significantly higher with RW or ERW insertion than that for cochleostomy insertion (p = 0.03), although cochleostomy insertion using the advanced off-stylet technique had a similar rate to RW or ERW insertion. The angular insertion depth values (average ± standard deviation) for perimodiolar electrodes (354.4 ± 29.44 degrees) were significantly smaller than those for Flex24 (464.8 ± 43.09 degrees) and Flex28 (518.2 ± 61.91 degrees) electrodes (p < 0.05). CONCLUSIONS: Evaluation of CI electrodes using intraoperative mCBCT was comparable to that with fan-beam CT or c-arm-based CBCT. Considering the low radiation dose of mCBCT and its availability in any operation room, mCBCT is the better modality for evaluating cochlear implant electrode arrays.

An imaging study, especially magnetic resonance imaging (MRI), is essential in order to differentiate idiopathic sudden sensorineural hearing loss from acute sensorineural hearing loss of any other etiology. As for MRI modalities to examine a tumor in the internal auditory canal and/or cerebellopontine angle, T1-weighted enhanced and T2-weighted imaging is useful. Recent reports indicate that fluid attenuated inversion recovery (FLAIR) imaging is sensitive in detecting elevated protein levels in fluid. A high intensity signal on FLAIR imaging in the inner ear suggests some pathology of the perilymph and endolymph such as hemorrhage, inflammation, or neoplasm (e.g. a schwannoma). We herein present four cases of acute sensorineural hearing loss with vertigo, which showed abnormal signals in the inner ear on FLAIR imaging and T1-weighted imaging. In all cases, the hearing levels showed no or little improvement despite high dose steroid therapy. These cases indicate the importance of evaluation of FLAIR and T1-weighted imaging in patients with acute sensorineural hearing loss and the possibility of novel etiological concepts of acute sensorineural hearing loss with vertigo established by MRI examinations.

In our aging society, it is important to maintain a healthy balance. However, the risk of falling gradually increases with age because of various hypofunctions such as vestibular disorders. In birds, hair cells regenerate after damage caused by ototoxic drugs; however, their regeneration in mammals is poor. To date, no curative therapy for vestibular disorders has been established. Therefore, the development of new treatments is an important theme in our aging society. In the mammalian vestibule, spontaneous regeneration has been reported morphologically. However, it is not clear whether regenerated hair cells possess their correct function. We investigated the mechano-electrical transduction (MET) function of hair cells by measuring Ca２＋ responses. We found an intact MET function in stimulated regenerated hair bundles. However, the self-repair of hair cells was only partial and insufficient to recover vestibular function. Therefore, additional treatments such as with anti-oxidant drugs, growth factors are needed. We also demonstrated that espin gene therapy restored stereocilia on regenerated hair cells after damage. Therefore, cell transplantation therapy might be promising for severe damage of the inner ear. We previously reported that induced pluripotent stem cells and human neural stem cells (hNSCs) differentiated into hair cells and vestibular ganglion cell-like cells, respectively. Therefore, these cells might be potential donor cells for the transplantation therapy of vestibular disorders. Currently, we are investigating the effectiveness of cell transplantation in vivo using an animal model. Morphologically, we confirmed the survival of transplanted cells in normal mice but without their differentiation into the desired cells. To evaluate vestibular function, we also examined the vestibulo-ocular reflex (VOR) and observed a decrease in VOR gain after the application of ototoxic drugs. We confirmed the functional effectiveness of cell transplantation in an animal model of vestibular disorders. Future studies should determine the optimal conditions for donors and recipients. Before new regenerative therapy can be established, further investigations are required.

Resident macrophages reside in all tissues throughout the body and play a central role in both tissue homeostasis and inflammation. Although the inner ear was once believed to be "immune-privileged," recent studies have shown that macrophages are distributed in the cochlea and may play important roles in the immune system thereof. Resident macrophages have heterogeneous origins among tissues and throughout developmental stages. However, the origins of embryonic cochlear macrophages remain unknown. Here, we show that the early development of resident macrophages in the mouse cochlea depends on yolk sac hematopoiesis. Accordingly, our results found that macrophages emerging around the developing otocyst at E10.5 exhibited dynamic changes in distribution and in situ proliferative capacity during embryonic and neonatal stages. Cochlear examination in Csf1r-null mice revealed a substantial decrease in the number of Iba1-positive macrophages in the spiral ganglion and spiral ligament, whereas they were still observed in the cochlear mesenchyme or on the intraluminal surface of the perilymphatic space. Our results demonstrated that two subtypes of resident macrophages are present in the embryonic cochlea, one being Csf1r-dependent macrophages that originate from the yolk sac and the other being Csf1r-independent macrophages that appear to be derived from the fetal liver via systemic circulation. We consider the present study to be a starting point for elucidating the roles of embryonic cochlear resident macrophages. Furthermore, resident macrophages in the embryonic cochlea could be a novel target for the treatment of various inner ear disorders.

