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DOI： 10.1136/bcr-2023-259348

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PURPOSE: Removal of the current calcium alginate packing materials to the middle meatus in endoscopic sinus surgery (ESS) is usually accompanied by discomfort or pain owing to the hard and brittle nature of these materials. Plus moist HS-W® is a new calcium alginate packing material released in 2022 developed to overcome this issue by changing the uronic acid component. We aimed to compare the discomfort/pain during the removal of Plus moist HS-W® with Kaltostat®, as well as their suitability as packing materials in ESS. METHODS: Kaltostat® and Plus moist HS-W® were used as packing materials in 22 and 21 patients who underwent ESS in 2021 and 2022, respectively. Patients were asked to rate the pain during the packing removal 10 days after ESS using the Numerical Rating Scale (NRS). The ratio of residual packing materials, number of suctions (insertions/extractions of the suction cannula), and time required to remove packing materials were measured. Postoperative complications such as hemorrhage, local infection, lateralization of the middle turbinate, and synechia of the middle meatus were also evaluated. RESULTS: The Plus moist HS-W® group exhibited significantly lower NRS pain scores, a lower ratio of residual packing materials, a reduced number of suctions, and a shorter time required to remove the packing. No obvious postoperative complications occurred in both groups except for one suspicious case of a slight infection in the Kaltostat® group. CONCLUSION: Compared with Kaltostat®, Plus moist HS-W®, characterized by better gelatinization than Kaltostat®, benefits patients by minimizing discomfort/pain during removal. LEVEL OF EVIDENCE: Level 3.

DOI： 10.1007/s00405-023-08437-4

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BACKGROUND: The optimal chemotherapy regimen in concurrent chemoradiotherapy (CCRT) for cisplatin-ineligible head and neck squamous cell carcinoma (HNSCC) has not been established. We aimed to evaluate the feasibility, efficacy, and safety of CCRT with weekly low-dose carboplatin for the treatment of advanced HNSCC in patients who are cisplatin-ineligible. METHODS: This prospective phase II study enrolled adult patients (age ≥ 20 years) with HNSCC receiving whole-neck irradiation including bilateral levels II-IV and who were aged (≥ 75-year-old patients with 40 mL/min estimated glomerular filtration rate [eGFR] or better) or had renal dysfunction (< 75-year-old patients with 30-60 mL/min eGFR). Carboplatin was administered weekly (area under the plasma concentration-time curve = 2.0) for up to seven cycles during concurrent radiotherapy (70 Gy/35 Fr). The primary endpoint was the completion rate of CCRT. Secondary endpoints included overall response rate and incidence of adverse events. RESULTS: Among the 30 patients enrolled, 28 were men. The median age was 73.5 years. Seventeen patients were < 75 years whereas 13 were ≥ 75 years old. The completion rate of CCRT was 90%. The overall response rate was 90%. Grade 3 adverse events that occurred in 10% or more patients were oral/pharyngeal mucositis (47%), leukocytopenia (20%), and neutropenia (10%). Grade 4 adverse events occurred in one patient (elevation of alanine aminotransferase level). No treatment-related deaths occurred. CONCLUSION: CCRT with weekly low-dose carboplatin is a promising treatment option, with favorable feasibility, efficacy, and acceptable toxicity, for patients who are cisplatin-ineligible with advanced HNSCC. CLINICAL TRIAL REGISTRATION NUMBER: jRCTs031190028.

DOI： 10.1007/s10147-023-02423-w

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Ectopic parathyroid lesions can be difficult to detect. In the present study, we used near-infrared autofluorescence imaging (NIFI) in three cases of ectopic parathyroid lesions. Our results suggest that NIFI may be a confirmation tool for parathyroid pathology and an intraoperative navigation tool in vivo and ex vivo. Laryngoscope, 134:496-500, 2024.

DOI： 10.1002/lary.30728

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Background: As a substantial waiting time is usually required for radical surgery, safe and effective preoperative neoadjuvant chemotherapy (NAC) is desired for the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC). However, the significance of NAC in advanced HNSCC is still unclear. This study aimed to assess the safety and efficacy of NAC using the paclitaxel, carboplatin, and cetuximab (PCE) regimen. Methods: We retrospectively evaluated the background characteristics, incidence of adverse events, overall response rate (ORR), pathological response, recurrence-free survival (RFS), and overall survival (OS) in 26 patients. Patients receiving the PCE regimen were further divided into two groups based on the number of chemotherapy cycles (one cycle or more) and eligibility for cisplatin. Patients aged ≥ 75 years and those with an estimated glomerular filtration rate (eGFR) < 60 mL/min were classified as ineligible for cisplatin. Results: The median age was 70 (27–81) years. The median eGFR at treatment initiation was 63.2 (41.1–89.7) mL/min. Fourteen (53.8%) patients were ineligible for cisplatin. Grade 3 or higher neutropenia was observed in 11 of 25 (42.3%) patients. No delay in or withdrawal from surgery was observed. The ORR was 65.4%. The 2-year RFS and OS were 61.5% and 76.7%, respectively. No significant differences in safety and efficacy between the number of chemotherapy cycles and cisplatin eligibility were observed. Conclusion: NAC using the PCE regimen for patients with locally advanced HNSCC, including cisplatin-ineligible patients, has acceptable toxicity and favorable efficacy.

DOI： 10.1007/s10147-024-02545-9

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The sarcopenia index (SI), calculated as [(serum creatinine/serum cystatin C) × 100], maybe a simpler alternative for measuring muscle mass than computed tomography (CT) and bioelectrical impedance analysis (BIA). We enrolled 112 patients with head and neck cancers (HNC). The correlation of the SI with muscle surface area measured by CT (CTMSA, n = 82) and muscle mass by BIA (BIA-MM, n = 41) was tested. Cutoff values were set for SI, CTMSA, and BIA-MM. Overall survival (OS) was compared between the high- and low-SI/CTMSA/BIA-MM groups. The SI was correlated with CTMSA (r = 0.43) and BIA-MM (r = 0.52). The optimal cutoff values of SI, CTMSA, and BIA-MM were 76.1 (area under the curve [AUC] = 0.67), 129.2 (AUC = 0.59), and 46.1 (AUC = 0.62), respectively. OS was significantly lower in the low-SI group (78% at 1 year and 69% at 2 years) than in the high-SI group (94% at 1 year and 86% at 2 years; p = 0.006). There was no significant difference in OS between the low-and high-CTMSA and -BIA-MM groups. The SI, which only requires a blood sample, is a useful marker of muscle mass that correlates with short-term prognosis in patients with HNC.

DOI： 10.1080/01635581.2023.2290299

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.oor.2023.100107

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INTRODUCTION: Immune-related adverse events (irAEs) are prognostic factors for patients on nivolumab. However, predictors of irAEs have not yet been identified. We aimed to investigate the predictors of irAEs occurrence and nivolumab discontinuation due to irAEs. METHODS: Sixty-two patients with recurrent/metastatic head and neck squamous cell carcinoma received nivolumab therapy between June 2017 and December 2020. Treatment outcome was compared between the groups with or without irAEs. The irAE (+) group was further divided by nivolumab discontinuation. Progression-free survival (PFS) and overall survival (OS) were compared between the groups. Predictors of irAE occurrence were analyzed. RESULTS: Twenty-one patients (33.9%) developed irAEs, and six (28.6%) discontinued nivolumab due to severe irAEs. The irAE (+) group had significantly longer PFS and OS than the irAE (-) group (median PFS, 12.7 vs. 1.9 months; median OS, 33.1 vs. 12.8 months). The treatment outcomes in the discontinuation group were comparable to those in the non-discontinuation group. The maximum absolute eosinophil count (AEC) during nivolumab therapy was significantly higher in the irAE (+) group than in the irAE (-) group (548.8 vs. 182) and higher in the discontinuation group than in the non-discontinuation group (729.3 vs. 368.6). The receiver operating characteristic curve showed that the maximum AEC had a moderate-to-high accuracy for predicting irAE occurrence (area under the curve [AUC], 0.757) and nivolumab discontinuation (AUC, 0.893). DISCUSSION: Monitoring AEC during nivolumab therapy may be useful in predicting irAE occurrence, nivolumab discontinuation, and disease prognosis.

DOI： 10.1002/cam4.6648

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DOI： 10.1016/j.oraloncology.2023.106501

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NRF2 is a transcription factor responsible for antioxidant stress responses that is usually regulated in a redox-dependent manner. p62 bodies formed by liquid-liquid phase separation contain Ser349-phosphorylated p62, which participates in the redox-independent activation of NRF2. However, the regulatory mechanism and physiological significance of p62 phosphorylation remain unclear. Here, we identify ULK1 as a kinase responsible for the phosphorylation of p62. ULK1 colocalizes with p62 bodies, directly interacting with p62. ULK1-dependent phosphorylation of p62 allows KEAP1 to be retained within p62 bodies, thus activating NRF2. p62S351E/+ mice are phosphomimetic knock-in mice in which Ser351, corresponding to human Ser349, is replaced by Glu. These mice, but not their phosphodefective p62S351A/S351A counterparts, exhibit NRF2 hyperactivation and growth retardation. This retardation is caused by malnutrition and dehydration due to obstruction of the esophagus and forestomach secondary to hyperkeratosis, a phenotype also observed in systemic Keap1-knockout mice. Our results expand our understanding of the physiological importance of the redox-independent NRF2 activation pathway and provide new insights into the role of phase separation in this process.

DOI： 10.15252/embj.2022113349

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BACKGROUND: During oral and head and neck surgery, oral vestibular incisions may require a transverse incision on the upper lip mucosa, resulting in possible sensory disturbances in the area innervated by infraorbital nerve (ION) branches. Although sensory disturbances are attributed to nerve injuries, anatomy textbooks have not showed the precise distribution patterns of the ION branches in the upper lip. Furthermore, no detailed study has been available on this issue. This study aimed to reveal the precise distribution patterns of ION branches in the upper lip by dissecting the detached upper lip and cheek area using a stereomicroscope. METHODS: During a gross anatomy course at Niigata University (2021-2022), nine human cadavers were examined with special focus on the relationship between ION branches in the upper lip and the layered structure of facial muscles. RESULTS: The ION branched to the inferior palpebral (IP), external and internal nasal, and superior labial (lateral and medial) nerves. The ION branches in the upper lip did not run in a horizontal pattern from outside to inside but showed a predominantly vertical pattern. Considering their course, incising the upper lip mucosa transversely may cause paresthesia of the ION branches. The internal nasal (IN) and medial superior labial (SLm) branches tended to penetrate the orbicularis oris and descend between this muscle and labial glands, whereas the lateral superior labial (SLl) branches tended to innervate the skin. CONCLUSIONS: These findings suggest that a lateral mucosal incision is recommended for oral vestibular incisions of the upper lip and that deeper incisions to the labial glands should be avoided when incising the medial side to preserve the ION during surgery from an anatomical point of view.

DOI： 10.1016/j.aanat.2023.152118

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On-site monitoring of plasma drug concentrations is required for effective therapies. Recently developed handy biosensors are not yet popular owing to insufficient evaluation of accuracy on clinical samples and the necessity of complicated costly fabrication processes. Here, we approached these bottlenecks via a strategy involving engineeringly unmodified boron-doped diamond (BDD), a sustainable electrochemical material. A sensing system based on a ∼1 cm2 BDD chip, when analysing rat plasma spiked with a molecular-targeting anticancer drug, pazopanib, detected clinically relevant concentrations. The response was stable in 60 sequential measurements on the same chip. In a clinical study, data obtained with a BDD chip were consistent with liquid chromatography-mass spectrometry results. Finally, the portable system with a palm-sized sensor containing the chip analysed ∼40 μL of whole blood from dosed rats within ∼10 min. This approach with the 'reusable' sensor may improve point-of-monitoring systems and personalised medicine while reducing medical costs.

DOI： 10.1016/j.heliyon.2023.e15963

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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INTRODUCTION: Persistent postural-perceptual dizziness (PPPD) is a functional chronic vestibular syndrome with symptom exacerbation by upright posture, motion, and complex visual stimuli. Among these exacerbating factors, visual exacerbation is the most specific characteristic of PPPD requiring further investigation. We hypothesized that stimulus-induced changes occur in the functional connectivity (FC) rather than simple neural activation that is involved in visual stimulation. The present study aimed to identify the neural basis of PPPD by investigating FC before and after visual stimulation. METHODS: Eleven patients with PPPD and 11 age- and sex-matched healthy controls (HCs) underwent resting-state fMRI (rs-fMRI) before and after task-based fMRI with visual stimuli. RESULTS: At pre-stimulus, FC between the vestibular cortex and visual areas was low, while that between the somatosensory and visual areas was high in PPPD compared with that in HCs. FC between the visuospatial (parahippocampal gyrus) and spatial cognitive areas (inferior parietal lobule) was elevated in PPPD even in the pre-stimulus condition, which no longer increased at post-stimulus as observed in HCs. In the post-stimulus condition, FC between the visual and spatial cognitive areas and that between the visual and prefrontal areas increased compared with that in the pre-stimulus condition in PPPD. Task-based fMRI demonstrated that no brain regions showed different activities between the HC and PPPD groups during visual stimulation. DISCUSSION: In PPPD, vestibular inputs may not be fully utilized in the vestibulo-visuo-somatosensory network. Given that the FC between visuospatial and spatial cognitive areas increased even in HCs after visual stimuli, elevated status of this FC in combination with the high FC between the somatosensory and visual areas would be involved in the visual exacerbation in PPPD. An increase in FC from the visual areas to spatial cognitive and prefrontal areas after visual stimuli may account for the prolonged symptoms after visual exacerbation and anxious status in PPPD.

DOI： 10.3389/fneur.2023.1215004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Tinnitus therapies have been combined with the use of varieties of sound/noise. For masking external sounds, location of the masker in space is important; however, effects of the spatial location of the masker on tinnitus are less understood. We aimed to test whether a masking sound location would affect the perception level of simulated tinnitus. The 4 kHz simulated tinnitus was induced in the right ear of healthy volunteers through an open-type earphone. White noise was presented to the right ear using a single-sided headphone or a speaker positioned on the right side at a distance of 1.8 m for masking the simulated tinnitus. In other sessions, monaurally recorded noise localized within the head (inside-head noise) or binaurally recorded noise localized outside the head (outside-head noise) was separately presented from a dual-sided headphone. The noise presented from a distant speaker and the outside-head noise masked the simulated tinnitus in 71.1% and 77.1% of measurements at a lower intensity compared to the noise beside the ear and the inside-head noise, respectively. In conclusion, spatial information regarding the masking noise may play a role in reducing the perception level of simulated tinnitus. Binaurally recorded sounds may be beneficial for an acoustic therapy of tinnitus.

DOI： 10.1038/s41598-022-05535-x

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Other Link： https://www.nature.com/articles/s41598-022-05535-x

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Posture and gait are maintained by sensory inputs from the vestibular, visual, and somatosensory systems and motor outputs. Upon vestibular damage, the visual and/or somatosensory systems functionally substitute by cortical mechanisms called "sensory reweighting". We investigated the cerebrocortical mechanisms underlying sensory reweighting after unilateral labyrinthectomy (UL) in mice. Arc-dVenus transgenic mice, in which the gene encoding the fluorescent protein dVenus is transcribed under the control of the promoter of the immediate early gene Arc, were used in combination with whole-brain three-dimensional (3D) imaging. Performance on the rotarod was measured as a behavioral correlate of sensory reweighting. Following left UL, all mice showed the head roll-tilt until UL10, indicating the vestibular periphery damage. The rotarod performance worsened in the UL mice from UL1 to UL3, which rapidly recovered. Whole-brain 3D imaging revealed that the number of activated neurons in S1, but not in V1, in UL7 was higher than that in sham-treated mice. At UL7, medial prefrontal cortex (mPFC) and agranular insular cortex (AIC) activation was also observed. Therefore, sensory reweighting to the somatosensory system could compensate for vestibular dysfunction following UL; further, mPFC and AIC contribute to the integration of sensory and motor functions to restore balance.

DOI： 10.1038/s41598-022-19678-4

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DOI： 10.1016/S1473-3099(22)00316-4

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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OBJECTIVE: Basal information of head and neck small-cell carcinoma (HNSmCC) including epidemiology, primary site, treatment, and prognosis remains sparse due to its rarity. We report here a multicenter retrospective study on the diagnosis, treatment, and outcomes of patients with HNSmCC. MATERIALS AND METHODS: This study involved 47 patients with HNSmCC from 10 participating institutions. Eight patients were excluded for whom no pathological specimens were available (n = 2) and for discrepant central pathological judgements (n = 6). The remaining 39 patients were processed for data analysis. RESULTS: As pretreatment examinations, computed tomography (CT) was performed for the brain (n = 8), neck (n = 39), and chest (n = 32), magnetic resonance imaging (MRI) for the brain (n = 4) and neck (n = 23), positron emission tomography-CT (PET-CT) in 23 patients, bone scintigraphy in 4, neck ultrasonography in 9, and tumor markers in 25. Primary sites were oral cavity (n = 1), nasal cavity/paranasal sinuses (n = 16), nasopharynx (n = 2), oropharynx (n = 4), hypopharynx (n = 2), larynx (n = 6), salivary gland (n = 3), thyroid (n = 2), and others (n = 3). Stages were II/III/IV-A/IV-B/IV-C/Not determined = 3/5/16/6/5/4; stage IV comprised 69%. No patient had brain metastases. First-line treatments were divided into 3 groups: the chemoradiotherapy (CRT) group (n = 27), non-CRT group (n = 8), and best supportive care group (n = 4). The CRT group included concurrent CRT (CCRT) (n = 17), chemotherapy (Chemo) followed by radiotherapy (RT) (n = 5), and surgery (Surg) followed by CCRT (n = 5). The non-CRT group included Surg followed by RT (n = 2), Surg followed by Chemo (n = 1), RT alone (n = 2), and Chemo alone (n = 3). The 1-year/2-year overall survival (OS) of all 39 patients was 65.3/53.3%. The 1-year OS of the CRT group (77.6%) was significantly better compared with the non-CRT group (31.3%). There were no significant differences in adverse events between the CCRT group (n = 22) and the Chemo without concurrent RT group (n = 9). CONCLUSION: Neck and chest CT, neck MRI, and PET-CT would be necessary and sufficient examinations in the diagnostic set up for HNSmCC. CCRT may be recommended as the first-line treatment. The 1-year/2-year OS was 65.3%/53.3%. This study would provide basal data for a proposing the diagnostic and treatment algorithms for HNSmCC.

DOI： 10.3389/fsurg.2022.1049116

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BACKGROUND: Head and neck mucosal melanoma (HNMM) is a rare and aggressive subtype of melanoma. HNMM often develops as a recurrent or metastatic disease, and its prognosis is worse than that of cutaneous melanoma. Recent large-scale clinical studies have reported favorable outcomes with immune checkpoint inhibitors (ICIs) for melanoma. However, these clinical trials included only a small number of HNMM cases. This study aimed to estimate treatment outcomes and prognostic predictors of ICIs for advanced HNMM. METHODS: Cases of advanced HNMM, defined as unresectable or metastatic HNMM at the initial diagnosis (five patients) or development of recurrent/metastatic HNMM after initial treatment (27 patients), were included in this study. Survival analysis and a search for prognostic factors were performed for these 32 patients. Furthermore, the detailed clinical course of patients who received ICI treatment was investigated. RESULTS: The median overall survival (OS) of 32 patients with advanced HNMM was 25.3 months. The estimated 1-, 3-, and 5-year OS rates were 68.4%, 42.8%, and 34.3%, respectively. Fourteen patients (43.7%) received ICIs, whereas 18 (56.3%) did not. Univariate analysis showed that ICI treatment was the only factor associated with a better 1-year OS. Patients who received ICI treatment had significantly longer OS (median OS: not reached, 1-year OS: 85.7%) than those who did not (median OS: 11.3 months, 1-year OS: 54.5%). The overall response and disease control rates of patients who received ICI treatment were 50% and 64.3%, respectively. Patients who achieved complete response (CR) or partial response (PR) to ICI treatment survived significantly longer (1-year OS: 100%) than those who did not (1-year OS: 71.4%). Among the five patients who discontinued ICI treatment due to severe immune-related adverse events (irAEs), four did not receive salvage treatments but showed durable treatment effects and survived for 9.8-54.2 months at the end of the follow-up period. CONCLUSIONS: ICI treatment achieved a favorable OS for advanced HNMM. CR/PR to ICI treatment and discontinuation owing to severe irAEs were favorable predictors of OS.

DOI： 10.3389/fsurg.2022.1032626

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OBJECTIVE: The global standard for chemoradiation therapy (CCRT) for head and neck squamous cell carcinoma is cisplatin 100 mg/m2 administered once every three weeks, although cisplatin 80 mg/m2 is also widely used as an alternative treatment to reduce adverse events in Japan. We aimed to assess the long-term survival outcomes and late adverse events associated with CCRT with a 3-weekly cisplatin dose of 80 mg/m2. METHODS: A phase 2 study on CCRT with a 3-weekly cisplatin dose of 80 mg/m2 was performed in 47 patients between April 2015 and December 2016 at four centers in Japan. Survival outcomes and late adverse events at 5 years after this phase 2 trial were investigated. RESULTS: The median follow-up period was 61 months. The 5-year progression-free survival/overall survival of all 47 patients was 66.0%/76.6%, while that of patients with stage III, IV disease (UICC) was 65.6%/71.9%. Seventeen patients (36%) experienced dysphagia as a late adverse event. Univariate and multivariate analyses revealed a significant association between acute mucositis/low body mass index (BMI) during CCRT and late dysphagia. CONCLUSION: The survival outcomes of CCRT with a 3-weekly cisplatin dose of 80 mg/m2 may be comparable to the previously reported dose of 100 mg/m2. Acute mucositis and low BMI at CCRT were risk factors for late dysphagia, indicating the importance of managing these conditions during CCRT to prevent late adverse events. Caution and care for acute mucositis and swallowing training in patients with low BMI may be important for preventing late-stage dysphagia.

DOI： 10.3389/fsurg.2022.1035349

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INTRODUCTION: Persistent postural-perceptual dizziness (PPPD) is a chronic vestibular syndrome lasting more than 3 months. The core vestibular symptoms are dizziness, unsteadiness, and non-spinning vertigo, which are exacerbated by upright posture or walking, active or passive motion, and exposure to moving or complex visual stimuli. Among these, visual exacerbation is a key feature of PPPD for which the neural mechanisms are unknown. We hypothesized that vestibular symptoms may be exacerbated by visual stimuli through gaze behavioral change after exposure to moving or complex visual stimuli. The study aimed to examine gaze stability after exposure to moving visual stimuli in patients with PPPD. METHODS: Fourteen healthy controls (HCs), 27 patients with PPPD, and 12 patients with unilateral vestibular hypofunction (UVH), showing chronic vestibular symptoms for >3 months, were enrolled in the study. The participants were instructed to fixate on the gazing point at the center of a screen for 30 s before and after 90 s of exposure to moving visual stimuli. Gaze stability, best represented by the bivariate contour ellipse area (BCEA), was compared among three groups, both before and after exposure to the moving visual stimuli. Comparisons between pre- and post-moving visual stimuli in BCEA were also conducted. Correlation between the post/pre ratio of BCEA and vestibular tests, several clinical symptom scales including the Dizziness Handicap Inventory, Niigata PPPD Questionnaire, and Hospital Anxiety and Depression Scale, and the exacerbation of dizziness by exposure to moving visual stimuli was examined in the PPPD group. RESULTS: BCEA, both before and after exposure to moving visual stimuli in the PPPD group, was not different from that in HC and UVH groups. In the PPPD group, BCEA increased significantly after exposure to moving visual stimuli. The post/pre ratio of BCEA correlated with the occurrence of exacerbation of the dizziness sensation by exposure to moving visual stimuli; however, it did not correlate with vestibular tests or clinical symptom scales. CONCLUSION: Patients with PPPD were more likely to exhibit gaze instability after exposure to moving visual stimuli, which potentially exacerbated vestibular symptoms. This phenomenon may help elucidate the neural mechanisms of visual exacerbation in patients with PPPD.

DOI： 10.3389/fnhum.2022.1056556

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OBJECTIVE: To examine the validity of head roll-tilt subjective visual vertical (HT-SVV) in diagnosing persistent postural-perceptual dizziness (PPPD). STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Sixty-one patients with PPPD, 10 with unilateral vestibular hypofunction (UVH), and 11 with psychogenic dizziness (PD), showing chronic vestibular symptoms for >3 months. INTERVENTIONS: Head-tilt perception gain (HTPG, i.e., mean perceptual gain [perceived/actual tilt angle]) during right or left head tilt of approximately 30° (HT-SVV) and conventional head-upright SVV (UP-SVV) were measured. Bithermal caloric testing, cervical and ocular vestibular-evoked myogenic potentials (cVEMP and oVEMP), and posturography were conducted. MAIN OUTCOME MEASURES: Multiple comparisons were performed for the HT-SVV and other vestibular tests among the disease groups. A receiver operating characteristic curve was created to predict PPPD using HTPG. RESULTS: HTPG was significantly greater in the PPPD group than in the UVH and PD groups. There were no significant differences in UP-SVV, cVEMP, oVEMP, and posturography (foam ratio and Romberg ratio on foam) among the disease groups, while the UVH group had the highest canal paresis compared to the other two groups. The area under the curve of the receiver operating characteristic curve for predicting PPPD was 0.764, and the HTPG value of 1.202 had a specificity of 95.2% for diagnosing PPPD. CONCLUSIONS: While conventional vestibular tests including UP-SVV, VEMPs, and posturography did not show abnormalities in PPPD, high HTPG in the HT-SVV test, an excessive perception of head tilt, can be a specific marker for discriminating PPPD from other chronic vestibular diseases.

DOI： 10.1097/MAO.0000000000003340

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Excitable cochlear hair cells convert the mechanical energy of sounds into the electrical signals necessary for neurotransmission. The key process is cellular depolarization via K+ entry from K+ -enriched endolymph through hair cells' mechanosensitive channels. Positive 80 mV potential in endolymph accelerates the K+ entry, thereby sensitizing hearing. This potential represents positive extracellular potential within the epithelial-like stria vascularis; the latter potential stems from K+ equilibrium potential (EK ) across the strial membrane. Extra- and intracellular [K+ ] determining EK are likely maintained by continuous unidirectional circulation of K+ through a putative K+ transport pathway containing hair cells and stria. Whether and how the non-excitable tissue stria vascularis responds to acoustic stimuli remains unclear. Therefore, we analysed a cochlear portion for the best frequency, 1 kHz, by theoretical and experimental approaches. We have previously developed a computational model that integrates ion channels and transporters in the stria and hair cells into a circuit and described a circulation current composed of K+ . Here, in this model, mimicking of hair cells' K+ flow induced by a 1 kHz sound modulated the circulation current and affected the strial ion transport mechanisms; the latter effect resulted in monotonically decreasing potential and increasing [K+ ] in the extracellular strial compartment. Similar results were obtained when the stria in acoustically stimulated animals was examined using microelectrodes detecting the potential and [K+ ]. Measured potential dynamics mirrored the EK change. Collectively, because stria vascularis is electrically coupled to hair cells by the circulation current in vivo too, the strial electrochemical properties respond to sounds. KEY POINTS: A highly positive potential of +80 mV in K+ -enriched endolymph in the mammalian cochlea accelerates sound-induced K+ entry into excitable sensory hair cells, a process that triggers hearing. This unique endolymphatic potential represents an EK -based battery for a non-excitable epithelial-like tissue, the stria vascularis. To examine whether and how the stria vascularis responds to sounds, we used our computational model, in which strial channels and transporters are serially connected to those hair cells in a closed-loop circuit, and found that mimicking hair cell excitation by acoustic stimuli resulted in increased extracellular [K+ ] and decreased the battery's potential within the stria. This observation was overall verified by electrophysiological experiments using live guinea pigs. The sensitivity of electrochemical properties of the stria to sounds indicates that this tissue is electrically coupled to hair cells by a radial ionic flow called a circulation current.

DOI： 10.1113/JP281981

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AVES  

Lemierre’s syndrome is characterized by internal jugular vein thrombosis and systemic septic embolism
it is a fatal complication of upper respiratory tract infections. To date, it has not been demonstrated how the upper respiratory tract inflammation spreads from the primary infection site to internal jugular vein and systemic thrombosis. We report a very rare case of Lemierre’s syndrome derived from malignant otitis externa in which the spread of infection and thrombosis process were identified by imaging. A 61-year-old man with severe diabetes mellitus visited our hospital with consciousness disturbance and right posterior neck pain. He complained of right ear pain and otorrhea several days prior to the neck pain. Contrast-enhanced computed tomography demonstrated thrombosis in internal jugular vein and multiple lung abscesses. Temporal bone images revealed continuous lesions from skull base osteomyelitis to suboccipital abscess and sigmoid sinus thrombosis. We diagnosed the patient as having Lemierre’s syndrome secondary to skull base osteomyelitis following malignant otitis externa. The patient clinically recovered with a combination of drainage of suboccipital abscess and long-term administration of antibiotics, which is the standard treatment of malignant otitis externa. Considering the details of imaging and bacterial examination is very useful for understanding the pathophysiology and determining appropriate treatment in Lemierre’s syndrome pathophysiology and determining appropriate treatment in Lemierre’s syndrome.