In the mammalian cochlea, resident macrophages settle in the spiral ligament, spiral ganglion, and stria vascularis, even at the steady state. Resident macrophages in the cochlea are believed to maintain homeostasis in the inner ear and become active, as part of the front line defense, following inner ear damage. However, the exact roles of cochlear resident macrophages require further clarification. Colony stimulating factor-1 (Csf1) signaling regulates survival, proliferation, and differentiation of resident macrophages and appears to be essential for resident macrophages in the inner ear. To examine the roles of Csf1 signaling in auditory function, we examined the ossicles and inner ear of homozygous Csf1 mutant (Csf1op/op ) mice. The ossicles including the incus and stapes of Csf1op/op mice macroscopically demonstrated bone thickening, and the otic capsules of the inner ear were also thick and opaque. Histological analyses demonstrated that the otic capsules in Csf1op/op mice were thickened and showed spongy bone degeneration. Measurements of the auditory brainstem response revealed significant elevation of thresholds in 4-week old Csf1op/op mice compared with wild-type littermates, indicating that Csf1op/op mice demonstrate hearing loss due to, at least in part, deformity of the ossicles and bone capsule of the inner ear. Furthermore, Csf1op/op mice are deficient in the number of resident macrophages in the spiral ligament and stria vascularis, but not in the spiral ganglion. These data provide evidence that Csf1 signaling is important not only for bone formation in the inner ear, but also for the maintenance of resident macrophages in the spiral ligament and stria vascularis in the adult mouse cochlea.

Objective: To investigate whether our original method can precisely evaluate the angle between slow and quick phases of nystagmus (vector angle) and to determine whether vector angle analysis is helpful in differentiating between horizontal nystagmus and mixed nystagmus with horizontal and vertical components. Methods: We included 20 healthy volunteers, 17 patients with horizontal nystagmus, and 15 patients with mixed nystagmus. Caloric nystagmus was recorded in healthy volunteers positional nystagmus was recorded in each patient. We extracted the velocity of nystagmus from eye movement of each subject and analysed the vector angle. Results: In caloric nystagmus, the vector angle approached 180 degrees as slow-phase velocity increased, suggesting that our vector angle measurement is more reliable with faster nystagmus. Importantly, in horizontal nystagmus from peripheral vestibular disease, the vector angle similarly approached 180 degrees as slow-phase velocity increased in contrast, the vector angle in cases of mixed nystagmus from vertebrobasilar insufficiency or spinocerebellar degeneration significantly differed from the angle of caloric nystagmus. Conclusions: Vector angle analysis using our original algorithm can precisely evaluate the diametric relationship in vestibular nystagmus it may be helpful in diagnosis of non-peripheral vestibular disorders.

Acute vestibular syndrome (AVS) is a clinical condition characterized by dizziness or vertigo that develops acutely with nausea/vomiting, gait instability, and/or head-motion intolerance and lasts for a day or more. Most patients presenting with AVS are diagnosed as having a benign peripheral condition commonly called vestibular neuritis. However, central causes of AVS can also closely mimic benign peripheral AVS, particularly vestibular neuritis. Herein, we report a case of lateral medullary syndrome in a patient who presented with acute vertigo, in whom showing differential diagnosis from peripheral vertigo proved difficult by initial magnetic resonance imaging (MRI). A 47-year-old male patient presented to the emergency room complaining of severe vertigo and headache. The initial brain MRI showed no evidence of bleeding or stroke. Physical examination revealed left-directional horizontal nystagmus and gait disorder. There were no abnormal findings on examination of the central nervous system, other than nystagmus. However, during the clinical course, several other neurological findings became evident. A follow-up MRI performed two days after the onset of vertigo showed lateral medullary infarction, suggestive of the diagnosis of lateral medullary syndrome, and the patient was admitted to a neurological department for further treatment. Lateral medullary syndrome is caused by injury to the lateral part of the medulla in the brain. It has been reported that initial MRI of the brain sometimes fails to show abnormal findings in cases of lateral medullary syndrome. In patients presenting with acute vertigo, we should consider the possibility of central vertigo due to brainstem or cerebellar infarction, even in young patients without risk factors for cerebro-vascular disorders. Although the initial MRI findings show no signs of brain infarction in some patients of the lateral medullary syndrome presenting with AVS, physicians should keep in mind the importance to repeated neurological examinations and also a second MRI examination, if needed, to rule out the diagnosis of lateral medullary syndrome.