DOI： 10.5152/iao.2021.20142

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media S.A.  

We examined the role of lateral temporal bone resection (LTBR) in the treatment of external ear canal (EAC) carcinoma between 2007 and 2018. The estimated 3-year disease-free survival (DFS) and disease-specific survival (DSS) according to the tumor stage and treatments were investigated in 36 patients with EAC squamous cell carcinoma. T stage classification according to the University of Pittsburgh staging system was as follows: 14 patients in T1, four patients in T2, nine patients in T3, and nine patients in T4. The 3-year DFS rate was 77.4% for T1 tumors, 100% for T2, 44.4% for T3 tumors, and 11.1% for T4 tumors (p &lt
001). The 3-year DSS rate was 100% for T1/T2 tumors, 87.5% for T3 tumors, and 11.1% for T4 tumors (p &lt
0.01). T1/T2 patients received mostly LTBR. Among nine T3 tumors, five patients (56%) received LTBR combined with preoperative chemotherapy and/or postoperative radiation (RT). Four of them had negative surgical margin and survived with no evidence of disease. The DFS of T3 patients who underwent concurrent chemoradiotherapy and LTBR was 0 and 80%, respectively (p = 0.048). For T1/T2 tumors, surgery achieved an excellent outcome. For T3 tumors, LTBR achieved negative surgical margin and showed good survival when combined with preoperative chemotherapy and/or postoperative RT. In contrast, the prognosis of T3 patients who could not undergo surgery was as poor as that of T4 patients. Therefore, in addition to subtotal temporal bone resection, LTBR-based treatment strategy may be a treatment option for limited cases of T3 patients.

DOI： 10.3389/fsurg.2021.708245

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Inc  

Objectives: To examine the role of autofluorescence (AF) monitoring with near-infrared fluorescence imaging (NIFI) in identifying parathyroid lesions in primary or secondary hyperparathyroidism (P-HPT or S-HPT) surgeries. Study Design: Prospective study. Methods: Twelve lesions each were resected from 12 and 3 patients with P-HPT and S-HPT, respectively. The mean and maximum AF intensities of the lesions normalized to that of the thyroid tissue for in situ and ex vivo preparations were compared between P-HPT and S-HPT. Subjective visual classifications of AF intensity were compared with postoperative quantitative assessments. The unevenness of AF distribution inside the lesions was assessed by determining the ratio of maximum to mean AF intensity and comparing them with the corresponding ratio for normal parathyroid glands (PGs). Results: In all quantitative comparisons (in situ/ex vivo, mean, and maximum AF), AF intensities of P-HPT were stronger than those of S-PHT. The AF-positive rate in in situ subjective visual classification was higher for P-HPT (100% vs. 33%). Subjective visual classifications showed a positive correlation with AF intensities. The ratio of maximum to mean AF was higher in P-HPT and S-HPT than in normal PGs. Conclusions: For P-HPT, AF intensity in both in situ and ex vivo preparations was sufficiently high and correlated with the subjective visual classification, suggesting that NIFI may be useful for confirming P-HPT lesions. In contrast, NIFI may have only a minor role in S-HPT surgeries owing to the weak-AF of S-HPT lesions. HPT lesions show an uneven AF intensity distribution compared with normal PGs. Level of Evidence: 3 Laryngoscope, 131:E2097–E2104, 2021.

DOI： 10.1002/lary.29310

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Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Hearing loss affects &amp;gt;5% of the global population and therefore, has a great social and clinical impact. Sensorineural hearing loss, which can be caused by different factors, such as acoustic trauma, aging, and administration of certain classes of drugs, stems primarily from a dysfunction of the cochlea in the inner ear. Few therapeutic strategies against sensorineural hearing loss are available. To develop effective treatments for this disease, it is crucial to precisely determine the behavior of ototoxic and therapeutic agents in the microenvironment of the cochlea in live animals. Since the 1980s, a number of studies have addressed this issue by different methodologies. However, there is much less information on pharmacokinetics in the cochlea than that in other organs; the delay in ontological pharmacology is likely due to technical difficulties with accessing the cochlea, a tiny organ that is encased with a bony wall and has a fine and complicated internal structure. In this review, we not only summarize the observations and insights obtained in classic and recent studies on pharmacokinetics in the cochlea but also describe relevant analytical techniques, with their strengths, limitations, and prospects.

DOI： 10.3389/fphar.2021.633505

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OBJECTIVES/HYPOTHESIS: To assess the ability of near-infrared fluorescence imaging (NIFI) to identify parathyroid glands (PGs) among histologically proven PG/non-PG specimens compared with a surgeon's visual acumen, and to determine NIFI sensitivity in detecting incidentally resected PGs from thyroidectomy specimens, compared to the surgeon's visual inspection. STUDY DESIGN: Prospective study. METHODS: With mean age of 61 years, 36 patients with various thyroid diseases were enrolled. Possible PGs (n = 28) and lymph nodes (n = 32) were identified by the experienced surgeon's visual inspection. Using NIFI, 15 PGs were further identified from thyroidectomy specimens. For these 75 specimens, the surgeon's judgments (PG vs. non-PG) were recorded. Histological evaluation was performed after examining the NIFI auto-fluorescence of each specimen. RESULTS: There were no significant differences in sensitivity, specificity, positive predictive value, and negative predictive value between the surgeon's visual inspection and NIFI in identifying PGs, with values of 100%/97.1%, 85.0%/87.5%, 85.4%/87.2%, and 100%/97.2%, respectively. The sensitivity of NIFI (82.9%) for detection of PGs from thyroidectomy specimens was significantly higher than that of the surgeon's visual inspection (61.0%). False negative specimens contained bleeding/congestion and/or encapsulation by thick tissues, whereas false positive specimens contained electrocoagulated tissues. CONCLUSIONS: NIFI showed results comparable to the experienced surgeon's visual inspection in identifying PGs. This could benefit novice surgeons. NIFI may be useful for experienced surgeons to locate incidentally resected PGs within thyroidectomy specimens for auto-transplantation. Prevention of intra-gland bleeding and congestion, careful removal of thick capsules, and bloodless surgeries without electrocoagulation are important for reducing false positive and false negative results. Laryngoscope, 131:1188-1193, 2021.

DOI： 10.1002/lary.29163

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media S.A.  

Background: Persistent postural-perceptual dizziness (PPPD) is a persistent chronic vestibular syndrome exacerbated by upright posture/walking, active or passive motion, and exposure to moving or complex visual stimuli. PPPD has four precursors: phobic postural vertigo, space-motion discomfort, visual vertigo, and chronic subjective dizziness. These four diseases share clinical features that form the basis of the diagnostic criteria for PPPD. Semiological similarities do not necessarily mean that PPPD is a single entity. However, if PPPD is not a single disorder but just a composite of four precursors, it may be subdivided according to the characteristics of each precursor. Objective: To test whether PPPD is a single disorder, we attempted a subtyping of PPPD. Methods: One-hundred-eight untreated patients with PPPD were enrolled in the study, who filled out the Niigata PPPD Questionnaire (NPQ) that consists of 12 questions on exacerbating factors for PPPD. A factor analysis of the patients' answers to the NPQ and a subsequent cluster analysis of the patients with PPPD using factors revealed by the factor analysis were performed. To validate our cluster classification, cluster differences were assessed using analysis of variance. Multiple comparison analyses were performed on demographical data, precipitating diseases, the Dizziness Handicap Inventory, the Hospital Anxiety and Depression Scale, and several vestibular tests to characterize each cluster. Results: Factor analysis revealed three underlying factors among the exacerbating factors in the NPQ. Exacerbation by visual stimuli (visual factor) accounted for 47.4% of total variance in the questionnaire. Exacerbation by walking/active motion (active-motion factor) and by passive motion/standing (passive-motion/standing factor) accounted for 12.0 and 7.67% of variance, respectively. Cluster analysis revealed three clusters: the visual-dominant subtype (n = 49)
the active motion-dominant subtype (n = 20)
and the mixed subtype (n = 39). The patients in the active motion-dominant subtype were significantly older than those in the visual-dominant subtype. There were no significant differences among the subtypes in other demographical data or conventional vestibular tests. Conclusions: The most common main exacerbating factor of PPPD was the visual factor. PPPD may be categorized into three subtypes. Conventional vestibular tests failed to point the characteristics of each subtype.

DOI： 10.3389/fneur.2021.652366

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

末梢挿入型中心静脈カテーテル(peripherally inserted central catheter、PICC)は安全性が高く頭頸部癌の薬物療法でも用いられるが、留置側の左右差に着目した報告は少ない。PICC留置後の先端位置移動と合併症発生率の左右差について検討した。PICC留置を行った頭頸部癌145例172件を対象とし後方視的な調査を行った。留置側は右36件、左136件で、留置期間中央値は65日であった。121例137件でX線による留置時・留置後の先端位置評価が可能であった。先端位置をZone A:上大静脈下半分と右心房上部、Zone B:上大静脈上半分と左腕頭静脈合流部、Zone C:左腕頭静脈に分類し、Zone A・Bを適正位置とした。右側では留置時33件(100%)、留置後30件(91%)が適正位置であったのに対し、左側では留置時97件(93%)、留置後82件(79%)が適正位置で、留置時と留置後では有意な変化を認めた(p=0.001)。そのほかの合併症発生率に左右差は認めなかった。左側からのPICC留置では上大静脈右側壁にカテーテル先端が当たり、Zone Aへの留置率が低い。さらに留置後の体位・肢位の変化により先端が移動し、適正位置であるZone A・Bに留まりにくい。不適正な先端位置は遅発性の上大静脈壁損傷や血栓症を招くため、右側からのPICC留置が望ましいと考えられた。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/ndt/gfaa319

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BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by mesangial polymeric IgA1 deposition. IgAN is believed to develop owing to aberrant mucosal immunoreaction against commensals in the tonsils. However, the exact interrelation between pathogenic IgA and mucosal microbiota in IgAN patients is unclear. METHODS: Biopsy-proven IgAN or recurrent tonsillitis (RT) patients who had undergone tonsillectomy were enrolled. We used 16S ribosomal RNA gene amplicon sequencing with a flow cytometry-based bacterial cell sorting technique) and immunoglobulin repertoire sequencing of the IgA heavy chain to characterize IgA-coated bacteria of the tonsillar microbiota (IgA-SEQ) and their corresponding IgA repertoire. Furthermore, we fractionated patient serum using gel-filtration chromatography and performed flow cytometry-based analysis of IgA binding to bacteria cultured from incised tonsils. RESULTS: Tonsillar proliferation-inducing ligand and B-cell activating factor levels were significantly higher in IgAN than in RT patients. IgA-SEQ for tonsillar microbiota revealed the preferential binding ability of IgA to Bacteroidetes in IgAN tonsils compared with those from RT patients. Expression of immunoglobulin heavy (IGH) constant alpha 1 with IGH variable 3-30 was significantly higher in IgAN than that in RT, and positively correlated with the IgA-coated enrichment score of Bacteroidetes. Serum polymeric IgA, comprising high levels of GdIgA1, exhibited considerable binding to Bacteroidetes strains cultured from the tonsils of IgAN patients. CONCLUSIONS: These findings provide evidence that aberrant mucosal immune responses to tonsillar anaerobic microbiota, primarily consisting of members of the phylum Bacteroidetes, are involved in IgAN pathophysiology.

DOI： 10.1093/ndt/gfaa223

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Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

<title>Abstract</title>
Auditory neurophysiological responses, such as steady-state responses, event-related potential P300/P3, and phase-amplitude coupling, are promising translational biomarkers for schizophrenia, but their molecular underpinning is poorly understood. Focusing on ErbB receptor signals that are implicated in both schizophrenia and auditory processing/cognition, we explored the causal biological links between ErbB signals and these auditory traits with an experimental intervention into rats. We peripherally challenged rat pups with one of the amniotic ErbB ligands, epidermal growth factor (EGF), and characterized its consequence on the series of these auditory electrocorticographic measures. Auditory brainstem responses (ABRs) and cortical ON responses were also assessed under anesthesia to estimate the influence of higher brain regions. An auditory steady-state paradigm revealed attenuation of spectral power and phase synchrony to 40-Hz stimuli in EGF-challenged rats. We observed a reduction in duration mismatch negativity-like potentials and a delay of P3a responses, all of which are relevant to the reported auditory pathophysiological traits of patients with schizophrenia. Moreover, the perinatal EGF challenges resulted in enhanced theta-alpha/beta and theta-gamma coupling within the auditory cortex and changes in ABRs. However, the EGF challenges retained the normal ranges of cortical ON responses, potentially ruling out their fundamental auditory deficits. Perinatal exposure of an ErbB ligand to rats strikingly reproduced the whole series of aberrant auditory responses and oscillations previously reported in patients with schizophrenia. Accordingly, these findings suggest that developmental deficits in ErbB/EGF signaling might be involved in the auditory pathophysiology associated with schizophrenia.

DOI： 10.1093/schizbullopen/sgaa070

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BACKGROUND: Early detection of head and neck carcinoma (HNC) as superficial HNC (SHNC) identified using recently developed optical techniques, such as magnifying endoscopy and narrow-band imaging (NBI), in combination with endoscopic surgeries enables minimally invasive treatment with favorable outcomes for HNC. This study aimed to identify the predictive factors for the rare but important clinical issue of SHNC, namely cervical lymph node metastasis (CLNM), following endoscopic resection. METHODS: Sixty-nine patients with SHNC who underwent endoscopic resection were enrolled in the study. Clinical data, preoperative endoscopic findings, pathological findings, and treatment outcomes were retrospectively reviewed. Because the pharyngeal mucosa lacks the muscularis mucosa, we measured tumor thickness in permanent pathology as an alternative to the depth of invasion. Correlations with the occurrence of CLNM were statistically examined. RESULTS: The 5-year disease-specific survival rate was 100%. Of 69 patients, 3 (4.3%) developed CLNM. All had subepithelial but not epithelial tumors. The 0-IIa type in the macroscopic findings, type B2/B3 vessels in narrow-band imaging, tumors ≥ pathological stage T2, lymphatic invasion, positive surgical margins, and tumor thickness >1,000 μm showed significant correlations with CLNM following endoscopic resection. Furthermore, the classification of type B vessels was significantly associated with tumor thickness. CONCLUSION: The treatment outcomes following endoscopic resection for SHNC were favorable. The risk of CLNM following endoscopic resection in SHNC can be predicted by several preoperative endoscopic and postoperative pathological findings. Among them, the classification of type B vessels, which correlated with both tumor thickness and CLNM, might be a useful predictive factor.

DOI： 10.3389/fsurg.2021.813260

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Society of Oto-Rhino-Laryngology Tokyo  

The diagnostic criteria for Persistent Postural-Perceptual Dizziness(PPPD)was defined by the Committee for the Classification of Vestibular Disorders of the Barany Society, and published in the Journal of Vestibular Research in 2017. PPPD is characterized by chronic vestibular syndrome persisting for ＞3 months, that is typically preceded by acute vestibular disorders. Antidepressant medication, vestibular rehabilitation, and cognitive behavioral therapy have been reported to be useful for the treatment of PPPD. In this study, we evaluated the efficacy of pharmacotherapy with antidepressants in 90 patients diagnosed as having PPPD. A selective serotonin reuptake inhibitor(SSRI)(escitalopram, 10-20 mg/day), serotonin and noradrenaline reuptake inhibitor(SNRI)(venlafaxine, 75mg/day), and noradrenergic and specific serotonergic antidepressant(NaSSA)(mirtazapine, 15mg/day)were used in this study. Antidepressant therapy led to improvement of the Dizziness Handicap Inventory(DHI)score, suggesting that it was effective for reducing the dizziness in patients with PPPD. On the other hand, in the non-treated group, consisting of patients who, for some reason, could not receive medication, there was no significant improvement in dizziness during the approximately 1-year follow-up period, suggesting the usefulness of therapeutic intervention for PPPD. While antidepressant drug therapy was shown to be effective, the incidence of adverse effects was high for all the drug classes, and the treatment continuation rate tended to decrease as the incidence of adverse effects increased, suggesting that appropriate control of adverse effects is important to achieve better treatment efficacy.

DOI： 10.3950/JIBIINKOKA.124.998

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media S.A.  

Background: Vestibular Meniere's disease (American Academy of Ophthalmology and Otolaryngology, 1972) also known as possible Meniere's disease (American Academy of Otolaryngology Head and Neck Surgery, 1995) or vestibular type of atypical Meniere's disease (V-AMD) (Japan Society for Equilibrium Research, 2017) is characterized by an episodic vertigo without hearing loss. Though named as Meniere's disease (MD), this entity may not be caused solely by endolymphatic hydrops (EH). Objective: To estimate the role of EH in vestibular Meniere's disease in comparison with definite Meniere's disease. Methods: Thirty patients with unilateral definite MD and 16 patients with vestibular Meniere's disease were included. Those who met the criteria for definite or probable vestibular migraine were excluded. All patients underwent vestibular assessments including inner ear MRI 4 h after intravenous gadolinium injection, bithermal caloric testing, directional preponderance of vestibulo-ocular reflex in rotatory chair test, cervical- and ocular-vestibular evoked myogenic potential, stepping test, dizziness handicap inventory (DHI), and hospital anxiety and depression scale (HADS). All above tests and frequency/duration of vertigo spells were compared between vestibular Meniere's disease and MD. Results: Even in unilateral MD, cochlear and vestibular endolymphatic hydrops (c-, v-EH) were demonstrated not only in the affected side but also in the healthy side in more than half of patients. Positive rate of v-EH in vestibular Meniere's disease (68.8%) was as high as that of MD (80%). In vestibular Meniere's disease, the number of bilateral EH was higher in the vestibule (56.3%) than that in the cochlea (25.0%). There were no differences in vestibular tests and DHI between vestibular Meniere's disease and MD
however, the frequency of vertigo spells was lower in vestibular Meniere's disease (p = 0.001). The total HADS score in the MD group was significantly higher than that in the vestibular Meniere's disease group. Conclusions: MD is a systemic disease with bilateral involvement of inner ears. V-EH is a major pathophysiology of vestibular Meniere's disease, which would precede c-EH in the development of vestibular Meniere's disease, a milder subtype of MD. MRI is useful for differentiating MD from other vertigo attacks caused by different pathologies in bringing EH into evidence.

DOI： 10.3389/fsurg.2020.601692

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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BACKGROUND: It was reported that treatment outcomes of the salvage chemotherapy (SCT) following nivolumab are fairly good compared with those of nivolumab itself. However, predictive factors of SCT for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) were not determined. METHODS: Twenty-one R/M HNSCC patients received SCT following nivolumab. The treatment outcome and predictive factors for the favorable response to SCT were investigated. RESULTS: The objective response rate (ORR) and the disease control rate of SCT were 52.4% and 81.0%, respectively. The median progression-free survival and the median overall survival time were 5.4 and 12.9 months, respectively. Patients with positive programmed death-ligand 1 (PD-L1) expression showed greater tumor shrinkage evaluated by the response evaluation criteria in solid tumors and higher ORR than those with negative PD-L1 expression. CONCLUSIONS: Treatment outcome of SCT following nivolumab in R/M HNSCC was favorable. PD-L1 expression may be a predictive factor of SCT.

DOI： 10.1002/hed.26374

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

Objective: Otitis media with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) is characterized by adult otitis media refractory to conventional treatments. OMAAV is either an aural manifestation of existing ANCA-associated vasculitis (AAV) or an initial aural manifestation of AAV. OMAAV occasionally causes an irreversible profound sensorineural hearing loss that may require a cochlear implant even in the latter case. In such a case, prompt diagnosis of OMAAV is important but sometimes difficult. When diagnosing OMAAV, repetitive otitis media with effusion (OME) in adults is the most difficult differential diagnosis. Precise evaluation of tympanic membrane (TM) findings would help to achieve a prompt diagnosis. The objective of this study was to discriminate OMAAV from adult OME based on tympanic TM findings. Methods: 10 with OMAAV and 10 with adult OME were included. We established a scoring system of OMAAV tympanic membrane (SCOT) to evaluate TM findings of OMAAV consisted of following three characteristic findings: thickening of pars tensa, vasodilation of pars tensa, and posterior wall swelling. Each TM finding in OMAAV and OME was scored from 0 to 3 by 20 otolaryngologists who never knew the diagnosis. Reliability of the scoring system in terms of consistency between examiners was evaluated by intraclass correlation coefficients (ICC). Validity was tested by comparing the TM scores between OMAAV and OME and by the area under the curve (AUC) of receiver operating characteristic (ROC) curve to discriminate OMAAV from OME. Correlations between the TM scores and various systemic markers of OMAAV including white blood cell count, C-reactive protein, myeloperoxidase-anti-neutrophil cytoplasmic antibody, and Birmingham Vasculitis Activity Score were examined. Results: The ICC of each score was over 0.95. Each of and the total TM scores were significantly higher in OMAAV than in OME. AUC of ROC curve was 0.9134. The cut-off value set at 2 points had the best combination of sensitivity (93.0%) and specificity (74.0%) to distinguish OMAAV from OME. No significant correlations were found between the total score of SCOT and systemic markers. However, the total score of SCOT significantly correlated with the average hearing level of both air (p = 0.021) and bone conductions (p = 0.032). Conclusion: Reliability and validity of SCOT in discriminating OMAAV from adult OME, the most difficult differential diagnosis, were demonstrated, suggesting that SCOT would be useful to make an early diagnosis of OMAAV. Correlation of SCOT with hearing level suggests that SCOT is also useful to evaluate disease status of OMAAV.

DOI： 10.1016/j.anl.2020.02.017

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

症例1は79歳男性で、突然の右耳閉感、右耳漏、右難聴を主訴に、前医にて髄液漏を疑われ紹介となった。症例2は44歳女性で、突然の右耳閉感、右耳漏を主訴に、前医にて難治性中耳炎を疑われ紹介となった。いずれの症例も髄膜炎症状はなく、側頭骨CTで右中頭蓋窩に骨の菲薄化を認めたが、MRIで髄膜脳瘤の合併は認めず、特発性耳性髄液漏と診断した。症例1は保存的治療で症状や検査所見は改善し、症例2は経乳突法による瘻孔閉鎖術を行い、症状の改善を認めた。

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NLM (Medline)  

OBJECTIVE: To present a case of pediatric cholesteatoma that invaded the petrous apex (PA) and discuss the usefulness of preoperative three-dimensional (3D) surgical simulation on a personal computer (PC) and patient-specific 3D printed model-assisted surgery. PATIENT: A 5-year-old boy with congenital cholesteatoma underwent a planned two-stage canal wall up mastoidectomy. The cholesteatoma had invaded the PA from a small space anterior to the superior semicircular canal (SSCC). During the removal of this lesion in the first surgery, the tip of a 1-mm round knife broke off and fell into the PA. The surgeon could not remove it, as it was thought that opening the space might damage the SSCC and the facial nerve (FN). INTERVENTION: Before the second surgery, a preoperative 3D surgical simulation on a PC was performed, and an approach to the PA via the triangle surrounded by the SSCC, FN, and middle cranial fossa, namely, the supracochlear approach, was discovered. A patient-specific 3D-printed model, which had been drilled to make each surface of the triangle including the SSCC, FN, and middle cranial fossa visible in the PC simulation surgery, was then created and a 3D-printed model-assisted surgery was planned. RESULTS: By placing the sterilized patient-specific 3D model close to the surgical field, the cholesteatoma and iatrogenic foreign body could be successfully removed from the PA without damaging the important surrounding structures. CONCLUSIONS: Preoperative 3D surgical simulations and intraoperative patient-specific 3D-printed model-assisted surgeries are new, powerful tools that aid in performing challenging surgeries on temporal bones.

DOI： 10.1097/MAO.0000000000002720

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Endoscopic submucosal dissection (ESD) has gained wide acceptance as a minimally invasive and curative surgery for superficial head and neck carcinoma. However, the safety of ESD for superficial pharyngeal carcinoma after radiotherapy has not been elucidated. Superficial hypopharyngeal carcinoma of the left pyriform sinus developed in a 76-year-old man who had undergone concurrent chemoradiotherapy for T2N2bM0 pyriform sinus carcinoma on the opposite side 12 months before. He underwent ESD without complications. Because tumor invasion into the muscular layer was a concern, the muscular layer was partially resected with the tumor. Twelve days after discharge, he presented with a sore throat and difficulty in swallowing. Endoscopy and computed tomography revealed necrosis due to wound infection with abscess formation around the left carotid artery. The common carotid artery subsequently ruptured. Although the surgical intervention was performed, he passed away 46 days after ESD due to carotid blowout. ESD is a minimally invasive treatment for superficial head and neck carcinoma, but carotid blowout can occur in cases after radiation. Prior radiotherapy and deeper dissection into the muscular layer may hamper wound epithelization, resulting in infection-induced necrosis and carotid blowout. Diligent monitoring of wound healing is essential in patients who have previously undergone irradiation.

DOI： 10.1016/j.anl.2020.08.020

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PURPOSE: Sarcopenia, defined as a decrease in the skeletal muscle mass and its function, is associated with a poor clinical outcome in several malignancies. We aimed to examine whether sarcopenia can be a predictor of incompletion of concurrent chemoradiotherapy (CCRT) and survival for head and neck cancer (HNC) patients. METHODS: Forty-one male HNC patients who received CCRT were enrolled in the study. Cross-sectional muscle areas at the third lumbar vertebral level were normalized by the squared height of the patients and were termed the lumbar skeletal muscle index (LSMI, cm2/m2), a marker of sarcopenia. Patients were divided into high (30/41, 73%) and low (11/41, 27%) LSMI groups. The LSMI cut-off value was set at 39.7 cm2/m2 based on a receiver operating characteristic curve for incompletion of CCRT. The groups were compared for survival rate by the Kaplan-Meier method. Factors predicting incompletion of CCRT were investigated among several variables. RESULTS: Multivariate analysis showed that a pre-treatment low LSMI (P = 0.033) and age over 70 years (P = 0.023) were the only significant predictors for incompletion of CCRT. The 2-year disease-specific survival (DSS) rate was significantly lower in the low LSMI group (61%) than in the high LSMI group (97%, P = 0.012), whereas there were no differences in the DSS rate between the low and high body mass index groups. CONCLUSION: The prevalence of sarcopenia in HNC patients receiving CCRT was 27%. Its presence before treatment was a significant predictor of incomplete CCRT and poor DSS rate in HNC patients.

DOI： 10.1007/s00405-020-06273-4

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PURPOSE: The importance of nivolumab for recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is rapidly increasing. However, prognostic factors have not been determined for predicting treatment outcome. We aimed to investigate the prognostic factors in R/M HNSCC patients treated with nivolumab. METHODS: This retrospective study included 42 patients with R/M HNSCC who received nivolumab therapy. Correlations of overall survival (OS) with various patient characteristics including age, recurrent/metastatic site, performance status (PS), programmed death-ligand 1 positivity, body mass index, neutrophil-to-lymphocyte ratio, modified Glasgow prognostic score (mGPS), previous cetuximab administration, and immune-related adverse events were investigated. RESULTS: The overall response rate and disease control rate were 16.7% and 45.2%, respectively. Estimated 1-year OS and progression-free survival (PFS) were 56.4% and 24.5%, respectively. Multivariate analysis revealed that PS = 2 (hazard ratio 0.147; 95% CI 0.041-0.527; p = 0.003) and mGPS = 2 (hazard ratio 0.188; 95% CI, 0.057-0.620; p = 0.006) were independent predictors of poor OS. Given that the PS and mGPS were independent prognostic factors, we classified patients into three groups according to PS and mGPS: Group 1, both PS and mGPS were 0 or 1 (n = 30); Group 2, either PS or mGPS was 2 (n = 9); Group 3, both PS and mGPS were 2 (n = 3). The OS curves were significantly stratified among the three groups. CONCLUSION: The combination of PS and mGPS accurately predicted OS after nivolumab therapy. Preventive intervention to maintain general condition without simultaneously exceeding level 2 of PS and mGPS might be important for improving treatment outcomes of nivolumab.

DOI： 10.1007/s00405-020-05945-5

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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OBJECTIVE: To test whether the threshold of nerve integrity monitor (NIM) responses during facial nerve decompression surgery can predict the postoperative outcome. STUDY DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Twenty peripheral facial palsy patients who underwent transmastoid decompression surgery. INTERVENTION: During decompression surgery, thresholds of NIM responses were measured via direct facial nerve stimulation at three sites: the geniculate ganglion (GG), the second genu (2 G), and the stylomastoid foramen. MAIN OUTCOME MEASURES: Facial nerve function was evaluated before and 6 months after surgery using the Yanagihara grading score (maximum score = 40 points). Complete recovery was defined as an improvement of the grading score to ≥ 36 points without synkinesis. Variables including age, sex, disease (Bell's palsy or Ramsay Hunt syndrome), time after onset, Yanagihara grading score, and electroneurography before surgery, and the thresholds of NIM responses during surgery were compared in the complete and incomplete recovery groups. NIM responders were defined as those exhibiting a NIM response of < 1.5 mA at any site. Postoperative Yanagihara grading scores in NIM responders and NIM nonresponders were compared. RESULTS: No variables differed significantly in the complete and incomplete recovery groups before surgery. NIM response thresholds in the complete recovery group at the GG and the 2nd G were significantly lower than the corresponding thresholds in the incomplete recovery group. The postoperative Yanagihara grading scores of NIM responders were significantly better than those of NIM nonresponders. CONCLUSION: NIM responses to intraoperative direct facial nerve stimulation were useful for predicting outcomes after decompression surgery.

DOI： 10.1097/MAO.0000000000002594

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DOI： 10.1097/MAO.0000000000002663

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DOI： 10.1097/MAO.0000000000002663

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Identifying the specific functional regulator of integrin family molecules in cancer cells is critical because they are directly involved in tumor invasion and metastasis. Here we report high expression of PLOD2 in oropharyngeal squamous cell carcinomas (SCCs) and its critical role as a stabilizer of integrin β1, enabling integrin β1 to initiate tumor invasion/metastasis. Integrin β1 stabilized by PLOD2-mediated hydroxylation was recruited to the plasma membrane, its functional site, and accelerated tumor cell motility, leading to tumor metastasis in vivo, whereas loss of PLOD2 expression abrogated it. In accordance with molecular analysis, examination of oropharyngeal SCC tissues from patients corroborated PLOD2 expression associated with integrin β1 at the invasive front of tumor nests. PLOD2 is thus implicated as the key regulator of integrin β1 that prominently regulates tumor invasion and metastasis, and it provides important clues engendering novel therapeutics for these intractable cancers.

DOI： 10.1016/j.isci.2020.100850

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Society of Practical Otolaryngology  

Spontaneous cerebrospinal fluid (CSF) effusion of the temporal bone is extremely rare in adults. Its local findings are similar to those of otitis media with effusion (OME) and the condition is often diagnosed by an intractable serous otorrhea that persists after paracentesis of the tympanic membrane (TM). We report two cases of spontaneous CSF effusion of the temporal bone which showed different clinical courses. Both patients presented with sudden aural fullness, without any trigger. They were initially diagnosed as having OME, however, pulsatile serous otorrhea persisted even after paracentesis of the TM/tube insertion. Temporal bone CT showed bone defects of the middle cranial fossa in both cases. The first case had a large amount of glucose-positive otorrhea, which led to the diagnosis of CSF effusion. Gauze packing of the external auditory meatus closed the perforation of the TM, the route of leakage of the CSF. Two months later, the hearing recovered, with no CSF leak, and four months later, the soft tissue density on the CT disappeared. In contrast, the second case showed just a small amount of otorrhea, which was glucose-negative. After removal of the ventilation tube, the perforation of the TM closed. However, pulsation of the TM and conductive hearing loss persisted. We performed a diagnostic/therapeutic operation seven months after the onset. During surgery, we found intermittent pulsatile liquid outflow from the middle cranial fossa, on the basis of which we made the diagnosis of spontaneous CSF effusion of the temporal bone. The leakage area confirmed by staining was covered by fascia, bone pate, and bone chips. Until now, 12 months after the surgery, there has been no recurrence. Adult-onset spontaneous CSF leakage may be cured by conservative treatments, as observed in case 1. As an initial treatment of spontaneous CSF effusion of the temporal bone, we propose removal of the ventilation tube, if in place, and/or the packing of the ear canal to close the CSF outflow route.

DOI： 10.5631/jibirin.113.615

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Society for Equilibrium Research  

Persistent postural-perceptual dizziness (PPPD) is a newly defined diagnostic syndrome that was included in the 11 th edition of the World Health Organization's International Classification of Diseases (ICD-11) in 2018. PPPD is characterized by persistent chronic vestibular syndrome, typically preceded by acute vestibular disorders, lasting for ôŠ¼3 months. The core vestibular symptoms of PPPD are dizziness, unsteadiness, and/or non-spinning vertigo and are exacerbated by upright posture/walking, active or passive movements, and exposure to moving or complex visual stimuli. PPPD is classified as a functional disorder, and not as a structural or psychiatric condition. No specific laboratory tests for the diagnosis of PPPD are available, and an assessment of the symptoms, exacerbating factors, and medical history is important for the precise diagnosis of PPPD. Although the exact pathophysiology of PPPD remains to be elucidated, data from physiological investigations and rapidly emerging advanced structural and functional neuroimaging studies have revealed some key mechanisms underlying the development of this disorder, including stiffened postural control, a shift in processing spatial orientation information to favor visual or somatosensory over vestibular inputs, and failure of higher cortical mechanisms to modulate the first two processes. Although PPPD is a relatively new diagnosis and will therefore be unfamiliar to many health professionals, undiagnosed or untreated dizzy patients who have been suffering for many years can be saved. Once recognized, PPPD can be managed by effective communication and individually tailored treatment strategies, including serotonergic medications, vestibular rehabilitation and cognitive behavioral therapy.

DOI： 10.3757/jser.79.62

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OBJECTIVE: To examine the association between hearing impairment and cognitive decline and to identify possible risk factors for presbycusis. STUDY DESIGN: Cross-sectional survey in prospective cohort study. SETTING: University hospital. PATIENTS: A total of 322 participants aged >60 years, for whom all the below data were available, were enrolled in the study. There were 168 females and 154 males with a median age of 71 years (range: 60-89 yrs). INTERVENTIONS: PROST (Project in Sado for Total Health), a medical database in Sado island Japan, was analyzed. MAIN OUTCOME MEASURES: Data on pure-tone audiometry, mini-mental state examination (MMSE), polymorphism of apolipoprotein E4 (ApoE4), diabetes mellitus, hypertension, smoking, and alcohol consumption were extracted. Hearing impairment was defined as an average frequency between 0.25 and 8 kHz that exceeded 30 dB. Multivariate analysis was used to identify which of the above factors could predict the hearing impairment. Hearing threshold of each Hz was compared between the ApoE4 (+/+), (+/-), and (-/-) groups. RESULTS: Among various factors, only low MMSE scores (<24) showed significant association with hearing impairment. There were no differences in the hearing threshold of all frequencies between ApoE status groups. CONCLUSIONS: Hearing impairment was associated with low MMSE sores, regardless of the ApoE4 status. If ApoE4 status would be a common upstream predictor for both the hearing and cognitive impairment, hearing threshold would be related to ApoE4 status. However, these results may suggest that hearing impairment may be causally related to the cognitive dysfunction, perhaps via the cognitive load mechanisms.

DOI： 10.1097/MAO.0000000000002415

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Language：Japanese   Publisher：(NPO)日本頭頸部外科学会  

再発転移頭頸部癌に対する外来化学療法の増加に伴い、安全な血管アクセスデバイス(VAD)が求められている。VADとしての末梢挿入型中心静脈カテーテル(PICC)27例と埋込型PICCである上腕ポート13例の安全性について比較した。両者に患者背景や治療内容に有意差を認めなかった。合併症発生数は上腕ポート群0例(0%、0/1,000カテーテル留置日)、PICC群8例(30%、1.8/1,000カテーテル留置日)で、上腕ポート群で有意に少なかった(p=0.037)。PICC群の合併症内訳はカテーテル閉塞4例、血栓症2例、カテーテル関連血流感染症1例、自己抜去1例であった。上腕ポートは安全なVADであり、頭頸部癌の外来化学療法において有用な選択肢と考えられた。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J04210&link_issn=&doc_id=20191115330005&doc_link_id=10.5106%2Fjjshns.29.123&url=https%3A%2F%2Fdoi.org%2F10.5106%2Fjjshns.29.123&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01099&link_issn=&doc_id=20190926390015&doc_link_id=%2Fdz0jibik%2F2019%2F012209%2F017%2F1269-1270%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz0jibik%2F2019%2F012209%2F017%2F1269-1270%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Lippincott Williams and Wilkins  

Objective:To establish a questionnaire to diagnose and assess the severity of persistent postural-perceptual dizziness (PPPD).Study Design:Retrospective chart review.Setting:Tertiary referral center.Patients:Fifty PPPD patients and 50 consecutive control patients with other vestibular disorders.Interventions:Patients answered questions on three exacerbating factors of PPPD (upright posture/walking, movement, and visual stimulation), and each factor was evaluated using four questions scoring the severity from 0 (none) to 6 (unbearable). Somatic and psychological distress was evaluated by the Visual Analog Scale (VAS) and the Hospital Anxiety and Depression Scale (HADS), respectively.Main Outcome Measures:The questionnaire's reliability was tested by Cronbach's alpha, and it was validated by examining the differences in the questionnaire's scores between PPPD patients and controls. The area under the curve (AUC) of the receiver operating characteristic curve for each factor was calculated.Results:Cronbach's alpha coefficient was &gt
0.8 for all factors, except the movement factor. There were no significant differences in the VAS and HADS scores between the two groups. However, the combined and individual questionnaire scores for each factor were higher in PPPD patients than in controls, indicating the questionnaire's high validity. The AUC was widest for the visual stimulation factor (0.830), and a score of 9 (full score 24) had the best sensitivity (82%) and specificity (74%) for discriminating PPPD patients from controls.Conclusions:We developed a questionnaire that exhibited high reliability and validity in evaluating PPPD severity. The visual stimulation factor may be the most characteristic among the three exacerbating factors.

DOI： 10.1097/MAO.0000000000002325

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

The authors regret that the Table 4 [Table presented] was incorrect. The correct version of the Table 4 is as follows. The authors would like to apologise for any inconvenience caused.

DOI： 10.1016/j.anl.2019.01.012

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Taylor and Francis Ltd  

Background: Regarding the relationship between psychiatric disorders and dizziness, anxiety is the most frequently seen psychiatric disorder in dizzy patients. Objective: We compared the effects of anti-anxious benzodiazepines (loflazepate) and anti-vertiginous cholinergic antagonist (diphenidol) on the subjective symptoms in chronic vestibular patients with secondary anxiety. Methods: Forty-three patients who had chronic dizziness lasting more than three months due to organic vestibular diseases with secondary anxiety. Anxiety was evaluated by the State-Trait Anxiety Inventory (STAI). Subjective handicaps due to dizziness were assessed by the validated questionnaire consisted of 14 questions that were categorized into two physical and three emotional factors. During the initial six months of the study, 21 patients were treated by anti-anxious benzodiazepines (loflazepate, 2 mg/day) for four weeks, whereas anti-vertiginous cholinergic antagonist (diphenidol, 75 mg/day) was used for four weeks for other 22 patients during the later six months-period. Subjective handicaps and STAI were compared between pre- and post-treatment. Results: Loflazepate improved not only three emotional factors and state anxiety but also one of the physical factors. Diphenidol improved two physical factors but no emotional factors nor state and trait anxiety. Conclusions: Targeting for comorbid anxiety was beneficial for subjective symptoms of chronic dizziness with secondary anxiety.

DOI： 10.1080/00016489.2019.1612531

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Verlag  

Purpose: To clarify the anatomical distribution of otosclerotic loci in otosclerosis. Methods: Ninety-five patients with surgically confirmed uni- or bilateral otosclerosis were enrolled into the study. Hypodense areas observed in the otic capsule by high-resolution computed tomography (HRCT) were defined as otosclerotic loci. The location and number of lesions were examined, and the probability of lesion overlap and correlation with age/hearing parameters (air and bone conduction threshold, air-bone gaps) were tested. Results: Otosclerotic loci were confirmed by HRCT in 77 out of 115 operated ears. The three commonly affected sites were the anterior part of the oval window (ant-OW), anterior part of the internal auditory canal (ant-IAC), and pericochlear area (PCochA), with lesions detected in 96.1%, 46.8%, and 26.0% of ears, respectively. Only the ant-OW area was affected in 48.1% of the ears
the ant-IAC in 3.9%
and PCochA in none with significant differences (p &lt
0.01). The ant-OW lesions preferentially overlapped with ant-IAC (44.6%) than PCochA lesions (27.0%) (p &lt
0.05). Among double sites diseases, triple sites diseases occurred more commonly in the ant-OW + PCochA group (80%) than ant-OW + ant-IAC group (48.5%) (p &lt
0.05). There was no correlation between a number of lesions and age/hearing parameters. Conclusions: Based on the probability of lesion overlap, otosclerotic lesions may initiate at ant-OW followed by ant-IAC and later PCochA. Although the number of lesions showed no immediate correlation with hearing level or age, anatomical stage of the disease estimated by the location and the number of otosclerotic loci could be useful in predicting the future hearing status.

DOI： 10.1007/s00405-019-05385-w

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DOI： 10.1016/j.anl.2018.11.007

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DOI： 10.1016/j.anl.2018.10.011

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

Objective: Globus sensation, a feeling of lump or something stuck in the throat, could be caused by structural, functional, and psychogenic diseases. Due to a possible multifactorial nature of the disease, neither diagnosing test battery nor standard treatment for globus sensation has been established. Therefore, a questionnaire to accurately identify globus patients and evaluate the severity of the disease is desired. Glasgow Edinburgh Throat Scale (GETS) is a 10-item questionnaire about the throat symptoms consisting of three subscales relating to dysphagia, globus sensation, and pain/swelling in the throat. It was reported that globus patients marked high scores specifically for the globus scale among three scales, indicating that GETS can be used as a valid symptom scale for globus sensation. Aims of this study were to translate GETS into Japanese and to test its reliability and validity. Methods: Fifty-five patients complaining of globus sensation without abnormal endoscopic and CT findings were enrolled into the study. They were asked to answer the questions of GETS translated into Japanese (GETS-J). Reliability (internal consistency) of the questionnaire was tested using Cronbach's coefficient alpha. To test the validity, principal components analysis was used to identify the factorial structure of the questionnaire and GETS-J data were compared with those reported in the original GETS. Contribution of psychiatric comorbidities to globus sensation was also investigated by examining the correlation between Hospital Anxiety and Depression Scale (HADS) and GETS-J. Results: Reliability of the questionnaire examined by the Cronbach's coefficient alpha was satisfactory and all higher than 0.75. Principal components analysis identified following three questions as the globus scale: Q1, Feeling something stuck in the throat
Q5, Throat closing off
Q9, Want to swallow all the time. Somatic distress, i.e., patients’ reaction to throat symptoms, was significantly correlated with globus scale (r = 0.680). Anxiety component of HADS was significantly correlated with somatic distress but not with globus scale. These results were consistent with those of the original GETS except for the replacement of Q3 (discomfort/irritation in the throat) to Q5 (throat closing off) for globus scale in GETS-J. Conclusion: Translation of GETS into Japanese showed high reliability and validity, suggesting that translation and cross-cultural adaptation were not problematic. High correlation of globus scale of GETS-J with somatic distress indicated that GETS-J could be a useful questionnaire to identify the globus patients and evaluate the severity of the disease. Anxiety may complicate the somatic distress in patients with globus sensation.

DOI： 10.1016/j.anl.2018.02.001

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

Objective: Recent data indicated that concurrent chemoradiotherapy (CCRT) using high dose cisplatin (CDDP) is the most useful treatment for advanced head and neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100 mg/m2 is most recommended in Western countries. However, in terms of a balance of efficacy and adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different among the different ethnic groups. In this multicenter phase I/II study, we aimed to identify the optimal dose of CDDP in CCRT for patients with advanced head and neck SCC in the Japanese. Methods: Patients were eligible for inclusion if they had head and neck SCC that was treated with radical CCRT comprising whole-neck irradiation of the primary lesion and level II–IV lymph nodes on both sides. For the phase I study, a CDDP dose was 70 mg/m2 for level 0, 80 mg/m2 for level 1, and 100 mg/m2 for level 2. Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) were examined by phase I trial, by which CDDP dose for phase II was determined. The primary endpoint for the phase II was CCRT completion rate, and the secondary endpoint was full-dose-CCRT completion rate, the percentage of patients receiving a total CDDP dose of ≥200 mg/m2, response rate, and incidences of adverse events. Results: A CDDP dose of 100 mg/m2 was the MTD for phase I, and the recommended dose for phase II was 80 mg/m2. Forty-seven patients were evaluated in the phase II trial. CCRT completion rate, full-dose-CCRT rate, and the percentage of patients receiving a total CDDP dose of ≥200 mg/m2, were 93.6%, 78.7%, and 93.6%, respectively. One patient (2.1%) developed grade 2 renal dysfunction, and no patient developed febrile neutropenia or a grade 4 adverse event. Conclusion: The present phase I study indicated that a CDDP dose of 80 mg/m2 is the optimal dose in terms of safety. The phase II study revealed that CCRT completion rate, response rate, and rates of adverse events were not inferior for a CDDP dose of 80 mg/m2 as compared with a dose of 100 mg/m2, and a dose of 80 mg/m2 is therefore recommended in CCRT for the Japanese. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR
identification No. UMIN000010369).

DOI： 10.1016/j.anl.2018.02.008

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

Cluster of acute flaccid paralysis and cranial nerve dysfunction was associated with a 2014 outbreak of enterovirus D68 (EV-D68) respiratory illness in US. We describe a 33 year-old male patient of refractory dysphagia due to EV-D68-induced brainstem encephalitis successfully treated by surgery. Following acute upper respiratory tract infection, he developed dysphagia and bilateral facial paralysis. A coughing reflex was readily produced when the laryngopharyngeal fiberscope touched the epiglottis, however, water infusion induced only very weak and slow swallowing reflex, suggesting that only motor component was impaired but sensory function was preserved during swallowing. Despite eight months-conservative rehabilitations, Food Intake Level Scale (FILS) remained level 4. Therefore, corrective surgeries including cricopharyngeal myotomy, laryngeal suspension, and pharyngeal flap were performed. Thirty-six days after surgery, FILS rapidly and dramatically improved to level 8. This is the first report describing a successful surgical intervention for EV-D68-induced refractory dysphagia. Surgical treatment was suitable for EV-D68-induced dysphagia, perhaps because sensory function was preserved and only motor disturbance was present during the pharyngeal stage of swallowing.

DOI： 10.1016/j.anl.2017.12.004

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

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OBJECTIVE: The presence of endolymphatic hydrops in the inner ear, which can be detected with gadolinium-enhanced magnetic resonance imaging (Gd-MRI), is widely recognized as the main pathological cause of Ménière's disease (MD). However, the precise mechanisms underlying the development of endolymphatic hydrops remains unclear. One hypothesis proposes a relationship between the presence of a high jugular bulb (HJB) and MD, which disrupts the vestibular aqueduct leading to the development of endolymphatic hydrops. This study sought to identify anatomical features in MD patients using computed tomography (CT) images of the temporal bone. METHODS: Fifty-nine MD patients meeting the AAO-HNS diagnostic criteria and exhibiting endolymphatic hydrops in Gd-MRI were enrolled between July 2009 and December 2015. We only included MD patients who showed unilateral endolymphatic hydrops in Gd-MRI. Sixty-six patients with otosclerosis or facial palsy were also enrolled as control participants. In both groups, patients with other pathologies (e.g., chronic otitis media or cholesteatoma) and patients <16years old were excluded. HJB was defined as a JB that was observable in the axial CT image at the level where the round window could be visualized. JB surface area was measured on the axial image at the level where the foramen spinosum could be visualized. Finally, to investigate the relationship between the pneumatization of perivestibular aqueductal air cells and the existence of endolymphatic hydrops, the development of the air cells was rated using a three-grade evaluation system and the distance between the posterior semicircular canal (PSCC) and the posterior fossa dura was measured. RESULTS: The presence of HJB was observed in 22 of 59 affected sides of MD patients and in 17 healthy sides. The likelihood that HJB was detected on an affected side (22/39) was not significantly above chance (50%). The HJB detection rate did not significantly differ between the three groups (MD affected side, MD healthy side, and control patients). Furthermore, there were no significant group differences in JB surface area, distance between the PSCC and posterior fossa dura, or the development of perivestibular aqueductal air cells. CONCLUSION: We did not find any relationship between the anatomy of the temporal bones and the existence of endolymphatic hydrops. Moreover, we found no evidence suggesting that HJB or poor development of perivestibular aqueductal air cells were the cause of endolymphatic hydrops in MD patients.

DOI： 10.1016/j.anl.2017.09.014

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1038/s41598-018-28034-4

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Other Link： http://www.nature.com/articles/s41598-018-28034-4

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

Oligodendrocytes (OLs) are glial cells that form myelin sheaths surrounding the axons in the central nervous system (CNS). Jimpy (jp) mutant mice are dysmyelinating disease models that show developmental abnormalities in myelinated OLs in the CNS. The causative gene in jp mice is the proteolipid protein (PLP) located on the X chromosome. Mutations in the jp allele result in exon 5 skipping and expression of abnormal PLP containing a C-terminal frame shift. Many lines of evidence suggest that abnormal PLP in OLs results in endoplasmic reticulum (ER) stress and cell death. To histologically detect glial responses in the jp mutant brain, we performed staining with lineage-specific markers. Using OL markers and OL progenitor cell marker staining, we identified reduced numbers of OL lineage cells in the jp mutant brain. Nuclear staining of the transcription factor Olig1 was observed in the Tabby-jp brain, whereas cytoplasmic Olig1 staining was observed in the wild-type brain at postnatal day 21, suggesting that active myelination was present in the mutant brain. Many microglial cells with activated morphology and intensive staining of CD11b microglia marker were observed in the internal capsule of the mutant brain, a region of white matter containing residual OLs. Activated astrocytes with high glial fibrillary acidic protein-immunoreactivity were also mainly observed in white matter. Finally, we performed in situ hybridization using C/EBP homologous protein (CHOP) antisense probes to detect ER stressed cells. CHOP mRNA was strongly expressed in residual OLs in the Tabby-jp mutant mice at postnatal stages. These data show that microglia and astrocytes exhibit dynamic glial activation in response to cell death of OLs during Tabby-jp pathogenesis, and that CHOP antisense probes may be a good marker for the detection of ER-stressed OLs in jp mutant mice.

DOI： 10.1007/s12565-016-0383-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

Diffuse idiopathic skeletal hyperostosis (DISH) is a common disease in which ossification lesions occur in the bones including the vertebrae. Dysphagia may occur in advanced cases, but there are few cases that require treatment. A 68-year-old man was diagnosed with hypopharyngeal cancer of the left pyriform sinus and asymptomatic DISH on the anterior cervical vertebrae. Due to prior history of radiation, partial laryngopharyngectomy was performed. After surgery, severe dysphagia and aspiration pneumonia occurred, and the patient needed to undergo total laryngectomy. It was determined that dysphagia was due to multiple factors, including insufficient laryngeal elevation and esophageal compression by osteophytes of DISH. Asymptomatic DISH can cause severe dysphagia after partial laryngopharyngectomy. We suggest that evaluation of the swallowing function and surgical options, including laryngeal suspension and cricopharyngeal myotomy should be considered when performing partial laryngopharyngectomy in patients with DISH, even if they demonstrated no difficulties in swallowing before treatment.

DOI： 10.1080/23772484.2018.1477508

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Objective: To examine the risk factors of recurrence in pediatric congenital cholesteatoma. Study Design: Retrospective chart review. Setting: University hospital. Patients: Sixty-seven patients having tympanic type of congenital cholesteatoma under 15-years old at surgery. Interventions: Canal wall-up tympanomastoidectomy (n=30) or transcanal atticotomy/tympanoplasty (n=37) was performed depending on cholesteatoma extension, 16 of which were followed by second-look surgery. Preoperative computed tomography (CT) before second-look surgery or follow-up CT was performed to detect residual recurrence 1 year after the surgery. Cholesteatoma found at the second surgery was also included in the recurrence. All patients had no recurrent cholesteatoma at the last follow-up (median, 61 mo after surgery). Main Outcome Measures: Possible predictive factors were compared between the groups. Results: Residual cholesteatoma and retraction cholesteatoma occurred in 21 and 6%, respectively. There was no significant difference in age, sex, and type of cholesteatoma (open or closed) between the groups
however, Potsic stage and status of stapes involvement were more advanced in the residual cholesteatoma group. All residual lesions could be detected by follow-up CT or by second-look surgery. All of four retraction cholesteatoma patients were male, young at the surgery and in stage IV. Conclusion: Recurrence mostly occurred as residual cholesteatoma, suggesting that CT is recommended as a follow-up tool for congenital cholesteatoma. Advanced lesions had the risk of residual cholesteatoma, suggesting that complete removal of epithelium is important. Although rare, young advanced-stage patients had risk of retraction cholesteatoma and therefore normal mucosa should be preserved as much as possible for these patients.

DOI： 10.1097/MAO.0000000000001587

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Lippincott Williams and Wilkins  

Hypothesis: The temporal bone shows regional differences in bone development. Background: The spreading pattern of acute mastoiditis shows age-related differences. In infants, it spreads laterally and causes retroauricular swelling, whereas in older children, it tends to spread medially and causes intracranial complications. We hypothesized that bone maturation may influence the spreading pattern of acute mastoiditis. Methods: Eighty participants with normal hearing, aged 3 months to 42 years, participated in this study. Computed tomography (CT) values (Hounsfield unit [HU]) in various regions of the temporal bone, such as the otic capsule (OC), lateral surface of the mastoid cavity (LS), posterior cranial fossa (PCF), and middle cranial fossa (MCF), were measured as markers of bone density. Bone density development curves, wherein CT values were plotted against age, were created for each region. The age at which the CT value exceeded 1000 HU, which is used as an indicator of bone maturation, was calculated from the development curves and compared between the regions. Results: The OC showed mature bone at birth, whereas the LS, PCF, and MCF showed rapid maturation in early childhood. However, there were significant regional differences in the ages of maturation: 1.7, 3.9, and 10.8 years for the LS, PCF, and MCF, respectively. Conclusion: To our knowledge, this is the first report to show regional differences in the maturation of temporal bone, which could partly account for the differences in the spreading pattern of acute mastoiditis in individuals of different ages.

DOI： 10.1097/MAO.0000000000001566

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Background: Immunoglobulin A nephropathy (IgAN) is the most prevalent primary chronic glomerular disease, in which the mucosal immune response elicited particularly in the tonsils or intestine has been estimated to be involved in the development of the disease. To explore the relationship between IgAN and bacterial flora in the tonsils, we conducted a comprehensive microbiome analysis. Methods: We enrolled 48 IgAN patients, 21 recurrent tonsillitis (RT) patients without urine abnormalities and 30 children with tonsillar hyperplasia (TH) who had undergone tonsillectomy previously. Genomic DNA from tonsillar crypts of each patient was extracted, and V4 regions of the 16S ribosomal RNA gene were amplified and analysed using a high-throughput multiplexed sequencing approach. Differences in genus composition among the three study groups were statistically analysed by permutational multivariate analysis of variance and visualized by principal component analysis (PCA). Results: Substantial diversity in bacterial composition was detected in each sample. Prevotella spp., Fusobacterium spp., Sphingomonas spp. and Treponema spp. were predominant in IgAN patients. The percentage of abundance of Prevotella spp., Haemophilus spp., Porphyromonas spp. and Treponema spp. in IgAN patients was significantly different from that in TH patients. However, there was no significant difference in the percentage of abundance of any bacterial genus between IgAN and RT patients. PCA did not distinguish IgAN from RT, although it discriminated TH. No significant differences in microbiome composition among the groups of IgAN patients according to clinicopathological parameters were observed. Conclusions: Similar patterns of bacteria are present in tonsillar crypts of both IgAN and RT patients, suggesting that the host response to these bacteria might be important in the development of IgAN.

DOI： 10.1093/ndt/gfw343

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Aim of this work is to establish evaluation criteria for identifying endolymphatic hydrops in the vestibule and cochlea using a magnetic resonance imaging (MRI) scanner. This is a retrospective diagnostic study. We evaluated 70 ears of 35 unilateral Meniere's disease patients. We performed 3-T MRI 4 h after intravenous gadolinium injection. Otologists manually traced the outline of vestibule, cochlea, and endolymphatic space of the vestibule and cochlea on two-dimensional fluid-attenuated inversion-recovery (2D-FLAIR) images. The traced area was measured, and rates of endolymphatic space to the vestibule and cochlea were calculated. The same otologists judged whether the low signal intensity area of the cochlea was at the edge of the cochlea. For measuring the rate of endolymphatic space to the vestibule, when the cut-off value was 30%, the presence of endolymphatic hydrops was determined with sensitivity of 87.1% and specificity of 94.3%. In contrast, the rate of endolymphatic space to the cochlea produced low accuracy. Therefore, when the presence of endolymphatic hydrops in the cochlea was judged by whether the low signal intensity area in the cochlea was at the edge of cochlea, endolymphatic hydrops could be detected with sensitivity of 91.4% and specificity of 94.3%. We were able to identify endolymphatic hydrops in the vestibule when the rate of endolymphatic space to the vestibule was greater than 30%, and could detect endolymphatic hydrops in the cochlea when a low signal intensity area was located at the edge of the cochlea in 2D-FLAIR images.