We report herein on two cases of otogenic complications caused by a cholesteatoma. Case 1: The patient was a 33-year-old male who was hospitalized because of confusion, fever, and anorexia. Computed tomography (CT) scan and magnetic resonance imaging (MRI) showed that he had an ear cholesteatoma with bone destruction of the cranial base, an abscess in the left temporal lobe of brain abscess and subperiosteal abscess. After drainage of the brain abscess, he underwent a radical mastoidectomy with meatoplasty. We finished the operation leaving some remnant cholesteatoma on the dura because of very strong dural adhesion by the cholesteatoma. The patient was transferred to a convalescent hospital without any side effects. Case 2: The patient was a 65-year-old female who was hospitalized because of left otitis media, meningitis and hydrocephalus. CT scan and MRI showed that she had a left side cholesteatoma with bone destruction of the cranial base and a fistula in the lateral semicircular canal. She underwent radical mastoidectomy with meatoplasty. We finished the operation leaving some remnant cholesteatoma on the dura for similar reasons as with case 1. The patient was transferred to a convalescent hospital without any side effects.

Fracture of the stapes following head injury is thought to be clinically less common than displacement of the incus or disarticulation of the incudostapedial joint. We present a case of traumatic fracture of the stapes due to an indirect force without dislocation of the incudostapedial joint. A 52-year-old male was referred to our hospital complaining of hearing loss on the left side four weeks after a traffic accident that had led to the patient sustaining multiple intracranial injuries with disturbance of consciousness. He recovered with conservative treatment and subsequently became aware of hearing loss in the left ear. A pure-tone audiogram showed a 70-dBHL conductive hearing loss with a 40-dB air-bone gap. Temporal bone computed tomography (CT) revealed disarticulation of the incudomalleolar joint and displacement of the stapes. After exploratory tympanotomy, we found disarticulation of the incudomalleolar joint, and fracture of both the stapedial crura, however, the incudostapedial joint and the footplate of the stapes were intact. Six months after type IV tympanoplasty, the patient achieved air-bone gap closure to within 15 dB. In the present case, the incudostapedial joint was preserved, while the patient had sustained considerably forceful head injury that caused multiple intracranial injuries and dislocation of the ossicles, which is a rare form in indirect trauma of the ossicular chain. In addition, multiplanar reconstruction images of temporal bone CT allowed us to accurately diagnose the pathology of the ossicular chain in the patient.

Sensorineural hearing loss (SNHL) is a common clinical condition resulting from dysfunction in one or more parts in the auditory pathway between the inner ear and auditory cortex. Despite the prevalence of SNHL, little is known about its etiopathology, although several mechanisms have been postulated including ischemia, viral infection or reactivation, and microtrauma. Immune-mediated inner ear disease has been introduced and accepted as one SNHL pathophysiology; it responds to immunosuppressive therapy and is one of the few reversible forms of bilateral SNHL. The concept of immune-mediated inner ear disease is straightforward and comprehensible, but criteria for clinical diagnosis and the precise mechanism of hearing loss have not been determined. Moreover, the therapeutic mechanisms of corticosteroids are unclear, leading to several misconceptions by both clinicians and investigators concerning corticosteroid therapy. This review addresses our current understanding of the immune system in the inner ear and its involvement in the pathophysiology in SNHL. Treatment of SNHL, including immune-mediated inner ear disorder, will be discussed with a focus on the immune mechanism and immunocompetent cells as therapeutic targets. Finally, possible interventions modulating the immune system in the inner ear to repair the tissue organization and improve hearing in patients with SNHL will be discussed. Tissue macrophages in the inner ear appear to be a potential target for modulating the immune response in the inner ear in the pathophysiology of SNHL.

Newborn hearing screening (NHS) has been conducted widely in Japan in the last decade, however, there seems to be some confusion regarding the significance of NHS or management of the results obtained from NHS among clinics and practitioners. The system of NHS in Japan should be improved and refined through continuous evaluation of NHS, in terms of cost effectiveness in particular, so that NHS can be conducted more efficiently and effectively. To achieve this goal, the authors thought it important to clarify the current status and roles of our department as a facility for infants with congenital hearing impairment. In the present study, we studied 106 infant cases who were referred to the Department of Otolaryngology in Kyoto University Hospital after NHS before the age of twelve months in a period of seven years from 2006 to 2012 via retrospective chart reviewing. 79.2% of 96 infants who were qualified as referred either unilaterally or bilaterally following NHS were diagnosed as having hearing impairment in any form, either unilateral or bilateral or conductive and/or sensorineural. The positive agreement rate was 88.7% in 53 cases who were qualified as referred bilaterally in NHS, demonstrating a high reliability of the NHS system. Twenty-four cases were diagnosed as having the need for hearing aids and were assigned to treatment and education. All the infants who underwent cochlear implantation in our department had severe bilateral hearing impairment of more than 105 dBnHL in both ears at the first examination. Moreover, a number of infants who were qualified as having passed in both ears in NHS or who had failed to receive NHS at birth were revealed as having hearing impairment and needed treatment later in the first year of their life suggesting thai NHS should be conducted in combination with periodical health checkups by family practitioners in order to identify infants with hearing impairment earlier in their life with higher efficacy.