DOI： 10.1007/s00405-017-4739-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Inc.  

Objective: The aim of this study was to profile and compare the middle ear microbiomes of human subjects with and without chronic otitis media. Study Design: Prospective multicenter cohort study. Methods: All consecutive patients undergoing tympanoplasty surgery for chronic otitis media or ear surgery for conditions other than otitis media were recruited. Sterile swab samples were collected from the middle ear mucosa during surgery. The variable region 4 of the 16S rRNA gene in each sample were amplified using region-specific primers adapted for the Illumina MiSeq sequencer (Illumina, CA, USA)). The sequences were subjected to local blast and classified using Metagenome@KIN (World Fusion, Tokyo, Japan). Results: In total, 155 participants were recruited from seven medical centers. Of these, 88 and 67 had chronic otitis media and normal middle ears, respectively. The most abundant bacterial phyla on the mucosal surfaces of the normal middle ears were Proteobacteria, followed by Actinobacteria, Firmicutes, and Bacteroidetes. The children and adults with normal middle ears differed significantly in terms of middle ear microbiomes. Subjects with chronic otitis media without active inflammation (dry ear) had similar middle ear microbiomes as the normal middle ears group. Subjects with chronic otitis media with active inflammation (wet ear) had a lower prevalence of Proteobacteria and a higher prevalence of Firmicutes than the normal middle ears. Conclusion: The human middle ear is inhabited by more diverse microbial communities than was previously thought. Alteration of the middle ear microbiome may contribute to the pathogenesis of chronic otitis media with active inflammation. Level of Evidence: 2b. Laryngoscope, 127:E371–E377, 2017.

DOI： 10.1002/lary.26579

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE PUBLICATIONS INC  

Objective: Making a 3-dimensional (3D) temporal bone model is simple using a plaster powder bed and an inkjet printer. However, it is difficult to reproduce air-containing spaces and precise middle ear structures. The objective of this study was to overcome these problems and create a temporal bone model that would be useful both as a training tool and for preoperative simulation.
Methods: Drainage holes were made to remove excess materials from air-containing spaces, ossicle ligaments were manually changed to bony structures, and small and/or soft tissue structures were colored differently while designing the 3D models. The outcomes were evaluated by 3 procedures: macroscopic and endoscopic inspection of the model, comparison of computed tomography (CT) images of the model to the original CT, and assessment of tactile sensation and reproducibility by 20 surgeons performing surgery on the model.
Results: Macroscopic and endoscopic inspection, CT images, and assessment by surgeons were in agreement in terms of reproducibility of model structures. Most structures could be reproduced, but the stapes, tympanic sinus, and mastoid air cells were unsatisfactory. Perioperative tactile sensation of the model was excellent.
Conclusions: Although this model still does not embody perfect reproducibility, it proved sufficiently practical for use in surgical training.

DOI： 10.1177/0003489417705395

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DOI： 10.18103/mra.v5i6

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

Conclusion: A 30s observation of geotropic positional nystagmus is sufficient to distinguish persistent geotropic positional nystagmus (PGPN) from transient geotropic positional nystagmus (TGPN) in patients with horizontal canal type of benign paroxysmal positional vertigo (H-BPPV) in ENT office.
Objective: As a canalith repositioning procedure effectively treats H-BPPV with TGPN, but not PGPN, the differentiation between patients with PGPN and with TGPN is essential. The purpose of this study is to determine the observation period enough to distinguish TGPN from PGPN.
Methods: This study first analyzed positional nystagmus images recorded with an infrared CCD camera three-dimensionally in 47 patients with H-BPPV. PGPN is distinguished from TGPN in patients with H-BPPV precisely by means of time constant calculated form analysis of positional nystagmus. Ten-second and 30-s movies were made of positional nystagmus of the all 47 patients. Ten independent otolaryngologists were then asked to distinguish TGPN from PGPN after a 10s or 30s observation of the geotropic positional nystagmus images in 47 patients with H-BPPV.
Results: The sensitivity and specificity to distinguish TGPN from PGPN was 100% and 97% after 30s observation, but 100% and 40% after 10s observation, respectively.

DOI： 10.1080/00016489.2016.1227478

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As a canalith repositioning procedure effectively treats H-BPPV with TGPN, but not PGPN, the differentiation between patients with PGPN and with TGPN is essential. The purpose of this study is to determine the observation period enough to distinguish TGPN from PGPN.

DOI： 10.1080/00016489.2016.1227478

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective: Otitis media (OM) with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) is a novel concept of ear disease that is characterized by progressive mixed or sensorineural hearing loss with occasional systemic involvement. Considering the accumulating knowledge about the characteristics of and treatment for auditory dysfunction in OMAAV, the objective of this study was to investigate the vestibular function and symptoms of patients with OMAAV.
Study Design: Retrospective chart review.
Setting: University hospital.
Patients: Thirty-one OMAAV patients met criteria proposed by the OMAAV study group in Japan.
Main Outcome Measures: Clinical characteristics and vestibular tests.
Results: Eleven of 31 OMAAV patients had vestibular symptoms; 3 patients had acute vertigo attack with sudden hearing loss and 8 patients had chronic dizziness. Episodic vertigo was not seen in any of the patients. Three patients who received a less intensive therapy without immunosuppressive agents developed intractable persistent dizziness. All symptomatic patients and six of the nine OMAAV patients without vestibular symptoms showed unilateral or bilateral caloric weakness; therefore, vestibular involvement was present in 84% of OMAAV patients. Gain of vestibuloocular reflex was reduced in symptomatic patients. The eye-tracking test and optokinetic nystagmus revealed no evidence of central dysfunction.
Conclusion: Vestibular dysfunction was seen in 84% of OMAAV patients. One-third of OMAAV patients showed vestibular symptoms such as acute vertigo attack or chronic dizziness, which are of peripheral origin. One-third of the symptomatic patients developed intractable dizziness. Initial intensive treatment by combination therapy with steroid and immunosuppressive agents may be essential for preventing the development of intractable dizziness.

DOI： 10.1097/MAO.0000000000001223

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Background: Chronic rhinosinusitis (CRS) is classified into eosinophilic CRS (ECRS) and non-ECRS. The objectives of this study were to evaluate lower airway inflammation by measuring the fractional concentration of exhaled nitric oxide (FeNO) and to examine the effects of endoscopic sinus surgery (ESS) on FeNO in patients with ECRS compared to non-ECRS. Methods: CRS patients with nasal polyps (23 with ECRS and 22 with non-ECRS) were enrolled into this study. ECRS was diagnosed based on the definition proposed by the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) study group. Several clinical markers including blood eosinophil counts, percent of eosinophils in white blood cells (WBC), number of eosinophils in nasal polyps, JESREC scores, total IgE, FeNO, and Lund-Mackay paranasal sinus CT scores were compared between ECRS and non-ECRS. These markers were also tested before and 2 months after ESS. Results: FeNO was significantly higher in patients with ECRS than in non-ECRS patients. When all CRS patients were tested, a significant correlation was found between FeNO and eosinophilic markers including blood eosinophil counts, percent of eosinophils in WBC, number of eosinophils in nasal polyps, and JESREC scores. FeNO showed a significant correlation with Lund-Mackay scores only in ECRS patients. Blood eosinophil counts, percent of eosinophils in WBC, and FeNO decreased after ESS only in ECRS patients. Conclusions: ECRS patients had lower airway inflammation as revealed by an elevated FeNO, which was parallel to the Lund-Mackay CT scores. ESS decreased the blood eosinophils and FeNO, leading to an improvement of the occult pulmonary dysfunction in ECRS patients. (C) 2017 S. Karger AG, Basel

DOI： 10.1159/000479387

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IOS PRESS  

This paper presents diagnostic criteria for persistent postural-perceptual dizziness (PPPD) to be included in the International Classification of Vestibular Disorders (ICVD). The term PPPD is new, but the disorder is not. Its diagnostic criteria were derived by expert consensus from an exhaustive review of 30 years of research on phobic postural vertigo, space-motion discomfort, visual vertigo, and chronic subjective dizziness. PPPD manifests with one or more symptoms of dizziness, unsteadiness, or non-spinning vertigo that are present on most days for three months or more and are exacerbated by upright posture, active or passive movement, and exposure to moving or complex visual stimuli. PPPD may be precipitated by conditions that disrupt balance or cause vertigo, unsteadiness, or dizziness, including peripheral or central vestibular disorders, other medical illnesses, or psychological distress. PPPD may be present alone or co-exist with other conditions. Possible subtypes await future identification and validation. The pathophysiologic processes underlying PPPD are not fully known. Emerging research suggests that it may arise from functional changes in postural control mechanisms, multi-sensory information processing, or cortical integration of spatial orientation and threat assessment. Thus, PPPD is classified as a chronic functional vestibular disorder. It is not a structural or psychiatric condition.

DOI： 10.3233/VES-170622

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMEDICAL RESEARCH PRESS LTD  

In the cochlea, a high K+ environment in the endolymph is essential for the maintenance of normal hearing function, and the transport of K+ ions through gap junctions of the cochlear epithelium is thought to play an important role in endolymphatic homeostasis. The aim of the present study was to demonstrate the three-dimensional (3D) ultrastructure of spiral ligament root cells and interdental cells, which are located at both ends of the gap junction system of the cochlea epithelium. Serial semi-thin sections of plastic-embedded rat cochlea were mounted on glass slides, stained with uranyl acetate and lead citrate, and observed by scanning electron microscopy (SEM) using the backscattered electron (BSE) mode. 3D reconstruction of BSE images of serial sections revealed that the root cells were linked together to form a branched structure like an elaborate "tree root" in the spiral ligament. The interdental cells were also connected to each other, forming a comb-shaped cellular network with a number of cellular strands in the spiral limbus. Furthermore, TEM studies of ultra-thin sections revealed the rich presence of gap junctions in both root cells and interdental cells. These findings suggest the possibility that both root cells and interdental cells contribute to K+ circulation as the end portion of the epithelial cell gap junction system of the cochlea.

DOI： 10.2220/biomedres.38.239

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IOS PRESS  

BACKGROUND: Due to spatial disorientation reported in space, spatial memory and navigation performances could be more largely impaired by gravity changes. Hippocampus, a key structure for spatial memory, receives inputs from gravity-sensing otolith organs.
OBJECTIVE: To determine the key molecules in the rat hippocampus that contribute to an adaptation to altered gravity in terms of spatial memory performance.
METHODS: Gene expression of hippocampus and spatial memory after continuous two-weeks exposure to 2G hypergravity (HG) were examined using a microarray analysis followed by real-time PCR methods and radial arm maze testing, respectively. Serum cortisol levels during HG load were measured as a stress marker.
RESULTS: Accuracy to enter the correct arms in HG rats was significantly lower than that of controls, indicating an impaired spatial memory due to gravity changes. Microarray analysis followed by real-time PCR confirmed an upregulation of insulin like growth factor binding protein 2 (IGFBP2) gene. Serum cortisol level was the same level as controls at the last day of hypergravity, suggesting the adaptation to HG-induced stress.
CONCLUSIONS: Given that the IGF systems are involved in neurotrophic and synaptic plasticity mechanisms, IGF system might contribute to the adaptation to altered gravity in terms of spatial memory.

DOI： 10.3233/VES-170521

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DOI： 10.1080/23772484.2017.1303605

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE PUBLICATIONS LTD  

Postoperative pain is a remaining issue in tonsillectomy. Polyglycolic acid (PGA) is a biocompatible material used for absorbent suture reinforcement, and its sheet has been applied for covering defects after resection of oral carcinoma. The aim of this study is to examine whether the attachment of a PGA sheet to surgical wounds would reduce posttonsillectomy pain. In this prospective single-blind study, 17 consecutive adult patients were recruited who needed to undergo tonsillectomy, mainly due to habitual tonsillitis. Following bilateral tonsillectomies, a PGA sheet was attached with fibrin glue to only 1 side, without notification to patients of which side. Postoperative pain of each side was separately evaluated with a visual analog scale at 4 time points: before each meal and before sleep. Postoperative pain of both the PGA sheet-attached and nonattached sides was most severe before breakfast among 4 time points. Postoperative pain measured before breakfast was significantly more severe in the PGA sheet-attached side than the nonattached side. As such, this study provided solid data on the negative effects of PGA sheeting on posttonsillectomy pain.

DOI： 10.1177/0194599816660072

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Although temporal information processing is important in auditory perception, the mechanisms for coding tonal offsets are unknown. We investigated cortical responses elicited at the offset of tonal stimuli using flavoprotein fluorescence imaging in mice. Off-responses were clearly observed at the offset of tonal stimuli lasting for 7 s, but not after stimuli lasting for 1 s. Off-responses to the short stimuli appeared in a similar cortical region, when conditioning tonal stimuli lasting for 5-20 s preceded the stimuli. MK-801, an inhibitor of NMDA receptors, suppressed the two types of off-responses, suggesting that disinhibition produced by NMDA receptor-dependent synaptic depression might be involved in the off-responses. The peak off-responses were localized in a small region adjacent to the primary auditory cortex, and no frequency-dependent shift of the response peaks was found. Frequency matching of preceding tonal stimuli with short test stimuli was not required for inducing off-responses to short stimuli. Two-photon calcium imaging demonstrated significantly larger neuronal off-responses to stimuli lasting for 7 s in this field, compared with off-responses to stimuli lasting for 1 s. The present results indicate the presence of an auditory cortical field responding to long-lasting tonal offsets, possibly for temporal information processing.

DOI： 10.1038/srep34421

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

新潟県には県内の癌治療施設が一堂に会する新潟県頭頸部癌悪性腫瘍登録委員会があり、県内の頭頸部悪性腫瘍症例のデータを四半世紀にわたって登録してきた。癌登録に関しては有用なデータではあるが、放射線療法や化学療法の進歩とともに施設間の治療内容および治療成績の格差が目立ってきて、全体の予後調査という点において信頼性が低下してしまった。そこでわれわれは県内の癌治療施設が一堂に会する利点を利用して「頭頸部扁平上皮癌に対する高用量CDDP+RTの県内多施設共同研究phase I/II study」を立ち上げた。phase Iにおいては12例が登録され、最大耐用量や用量限界毒性、化学療法減量・中止基準、phase IIにおけるCDDP推奨投与量などが検討され、その結果CDDP推奨投与量は80mg/m2となった。今後はCCRT完遂率などをendpointとしたphase IIを開始する予定である。地方における治療の一つのモデルケースとして、現状の経過を報告する。(著者抄録)

DOI： 10.5981/jjhnc.42.70

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

人体には構成細胞数の10倍以上の微生物が存在し、それらを細菌叢(マイクロバイオーム)と呼んでいる。近年、マイクロバイオームは肥満や免疫疾患など人体の健康状態へ影響を及ぼすことが判明しつつある。口蓋扁桃にも多数の常在細菌が存在し、マイクロバイオームが各種疾患発症に関与している可能性が考えられる。今回、その基礎となるデータとして、感染のない小児口蓋扁桃の細菌叢に関し検討した。OSASに対して手術目的で摘出した小児口蓋扁桃の深部から組織を切り出し、その細菌叢を16S rRNA解析にて同定し、細菌培養結果および北欧におけるJensenらの報告と比較した。その結果、Haemophilus属の検出が最多であり、Sphingomonas属、嫌気性菌であるPrevotella属、Fusobacterium属がそれらに続いた。Jensenらの報告では、Streptococcus属、Neisseria属、Prevotella属の順であり、人種差、食習慣および採取部位による相違の可能性が考えられた。培養検査では、Haemophilus属、続いてStreptococcus属、Neiserria属が多く検出され、Prevotella属、Fusobacterium属など嫌気性菌の検出は低かった。培養検査ではStreptococcus属との共存下では嫌気性菌の発育が抑制されることが一因と考えられた。細菌培養検査と異なり、PCRを用いた16S rRNA解析では難培養性の常在細菌叢に関する検討が可能であり、マイクロバイオームに関する研究には必要不可欠の手技と考える。今後は成人例との比較や病巣扁桃における口蓋扁桃細菌叢の変化に関して検討を行いたい。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J01099&link_issn=&doc_id=20160204510005&doc_link_id=%2Fdz0jibik%2F2016%2F011901%2F005%2F0029-0036%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz0jibik%2F2016%2F011901%2F005%2F0029-0036%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

Conclusions Defibrinogenation therapy rather than corticosteroids therapy should be chosen for patients specifically with profound hearing loss and with initial high fibrinogen. Objectives Corticosteroids therapy is the standard treatment for sudden sensorineural hearing loss (SSNHL) and prognostic factors by this therapy were reported. Defibrinogenation therapy is one of the treatment options for SSNHL. Aims of this study were to identify prognostic factors and correlative markers with hearing improvement in treating SSNHL by defibrinogenation therapy. Methods During the early phase of the study, consecutive 61 patients were treated by defibrinogenation therapy with batroxobin (50 units), whereas corticosteroids (500 mg/day of hydrocortisone tapered by 9 days) were used for consecutive 64 patients during the late phase. Blood data that could predict a complete recovery were identified. Coagulation/fibrinolysis markers correlated with hearing improvement by defibrinogenation therapy were investigated. Results Although there were no overall differences in hearing improvement between the two therapies, recovery rate in profound hearing loss patients was better in defibrinogenation therapy. In patients who showed complete recovery, serum fibrinogen level before treatment was significantly higher in the defibrinogenation group than the corticosteroid group. Responses of several fibrinolysis markers to defibrinogenation therapy evaluated by post-/pre-values were negatively correlated with hearing improvement.

DOI： 10.3109/00016489.2015.1104723

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

We conducted the first survey of otorhinolaryngological (ORL) screening at educational institutions, from kindergarten to high school, in Niigata Prefecture. The survey results showed that ORL screening is not performed in 62.1% of kindergartens and nursery schools, and that screening was conducted by non-ENT doctors in 23.9% of them. At elementary school entry health check-ups, ORL screening was performed by otorhinolaryngologists in only 4.2% of children overall. ORL screening was conducted in students in all grades by 51.7% of all elementary schools and 31.6% of all junior high schools. Audiometry was performed in students in all grades by over 80% of elementary schools and junior high schools. With regard to high schools, ORL screening was performed in students in all grades at only three schools among 105 high school
ORL screening and audiometry were conducted primarily in the first-year students. In addition to the above results, the survey revealed that no ORL screening whatsoever was performed during a period of 9 years at an elementary school and a junior high school in a certain municipality
as a result of discussion with the relevant municipality, it was decided that screening will be conducted starting at 2016. From the viewpoint of reinforcing the structure of conducting ORL screening in infants in whom ORL findings are identified at a high frequency, we requested that Niigata City conduct ORL screening at private kindergartens in Niigata City where the ORL screening rate is low. We consider this survey to have been productive, as it identified meaningful new facts and measures that could be devised to address the relevant issues. It is our aim to become more proactively than ever involved in school health including health check-ups.

DOI： 10.3950/jibiinkoka.119.941

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IOS PRESS  

BACKGROUND: Psychiatric comorbidities are an important issue in the treatment of chronic dizziness patients.
OBJECTIVE: To test the correlation between psychiatric status and subjective handicaps and to examine the effects of milnacipran on handicaps.
METHODS: Hospital anxiety and depression scale (HADS) and handicaps were assessed by a questionnaire before and eight weeks after milnacipran treatment (50 mg/day) in 29 consecutive patients with chronic dizziness. Effects of milnaciplan were compared with fluvoxamine (200 mg/day).
RESULTS: A significant correlation was found between anxious and depressive scale scores and also between HADS and handicaps. Duration of symptomswas longer in the anxious/depressive group( HADS &gt;= 13) than in the non-anxious/depressive group. Handicaps and HADS were significantly decreased after treatment only in the anxious/depressive group. There were no overall differences in drug effects between milnaciplan and fluvoxamine. However, the rate of patients with a post/pre ratio of handicaps &lt;80% was higher in milnaciplan group compared with the fluvoxamine group.
CONCLUSIONS: Not only anxiety disorders but also depression should be considered as comorbid psychiatric disorders in patients with chronic dizziness. Dizzy patients with psychiatric comorbidities have a longer duration of symptoms and more handicaps than those without psychiatric disorders. Milnacipran may be chosen as a treatment for patients with chronic dizziness with comorbid psychiatric disorders in case of and insufficient response to SSRIs.

DOI： 10.3233/VES-160582

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Transient receptor potential vanilloid (TRPV) 4 is a nonselective cation channel expressed in sensory neurons such as those in the dorsal root and trigeminal ganglia, kidney, and inner ear. TRPV4 is activated by mechanical stress, heat, low osmotic pressure, low pH, and phorbol derivatives such as 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD). We investigated the expression of TRPV4 in rat vestibular ganglion (VG) neurons. The TRPV4 gene was successfully amplified from VG neuron mRNA using reverse-transcription polymerase chain reaction. Furthermore, immunoblotting showed positive expression of TRPV4 protein in VG neurons. Immunohistochemistry indicated that TRPV4 was localized predominantly on the plasma membrane of VG neurons. Calcium (Ca2+) imaging of VG neurons showed that 4 alpha-PDD and/or hypotonic stimuli caused an increase in intracellular Ca2+ concentration ([Ca2+](i)) that was almost completely inhibited by ruthenium red, a selective antagonist of TRPV channels. Interestingly, a [Ca2+](i) increase was evoked by both hypotonic stimuli and 4 alpha-PDD in approximately 38% of VG neurons. These data indicate that TRPV4 is functionally expressed in VG neurons as an ion channel and that TRPV4 likely participates in VG neurons for vestibular neurotransmission as an osmoreceptor and/or mechanoreceptor. (C) 2016 S. Karger AG, Basel

DOI： 10.1159/000449238

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

In recent years, human papillomavirus(HPV)-positive oropharyngeal carcinomas have been increasing. The first manifestation of these tumors is frequently as cystic metastasis to cervical lymph nodes that may precede recognition of the primary tumor, so, they often result in misdiagnosis as branchial cleft cysts. We report a case of cystic cervical lymph node metastasis of HPV-positive tonsil cancer. The patient was a 70-years-old man who noticed a mass on his left neck. The tumor was large and soft, and it was diagnosed as benign in fine-needle aspiration cytology. We diagnosed the tumor as a branchial cleft cyst and undertook surgery. The histopathological diagnosis was squamous cell carcinoma arising from a branchiogenic cyst. However, because it did not satisfy the diagnostic criteria, we diagnosed the tumor as an unknown primary tumor. One year later, left tonsil cancer was suspected based on PET-CT imaging and a left tonsillectomy was undertaken, whereafter tonsil cancer was found. In p16 immunostaining, it was positive in both cystic mass and tonsil. The cervical mass was cystic lymph node metastasis of HPV-positive tonsil cancer. It is important to investigate the oropharynx, when we found cystic cervical mass, because HPV-positive oropharyngeal carcinoma frequently results in cystic neck metastasis.

DOI： 10.3950/jibiinkoka.119.118

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DOI： 10.1080/23772484.2016.1256214

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Society of Practical Otolaryngology  

Malignant external otitis is a severe infection of the external auditory canal, most commonly caused by Pseudomonas aeruginosa in elderly patients with diabetes. Due to the host's immunocompromised state, malignant external otitis may easily lead to osteomyelitis of the skull base, which may be associated with potential life-threatening complications needing urgent treatment. Treatment of osteomyelitis consists of debridement, systemic antibiotic administration and management of the immunosuppressed state of the patient. However, in the case of skull base osteomyelitis, complete debridement is often difficult because of anatomical constraints. We present a case of atypical temporal bone osteomyelitis occurring in a healthy woman without diabetes or pseudomonas infection. A 25-year-old woman was admitted to our hospital with the chief complaint of severe right otalgia which could not be controlled even by thrice-daily intake of painkillers. A slightly reddened skin lesion was found in the bony ear canal
however, neither active aural discharge nor inflammatory stenosis of the canal was found. CT scan showed an osteolytic lesion in the right bony ear canal. Malignancy, osteomyelitis or other unspecified lesion was suspected, and exploratory surgery was performed. Elevation of the tympanomeatal flap revealed eroded bones just beneath the reddened skin, which were completely drilled out by retroauricular mastoidectomy. The dissected specimens were composed of eroded bones, with fibrosis and infiltration by lymphoid and plasma cells. Therefore, the patient was finally diagnosed as having osteomyelitis of the temporal bone. Her clinical symptoms resolved immediately after the surgery, suggesting that complete debridement was effective for controlling the disease. In cases of prolonged and severe otalgia not responsive to ordinary treatments, osteomyelitis should be considered and CT is recommended for early diagnosis and surgical intervention.

DOI： 10.5631/jibirin.109.83

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

A 62-year-old woman, who had dysesthesia in the throat, and polyposia the previous year, was admitted in a coma because of respiratory failure. Computed tomography scans demonstrated dilatation of the esophagus and stenosis of the trachea. After emergency intubation, extubation was not possible due to a collapsed trachea, so we performed a tracheostomy. The tracheoscopy from the stoma showed an esophagus-like trachea due to disappearance of the tracheal cartilage and the straight pattern on the membranous portion, and the lumen deformed with coughing. With the continuous dyspnea episode, the patient was diagnosed as having tracheomalacia. Anti-type II collagen antibody and pathological findings of the trachea led us to the diagnosis of Relapsing Polychondritis.

DOI： 10.3950/jibiinkoka.118.1150

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

症例は62歳、女性。2012年12月、のどの違和感のため多量に飲水するようになった。2013年10月、呼吸不全からJCS200の意識障害を来し当院に救急搬送された。CTで食道の拡張と気管の閉塞を認め、気管内挿管により呼吸状態は改善したが、抜管困難と判断し気管切開を施行した。気管切開後の気管内腔は、咳嗽に伴い変形狭窄し、膜様部の縦縞や気管軟骨輪も消失し、頻回の呼吸困難発作もみられるため、気管軟化症と診断した。気管切開時に生検した気管軟骨の病理所見と抗II型コラーゲン抗体陽性所見より、気管軟化症で初発した再発性多発軟骨炎と診断した。本症例の病態につき、文献的考察を加え報告する。(著者抄録)

DOI： 10.3950/jibiinkoka.118.1150

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

Intravascular large B-cell lymphomas (IVLBCL) are a rare and aggressive non-Hodgkin Lymphoma characterized by proliferation of malignant lymphoid cells into the small blood vessels of the whole body. Making a diagnosis is very difficult due to the lack of mass formation and lymph node enlargement, resulting in a poor prognosis. We report herein on a case of IVLBCL which was proved by a biopsy of the nasal mucosa during endoscopic sinus surgery. A 77-year-old woman was admitted with complaints of headache, rhinorrhea, and fever. Computed tomography showed a shadow in the ethmoid sinus on both sides but without polyps. We suspected acute sinusitis and started therapy, however, high fever persisted with worsening of the patient's general condition. Pathological analysis of biopsy specimens from the nasal cavity and sinuses revealed proliferation of malignant lymphoid cells into the small blood vessels and the final diagnosis was IVLBCL. Chemotherapy was initially effective for her general condition but she died 13 months after the first visit. It is important to suspect IVLBCL, if there is any deterioration of the patient's general condition and persistence of the disease against treatment. The nasal cavity is recommended as a site of random biopsy because of its rich population of small blood vessels.

DOI： 10.3950/jibiinkoka.118.770

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Hematuria is the first manifestation of urinary abnormality in immunoglobulin A nephropathy (IgAN). Hematuria has recently been reported as a risk factor for deterioration of renal function; however, its cause remains unknown.
We analyzed the surface marker of peripheral blood mononuclear cells before and immediately after tonsillectomy in IgAN patients and controls (chronic tonsillitis or tonsillar hypertrophy) by flow cytometry and investigated the association with hematuria. To prove our hypothesis that NK cells induce hematuria, we administered IL-12, activator of NK cells, to HIGA mice. In addition, we transferred cultured NK cells to nude rats and transferred the CD16(+)CD56(+) cells, including NK cells, that are derived from the peripheral blood of IgAN patients immediately after tonsillectomy to nude rats to assess the hematuria level and renal histology of the recipients. We also performed cytotoxicity assays against glomerular endothelial cells by NK cells.
We found that IgAN patients who showed rapid deterioration of hematuria after tonsillectomy also displayed a significant increase in CD16(+)CD56(+) cells in the peripheral blood immediately after tonsillectomy. Exogenous administration of IL-12 to HIGA mice induced hematuria. Adoptive transfer of either cells of an NK cell line, or of CD16(+)CD56(+) cells derived from IgAN patients, into nude rats induced hematuria in the recipients. In vitro analysis showed that NK cells exert cytotoxic activity toward human glomerular endothelial cells in a dose-dependent manner.
CD16(+)CD56(+) cells seem to be responsible for hematuria in IgAN.

DOI： 10.1007/s10157-014-0968-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

Conclusions: Postural control is dependent on the visual system in normal conditions. Shift from visual to somatosensory dependence in dizzy patients suggests that utilizing the stable visual references is recommended for the rehabilitation of dizzy patients. Objectives: To investigate which of the visual or somatosensory system is mainly used for substitution of the impaired spatial orientation in dizzy patients. Methods: We recruited 189 consecutive patients with or without dizziness and vestibular dysfunction. Dizzy patients were divided into three groups: acute, episodic, and chronic dizziness. Vestibular function was assessed by caloric test, traditional head impulse test, and head shaking nystagmus. Visual or somatosensory dependence of spatial orientation was assessed by posturography on a solid surface or on foam in eyes open or closed condition. The foam ratio (posturography with/without foam) when eyes were closed was indicative of somatosensory dependence of postural control, whereas the Romberg ratio on foam showed visual dependence. (Romberg ratio on foam)/(foam ratio with eyes closed) was calculated and used as an index of the visual/somatosensory dependence of postural control. Results: The visual/somatosensory ratio of postural control was significantly lower in dizzy patients as well as patients with vestibular dysfunction, however, no differences were found between acute, episodic, and chronic dizziness.

DOI： 10.3109/00016489.2015.1040172

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

Conclusion: Contrast-enhanced magnetic resonance imaging (MRI) reveals variations in the endolymphatic morphology of the cystic lateral semicircular canal (CLSC) that correlate with inner ear function. This report is the first to suggest a relationship between the morphology and function of this common inner ear malformation in clinical cases. Objectives: This study investigated the radiological and functional findings of a common inner ear malformation using computed tomography (CT), gadolinium contrast-enhanced magnetic resonance imaging (MRI), caloric testing, and cervical and ocular vestibular evoked myogenic potential (VEMP) testing. Method: Four ears in three patients who were radiologically diagnosed with a CLSC and a normal cochlea on high-resolution CT and contrast-enhanced MRI were included. Semicircular canal and vestibular functions were analyzed using the caloric test and cervical and ocular VEMP testing. Results: Unilateral and bilateral cystic canals were found in two and one patients, respectively. In the first patient, the malformed vestibule and cystic space were separate on imaging, and perilymph filled the cystic space. The functional test results were normal. In the second patient, endolymph filled both cystic spaces, and the functional responses were poor. In the third patient, endolymph filled the cystic space, and the ear did not respond during functional testing.

DOI： 10.3109/00016489.2015.1043143

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMJ PUBLISHING GROUP  

Objective: To clarify the pathophysiological basis of persistent geotropic positional nystagmus (PGN) in patients with the horizontal canal type of benign paroxysmal positional vertigo (H-BPPV), the time constant (TC) of nystagmus and the relationship between its slow phase eye velocity (SPV) and the angle of head rotation in supine were defined.
Methods: Geotropic or apogeotropic positional nystagmus was recorded by video-oculography and analysed three-dimensionally.
Results: Geotropic positional nystagmuses in patients with H-BPPV were classified as transient geotropic positional nystagmus with a TC of &lt;= 35 s or PGN with a TC of &gt;35 s. Alternatively, the TC of persistent apogeotropic positional nystagmus (AN) in patients with H-BPPV was &gt;35 s. The direction of the SPV of patients with PGN was opposite to that of patients with AN at each head position across the range of neutral head positions. The relationship between the SPV of patients with PGN and the angle of head rotation was linearly symmetrical against that of patients with AN with respect to a line drawn on the neutral head position.
Conclusions: Since its TC was &gt;35 s, it is suggested that PGN is induced by cupula deviation in response to gravity at each head position. It is also suggested that the direction of cupula deviation in patients with PGN is opposite to that of patients with AN across the neutral head positional range with no nystagmus where the long axis of cupula is in alignment with the axis of gravity. Since the pathophysiological basis of AN is considered a heavy cupula, it is suggested that PGN is conversely induced by a light cupula.

DOI： 10.1136/bmjopen-2014-006607

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Society for Equilibrium Research  

Bow-tie nystagmus is a rare phenomenon, which is reportedly associated with cerebellar infarction, brain stem anomalies, and so on. We analyzed herein bow-tie nystagmus in a patient with an Arnold-Chiari malformation using a three-dimensional 240 Hz high speed video oculography (VOG) system. The patient's nystagmus consisted of two aspects-slow phases directed upward and quick phases altering the direction obliquely right to left downward in turn (square wave jerks). The dominant frequency of the vertical component was 3.1 Hz, which was exactly twice as fast as that of the horizontal component at 1.55 Hz. Appearance of slow phases of horizontal components suppressed the square wave jerks. Square wave jerks were not only synchronized with quick phases of downbeat nystagmus but also with quick phases of upbeat or torsional nystagmus. Therefore their frequency was not regular but depended on the frequencies of the vertical or torsional component. These data suggest that bow-tie nystagmus is not generated by a common bow-tie nystagmus generator. We propose that bow-tie nystagmus is composed of quick phases of a horizontal component corresponding to the slow phases of the vertical or torsional component which alters its direction left to right in turn in order to avoid lateralization of the position of the eyes.

DOI： 10.3757/jser.74.66

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective: The aim of the present study, which involved a 2-year observation period and a nonsurgical control group, was to determine whether endolymphatic sac decompression surgery (ESDS) has the potential to prevent the progression of vertigo and hearing loss in patients with intractable bilateral Meniere's disease (MD).
Study Design: Prospective case-control study.
Setting: Tertiary referral center.
Methods: Between 1996 and 2008, we subjected 67 patients with intractable bilateral MD to ESDS and local corticosteroid treatment. Another 34 patients with intractable bilateral MD who declined ESDS were treated with the best available medical therapies. All of the patients underwent regular follow-up examinations for at least 2 years.
Results: Vertigo was resolved in 22 of 34 patients in the non-ESDS group and 60 of 67 patients in the ESDS group (p = 0.055, Fisher's exact test). Of the 24 patients in the non-ESDS group and 55 patients in the ESDS group in whom the ipsilateral ear (the treated ear) exhibited worse hearing function than the contralateral ear, the hearing level of the former ear was preserved in 13 and 52 patients, respectively (p = 0.007, Fisher's exact test). Of the 10 patients in the nonsurgical group and 12 patients in the surgical group in whom the ipsilateral ear exhibited better hearing function than the contralateral ear, the hearing level of the former ear was preserved in 2 and 11 patients, respectively (p = 0.035, Fisher's exact test).
Conclusion: The present findings suggest that ESDS combined with local corticosteroid treatment can control progressive hearing loss in both ears in patients with bilateral MD at least during the first 2 postoperative years.

DOI： 10.1097/MAO.0000000000000469

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective: The aim of the present study, which involved a 2-year observation period and a nonsurgical control group, was to determine whether endolymphatic sac decompression surgery (ESDS) has the potential to prevent the progression of vertigo and hearing loss in patients with intractable bilateral Meniere's disease (MD).
Study Design: Prospective case-control study.
Setting: Tertiary referral center.
Methods: Between 1996 and 2008, we subjected 67 patients with intractable bilateral MD to ESDS and local corticosteroid treatment. Another 34 patients with intractable bilateral MD who declined ESDS were treated with the best available medical therapies. All of the patients underwent regular follow-up examinations for at least 2 years.
Results: Vertigo was resolved in 22 of 34 patients in the non-ESDS group and 60 of 67 patients in the ESDS group (p = 0.055, Fisher's exact test). Of the 24 patients in the non-ESDS group and 55 patients in the ESDS group in whom the ipsilateral ear (the treated ear) exhibited worse hearing function than the contralateral ear, the hearing level of the former ear was preserved in 13 and 52 patients, respectively (p = 0.007, Fisher's exact test). Of the 10 patients in the nonsurgical group and 12 patients in the surgical group in whom the ipsilateral ear exhibited better hearing function than the contralateral ear, the hearing level of the former ear was preserved in 2 and 11 patients, respectively (p = 0.035, Fisher's exact test).
Conclusion: The present findings suggest that ESDS combined with local corticosteroid treatment can control progressive hearing loss in both ears in patients with bilateral MD at least during the first 2 postoperative years.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INFORMA HEALTHCARE  

Conclusion: The finding of deteriorated hearing loss at the initial visit at middle to high frequencies is a factor of poor hearing prognosis in Meniere's disease. Early intervention with instructions for lifestyle changes may lead to good outcomes in hearing. Objective: An attempt was made to examine long-term changes in hearing loss in unilateral Meniere's disease and factors associated with prognosis of hearing loss retrospectively. Methods: Based on their last hearing level of the affected ear, 36 patients were subdivided into two groups: the poor prognosis of hearing (PPH) group and the good prognosis of hearing (GPH) group. Results: In the PPH group, the hearing levels at the initial visit at middle and high frequencies were significantly worse than those in the GPH group. Moreover, the hearing loss progressed during the first 2 years of the disease, and stayed flat to approximately 50 dB at the later stage. Conversely, the hearing loss at the onset in the GPH group showed no further progression over the first 2 years, and remained constant to approximately 35 dB at the later stage. In addition, the mean intervals from the onset to the initial visit in the PPH group were significantly longer than those in the GPH group.

DOI： 10.3109/00016489.2014.923114

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Objectives/Hypothesis: The aim of the study was to elucidate whether endolymphatic sac decompression surgery (ESDS) has the potential to prevent unilateral Meniere disease (MD) from becoming bilateral.
Study Design: Prospective case-control study at tertiary referral center.
Methods: Between 1996 and 2008, we performed a glycerol test (G-test) and electrocochleography (ECoG) on 237 patients with intractable unilateral MD. We performed ESDS on 179 patients (144 with no endolymphatic hydrops and 35 with silent endolymphatic hydrops in the contralateral ear). The other 58 patients (40 without endolymphatic hydrops and 18 with silent endolymphatic hydrops in the contralateral ear) were given available medical treatments. All underwent regular follow-up for at least 5 years.
Results: Altogether, 22.4% (53 of 237) of patients with clinically diagnosed unilateral intractable MD had silent endolymphatic hydrops in the contralateral ear using G-test and ECoG. In the nonsurgical group, six of 40 patients with unilateral MD with no endolymphatic hydrops in the contralateral ear developed bilateral disease, whereas in the surgical group 12 of 144 patients did so (P=.231, Fisher test). In the nonsurgical group, nine of 18 patients with unilateral MD and silent endolymphatic hydrops developed the disease in the contralateral ear, whereas in the surgical group six of 35 patients developed bilateral disease (P=.022, Fisher test).
Conclusions: The present findings suggest that ESDS may decrease the incidence of developing MD in silent endolymphatic hydronic contralateral ears diagnosed with G-test and ECoG within the first 5 postoperative years.

DOI： 10.1002/lary.24614

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Language：Japanese   Publisher：(NPO)日本気管食道科学会  

混合性喉頭麻痺とは、声帯麻痺に他の脳神経麻痺を合併したものであり、多彩な臨床症状を呈する。今回われわれは、頭部外傷の後、高度嚥下障害を発症した両側の混合性喉頭麻痺症例に対して手術的加療を行い、良好な結果を得たので報告する。症例は78歳男性。木から転落して頭部を打撲し、救急救命専門施設に搬送された。頭部CT検査において、くも膜下出血および右側頸静脈孔・舌下神経管周囲に骨折が認められた。全身状態および意識レベルの改善の後、失声・嚥下障害が判明した。嚥下障害の治療のため当科に紹介受診された。内視鏡検査下に、右声帯は傍正中位に、左声帯は中間位に完全固定していた。嚥下造影検査において、バリウム嚥下を試みるも嚥下反射は全く生じなかった。嚥下改善目的に両側輪状咽頭筋切断術・喉頭挙上術・気管喉頭分離術・喉頭閉鎖術を施行した。術後、肉の塊を除く多様な形態の食物が摂食可能となった。また後日プロテーゼを挿入して言語コミュニケーションが可能となった。以上より、複数の脳神経損傷に起因する咽喉頭の機能障害であっても、種々の機能外科的手術を適切に組み合わせることにより生活の質の改善が期待できると考えられた。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J01054&link_issn=&doc_id=20140821390004&doc_link_id=%2Fea4broes%2F2014%2F006504%2F004%2F0322-0329%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fea4broes%2F2014%2F006504%2F004%2F0322-0329%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)  

Abstract Conclusion: The finding of deteriorated hearing loss at the initial visit at middle to high frequencies is a factor of poor hearing prognosis in M?ni?re&#039;s disease. Early intervention with instructions for lifestyle changes may lead to good outcomes in hearing. Objective: An attempt was made to examine long-term changes in hearing loss in unilateral M?ni?re&#039;s disease and factors associated with prognosis of hearing loss retrospectively. Methods: Based on their last hearing level of the affected ear, 36 patients were subdivided into two groups: the poor prognosis of hearing (PPH) group and the good prognosis of hearing (GPH) group. Results: In the PPH group, the hearing levels at the initial visit at middle and high frequencies were significantly worse than those in the GPH group. Moreover, the hearing loss progressed during the first 2 years of the disease, and stayed flat to approximately 50 dB at the later stage. Conversely, the hearing loss at the onset in the GPH group showed no further progression over the first 2 years, and remained constant to approximately 35 dB at the later stage. In addition, the mean intervals from the onset to the initial visit in the PPH group were significantly longer than those in the GPH group.

DOI： 10.3109/00016489.2014.923114

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective: To understand the third mobile window effect of chronic otitis media with cholesteatoma with inner ear fistula on the bone conduction threshold, we examined changes in the bone conduction audiogram after tympanoplasty with mastoidectomy for chronic otitis media with cholesteatoma with canal fistula.
Study Design: Retrospective case review.
Setting: Tertiary referral center. Patients: According to the intraoperative classification of Dornhoffer and Milewski, we focused especially on Type IIa (anatomic bony fistula with no perilymph leak). We checked the bone conduction threshold at least 3 times: just before, just after, and 6 months after surgery in 20 ears with Type IIa lateral semicircular canal fistula. Intervention: Tympanoplasty with mastoidectomy.
Main Outcome Measure: Bone conduction thresholds before and after tympanoplasty with mastoidectomy.
Results: Compared with the preoperative bone conduction threshold, 6 cases were better, 12 cases were unchanged, and 2 cases were worse within the first postoperative week. Finally, 1 case was better, 15 cases were unchanged, and 4 cases were worse at the sixth postoperative month. Patients with a better bone conduction threshold in the low-tone frequencies immediately after surgery had a tendency to show no preoperative fistula symptoms. Postoperative spontaneous nystagmus had a tendency to be observed in patients with a worse bone conduction threshold in the high-tone frequencies.
Conclusion: The better bone conduction threshold at low-tone frequencies immediately after tympanoplasty with mastoidectomy and no preoperative fistula symptoms might imply the third mobile window theory. The worse bone conduction threshold in high-tone frequencies with spontaneous nystagmus after surgery might indicate inner ear damage.

DOI： 10.1097/MAO.0000000000000306

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective: To understand the third mobile window effect of chronic otitis media with cholesteatoma with inner ear fistula on the bone conduction threshold, we examined changes in the bone conduction audiogram after tympanoplasty with mastoidectomy for chronic otitis media with cholesteatoma with canal fistula.
Study Design: Retrospective case review.
Setting: Tertiary referral center. Patients: According to the intraoperative classification of Dornhoffer and Milewski, we focused especially on Type IIa (anatomic bony fistula with no perilymph leak). We checked the bone conduction threshold at least 3 times: just before, just after, and 6 months after surgery in 20 ears with Type IIa lateral semicircular canal fistula. Intervention: Tympanoplasty with mastoidectomy.
Main Outcome Measure: Bone conduction thresholds before and after tympanoplasty with mastoidectomy.
Results: Compared with the preoperative bone conduction threshold, 6 cases were better, 12 cases were unchanged, and 2 cases were worse within the first postoperative week. Finally, 1 case was better, 15 cases were unchanged, and 4 cases were worse at the sixth postoperative month. Patients with a better bone conduction threshold in the low-tone frequencies immediately after surgery had a tendency to show no preoperative fistula symptoms. Postoperative spontaneous nystagmus had a tendency to be observed in patients with a worse bone conduction threshold in the high-tone frequencies.
Conclusion: The better bone conduction threshold at low-tone frequencies immediately after tympanoplasty with mastoidectomy and no preoperative fistula symptoms might imply the third mobile window theory. The worse bone conduction threshold in high-tone frequencies with spontaneous nystagmus after surgery might indicate inner ear damage.

DOI： 10.1097/MAO.0000000000000306

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

The 5-hydroxytryptamine type 3 (5-HT3) receptor is a ligand-gated ion channel and a member of the Cys-loop family of receptors. Previous studies have shown 5-HT3 receptor expression in various neural cells of the central and peripheral nervous systems. Although the function and distribution of the 5-HT3 receptor has been well established, its role in the inner ear is still poorly understood. Moreover, no study has yet determined its localization and function in the peripheral vestibular nervous system. In the present study, we reveal mRNA expression of both 5-HT3A and 5-HT3B receptor subunits in the mouse vestibular ganglion (VG) by RT-PCR and in situ hybridization (ISH). We also show by ISH that 5-HT3 receptor mFtNA is only expressed in the VG (superior and inferior division) in the peripheral vestibular nervous system. Moreover, we performed Ca2+ imaging to determine whether functional 5-HT3 receptors are present in the mouse VG, using a selective 5-HT3 receptor agonist, SR57227A. In wild mice, 32% of VG neurons responded to the agonist, whereas there was no response in 5-HT3A receptor knockout mice. These results indicate that VG cells express functional 5-HT3 receptor channels and might play a modulatory role in the peripheral vestibular nervous system. (C) 2014 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2014.02.016

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

めまいを主訴に初診した患者137例を対象に、著者等が試作した選択式の問診票を用いて良性発作性頭位めまい症(BPPV)の診断を行い、検討した。その結果、BPPV確実例は38例で、うち問診からBPPVと推定された症例は35例であり、感度は92%、特異度は44%であった。BPPV確実例のうちBPPVのタイプと患側まで正しく推定できたものは14例(37%)で、内訳はP-BPPVが9例、GH-BPPVが2例、AH-BPPVが3例であった。今回、軸位面の頭部の動きでめまいが誘発された場合をAH-BPPVと推定したが、この推定方法での問題があり、今後改善する必要があることが明らかとなった。また、血圧調節障害の症例が問診のみではBPPVと推定されることが多く、BPPVが疑われBPPVの頭位・頭位変換眼振が認められない場合には、シェロングテストを施行し血圧調節障害の有無を検索する必要があると考えられた。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Background: Immunoglobulin (Ig) A nephropathy (IgAN) is the most common form of primary glomerulonephritis in the world. Some bacteria were reported to be the candidate of the antigen or the pathogenesis of IgAN, but systematic analysis of bacterial flora in tonsil with IgAN has not been reported. Moreover, these bacteria specific to IgAN might be candidate for the indicator which can predict the remission of IgAN treated by the combination of tonsillectomy and steroid pulse.
Methods and Findings: We made a comprehensive analysis of tonsil flora in 68 IgAN patients and 28 control patients using Denaturing gradient gel electrophoresis methods. We also analyzed the relationship between several bacteria specific to the IgAN and the prognosis of the IgAN. Treponema sp. were identified in 24% IgAN patients, while in 7% control patients (P = 0.062). Haemophilus segnis were detected in 53% IgAN patients, while in 25% control patients (P = 0.012). Campylobacter rectus were identified in 49% IgAN patients, while in 14% control patients (P = 0.002). Multiple Cox proportional-hazards model revealed that Treponema sp. or Campylobactor rectus are significant for the remission of proteinuria (Hazard ratio 2.35, p = 0.019). There was significant difference in remission rates between IgAN patients with Treponema sp. and those without the bacterium (p = 0.046), and in remission rates between IgAN patients with Campylobacter rectus and those without the bacterium (p = 0.037) by Kaplan-Meier analysis. Those bacteria are well known to be related with the periodontal disease. Periodontal bacteria has known to cause immune reaction and many diseases, and also might cause IgA nephropathy.
Conclusion: This insight into IgAN might be useful for diagnosis of the IgAN patients and the decision of treatment of IgAN.

DOI： 10.1371/journal.pone.0081636

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Conclusions: The present findings suggest that complete control of vertigo after endolymphatic sac decompression surgery (ESDS) does not always depend on improved vestibular function or reduced endolymphatic hydrops. Vertigo control is, however, associated with hearing stability. Objective: Among surgical treatments for intractable Meniere's disease, ESDS is performed to preserve and improve inner ear function. We examined the correlation between changes in vertigo frequency and neuro-otologic function to understand the condition of the inner ear in patients whose vertigo was completely controlled after undergoing ESDS. Methods: This was a retrospective cross-tabulation study. Between 1997 and 2001, we treated 52 patients with intractable vertigo using ESDS and followed the patients regularly for 2 years. Postoperatively we evaluated and recorded changes in vertigo attack frequency, maximum slow phase eye velocity, worst hearing level, and glycerol test results according to modified American Academy of Otolaryngology-Head and Neck Surgery 1995 criteria. Results: We found no correlation between vertigo control and vestibular function. There was also no correlation between vertigo control and negative conversion of the glycerol test. There was a significant correlation between vertigo control and hearing control . © 2013 Informa Healthcare.

DOI： 10.3109/00016489.2013.831480

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Objectives: Meniere's disease is a common inner ear disease characterized by vertigo, hearing loss and tinnitus. Since Meniere's disease is thought to be triggered by an immune insult to inner ear hydrops, we examined endolymphatic sac drainage with intra-endolymphatic sac application of large doses of steroids for intractable Meniere's patients and observed long-term results from 2 years to over a decade until 13 years. Methods: Between 1998 and 2009, we enrolled and assigned 286 intractable Meniere's patients to two groups: group-I (G-I) included patients who underwent endolymphatic sac drainage with steroid instillation and group-II (G-II) included those who declined endolymphatic sac drainage. Definitive spells and hearing improvement in these two groups were determined for 2-13 years after treatment. Results: According to the established criteria, vertigo was completely controlled in 88% of patients in G-I in the 2nd year, in 73% in the 12th year and in 70% in the 13th year. These results in G-I were significantly better than those in G-II for 13 years after treatment. Hearing was improved in 49% of patients in G-I in the 2nd year, in 27% in the 12th year and in 25% in the 13th year. These results in G-I were significantly better than those in G-II for 12 years after treatment, but this was not significant in the 13th year. Conclusions: Endolymphatic sac drainage with intra-endolymphatic sac application of large doses of steroids could improve long-term follow-up results of hearing as well as vertigo control. This means that the drainage with local steroids could also improve patients' long-term quality in the prime of life. © 2012 Elsevier Ireland Ltd.

DOI： 10.1016/j.anl.2012.11.008

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

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Language：Japanese   Publisher：(一社)日本耳科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INFORMA HEALTHCARE  

Conclusion: Endolymphatic hydrops could be a reversible inner ear pathological condition. After sac surgery, hydrops was reduced and symptoms went into remission in some cases, although vertigo suppression was not always a result of the reduced hydrops. Objective: To examine the changes in endolymphatic hydrops detected by gadolinium (Gd) contrast-enhanced magnetic resonance imaging (MRI) before and 6 months after endolymphatic sac surgery in patients with unilateral Meniere's disease. Methods: Fluid-attenuated inversion recovery MRI was obtained 4 h after intravenous administration or 24 h after intratympanic administration of Gd contrast medium. An enlarged negative stain corresponding to the cochlear duct and endolymphatic space of the vestibule was assessed as hydrops. Results: Of seven patients with hydrops confirmed by MRI before surgery, both cochlear and vestibular hydrops became negative in two, cochlear hydrops became negative in one, both hydrops were present, but reduced, in one, and there was no change in three patients. The number of vertigo spells was reduced in all cases at 6-12 months after surgery. As for the three cases of negative hydrops, vertigo was completely suppressed. In two cases in which hearing level improved, hydrops became negative after surgery.

DOI： 10.3109/00016489.2013.795290

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Both TRPV1 and TRPA1 are non-selective cation channels. They are co-expressed, and interact in sensory neurons such as dorsal root ganglia (DRG) and trigeminal ganglia (TG), and are involved in nociception, being activated by nociceptive stimuli. Immunohistological localization of TRPV1 in vestibular ganglion (VG) neurons has been reported. Although TRPA1 is co-expressed with TRPV1 in DRG and TG neurons, it is unclear whether TRPA1 channels are expressed in VG neurons. Moreover, it is unknown whether TRPV1 and TRPA1 channels are functional in VG neurons. We investigated the expression of TRPV1 and TRPA1 in rat VG neurons by RT-PCR, in situ hybridization, immunohistochemistry, and Ca2+ imaging experiments. Both TRPV1 and TRPA1 RT-PCR products were amplified from the mRNA of rat VG neurons. In situ hybridization experiments showed TRPV1 and TRPA1 mRNA expression in the majority of VG neurons. Immunohistochemistry experiments confirmed TRPV1 protein expression. In Ca2+ imaging experiments, capsaicin, a TRPV1 agonist, induced a significant increase in intracellular calcium ion concentration ([Ca2+](i)) in rat primary cultured VG neurons, which was almost completely blocked by capsazepine, a TRPV1-specific antagonist. Cinnamaldehyde, a TRPA1 agonist, also caused an increase in [Ca2+](i), which was completely inhibited by HC030031, a TRPA1-specific antagonist. Moreover, in some VG neurons, a [Ca2+](i); increase was evoked by both capsaicin and cinnamaldehyde in the same neuron. In summary, our histological and physiological studies reveal that TRPV1 and TRPA1 are expressed in VG neurons. It is suggested that TRPV1 and TRPA1 in VG neurons might participate in vestibular function and/or dysfunction such as vertigo. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2013.07.019

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

内リンパ水腫の診断にMRIによる画像診断が導入されてきた。当施設での内耳造影MRIによる内リンパ水腫検出について、造影剤投与法による違い、また従来からの水腫推定検査である蝸電図、グリセロールテストとの比較を行った。めまい発作の頻度が高い、一側性メニエール病あるいは遅発性内リンパ水腫例に対し、造影剤を鼓室内投与(17例)あるいは経静脈的に投与(10例)し、3テスラMRIによる2D-FLAIR像を得た。内耳の外リンパ液は高信号に描出され、内リンパ腔は低信号域となる。蝸牛管に相当する部分に明らかな低信号領域を認めた場合を蝸牛水腫と判断し、前庭の写るスライスの過半数で大部分に低信号領域がみられた場合を前庭水腫とした。鼓室内投与法では88%(15/17例)に、静注法では90%(9/10例)に内リンパ水腫を検出した。静注法の対側耳では20%(2/10例)に水腫を検出した。蝸電図やグリセロールテストは、難聴が進行している例では評価が困難で、それぞれ陽性例は患側耳で15例と6例のみにとどまった。ただ蝸電図は波形の分析が可能であれば陽性率は高く、患側耳の88%(15/17耳)に相当した。MRIと蝸電図の両者の結果が得られた例では、静注法で得られた対側耳の結果も含めて78%(21/27耳)が一致した。定性的な水腫の有無について、鼓室内投与法と静注法による検出率は同等であった。内耳造影MRIは内リンパ水腫診断において従来の検査以上に有効と考えられる。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INFORMA HEALTHCARE  

Conclusion: Because nystagmus induced by ampullopetal inhibition of the posterior semicircular canal (PSCC) rotates around the axis perpendicular to the plane of the anterior semicircular canal (ASCC) of the other side, when free-floating debris is initially located at the distal portion of the PSCC, a patient showing positional nystagmus appears to have the ASCC type of benign paroxysmal positional nystagmus. We name this 'pseudo-anterior canalolithiasis'. Objective: We report on pseudo-anterior canalolithiasis originating in the PSCC and discuss the differential findings between pseudo-anterior and true anterior canalolithiasis by means of three-dimensional (3D) analysis of the positional nystagmus. Methods: We performed 3D analysis of the positional nystagmus in a patient with true anterior canalolithiasis and in another patient with pseudo-anterior canalolithiasis. Results: In the patient with true anterior canalolithiasis, the direction of positional nystagmus during reverse Epley maneuver was constant and its axis was perpendicular to the plane of the right ASCC three-dimensionally. In contrast, in the patient with pseudo-anterior canalolithiasis, the first positional nystagmus of which the axis was perpendicular to the plane of the left ASCC became a second positional nystagmus of which the axis was perpendicular to the plane of the right PSCC during the reverse Epley maneuver.

DOI： 10.3109/00016489.2012.763180

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Conclusions: Physicians should consider additional treatment strategies for Meniere's disease patients with a long history of disease and hearing loss in the secondary affected ear and also provide psychological support regarding future progressive bilateral hearing loss. Objectives: To treat intractable Meniere's disease patients effectively, we need to understand the psychological condition of each patient. We examined the state of neurosis and depression in patients and correlated this with demographic and background information. Methods: Between 1998 and 2009, we enrolled 207 patients with intractable Meniere's disease in this prospective study. We used the Cornell Medical Index and the Self-rating Depression Scale to evaluate their psychological condition. We also obtained demographic and background information relating to sex, age, duration of disease, vertigo frequency, hearing level in bilateral sides, and plasma vasopressin level. Results: Neurosis and depression was diagnosed in 40.1% and 60.4%, respectively, of patients with intractable Meniere's disease. Our results showed that surgical treatment significantly improved vertigo and hearing ability in patients with no psychological symptoms compared with those exhibiting psychological symptoms. Patients with a longer duration and worse hearing level in the secondary affected ear had a significantly higher incidence of mental illness than those with a shorter duration and better level of hearing. © 2013 Informa Healthcare.

DOI： 10.3109/00016489.2012.759274

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In the patient with true anterior canalolithiasis, the direction of positional nystagmus during reverse Epley maneuver was constant and its axis was perpendicular to the plane of the right ASCC three-dimensionally. In contrast, in the patient with pseudo-anterior canalolithiasis, the first positional nystagmus of which the axis was perpendicular to the plane of the left ASCC became a second positional nystagmus of which the axis was perpendicular to the plane of the right PSCC during the reverse Epley maneuver.

DOI： 10.3109/00016489.2012.763180

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Conclusions: Because the basic strategies to stop walking are stored as motor programs, visual stimulation may have little influence on body deviation during gait termination and its time course. Walking velocity, however, demonstrated dynamic flexible changes, which may subserve the stable process of gait termination under variable circumstantial changes such as optic flow. Objective: The aim of this study was to examine the effect of repeated optic flow on body deviation and walking velocity during gait termination, which may be more complicated than continuous standing or walking. Methods: Twenty-three healthy subjects were instructed to start walking upon an acoustic cue and to stop walking when the scenery changed in a virtual reality environment. Subjects underwent eight control trials without optic flow and three sets of optic flow conditions including four trials each of optic horizontal and rotational movement randomly. Results: Repeated optic flow caused no significant change of body deviation or the time course of the gait termination process in comparison with that in the control. The walking velocity at the start of the termination process showed short-term flexibility that denoted a gradual increase over the trial for within-set and long-term flexibility that denoted a gradual decrease for between-set. © 2013 Informa Healthcare.

DOI： 10.3109/00016489.2012.740163

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Conclusions: This study showed that patients with acoustic tumor (AT) with hearing loss in the contralateral side had severe mood disturbances. It is important for physicians to provide patients who have better hearing in the tumor side with adequate information regarding the possibility of profound bilateral hearing loss and how to communicate with others in such situations. Objectives: We examined the pretreatment status as regards neurosis and/or depression of patients with an AT using the Cornell Medical Index (CMI) and Self-rating Depression Scale (SDS) and clarified the relationship with the patients' background. Methods: We enrolled 30 patients with unilateral AT between 1997 and 2010. At the time of diagnosis, we examined each patient's psychological condition, sex, age, laterality, tumor size, hearing level on bilateral side, facial paresis, headache, and canal paresis. Results: In all, 20.0% of AT patients were diagnosed with neurosis using the CMI and 26.7% had depression according to the SDS. chi(2) analysis showed that patients with AT with hearing deterioration on the contralateral side had mental illness significantly more often than those with normal hearing on the contralateral side. Multivariable regression analysis revealed that the pretreatment status of hearing level on the contralateral side significantly affected the patients' psychological condition.

DOI： 10.3109/00016489.2012.709322

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

Objective: Gadolinium (Gd) contrast-enhanced MRI has recently been introduced to clinical practice to detect endolymphatic hydrops. However, since the image depends on the hardware, pulse sequence or the way of Gd administration, the protocol and the evaluating criteria for hydrops on MRI have not yet been standardized. In this study, we assessed the usefulness of the hydrops detection by MRI following the intratympanic or intravenous Gd administration methods, and compared these findings with the electrocochleography and glycerol test. Methods: MRI was taken in 27 patients with Meniere's disease or delayed endolymphatic hydrops. All patients had frequent episodes of vertigo attacks which were clinically considered as of unilateral ear origin. Two types of Gd administration were used
injection into the tympanic cavity in 17 patients or intravenous injection in 10 patients. Axial 2D-FLAJR images were obtained with a 3.0T MRI unit, 24 and 4 h after intratympanic or intravenous administration, respectively. The endolymphatic space was detected as a low signal intensity area, while the surrounding perilymphatic space showed high intensity with Gd contrast. Those cases in which low signal areas corresponding to the cochlear duct could be clearly noticed, were classified as cochlear hydrops. When the greater part of the vestibule was occupied by a low signal area in more than half of the images, it was classified as vestibular hydrops. Results: Endolymphatic hydrops was detected in 88% (15/17 cases) by the intratympanic Gd administration method, and 90% (9/10) by the intravenous method. In the contralateral ears, 20% (2/10) showed hydrops, detected by the intravenous method. ECochG and the glycerol test were difficult when the hearing of the patient was severely impaired. Positive results of EcochG and the glycerol test were obtained only in 15 and 6 cases, respectively. However, as far as the waves could be obtained, ECochG showed a high detection rate of 88% (15/17) in the affected ear. In those cases in which both MRI and EcochG could be obtained, including both ears, the results were matched in 78% (21/27ears). Conclusion: For the qualitative detection of hydrops, intratympanic and intravenous Gd administration methods were equivalent. Inner ear Gd contrast-enhanced MRI had higher efficacy in the detection of hydrops than the conventional tests.

DOI： 10.3950/jibiinkoka.116.960

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In this study, we examined the effects of sensory inputs of visual-vestibulosomatosensory conflict induced by virtual reality (VR) on subjective dizziness, posture stability and visual dependency on postural control in humans. Eleven healthy young volunteers were immersed in two different VR conditions. In the control condition, subjects walked voluntarily with the background images of interactive computer graphics proportionally synchronized to their walking pace. In the visual-vestibulosomatosensory conflict condition, subjects kept still, but the background images that subjects experienced in the control condition were presented. The scores of both Graybiel's and Hamilton's criteria, postural instability and Romberg ratio were measured before and after the two conditions. After immersion in the conflict condition, both subjective dizziness and objective postural instability were significantly increased, and Romberg ratio, an index of the visual dependency on postural control, was slightly decreased. These findings suggest that sensory inputs of visual-vestibulosomatosensory conflict induced by VR induced motion sickness, resulting in subjective dizziness and postural instability. They also suggest that adaptation to the conflict condition decreases the contribution of visual inputs to postural control with re-weighing of vestibulosomatosensory inputs. VR may be used as a rehabilitation tool for dizzy patients by its ability to induce sensory re-weighing of postural control.

DOI： 10.2152/jmi.60.236

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Objective: We report a case of benign paroxysmal positional vertigo (BPPV) showing sequential translation of four types of nystagmus and discuss its pathophysiology.
Methods: The case was 65-year-old female. We analyzed her nystagmus three-dimensionally. Results: At the first visit, she showed vertical-torsio nystagmus of the posterior canal type of BPPV (P-BPPV) and subsequently showed recently reported geotropic nystagmus with a long time constant. Two weeks later, she showed apogeotropic nystagmus of the horizontal canal type of BPPV (AH-BPPV) and subsequently a geotropic nystagmus with a short time constant of the horizontal canal type of BPPV (GH-BPPV).
Conclusions: Three kind of nystagmus, namely P-BPPV, AH-BPPV and GH-BPPV can be explained by the otoconial debris hypothesis of the same ear. Finally, the recently reported geotropic nystagmus with a long time constant may be explained by a reversible lesion such as the denatured cupula or utricular imbalance of the same ear. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.anl.2011.10.007

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Three kind of nystagmus, namely P-BPPV, AH-BPPV and GH-BPPV can be explained by the otoconial debris hypothesis of the same ear. Finally, the recently reported geotropic nystagmus with a long time constant may be explained by a reversible lesion such as the denatured cupula or utricular imbalance of the same ear.

DOI： 10.1016/j.anl.2011.10.007

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Objectives: The aim of the present study was to elucidate the time course and frequency patterns of transient low-tone air-bone gaps (ABGs) after canal plugging for intractable BPPV.
Methods: We investigated eight patients with intractable BPPV who underwent canal plugging. Four were cases with posterior type (pBPPV) and the other four were those with horizontal type (hBPPV). Pure-tone audiometries (PTAs) were performed before and 7 days, 1 month and 6 months after surgery. ABGs (+) were defined as the three-tone-average &gt;= 20 dB formulated by (a + b + c)/3, where a, b, and c are ABGs at 0.25, 0.5, and 1 kHz, respectively.
Results: The ratio of the number of patients with ABGs (+) at the post-operative 7th day and 1st month was 100.0% (8/8). The ratio at the post-operative 6th month was 0.0% (0/8). There were no significant differences in the time course or frequency patterns of the ABGs between pBPPV and hBPPV.
Conclusions: We clearly demonstrated eight cases with intractable BPPV showing transient low-tone ABGs during convalescence immediately after canal plugging. During that period, patients also complained of motion-evoked dizziness. All these findings suggest that, during such a convalescence period, the plugged area might not be fixed yet and could still induce the dizziness and low-tone ABGs, as enlarged vestibular aqueduct syndrome and superior semicircular canal deficiency syndrome exhibit low-tone ABGs due to the third mobile inner ear window. More than one month after surgery, both the ABGs and dizziness could disappear according to fixation of the plugged area. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.anl.2011.06.005

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Aims: We report the case of a 58-year-old female patient who consulted our Department complaining of positional vertigo and showing spontaneous upbeat nystagmus (UBN) in darkness.
Method: We analyzed her UBN three-dimensionally. The MRI scan revealed the astrocytoma in the left cerebellum involving the cerebellar vermis.
Result: Three-dimensional analysis showed a spontaneous UBN rotating around the intra-aural axis in the pitch plane.
Conclusion: Since the cerebellar vermis is known to plays an inhibitory role on the central vertical vestibule-ocular reflex (VOR), the present results suggest that the spontaneous UBN in darkness observed in this patient was induced by an imbalance of central vertical VOR tone. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.anl.2011.03.005

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Since the cerebellar vermis is known to plays an inhibitory role on the central vertical vestibule-ocular reflex (VOR), the present results suggest that the spontaneous UBN in darkness observed in this patient was induced by an imbalance of central vertical VOR tone.

DOI： 10.1016/j.anl.2011.03.005

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In the present study, to elucidate the role of vestibular ganglion (VG) after the unilateral labyrinthine damage, we examined quantitative changes in mRNA expression of beta-adrenergic receptors (bARs) and AMP-activated protein kinase alpha catalytic subunits (aAMPKs) in VG after unilateral labyrinthectomy (UL) in rats. Using the real-time PCR method, beta2 AR mRNA expression in bilateral VG and AMPK alpha2 mRNA expression in the ipsilateral VG were significantly up-regulated with the maximum increase at the postoperative 7 day and 1 day, respectively. The up-regulation of beta2 AR in bilateral VG was long-lasting until 28 days after UL and that of AMPK alpha2 in the ipsilateral VG was just transient within 7 days after UL These mRNA changes were supported by immunohistochemical data. According to previous reports, both of bARs and aAMPKs could regulate mitochondrial uncoupling protein (UCP) mRNA expression in several kinds of tissues and therefore might have thermogenic neurotransmission and antioxidant neuroprotective roles in neuronal tissues. UL requires not only long-lasting response of VG for central vestibular neuro-plasticity around 2-4 weeks but rapid response of VG against apoptosis of peripheral vestibular epithelia-neuronal synapses. The present findings suggest that beta2 AR in bilateral VG and AMPK alpha2 in the ipsilateral VG might play important signaling roles after the unilateral labyrinthine damage. (C) 2011 Elsevier Ireland Ltd and the japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2011.11.007

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We previously reported that motion sickness was prevented in rats with amygdala lesion and that provocative motion stimuli increased the number of Fos-positive neurons in the amygdala, suggesting that the amygdala is one of the neural substrates involved in the development of motion sickness. NK-1 receptors in the brain stem and amygdala are thought to play an important role in emesis and affective disorders, respectively. In the present study, to elucidate a role of substance P neuronal system and NK-1 receptors in the brain stem and amygdala in the development of motion sickness, we measured changes in gene expression of NK-1 receptors and preprotachykinin, a precursor of substance P, using quantitative real-time PCR methods in solitary tract nucleus and amygdala in rats after provocative motion stimuli induced by 2G hypergravity load. Effects of systemic administration of CP-99,994, an antagonist for NK-1 receptors, on hypergravity-induced motion sickness were also examined using pica behavior, eating non-nutritive substances such as kaolin, as an index of motion sickness in rats. Hypergravity-induced motion sickness was inhibited by CP-99,994 with a dose-dependent and enantioselective manner. Preprotachykinin mRNA expression was increased in basolateral nucleus of amygdala and solitary tract nucleus after hypergravity load for 3 h, whereas NK-1 receptor mRNA expression was not changed by hypergravity in amygdala and solitary tract nucleus. Present results suggest that 2G hypergravity load activated the substance P neuronal system in amygdala as well as in the brain stem and this activation would be related to the development of motion sickness. (C) 2011 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2011.11.047

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We previously reported that motion sickness was prevented in rats with amygdala lesion and that provocative motion stimuli increased the number of Fos-positive neurons in the amygdala, suggesting that the amygdala is one of the neural substrates involved in the development of motion sickness. NK-1 receptors in the brain stem and amygdala are thought to play an important role in emesis and affective disorders, respectively. In the present study, to elucidate a role of substance P neuronal system and NK-1 receptors in the brain stem and amygdala in the development of motion sickness, we measured changes in gene expression of NK-1 receptors and preprotachykinin, a precursor of substance P, using quantitative real-time PCR methods in solitary tract nucleus and amygdala in rats after provocative motion stimuli induced by 2G hypergravity load. Effects of systemic administration of CP-99,994, an antagonist for NK-1 receptors, on hypergravity-induced motion sickness were also examined using pica behavior, eating non-nutritive substances such as kaolin, as an index of motion sickness in rats. Hypergravity-induced motion sickness was inhibited by CP-99,994 with a dose-dependent and enantioselective manner. Preprotachykinin mRNA expression was increased in basolateral nucleus of amygdala and solitary tract nucleus after hypergravity load for 3h, whereas NK-1 receptor mRNA expression was not changed by hypergravity in amygdala and solitary tract nucleus. Present results suggest that 2G hypergravity load activated the substance P neuronal system in amygdala as well as in the brain stem and this activation would be related to the development of motion sickness.

DOI： 10.1016/j.brainres.2011.11.047

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Conclusion: The prediction of subtype and the affected ear of benign paroxysmal positional vertigo (BPPV) derived from the answers to our questionnaire can support the definitive diagnosis of BPPV. Objectives: We examined to what extent the diagnosis of subtype and the affected ear of BPPV judged from answers to a questionnaire agreed with the diagnosis decided by the results of the positional nystagmus test. Methods: We asked the following questions: 'What kind of head movements induce vertigo?' and 'How long does the vertigo continue?'. As for the affected ear, we asked which ear was lower during stronger vertigo when induced in a supine position or during sleep. Results: The percentages of correct diagnosis speculated by the combined answers were 69% in posterior canal-type BPPV, 48% in BPPV with geotropic nystagmus, and 39% in BPPV with apogeotropic nystagmus. The percentage of correct diagnoses of the affected ear was more than 80%.

DOI： 10.3109/00016489.2011.611535

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Conclusion: We reported previously that hyperactivation of vasopressin type-2 receptor (V2R)-mediated signaling in the endolymphatic sac could affect endolymphatic fluid metabolism, resulting in the pathogenesis of endolymphatic hydrops. Taken together with the present endolymphatic sac tumor (ELST) study, it is suggested that disorder of V2R signaling in the endolymphatic sac for any reason could be involved in the pathogenesis of endolymphatic hydrops. Although it is due to tumor genesis in ELST, it is idiopathic in nature in Meniere&apos;s disease. Objective: We encountered two cases of ELST showing Meniere&apos;s disease-like symptoms. Both cases were suspected of having endolymphatic hydrops using neuro-otological examinations. To clarify the histopathological diagnosis of ELST and the molecular pathogenesis of endolymphatic hydrops, we performed histopathological and molecular biological examinations of the endolymphatic sac. Methods: ELSTs in two rare cases were removed completely through the transmastoidal approach. V2R mRNA expression was examined using real-time PCR. Results: The first case was diagnosed as inflammatory granulation adjacent to the endolymphatic sac, i.e. pseudo-ELST, and the second case was diagnosed as papillary adenoma of ELST. V2R mRNA expression was up-regulated in the endolymphatic sac of both cases as seen in Meniere&apos;s disease compared with controls.

DOI： 10.3109/00016489.2011.580004

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Objective: To search for prognostic predictors and reexamine the usefulness of electroneurography (ENoG) in predicting the prognosis of peripheral facial palsy using statistical methods.
Study Design: Prospective study.
Setting: Tertiary referral center.
Patients: Consecutive 142 patients with Bell&apos;s palsy and 26 with Ramsay Hunt syndrome treated with steroid plus antiviral agents.
Interventions: Multivariate analysis was used to identify which factors, including Yanagihara grading score and ENoG, predict better recovery. Receiver operating characteristic (ROC) curves were constructed for ENoG and grading score. The cumulative recovery rate by ENoG was calculated using Kaplan-Meier analysis. Recovery was defined as the improvement of grading score to 36 points or more (full score, 40) without synkinesis.
Results: Multivariate analysis revealed that Ramsay Hunt syndrome, the worst grading score and ENoG were the significant prognostic predictors. The area under the ROC curve for ENoG was broader than those for grading score, indicating that ENoG was superior to grading score in terms of accuracy for prognosis prediction. The ROC curve revealed that more than 85% degeneration on ENoG had the best specificity (77.8%) and sensitivity (71.4%) to predict nonrecovery. When ENoG was subjected to the analysis of cumulative recovery rate using Kaplan-Meier plots, patients with more than 85% degeneration on ENoG had significantly poorer prognosis.
Conclusion: ENoG was the most effective factor for prediction of the prognosis of peripheral facial palsy, and more than 85% degeneration had the best specificity and sensitivity to predict nonrecovery.

DOI： 10.1097/MAO.0b013e31822558de

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Conclusion: Bipolar scissors tonsillectomy followed by cooling down the pharyngeal mucosa has advantages in terms of postoperative pain and intraoperative blood loss compared with cold dissection. Objectives: The purpose of this study was to compare the postoperative pain between bipolar scissors tonsillectomy followed by cooling the pharyngeal mucosa and a traditional cold dissection. Methods: A total of 189 patients aged more than 16 years were operated due to habitual tonsillitis, obstructive sleep apnea syndrome, and IgA nephropathy. Of these, 79 patients were operated using bipolar scissors followed by cooling the pharyngeal mucosa with 4 degrees C saline for 10 min just after the removal of tonsils. The other 110 patients underwent cold dissection tonsillectomy. Outcome measures were intraoperative blood loss, operative time, postoperative pain evaluated on a visual analog scale, and postoperative secondary hemorrhage. Results: Significantly lower levels of intraoperative blood loss and less postoperative pain were obtained in bipolar scissors tonsillectomy followed by cooling the pharyngeal mucosa compared with cold dissection. Postoperative hemorrhage needing hemostatic surgery occurred in 2 of 79 patients who underwent bipolar scissors tonsillectomy with cooling, while it occurred in 1 of 110 patients after cold dissection. However, the difference was not statistically significant.

DOI： 10.3109/00016489.2011.566580

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Conclusion: The detection rate of endolymphatic hydrops was significantly higher in patients with Meniere's disease compared with those with sudden deafness, indicating that 3 T magnetic resonance imaging (MRI) with intratympanic gadolinium injection was effective in diagnosing endolymphatic hydrops. Objectives: To compare the detection rate of endolymphatic hydrops between patients with Meniere's disease and sudden deafness as controls by 3 T MRI after intratympanic gadolinium injection with conventional pulse sequence such as two-dimensional fluid-attenuated inversion recovery. Methods: Ten patients with unilateral Meniere's disease and eight with sudden deafness underwent inner ear MRI 24 h after intratympanic gadolinium injection. Results: The endolymphatic space was detected as a low signal intensity area, while the perilymphatic space showed high intensity by gadolinium enhancement. Due to faint enhancement, images could not be evaluated in 1 of 10 patients with Meniere's disease. However, the other nine patients together with two of the eight with sudden deafness were diagnosed as having hydrops. The difference in detection rates between the two diseases was statistically significant. Two hydrops-positive cases with sudden deafness were considered to be of the secondary type of hydrops, because images were taken after partial recovery from hearing loss several months after the onset of the disease.

DOI： 10.3109/00016489.2010.548403

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Objectives: We detected chronic low-tone air-bone gaps (LTABGs) in some patients with Meniere&apos;s disease after endolymphatic sac surgery. The aim of the present study was to elucidate the mechanism of LTABGs after endolymphatic sac surgery.
Methods: We investigated 50 patients with Meniere&apos;s disease, who underwent surgery more than two years prior. LTABGs were defined as the three-tone-average = 20 dB formulated by (a + b + c)/3, where a, b, and c are ABGs at 0.25, 0.5, and 1 kHz, respectively (ABG +/-). The intra-operative finding was focused on identifying operculum (OPC +/-).
Results: The ratio of post-operative ABG(+) was 50.0% (25/50). The ratio of intra-operative OPC(+) was 72.0% (36/50). The surgery results were as follows: the ratio of complete vertigo suppression (VS(+)) was 84.0% (42/50), air-conduction hearing gain (aHG(+)) was 40% (20/50), bone-conduction hearing gain (bHG(+)) was 64% (32/50), and speech discrimination gain (SDG(+)) was 28% (14/50). The postoperative ABG(+) was commonly observed in patients with intra-operative OPC(+) (chi-square test, p = 0.013). aHG(+) and SDG(+) results were related to the post-operative ABG(+) (chi-square test, p = 0.021 and p = 0.0018, respectively).
Conclusions: These data suggest that intra-operative OPC(+) may be causative for post-operative ABG(+), resulting in post-operative aHG(+) and SDG(+). Thus, as enlarged vestibular aqueduct syndrome and superior semicircular canal deficiency syndrome exhibit LTABGs due to the third mobile inner ear window, endolymphatic sac surgery with adequate endolymphatic sac decompression and exposure to high doses of steroids, might induce LTABGs and the beneficial results of endolymphatic sac surgery. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.anl.2010.08.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDITERRANEAN SOC OTOLOGY & AUDIOLOGY  

Objective: Delayed facial nerve palsy (DFP) after otological and neurotological surgeries is always observed ipsilateral to the operated side, while it is rare in other types of ENT surgery including head and neck, suggesting that DFP may result from procedures selective to temporal bone surgery. Herein, we present a rare case of DFP after endolymphatic sac surgery, and review the pathogenesis and prevention of DFP after otological and neurotological surgeries.
Materials and Methods: The incidence of DFP after endolymphatic sac surgery from 1998 to 2008 at our hospital was 0.67% (1 out of 150 cases). A 44-year-old male with complaints of repeated vertigo attacks and cochlear symptoms such as persistent tinnitus and fluctuating hearing loss of the right ear. The patient received endolymphatic sac surgery on the right ear for treatment of intractable Meniere's disease, resulting in the onset of DFP.
Results: DFP onset occurred at post-operative day 8, with the House-Brackmann grade III. HSV and VZV serum tests were negative.
Conclusion: The later onset DFP observed in the present case after endolymphatic sac surgery might relate to the reactivation of a virus other than HSV and VZV in the geniculate ganglion induced by surgery.

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Objective of this report is to alert the existence of secondary endolymphatic hydrops at the beginning of the era for diagnosing the hydrops by image analyses. A 64 years-old female who showed partial recovery of hearing disturbance two months after the onset of sudden deafness underwent inner ear MRI in combination with intratympanic injection of gadolinium. Two-dimensional fluid-attenuated inversion recovery (2D-FLAIR) sequences taken by 3 tesla MR unit showed endolymphatic hydrops in the cochlea. Electrocochleogram could not be performed due to high tone hearing loss. At present, inner ear MRI in combination with intratympanic injection of gadolinium has been mainly used for Meniere's patients to detect endolymphatic hydrops. However, this tool cannot distinguish the secondary hydrops as seen in our case from Meniere's disease and thus should be used with careful attention if used as a routine test for inner ear diseases.

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：KARGER  

IgA nephropathy (IgAN) is the most common primary glomerulonephritis. Its close relation with the tonsils is well known because tonsillitis sometimes causes aggravation of urinary findings or macrohematuria. However, the genes specific to the tonsils of IgAN patients are not clarified. To clarify the specific gene expression in the tonsils of IgAN patients, we performed tonsillectomy and corticosteroid IV therapy as a treatment of IgAN, analyzed the gene expression in the tonsils by microarray and compared it with that in tonsils from chronic tonsillitis patients. The upregulated genes seem to be categorized into two groups: muscle-related genes and immunerelated genes. The downregulated genes include the polymeric ig receptor (plgR) which was reportedly involved in single nucleotide polymorphism (SNP) of Japanese IgAN patients. Copyright (C) 2011 S. Karger AG, Basel

DOI： 10.1159/000324611

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We report a case showing apogeotropic nystagmus with the lesion of the brain stem, and discuss a possible mechanism of central apogeotropic nystagmus. The case was a 73-year-old male. We analyzed his nystagmus three-dimensionally. He showed apogeotropic nystagmus. Axis angles of slow phase eye velocity of his apogeotropic nystagmus were not in line with the axes perpendicular to the plane of horizontal semicircular canals, but with the patient&apos;s vertical axis. We then found that his nystagmus including the apogeotropic nystagmus was positioning, but not positional and that the direction of his positioning nystagmus was the same direction of postrotatory nystagmus after his head movement. His M RI scans showed an infarction around the prepositus hypoglossi nucleus of the brain. His apogeotropic nystagmus seemed to consist of a combination of prolonged postrotatory nystagmus after his head rotation to the left and right lateral position because the axis of postrotatory nystamus was in line with the axis of the head rotation. Therefore, it is suggested that a possible mechanism of central apogeotropic nystagmus is a prolonged postrotatory nystagmus after his head movement in the supine position due to the brain lesion involving the velocity storage mechanisms. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.anl.2010.04.004

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We report a case showing apogeotropic nystagmus with the lesion of the brain stem, and discuss a possible mechanism of central apogeotropic nystagmus. The case was a 73-year-old male. We analyzed his nystagmus three-dimensionally. He showed apogeotropic nystagmus. Axis angles of slow phase eye velocity of his apogeotropic nystagmus were not in line with the axes perpendicular to the plane of horizontal semicircular canals, but with the patient&amp;apos;s vertical axis. We then found that his nystagmus including the apogeotropic nystagmus was positioning, but not positional and that the direction of his positioning nystagmus was the same direction of postrotatory nystagmus after his head movement. His MRI scans showed an infarction around the prepositus hypoglossi nucleus of the brain. His apogeotropic nystagmus seemed to consist of a combination of prolonged postrotatory nystagmus after his head rotation to the left and right lateral position because the axis of postrotatory nystamus was in line with the axis of the head rotation. Therefore, it is suggested that a possible mechanism of central apogeotropic nystagmus is a prolonged postrotatory nystagmus after his head movement in the supine position due to the brain lesion involving the velocity storage mechanisms.

DOI： 10.1016/j.anl.2010.04.004

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Language：Japanese   Publishing type：Research paper (scientific journal)  

In treating patients with Ménière's disease, isosorbide, one of the osmotic diuretics, is an essential drug to reduce endolymphatic hydrops. However, isosorbide liquid tastes bad, and tends to reduce patient compliance for taking this drug. To solve this problem, isosorbide jelly has been developed. Although the taste has still problems, isosorbide jelly has the advantage that it can be conveniently carried in a handy pack. In this study, we compared the compliance in 16 Ménière's patients between taking isosorbide liquid in bottles and individual handy packs. Patients were also asked to comment on the differences in taste between isosorbide liquid and isosorbide jelly. It was hypothesized that the patient compliance for the packed products would be better than bottled ones so that dizziness handicaps would be reduced in patients who were prescribed the packed products. The results showed patient compliance for the packed products was significantly better than that for bottled ones and that the dizziness score was significantly lower in patients in whom the packed product was prescribed. Four of 5 patients had the impression that isosorbide liquid tasted better than isosorbide jelly. We concluded that isosorbide liquid tasted better than isosorbide jelly and that the packed products were superior to bottled ones in terms of patient compliance in taking the drug. At this stage, isosorbide liquid in packs is the most recommended osmotic diuretic in terms of ensuring patient compliance with their medication when treating Ménière's patients.

DOI： 10.3757/jser.69.96

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Background: Recently, combination of tonsillectomy and steroid pulse therapy was reported to be effective as the treatment of the immunoglobulin A nephropathy (IgAN). However, the gene expression difference between the tonsils in patients with IgAN and those in control patients is not established.
Methods: We performed tonsillectomy combined with steroid pulse as a treatment to IgAN, analyzed the gene expression in the tonsils (N = 23) using microarray, compared with those with patients suffering from chronic tonsillitis (N = 22). From some candidate genes related with IgAN, we confirmed the apolipoprotein B messenger RNA-editing enzyme catalytic polypeptides 2 (APOBEC2) gene expression in the tonsil and we also analyzed its expression levels and clinical features.
Results: Up-regulated genes seem to be categorized into two groups. One group belongs to the muscle related genes which might be caused by structural differences. The other group includes the immune system-related genes, such as APOBEC2, CALB2, DUSP27, and CXCL11. APOBEC2 was positively stained in the epithelium and the peripheral region of the germinal center in both tonsils. APOBEC2 expression level was negatively related with serum igg level, but did not correlate with clinical course after tonsillectomy.
Conclusion: We confirmed gene expression differences related with immune system and muscle structure. The APOBEC2 was confirmed to be elevated in the tonsils with IgAN patients, and the gene expression level was negatively related with serum igg level in overall patients. These results might be helpful to reveal the mechanism of IgAN. (C) 2010 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2010.01.120

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Tinnitus is a non-observable phantom sensation. As such, it is a difficult condition to investigate and, to date, no effective treatment has been developed. To approach this phantom sensation, we aimed to develop a rat behavioral model of tinnitus using salicylate, an active component of aspirin known to induce tinnitus. We also aimed to establish a molecular marker of tinnitus by assessing the expression of transient receptor potential cation channel superfamily V-1 (TRPV1) in the rat auditory pathway during salicylate-induced tinnitus. Animals were trained to perform "an active avoidance task": animals were conditioned by electrical footshock to move to the other side of the conditioning box when hearing a sound. Animals received a single injection of saline or salicylate (400 mg/kg i.p.) and false positive responses were measured 2 h after injection as the number of movements during a silent period. The number of responses in salicylate-treated animals was highest when the conditioned stimulus was 60 dB sound pressure level (SPL) and 16 kHz. This indicates that animals could feel tinnitus 2 h after salicylate injection, equivalent to that induced by 60 dB SPL and 16 kHz. By means of real-time PCR and western blot analysis, TRPV1 expression was significantly upregulated in spiral ganglion cells 2 h after salicylate injection and this upregulation together with the increase in the number of false positive responses was significantly suppressed by capsazepine (10 mg/kg i.p.), a specific antagonist of TRPV1. This suggests that salicylate could induce tinnitus through activation of TRPV1 in the rat auditory pathway.

DOI： 10.1016/j.neuroscience.2009.11.048

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective: To investigate the occurrence rate, prognosis, and inner ear abnormality in intractable benign paroxysmal positioning vertigo (BPPV).
Study Design: A prospective study.
Setting: Tertiary referral university hospital.
Patients: Intractable BPPV was defined in case of either a persistent nystagmus or a frequent relapse each lasting more than 1 year after the initial diagnosis.
Intervention: T2-weighted 3-dimensional fast imaging employing steady-state acquisition sequences of magnetic resonance imaging (MRI) were reconstructed 3-dimensionally for 13 intractable BPPV patients and 14 control volunteers.
Main Outcome Measure: Transition and relapse of nystagmus were monitored. Semicircular canals were evaluated for a stenosis or filling defect (obturation).
Results: Eighteen patients (4 with posterior canal type, 2 with horizontal canal type with geotropic nystagmus, and 12 with apogeotropic nystagmus) fulfilled the above criteria for intractability among 495 BPPV patients. The occurrence rate of intractable BPPV was 3.6%. Also, the rate of nystagmus transition was significantly higher in patients with geotropic nystagmus and the posterior canal type (100%) compared with those with apogeotropic nystagmus (33.3%). Of the 13 intractable BPPV patients who underwent MRI, 11 (84.6%) had a total of 23 canals with abnormal appearance (29.5%), showing a significantly higher incidence compared with controls. There was no correlation between the affected canal diagnosed by MRI and the type of nystagmus.
Conclusion: The low incidence of nystagmus transition in patients with apogeotropic nystagmus suggests a difference in pathophysiology between apogeotropic nystagmus and other types of BPPV. Stenosis and filling defect (obturation) of canals on MRI, which would indicate an innate narrowing and/or an otoconial jam of the semicircular canal, may account for the intractability of BPPV.

DOI： 10.1097/MAO.0b013e3181cabd77

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS AS  

Conclusions. The &apos;tinnitus-rare&apos; group had a poorer prognosis for hearing than the &apos;tinnitus-often&apos; group in all sudden sensorineural hearing loss (SSNHL), although the &apos;shorter duration&apos; group had better prognosis than the &apos;longer duration&apos; when restricted to SSNHL accompanied by tinnitus. This indicates that tinnitus itself may not be a sign for poor hearing prognosis but might be an essential sound for the initiation of repair of a damaged auditory system. Objectives. We examined the hearing improvement rate (HIR) and tinnitus at the onset of SSNHL to elucidate the prognostic value of tinnitus accompanying SSNHL. Patients and methods. Fifty patients with SSNHL were treated with systemic administration of steroids. Hearing recovery was determined by comparing the hearing levels before and after treatment. Tinnitus was subjectively evaluated by the tinnitus scoring questionnaire. The score for the five-step evaluation of the subjective tinnitus feelings &apos;loudness&apos;, &apos;duration&apos; and &apos;annoyance&apos; was obtained at the onset. Results. In terms of &apos;duration&apos;, when we divided all the cases into &apos;tinnitus-rare&apos; group and &apos;tinnitus-often&apos; group, HIR in the &apos;tinnitus-rare&apos; group was significantly lower than that in &apos;tinnitus-often&apos; group. When restricted to the &apos;tinnitus-often&apos; group, HIR for &apos;shorter duration&apos; was significantly higher than that for &apos;longer duration&apos;.

DOI： 10.3109/00016480902897715

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

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Objective: There are some kinds of sicknesses provoked by inadequate adaptation to physical and/or psychogenic stress in daily life. Delayed endolymphatic hydrops (DEH) is an inner ear disease like Meniere&apos;s disease (MD) characterized by episodic vertigo in the setting of preexisting unilateral deafness that especially occurs in civilized people with a stressful lifestyle. Its otopathologic finding was demonstrated to be inner ear endolymphatic hydrops through a temporal bone study in 1976, as in the case with MD in 1938. To elucidate the relationship between stress and the inner ear, we examined the plasma antidiuretic stress hormone vasopressin (pAVP) and its type 2 receptor (V2R) expression in the endolymphatic sac in patients with DEH.
Study Design: A prospective molecular biological study.
Methods: Between 1998 and 2007, we enrolled 20 patients with ipsilateral DEH to examine their pAVP during remission from vertigo attacks. Plasma vasopressin was also examined in 87 patients with unilateral MD and 30 control patients with chronic otitis media. Using the real-time polymerase chain reaction method with tissue samples obtained during surgery, we examined V2R mRNA expression in the endolymphatic sac in 6 patients with ipsilateral DEH, 9 patients with unilateral MD, and 6 control patients with acoustic neuroma.
Results: Plasma vasopressin (1.5 times versus controls; unpaired t test, p = 0.140) and V2R mRNA expression in the endolymphatic sac (35.8 times versus controls; unpaired t test, p = 0.002) were higher in patients with DEH compared with those with acoustic neuroma. There were no significant differences in pAVP or V2R expression in the endolymphatic sac between DEH and MD. Patients with DEH showed a significantly negative correlation between pAVP and V2R (Pearson test, r = -0.92, p = 0.009) as in those with MD (Pearson test, r = -0.68, p = 0.043).
Conclusion: Civilized people are frequently exposed to stress in their daily life, and pAVP can easily become elevated at any time. Therefore, a negative feedback system between pAVP and V2R in the endolymphatic sac may function for inner ear fluid homeostasis against stress-induced increases in pAVP. For the pathogenesis of endolymphatic hydrops resulting in vertigo attacks in patients with DEH as well as MD, pAVP may represent a matter of consequence, but V2R overexpression in the endolymphatic sac could be much more essential as a basis for these diseases.

DOI： 10.1097/MAO.0b013e3181b11db5

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CONCLUSIONS: We conclude that neck imaging should be carried out for patients with persistent paroxysmal positional vertigo following diagnostic and/or therapeutic maneuvers. OBJECTIVE: It is sometimes complicated to diagnose patients with vertigo that is transiently induced by head and neck positioning. Neck-vestibular diseases also induce vertiginous sensation with head and neck movement and need to be ruled out for the diagnosis of benign paroxysmal positional vertigo (BPPV). PATIENTS AND METHODS: Two elderly female patients visited our hospital with complaints of transient vertigo induced by Dix-Hallpike positioning, suggesting posterior canal BPPV. We carried out gadolinium-enhanced neck MRI in both these cases. RESULTS: The positional nystagmus was not clearly observed or vertiginous sensation did not show any decay during repeated vestibular examination in either case. These cases were finally diagnosed as spinal cord intradural extramedullary tumor (C3-C4) by means of neck MRI.

DOI： 10.1080/00016480902915673

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An extremely rare case with labyrinthine anomaly with normal hearing was demonstrated. This case firstly showed transient positioning vertigo like benign paroxysmal positional vertigo (BPPV) and subsequently episodic vertigo like Meniere&apos;s disease. A 55-year-old mate attended our hospital, complaining of transient but persistent positioning vertigo in 2004. The apogeotropic positioning nystagmus was observed in spine position. In 2005, he came to feel episodic vertigo continuously for more than 30 min like Meniere&apos;s disease. We examined CT scan and 3D-MRI, indicating the hypoplastic lateral semicircular canal (L-SCC) fused together with enlarged vestibule on the left side. We finally diagnosed this case as Mondini anomaly on the left side.
The imaging analysis is the most useful for differential diagnosis of Mondini anomalies, because symptoms in these patients are actually various due to the individual inner ear condition. The mechanism of generation of BPPV-Iike vertigo: the otolith in deformed utricle might be transferred into the fused space with vestibule and L-SCC, resulting in the irrigation of the hypoplastic cupula. The mechanism of generation of Meniere&apos;s disease-like vertigo: neuro-otologic findings with furosemide test implied endolymphatic hydrops on the left side. Meniere&apos;s disease-like episodic vertigo could be due to subsequently generated endolymphatic hydrops. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.anl.2008.04.010

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The study findings suggest that histamine was released from the axon terminals in the hypothalamus and brainstem and the released histamine activated post-synaptic H1 receptors there, resulting in the development of motion sickness. We first examined which subtype of post-synaptic histaminergic receptor was responsible for the development of motion sickness. We then examined whether H1 receptors were up-regulated in various areas of the rat brain after 2 G hypergravity load, because the stimulation of H1 receptor was reported to up-regulate the level of H1 receptor protein expression through augmentation of H1 receptor mRNA expression. For this purpose, we used an animal model of motion sickness, using pica (eating non-nutritive substances such as kaolin), as a behavioral index in rats. After 2 G hypergravity load, rats ate a significant amount of kaolin, indicating that they suffered from motion sickness. The hypergravity-induced kaolin intake was suppressed by mepyramine, but not by terfinadine or zolantizine. This finding indicates that cerebral post-synaptic H1 but not H2 or peripheral H1 receptors play an important role in the development of motion sickness. The expression of H1 receptor mRNA was up-regulated in the hypothalamus and brainstem, but not in the cerebral cortex after 2 G hypergravity load in rats.

DOI： 10.1080/00016480802008173

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS AS  

Conclusions. We conclude that neck imaging should be carried out for patients with persistent paroxysmal positional vertigo following diagnostic and/or therapeutic maneuvers. Objective. It is sometimes complicated to diagnose patients with vertigo that is transiently induced by head and neck positioning. Neck-vestibular diseases also induce vertiginous sensation with head and neck movement and need to be ruled out for the diagnosis of benign paroxysmal positional vertigo (BPPV). Patients and methods. Two elderly female patients visited our hospital with complaints of transient vertigo induced by Dix-Hallpike positioning, suggesting posterior canal BPPV. We carried out gadolinium-enhanced neck MRI in both these cases. Results. The positional nystagmus was not clearly observed or vertiginous sensation did not show any decay during repeated vestibular examination in either case. These cases were finally diagnosed as spinal cord intradural extramedullary tumor (C3-C4) by means of neck MRI.

DOI： 10.1080/00016480902915673

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS AS  

Conclusion: The study findings suggest that histamine was released from the axon terminals in the hypothalamus and brainstem and the released histamine activated post-synaptic H1 receptors there, resulting in the development of motion sickness. Objectives: We first examined which subtype of post-synaptic histaminergic receptor was responsible for the development of motion sickness. We then examined whether H1 receptors were up-regulated in various areas of the rat brain after 2 G hypergravity load, because the stimulation of H1 receptor was reported to up-regulate the level of H1 receptor protein expression through augmentation of H1 receptor mRNA expression. Materials and methods: For this purpose, we used an animal model of motion sickness, using pica (eating non-nutritive substances such as kaolin), as a behavioral index in rats. Results: After 2 G hypergravity load, rats ate a significant amount of kaolin, indicating that they suffered from motion sickness. The hypergravity-induced kaolin intake was suppressed by mepyramine, but not by terfinadine or zolantizine. This finding indicates that cerebral post-synaptic H1 but not H2 or peripheral H1 receptors play an important role in the development of motion sickness. The expression of H1 receptor mRNA was up-regulated in the hypothalamus and brainstem, but not in the cerebral cortex after 2 G hypergravity load in rats.

DOI： 10.1080/00016480802008173

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DOI： 10.1259/dmfr/69946733

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DOI： 10.1111/j.1365-2826.2008.01792.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

In the present study, to elucidate the role of mitochondrial uncoupling proteins (UCPs) in inner ear, we examined quantitative changes in the mRNA expression in vestibular ganglion (VG) after unilateral labyrinthectomy (UL) in rats. Using real-time PCR methods, UCP2, 3 and 4 mRNA expressions in the ipsilateral VG were significantly up-regulated with the maximum increase at the post-operative 1 day and all but UCP2 returned to the control level 1 week after UL. UCP2 mRNA expression was significantly up-regulated even 4 weeks after UL. Only UCP2 mRNA expression in the contralateral VG was gradually up-regulated between 1 and 4 weeks after UL. According to previous reports, UCP2 and 3 as well as UCP1 were thermogenic in yeast and brain UCP2 was suggested to modulate pre- and post-synaptic events by axonal thermogenesis. It was also reported that UCP1, 2 and 3 responses to superoxide application were an antioxidant protective mechanism. These findings suggest that mitochondrial UCPs could play both a neuro-protective role against oxidative damage and a thermal signaling role for neuro-modulation in vestibular nerve. (C) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2007.07.001

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Vestibular compensation, or neuronal plasticity in the central vestibular system, is quite an important process in patients with acute unilateral peripheral vestibular disease, allowing them to lead a comfortable daily life when medical treatments fail to cure the peripheral vestibular function. Is the residual unilateral vestibular input from damaged vestibular endo-organs a positive or negative factor for the development of dynamic vestibular compensation in the central nervous system? To elucidate the true mechanism of vestibular compensation, we examined the ENG findings and dizziness handicap inventory questionnaire in patients with vestibular neuronitis (VN), sudden deafness with vertigo (SDV), Meniere's disease (MD) and acoustic tumor (AT) during remission of the vertigo attacks. We obtained neuro-otological findings from caloric tests and head shaking after nystagmus using ENG and information on motion-evoked dizziness in daily life using the questionnaire. There were no significant differences in the sex, age or canal paresis % (CP%) among the four groups. The results of the present study showed that dynamic vestibular compensation processes developed progressively in the order of patients with SDV, VN, MD and AT (Kruskal-Wallis : p&lt
0.05). This finding suggests that processes of dynamic vestibular compensation could be accelerated in patients with fixed vestibular lesions caused by SDV and VN more than in those with fluctuating vestibular functions caused by MD and AT. In patients with fixed vestibular lesions caused by SDV and VN, patients with lower CP% showed dynamic vestibular compensation (i.e. disappearance of head shaking after nystagmus (chi-square : p&lt
0.05) and motion-evoked dizziness (Mann-Whitney : p&lt
0.0005)) more rapidly than those with higher CP%. In patients with fluctuating vestibular functions caused by MD and AT, patients with lower CP% did not always develop dynamic vestibular compensation more smoothly than those with higher CP%.

DOI： 10.3950/jibiinkoka.110.720

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Inquiries into the neurochemical mechanisms of vestibular compensation, a model of lesion-induced neuronal plasticity, reveal the involvement of both voltage-gated Ca2+ channels (VGCC) and intracellular Ca2+ signaling. Indeed, our previous microarray analysis showed an up-regulation of some calcium signaling-related genes such as the alpha 2 subunit of L-type calcium channels, calcineurin, and plasma membrane Ca2+ ATPase 1 (PMCA1) in the ipsilateral vestibular nuclear complex (VNC) following unilateral vestibular deafferentation (UVD). To further elucidate the role of calcium signaling-related molecules in vestibular compensation, we used a quantitative real-time polymerase chain reaction (PCR) method to confirm the microarray results and investigated changes in expression of these molecules at various stages of compensation (6 h to 2 weeks after UVD). We also investigated the changes in gene expression during Bechterew's phenomenon and the effects of a calcineurin inhibitor on vestibular compensation. Real-time PCR showed that genes for the alpha 2 subunit of VGCC, PMCA2, and calcineurin were transiently up-regulated 6 h after UVD in ipsilateral VNC. A subsequent UVD, which induced Bechterew's phenomenon, reproduced a complete mirror image of the changes in gene expressions of PMCA2 and calcineurin seen in the initial UVD, while the a2 subunit of VGCC gene had a trend to increase in VNC ipsilateral to the second lesion. Pre-treatment by FK506, a calcineurin inhibitor, decelerated the vestibular compensation in a dose-dependent manner. Although it is still uncertain whether these changes in gene expression are causally related to the molecular mechanisms of vestibular compensation, this observation suggests that after increasing the Ca2+ influx into the ipsilateral VNC neurons via up-regulated VGCC, calcineurin may be involved in their synaptic plasticity. Conversely, an up-regulation of PMCA2, a brain-specific Ca2+ pump, would increase an efflux of Ca2+ from those neurons and perhaps prevent cell damage following UVD. (c) 2007 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2006.12.072

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A prospective, open-label clinical trial was conducted for two aims: first, to evaluate the role of fluvoxamine, one of selective serotonin reuptake inhibitors, in the treatment of dizziness for the first time and to investigate its effective mechanisms. Second, to test the hypothesis that dizziness in patients without abnormal neuro-otologic findings would be induced by psychiatric disorders rather than by unnoticed neuro-otologic diseases. Nineteen patients with neuro-otologic diseases (Group I) and 22 patients in whom standard vestibular tests revealed no abnormal findings (Group II) were treated by fluvoxamine (200 mg/day) for eight weeks. Subjective handicaps due to dizziness using a questionnaire, anxiety and depressive symptoms measured with the Hospital Anxiety and Depression Scale (HADS), and stress hormones (vasopressin and cortisol) were examined before and 8 weeks after treatment. Overall, fluvoxamine decreased subjective handicaps of both Groups I and II. Fluvoxamine decreased HADS of only patients whose subjective handicaps were reduced (= responders) in both groups, suggesting that fluvoxamine was effective for dizziness via psychiatric action rather than a recovery of vestibular function through serotonergic activation. In non-responders of Group II, pre-treatment HADS was higher than in Group I non-responders and it was not decreased by the treatment, suggesting that dizziness of Group II non-responders was due to severe psychiatric disorders rather than unnoticed neuro-otologic diseases. Anxiety and depression components of HADS showed a good correlation at both pre- and post-treatment periods. No post-therapeutic decrease was observed in either vasopressin or cortisol even in responders, suggesting that dizziness was not the sole cause of stress in chronic dizziness patients. In conclusion, patients with or without physical neuro-otologic deficits who report chronic dizziness accompanied by anxiety and depression (as measured by HADS) showed improvements across a full range of subjective handicaps and psychological distress, while patients with physical neuro-otologic defects and minimal anxiety or depression did not benefit. The main causes of dizziness in patients without physical neuro-otologic findings were psychiatric disorders.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective: To look for factors relating to the vertigo control and hearing changes after intratympanic injections of gentamicin (GM).
Study design: Prospective.
Setting: Tertiary referral medical center.
Patients: Twenty-eight patients with intractable Meniere's disease.
Interventions: Three intratympanic injections of GM (once per day for three consecutive days).
Main Outcome Measures: Although five patients needed further GM injections or vestibular neurectomy because of poor control (Group I), 23 patients had their vertigo controlled for more than two years without further treatment (Group II). The number of vertigo spells per month, pure-tone audiometry, electrocochleography, caloric response, post-head shake nystagmus, and plasma vasopressin as a stress marker were examined.
Results: Before GM injections, there was no difference in the number of vertigo spells per month between Groups I and II. However, the hearing thresholds were higher in Group I. Hearing improvement, increase in percentage of canal paresis and induction of post-head shake nystagmus were observed after GM injections only in Group II. Even in the I I patients who showed an improvement in hearing of more than 10 dB (hearing improvement group), percentage of canal paresis was increased after GM. More, premedication plasma vasopressin levels were lower in the hearing improvement group as compared with the hearing loss/no changes group. Four of eight patients became negative for dominant negative summating potential in electrocochleography after GM injections in the hearing improvement group.
Conclusion: Our data indicate that the frequency of vertigo is not a key factor in the vertigo control after GM injections, that induction of vestibular damage in the injected ear is essential for the control of vertigo and this effect is mostly pronounced in patients with milder hearing loss, and that hearing improvement is not only a consequence of good vertigo control but also affected by the stress level before treatment.

DOI： 10.1097/01.mao.0000227663.79210.c1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER PHYSIOLOGICAL SOC  

The hippocampus has a major role in memory for spatial location. Theta is a rhythmic hippocampal EEG oscillation that occurs at similar to 8 Hz during voluntary movement and that may have some role in encoding spatial information. We investigated whether, as part of this process, theta might be influenced by self-movement signals provided by the vestibular system. The effects of bilateral peripheral vestibular lesions, made &gt;= 60 days prior to recording, were assessed in freely moving rats. Power spectral analysis revealed that theta in the lesioned animals had a lower power and frequency compared with that recorded in the control animals. When the electroencephalography (EEG) was compared in epochs matched for speed of movement and acceleration, theta was less rhythmic in the lesioned group, indicating that the effect was not a result of between-group differences in this behavior. Blood measurements of corticosterone were also similar in the two groups indicating that the results could not be attributed to changes in stress levels. Despite the changes in theta EEG, individual neurons in the CA1 region of lesioned animals continued to fire with a periodicity of similar to 8 Hz. The positive correlation between cell firing rate and movement velocity that is observed in CA1 neurons of normal animals was also maintained in cells recorded from lesion group animals. These findings indicate that although vestibular signals may contribute to theta rhythm generation, velocity-related firing in hippocampal neurons is dependent on nonvestibular signals such as sensory flow, proprioception, or motor efference copy.

DOI： 10.1152/jn.00953.2005

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-LISS  

In the present study, we first observed up-regulation in preproenkephalin (PPE)-like immunoreactivity (-LIR), a precursor of Met- and Leu-enkephalin, in the rat ipsilateral medial vestibular nucleus (ipsi-MVN) after unilateral labyrinthectomy (UL). By means of double-staining immunohistochemistry with PPE and Fos, a putative regulator of PPE gene expression, we revealed that some of these PPE-LIR neurons were also Fos immunopositive. The time course of decay of these double-stained neurons was quite parallel to that of UL-induced behavioral deficits. This suggests that these double-labeled neurons could have something to do with development of vestibular compensation. We next examined correlation between Fos and PPE expression in the ipsi-MVN by means of a 15-min pre-UL application of antisense oligonucleotide probes against c-fos mRNA into the ipsi-MVN. Gel shift assay and Western blotting revealed that elimination of Fos expression significantly reduced both AP-1 DNA binding activity and PPE expression in the ipsi-MVN after UL. C-fos antisense study also revealed that depression of Fos-PPE signaling in the ipsi-MVN caused significantly more severe behavioral deficits during vestibular compensation. Furthermore, studies with PPE antisense and naloxone, an opioid receptor antagonist, demonstrated that specific depression of enkephalinergic effects in the ipsi-MVN significantly delayed vestibular compensation. All these findings suggest that, immediately after UL, Fos induced in some of the ipsi-MVN neurons could regulate consequent PPE expression via the AP-1 activation and facilitate the restoration of balance between bilateral MVN activities via the opioid receptor activation, resulting in progress of vestibular compensation. (c) 2006 Wiley-Liss, Inc.

DOI： 10.1002/jnr.20830

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS AS  

Relapsing polychondritis ( RP) is characterized by inflammation and subsequent degeneration of cartilage. We report a 61-year-old woman who had RP with audio-vestibular manifestations. She was also diagnosed as having a myelofibrosis with myeloid metaplasia (MMM). Bilateral endolymphatic hydrops ( EH) was confirmed by dominant - SP/AP of the electrocochleogram (ECochG). When thalidomide and prednisolone were prescribed for the treatment of MMM, symptoms of RP - including the inner ear dysfunction - were ameliorated. Isosorbide, one of the osmotic diuretics commonly used for the treatment of Meniere's disease ( MD) in Japan, was also effective in keeping her free from inner ear dysfunction. This is the first report to confirm the existence of EH in a patient with RP with audio-vestibular manifestations. We suppose that an immunological imbalance due to MMM, in conjunction with a specific immunogenetic background, may have played a role in the pathogenesis of RP and the formation of EH in this patient.

DOI： 10.1080/00016480500437369

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Syringocystadenoma papilliferum (SCAP) usually occurs on the face or the scalp and is very rare in the external auditory canal (EAC). There has been no information on magnetic resonance (MR) imaging of this tumor irrespective of its site. We report here a case of 57-year-old man having this tumor. which was surgically removed and its histopathology was confirmed. MR imaging demonstrated a lobulated 4-cm mass with clearly defined margins in the EAC. Although the tumor was bulky, these MR findings were different from the malignancies. The mass lesion showed intermediate signal intensity both on T1- and T2-weighted MR images and showed slight enhancement on gadolinium-enhanced T1-weighted images. signal intensities oil T2-weighted images of this tumor were low compared to those of pleomorphic adenoma. All ceruminous gland tumors including SCAP are thought to be potentially malignant therefore, pre-operative biopsy should not be performed. Even though incisional biopsy is sometimes needed as in our case, the current MR features would be helpful for differential diagnosis of this rare condition and assessing the extension of the tumor. (C) 2005 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.anl.2005.07.011

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS AS  

When diagnosing and treating patients with acute vertigo, the clinician must differentiate brain lesions from benign peripheral disorders. We here report a rare case of acute vertigo caused by intracranial vertebral artery dissection mimicking peripheral disease. A 67-year-old man presented with spontaneous nystagmus and moderate ataxia preceded by neck pain. No other neurological signs were observed, suggesting acute peripheral vertigo. However, magnetic resonance imaging (MRI) demonstrated a cerebellar infarction. Simultaneous magnetic resonance angiography (MRA) showed no flow void of the left vertebral artery and contrast-enhanced MRA demonstrated a double lumen sign, suggesting that vertebral artery dissection was a cause of infarction. The clinical course was favorable without anticoagulation drugs, which are sometimes contraindicated because of the potential risk of subarachnoid hemorrhage. Vertebral artery dissection can cause cerebellar infarction in patients without vascular risk factors mimicking acute peripheral vertigo. Careful history regarding the neck pain is important and MRA in combination with MRI can replace angiography in diagnosing this disorder.

DOI： 10.1080/00016480500279977

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

Delayed facial nerve palsy (DFP) is rarely experienced after otologic surgeries that do not directly touch the facial nerves, such as tympano-mastoidectomy, cochlear implants, and stapes surgery, and is troublesome to both surgeons and patients if it happens. Here, we report 7 cases of DFP, including one case that developed DFP after endolymphatic sac surgery. The ratios of occurrence were as follows: 0.7% (2/305) for tympano-mastoidectomy, 0.8% (3/354) for cochlear implant, 0.4% (1/260) for stapes surgery and 1.0% (1/98) for endolymphatic sac surgery. All otologic surgeries, except for endolymphatic sac surgery, exposed the chorda tympani, and all surgeries, except for stapes surgery, underwent drilling for a mastoidectomy. Furthermore, DFP was always observed ipsilaterally to the operated ear after otologic surgeries and was never seen after benign parotid tumor surgery or total laryngectomy. Therefore, there may be a strong relationship between DFP and the procedures, used during otologic surgeries.

DOI： 10.3950/jibiinkoka.109.600

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Society for Equilibrium Research  

Motion sickness is induced by unusual patterns of spatial information input, but not by a simple strong acceleration. Thus, in the process of the development of motion sickness, the disturbance of spatial orientation is noticed somewhere in the brain, leading to the expression of autonomic signs and symptoms. What part of the brain plays this key role? Peripheral vestibular input has repeatedly been proven to be necessary for motion sickness, even for visually-evoked motion sickness. The vestibular nucleus in the brain stem where spatial information including visual and somatosensory as well as vestibular inputs converge, is the primary candidate for this key structure. In the higher brain, the limbic system, particularly the amygdala, is another candidate. In our rat animal model, bilateral amygdala lesions significantly suppressed motion sickness signs, whereas hippocampus lesions did not. Using cFos protein expression as a marker for neuronal activation, we also showed that the central nucleus of the amygdala was activated by vestibular information during the hypergravity stimulation that induced motion sickness in rats. Involvement of the amygdala may explain some characteristic features of motion sickness, such as its diversity of signs ranging from sympathetic to parasympathetic, and its conditioned occurrence where by some susceptible persons become sick even in motionless vehicles.

DOI： 10.3757/jser.65.213

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Interest in interaction between the vestibular system and the hippocampus was stimulated by evidence that peripheral vestibular lesions could impair performance in learning and memory tasks requiring spatial information processing. By the 1990s, electrophysiological data were emerging that the brainstem vestibular nucleus complex (VNC) and the hippocampus were connected polysynaptically and that hippocampal place cells could respond to vestibular stimulation. The aim of this review is to summarise and critically evaluate research published in the last 5 years that has seen major progress in understanding the effects of vestibular damage on the hippocampus. In addition to new behavioural studies demonstrating that animals with vestibular lesions exhibit impairments in spatial memory tasks, electrophysiological studies have confirmed long-latency, polysynaptic pathways between the VNC and the hippocampus. Peripheral vestibular lesions have been shown to cause long-term changes in place cell function, hippocampal EEG activity and even CA1 field potentials in brain slices maintained in vitro. During the same period, neurochemical investigations have shown that some hippocampal subregions exhibit long-term changes in the expression of neuronal nitric oxide synthase, arginase I and II, and the NR1 and NR2A N-methyl-D-aspartate (NMDA) receptor subunits following peripheral vestibular damage. Despite the progress, a number of important issues remain to be resolved, such as the possible contribution of auditory damage associated with vestibular lesions, to the hippocampal effects observed. Furthermore, although these studies demonstrate that damage to the vestibular system does have a long-term impact on the electrophysiological and neurochemical function of the hippocampus, they do not indicate precisely how vestibular information might be used in hippocampal functions such as developing spatial representations of the environment. Understanding this will require detailed electrical stimulation and lesion studies to elucidate the way in which different kinds of vestibular information are transmitted to various hippocampal subregions. (c) 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.pneurobio.2005.04.004

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The process of behavioural recovery that occurs following damage to one vestibular labyrinth, vestibular compensation, has been attributed in part to a down-regulation of GABA(B) receptors in the vestibular nucleus complex (VNC) ipsilateral to the lesion, which could potentially reduce commissural inhibition from the contralateral VNC. In this study, we tested the possibility that this occurs through a decrease in the expression of either the GABA(B1) or GABA(B2) subunits of the GABA(B) receptor. We used Western blotting to quantify the expression of these subunits in the VNC at 10 h and 50 h following unilateral vestibular deafferentation (UVD) or sham surgery in rats. We then used immunocytochemistry and stereological counting methods to estimate the number of neurons expressing these subunits in the MVN at 10 h and 2 weeks following UVD or sham surgery. Compared to sham controls, we found no significant changes in either the expression of the two GABA(B) receptor subunits in the VNC or in the number of MVN neurons expressing these GABA(B) receptor subunits post-UVD. These results suggest that GABA(B) receptor expression does not change substantially in the VNC during the process of vestibular compensation. (c) 2005 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2005.01.018

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IOS PRESS  

For more than a decade, evidence from animal studies has suggested that damage to the vestibular system leads to deficits in spatial navigation which are indicative of impaired spatial learning and memory. More recently, direct evidence has emerged to demonstrate that humans with vestibular disorders exhibit a range of cognitive deficits that are not just spatial in nature, but also include non-spatial functions such as object recognition memory. Vestibular dysfunction has been shown to adversely affect attentional processes and increased attentional demands can worsen the postural sway associated with vestibular disorders. Recent MRI studies also show that humans with bilateral vestibular damage undergo atrophy of the hippocampus which correlates with their degree of impairment on spatial memory tasks. These results are consistent with those from animal studies and, together, suggest that humans with vestibular disorders are likely to experience cognitive dysfunction which is not necessarily related to any particular episode of vertigo or dizziness, and therefore may occur even in patients who are otherwise well compensated. These findings may be related to the observation that patients with vestibular deficits experience a high incidence of depression and anxiety disorders.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Although the bases for both the sporadic and inherited forms of Meniere's disease (MD) remain undefined, it is likely to be multifactorial, one of the factors being a genetic predisposition. Recently, genetic association studies on complex diseases have become very popular and most of them are case-control studies using single nucleotide polymorphisms (SNPs) as markers. Mutations/ polymorphisms in KCNE potassium channel genes might play a causative role in MD, because KCNE potassium channels have been suggested to be present and active in transmembrane ion and water transports in the inner ear. In the present study, to identify MD susceptibility genes, we have conducted a genetic association study with optimized sampling, optimized phenotyping/genotyping, and a selection of KCNE genes as the candidate genes. The SNPs analyses identified 112G/A SNP in the KCNE1 gene and 198T/C SNP in the KCNE3 gene in 63 definite MD cases as well as 205 and 237 non-MD control subjects. For both KCNE1 and KCNE3 genes, a significant difference in frequency of each SNP was confirmed between MD cases and non-MD control subjects. The result indicates that 112G/A SNP in the KCNE1 gene and 198T/ C SNP in the KCNE3 gene could determine an increased susceptibility to develop MD. Copyright (C) 2005 S. Karger AG, Basel.

DOI： 10.1159/000089410

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Most astronauts experience spatial disorientation after exposure to weightlessness, indicating that constant gravity is utilized as a stable external reference during spatial cognition. We attempted to elucidate the role of constant gravity in spatial learning using a radial arm maze test on rats housed in a hypergravity environment (HG) produced by a centrifuge device. Male Wistar rats were kept in 2G linear acceleration for 2 weeks before the spatial learning task, which lasted for 10 days. The control rats were placed close to the centrifuge device but not exposed to hypergravity. Spatial learning was evaluated by the accuracy and the re-entry rate, which were the rate of correct arm entries and the rate of entries into the arms that they had already visited, respectively. Locomotor activity was measured by number of entries per minute. The number of baits the animal took per minute was also measured. The results showed that accuracy was significantly inferior and the re-entry rate was significantly higher in the HG rats than in the controls, suggesting that animals use a constant gravity as a stable external reference in spatial learning. However, these differences disappeared at 5 days later, indicating that the HG rats learned the spatial task more rapidly than the controls. Locomotor activity was higher in the HG rats and there was no difference in number of baits per minute between the HG and control animals. In conclusion, if one sensory cue necessary for spatial cognition is disturbed by gravity change, animals can subsidize with other sensory Cues Such as proprioceptive and motor efference copy signals through increased locomotor activities. (C) 2004 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.cogbrainres.2004.08.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING LTD  

To investigate the molecular background of vestibular compensation, a model of lesion-induced plasticity, we used a microarray analysis to examine genes that show asymmetrical expression between the bilateral vestibular nucleus complexes (VNCs) 6 h following unilateral vestibular deafferentation (UVD). Asymmetrical gene expression was then validated by a real-time quantitative PCR. Among the 88 genes for which the ipsilateral (ipsi) : contralateral (contra) was &gt; 1.35, the number of known genes was 33 (38%), and the number of expressed sequence tag (EST) sequences was 55 (62%). Among the 130 genes for which the contra : ipsi was &gt; 1.35, the number of known genes was 55 (42%), and the number of EST sequences was 75 (58%). Changes in some of the genes were consistent with previous studies; however, we found several new genes which could be functionally related to the molecular basis of the electrophysiological asymmetry between the VNCs following UVD. Ipsi &gt; contra genes included the GABA(A) receptor rho subunit, regulatory proteins of G protein signaling, calcium signaling related molecules such as the voltage-dependent calcium channel alpha2/delta subunit 1, calcineurin subunit Abeta and Ca2+ pump. Contra &gt; ipsi genes included the neuronal high affinity glutamate transporter, 5-hydroxytryptamine receptor 1D, mitogen-activated protein kinase 12 and ubiquitin carboxy-terminal hydrolase L1.

DOI： 10.1111/j.1471-4159.2004.02781.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective and Study Design: When treating dizzy patients, the psychiatric aspect should be carefully addressed regardless of whether a well-defined organic disease is present. In this prospective study, we aimed to elucidate the role of paroxetine, a selective serotonin reuptake inhibitor, in the treatment of dizziness.
Setting and Patients: Forty-seven patients who complained of dizziness were treated with 20 mg of paroxetine per day. The depressive state of the patient was evaluated by the Zung Self-Rating Depression Scale (SDS). Treatment outcomes were measured with self-assessment of subjective handicaps in daily life using a dizziness and unsteadiness questionnaire. The questionnaire consisted of five factors related to emotional or bodily dysfunction that could be affected by dizziness: Changes in Self-Rating Depression Scale scores and subjective handicaps were assessed at 4 and 8. weeks after the start of paroxetine.
Results: In patients having well-defined organic diseases with high Self-Rating Depression Scale scores, paroxetine improved all five subjective handicap factors as well as Self-Rating Depression Scale scores. The decline in Self-Rating Depression Scale scores showed a significant correlation with improvement of subjective handicaps, which was related to emotional problems but not factors related to bodily dysfunction. Paroxetine was also effective for an improvement of factors related to emotional problems and Self-Rating Depression Scale scores in patients not having organic diseases but with high Self-Rating Depression Scale scores. In patients either with or without organic diseases with low Self-Rating Depression Scale scores, paroxetine had no effect on any subjective handicap factors and Self-Rating Depression Scale scores.
Conclusion: In the treatment of dizzy patients, paroxetine was effective at relieving subjective handicaps caused by dizziness, specifically, in patients with high Self-Rating Depression Scale scores.

DOI： 10.1097/00129492-200407000-00022

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Language：Japanese   Publishing type：Research paper (scientific journal)  

According to the cognitive (spatial) map theory by O'Keefe and Nadel (1978), correct navigation can be achieved by the combination of an allocentric cue and an egocentric "self motion" cue. In this review, we summarized our recent data on the role of the vestibular system in spatial navigation and reviewed recent articles from other institutions. Firing of complex spike cells (CS cells) in the CA1 region of the rat hippocampus, which function as "place cells" in awake conditions, showed a current intensity-dependent increase by electrical stimulation of the vestibular nucleus complex (VNC). Control stimulation adjacent to but not in the VNC had no effects on CS cell firing. The place field of place cells in the bilaterally labyrinthectomized rat was unstable and showed less specificity to the place compared to sham animals. Marked deficits of spatial navigation were found in the bilaterally labyrinthectomized animals as assessed by a radial arm maze test. These findings suggest that vestibular information reaches the hippocampus to modulate hippocampal place cell function and has an important role in spatial navigation. The anatomical route from the vestibular system to the hippocampus, biochemical evidence of vestibulo-hippocampal interaction, and the neural basis of spatial navigation were also discussed.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER-VERLAG  

Vestibular information is known to be important for accurate spatial orientation and navigation. Hippocampal place cells, which appear to encode an animal's location within the environment, are also thought to play an essential role in spatial orientation. Therefore, it can be hypothesized that vestibular information may influence cornu ammonis region 1 (CA1) hippocampal neuronal activity. To explore this possibility, the effects of electrical stimulation of the medial vestibular nucleus (MVN) on the firing rates of hippocampal CA1 neurons in the urethane-anesthetized rat were investigated using extracellular single unit recordings. The firing rates of CA1 complex spike cells (n=29), which most likely correspond to place cells, consistently increased during electrical stimulation of the MVN in a current intensity dependent manner. Stimulation applied adjacent to the MVN failed to elicit a response. Overall, the firing rates of non-complex spike cells (n=22) did not show a consistent response to vestibular stimulation, although in some cells clear responses to the stimulation were observed. These findings suggest that vestibular inputs may contribute to spatial information processing in the hippocampus.

DOI： 10.1007/s00221-003-1725-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

Musashi1 (Msi1) is an RNA-binding protein expressed in neural stem/progenitor cells, astroglial progenitor cells and astrocytes in the vertebrate central nervous system. We hypothesized that Msi I is expressed in only some of the supporting cells in the cochlea, which could become hair cell progenitors under special circumstances after an injury. To observe this, we investigated Msi1 expression in young adult mouse cochlea by immunohistochemistry using monoclonal antibody against Msi1. Msi1 immunostaining was found in a variety of supporting cells but not in outer hair cells in the organ of Corti. Although an immunoreactive ring was found around the inner hair cells, it also seemed to originate from the supporting cells. We suppose that this wide expression of Msi1 in supporting cells indicates that those cells might have the potential to become hair cell progenitors if injured, but that some other mechanisms strictly inhibit this ability. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2003.10.036

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

To elucidate the role of the GABAergic neuronal system in the recovery from peripheral vestibular damage (unilateral labyrinthectomy), we used a real-time quantitative reverse transcription-polymerase chain reaction method to investigate the mRNA expression of GAD65, GAD67, the GABA(A) receptor alpha1 subunit, the GABA(B) R1 subunit, and the GABA transporter GATI, in the vestibular nucleus complex of the rat 6 and 50 h following the lesion GAD65 and GAD67 gene expression were also measured in the flocculus. The GABAA alpha1 subunit mRNA was up-regulated in the ipsilateral vestibular nucleus 6 h post-lesion but decreased in expression thereafter. GAD65 mRNA was up-regulated in the vestibular nuclei bilaterally 50 h after the lesion. In the flocculus, GAD65 mRNA expression was bilaterally up-regulated 50 h post-operatively. GATI mRNA expression was initially up-regulated in the ipsilateral vestibular nucleus and then underwent a bilateral increase 50h post-operatively. These results demonstrate that following unilateral labyrinthectomy, major changes in the expression of GAD, GAT and GABA receptor subunit genes occur in the vestibular nucleus, which are likely to affect the process of behavioural recovery. (C) 2003 Lippincott Williams Wilkins.

DOI： 10.1097/01.wnr.0000102266.71579.6c

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：HEADLEY BROTHERS LTD  

Pleomorphic adenoma arising from the external auditory canal is a very rare neoplasm, and there has been no report on magnetic resonance (MR) imaging of pleomorphic adenoma of the external auditory canal. We report here a case of 65-year-old male with this tumour, measuring 12 mm in a diameter. Histopathology was confirmed from the specimen obtained at the surgical excision. MR revealed that the tumour had a well-defined margin showing hypointensity on T1-weighted images and hyperintensity on T2-weighted images relative to the parotid gland. The tumour was well enhanced by contrast material. No invasion to the surrounding tissue was observed. These MR findings were compatible with pleomorphic adenoma of the salivary gland origin. In treating pleomorphic adenoma of the external auditory canal, complete surgical excision is essential for the prevention of recurrence. It can be concluded that MR imaging is helpful for making a differential diagnosis of external auditory canal tumours and selection of adequate treatment.

DOI： 10.1258/002221503322542980

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Altered gravity environments including both hypo- and hypergravity can elicit motion sickness. Vestibular information is known to be essential for motion sickness, but its other neural substrates are poorly understood. We previously showed that bilateral lesions of the amygdala suppressed hypergravity-induced motion sickness in rats, using pica behavior as an emetic index. We show in the present study that during hypergravity stimulation, vestibular information activated the central nucleus of the amygdala (CeA), as determined by the induction of Fos expression, in comparison between normal and bilaterally labyrinthectomized rats. The finding that Fos expression was confined to the CeA and almost completely absent in other subnuclei of the amygdala contrasted with many previous studies that used other stressful stimuli such as foot shock, restraint and forced swimming, suggesting a specific vestibular effects on the amygdala. Prolongation of hypergravity resulted in reduction of Fos expression in the CeA, suggesting a process of habituation. Such decreases appeared earlier than in the vestibular nucleus, suggesting that adaptive changes in the CeA to hypergravity were independent of changes in the vestibular input. Our results suggest the amygdala is a neural substrate involved in the development of and habituation to motion sickness. (C) 2003 Elsevier B.V. All rights reserved.

DOI： 10.1016/S0006-8993(03)03220-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SOC NEUROSCIENCE  

The hippocampus is thought to be important for spatial representation processes that depend on the integration of both self-movement and allocentric cues. The vestibular system is a particularly important source of self-movement information that may contribute to this spatial representation. To test the hypothesis that the vestibular system provides self-movement information to the hippocampus, rats were given either a bilateral labyrinthectomy ( n = 6) or a sham surgery ( n = 6), and at least 60 d after surgery hippocampal CA1 neurons were recorded extracellularly while the animals foraged freely in an open arena. Recorded cells were classified as complex spiking ( n = 80) or noncomplex spiking ( n = 33) neurons, and their spatial firing fields ( place fields) were examined. The most striking effect of the lesion was that it appeared to completely abolish location-related firing. The results of this and previous studies provide converging evidence demonstrating that vestibular information is processed by the hippocampus. The disruption of the vestibular input to the hippocampus may interfere with the reconciliation of internal self-movement signals with the changes to the external sensory inputs that occur as a result of that movement. This would disrupt the ability of the animal to integrate allocentric and egocentric information into a coherent representation of space.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：FOREFRONT PUBL GROUP  

Vestibular neuritis (VN) rapidly damages unilateral vestibular periphery; inducing severe balance disorders. In most cases, such vestibular imbalance is gradually restored to within the normal level after clinical therapies. This successive clinical recovery occurs due to regeneration of vestibular periphery and/or accomplishment of central vestibular compensation. We experienced 36 patients with VN treated at our hospital, including cases in our previous preliminary report: To elucidate effects of steroid therapy both on the recovery of peripheral function and on the adaptation of central vestibular compensation, we examined caloric test and several questionnaires with two randomly divided groups, 18 steroid-treated and 18 nonsteroid-treated patients, overt two years after the onset. These examinations revealed that steroid-treated patients had a tendency of better canal improvements (13/18, 72%) than nonsteroid-treated ones (10/18, 55.6%). However, there was no significant difference between these two groups. In cases with persistent canal paresis, steroid-treated patients (n = 5) reduced handicaps in their everyday life due to the dizziness induced by head and/or body movements and the disturbance of their mood, more effectively than those with nonsteroid therapy (n = 8). These findings suggest that steroid therapy with VN could be effective on not only vestibular periphery but central vestibular system, to restore the balance.

DOI： 10.1179/016164103101201364

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

A 54-year-old woman complained of positional vertigo. During 3 months' observation, the patient showed mostly geotropic or apogeotropic nystagmus due to right canalolithiasis or cupulolithiasis, however, she sometimes showed nystagmus which suggested left horizontal canalolithiasis. We suspected that she suffered from bilateral horizontal canal type benign paroxysmal positional vertigo (BPPV) and performed Lempert's maneuver for both directions, however, they were ineffective. She underwent canal plugging for right horizontal canal. After surgery she showed no positional nystagmus of right horizontal canal origin. However, apogeotropic nystagmus of the left horizontal canal origin was still observed. This nystagmus changed to geotropic nystagmus and finally disappeared following Lempert's maneuver for the left side. Bilateral horizontal canal BPPV is difficult to be resolved, probably because physical treatment for one side would move debris to the cupula in the other canal. Canal plugging combined with Lempert's maneuver to the other side is one treatment option for intractable bilateral horizontal canal BPPV. Copyright (C) 2003 S. Karger AG, Basel.

DOI： 10.1159/000076056

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IOS PRESS  

In order to investigate whether bilateral peripheral vestibular lesions cause long-term impairment of spatial learning, rats were tested in a reference memory radial arm maze learning task at least 5 weeks following a bilateral labyrinthectomy (BL) or sham control lesion. All control rats reached criterion (i.e., 1 error or less, averaged across 7 trials for 3 consecutive days of training) but only 4 of the 8 BL rats had reached criterion by day 21 of the training sessions. The control rats reached criterion more quickly than the lesioned rats (Control, 7.0 +/- 0.63 days, Lesioned, 15.8 +/- 1.4 days, t(10) = 5.84, p &lt; 0.0001). This difference resulted from the greater number of errors made by the BL animals. However, the latency to respond was comparable as a result of the increased locomotor activity of the BL group (i.e., 'hyperkinesis), and the overall rate of acquisition of the task, as indicated by analysis of the exponential decrease in errors over the entire training period, was not significantly different between the 2 groups. The results of this study demonstrate that BL in rats produces long-term changes in performance in a spatial reference memory task, which are not simply due to the inability to move but may relate to the way that the brain uses vestibular information to create spatial representations and determines behavioural strategies on the basis of these representations.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING LTD  

In order to investigate the mechanisms responsible for adaptation to altered gravity, we assessed the changes in mRNA expression of glutamate receptors in vestibular ganglion cells, medial vestibular nucleus, spinal vestibular nucleus/lateral vestibular nucleus, cerebellar flocculus, and uvula/nodulus from rats exposed to hypergravity for 2 h to 1 week using real-time quantitative RT-PCR methods. The mRNA expression of GluR2 and NR1 receptors in the uvula/nodulus and NR1 receptors in the medial vestibular nucleus increased in animals exposed to 2 h of hypergravity, and it decreased gradually to the control level. The mRNA expression of GluR2 receptors in vestibular ganglion cells decreased in animals exposed to 1 week of hypergravity. Neither the metabotropic glutamate receptor 1 nor delta2 glutamate receptor in flocculus and uvula/nodulus was affected by a hypergravity load for 2 h to 1 week. It is suggested that the animals adapted to the hypergravity by enhancing the cerebellar inhibition of the vestibular nucleus neurons through activation of the NR1 and GluR2 receptors on the Purkinje cells in uvula/nodulus especially at the early phase following hypergravity. In the later phase following hypergravity, the animals adapted to the hypergravity by reducing the neurotransmission between the vestibular hair cells and the primary vestibular neurons via down-regulation of the postsynaptic GluR2 receptors in the vestibular periphery.

DOI： 10.1046/j.1471-4159.2002.00933.x

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.3950/jibiinkoka.105.5_557

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Reverse transcription-polymerase chain reaction (RT-PCR) is a powerful tool to detect specific gene expression from a small amount of tissue, which is superior to the traditional RNA assays such as Northern blotting and in situ hybridization (ISH) in terms of sensitivity. However, conventional RT-PCR is not suitable for quantification due to its exponential nature. Recently, a real-time quantitative PCR method has been developed to overcome the weak points of RT-PCR, e.g. quantification. Here we describe the use of real-time quantitative PCR using a fluorescent TaqMan probe, to study the regional differences in expression of glutamate receptor subunit/subtype genes (NR1, NR2A, GluR2, KA2, mGluR1, mGluR7) in the central vestibular system including the vestibular nucleus complex, inferior olive and cerebellar flocculus. We found that real-time quantitative PCR yielded similar results to other techniques such as ISH but offered several advantages in terms of relative speed and ability to detect low levels of gene expression. We suggest that real-time quantitative PCR is a useful method to study gene expression for other neurotransmitter receptors in the vestibular brainstem and cerebellum, and is also expected to be more accurate to assess the changes in gene expression following any treatment. (C) 2002 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S1385-299X(01)00139-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS AS  

In order to elucidate the role of the vestibulocerebellar neural circuits during two-stage bilateral labyrinthectomy (BL) we examined Fos-like immunoreactive (-LIR) neurons as a marker of neural activation in the rat brainstem after BL and the projections of these neurons into the vestibulocerebellum using retrograde tracing and immunohistochemical techniques. Simultaneous BL did not show any Fos expression in the medial vestibular nucleus (MVe). However, with an interval of &gt; 6 h between the two stages of BL, Fos-LIR neurons were induced in the ipsilateral (ipsi-) MVe of the side operated on second, partially projecting into the ipsi- vestibulocerebellum. A previous study demonstrated that some of the unilateral labyrinthectomy-induced Fos-LIR neurons in the ipsi- MVe projected into the ipsi- vestibulocerebellum and inhibited the contra-MVe neurons, resulting in the restoration of the right-left balance. Taken together with our present data, it is suggested that some of the labyrinthectomy-induced Fos expression in the ipsi- MVe is representative of a switch-on signal for the vestibulo-cerebello-vestibular inhibitory neural circuits, which remain turned off after symmetrical lesions such as simultaneous BL but are turned on after severe asymmetrical lesions in order to restore the balance.

DOI： 10.1080/000164802320396295

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SCANDINAVIAN UNIVERSITY PRESS  

We investigated the DNA ploidy pattern. cell cycle and the percentage of Ki-67 positive fractions in Fresh surgical material from 17 benign and 33 malignant thyroid tumours using flow cytometry. DNA aneuploidy was not seen at all in benign tumours. but was seen in 3 out of 33 malignant rumours. suggesting that detection of DNA,4 aneuploidy indicates malignancy, although the detection sensitivity was low. Regarding the cell cycle. there was no difference in the percentage of S-phase fractions (SPF) or G2 plus M phase fractions (G2M) between benign and malignant rumours. However. the percentage of Ki-69 positive fractions in malignant rumours (39.9 +/- 3.9) was significantly higher than that in benign rumours (9.4 +/- 2.1%,), indicating that malignant thyroid rumours contained a large population of G1 phase cells. When a cut-off value of 20%; was used for Ki-67 positive Fractions. sensitivity was 82%;, specificity was 88% and accuracy was 84% fur the diagnosis of malignant tumours. Although this study was carried our on surgically derived marerials, it is possible that flow cytometric analysis of fine needle aspiration-derived materials may have a place in preoperative histopathological assessment of thyroid tumours.

DOI： 10.1080/00016489950180883

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.3950/jibiinkoka.101.12_1385

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DOI： 10.1111/j.1749-6632.1996.tb15743.x

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DOI： 10.3950/jibiinkoka.99.277

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing Ltd  

Using a microdialysis method, we investigated the effects of the nipecotic acid-induced increase in content of endogenous GABA on in vivo release of histamine from the anterior hypothalamus (AHy) of urethane-anesthetized rats. Nipecotic acid (0.5 mM), an inhibitor of GABA uptake, decreased histamine release to ~60% of the basal level. This effect was partially antagonized by picrotoxin (0.1 mM), an antagonist of GABA(A) receptors, or phaclofen (0.1 mM), an antagonist of GABA(B) receptors. These results suggest that histamine release is modulated by endogenous GABA through both GABA(A) and GABA(B) receptors. When the tuberomammillary nucleus, where the cell bodies of the histaminergic neurons are localized, was stimulated electrically, the evoked release of histamine from the nerve terminals in the AHy was significantly enhanced by phaclofen, suggesting that GABA(B) receptors may be located on the histaminergic nerve terminals and modulate histamine release presynaptically. On the other hand, picrotoxin caused an increase in histamine release to ~170% of the basal level, and this increase was diminished by coinfusion with D(-)-2-amino-5-phosphonopentanoic acid (0.1 mM), an antagonist of NMDA receptors. Previously, we demonstrated tonic control of histamine release by glutamate mediated through NMDA receptors located on the histaminergic terminals in the AHy. These results suggest the possible localization of GABA(A) receptors on glutamatergic nerve terminals and that the receptors may regulate the basal release of histamine indirectly.

DOI： 10.1046/j.1471-4159.1996.67010171.x

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DOI： 10.1152/jn.1994.72.2.605

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DOI： 10.1046/j.1471-4159.1994.62062275.x

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1. We investigated the effect of unilateral vestibular stimulation on histamine release from the anterior hypothalamic area of urethan-anesthetized rats in vivo, using a brain microdialysis method coupled with high- performance liquid chromatography fluorometry. 2. The histamine release was increased to ~180% of the basal release by the electrical stimulation of the inner ear with 1 Hz, 500 μA, and 200 ms for 20 min. This effect was dependent on the current intensity. 3. Activation of the unilateral horizontal semicircular canal by middle ear irrigation for 15 min with 45°C water increased the histamine release to ~200% of the basal release. 4. Irrigation of the middle ear with ice water for 15 min increased the histamine release to ~190% of the basal release. 5. The histamine release was not changed by the irrigation of the middle ear with 37°C water and the irrigation of the auricle with ice water, which suggests that neither somatosensory stimulation to the middle ear nor nonspecific cold stress affects the histamine release. 6. All these findings suggest that the sensory mismatch signals induced by caloric stimulation and unilateral electrical vestibular stimulation activate the histaminergic neuron system in the brain.

DOI： 10.1152/jn.1993.70.5.1822

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Language：Japanese   Publishing type：Book review, literature introduction, etc.   Publisher：Society of Oto-Rhino-Laryngology Tokyo  

DOI： 10.3950/jibiinkoka.123.1337

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Language：Japanese   Publisher：日本認知療法・認知行動療法学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01099&link_issn=&doc_id=20200930440012&doc_link_id=%2Fdz0jibik%2F2020%2F012309%2F012%2F1214-1215%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz0jibik%2F2020%2F012309%2F012%2F1214-1215%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publishing type：Book review, literature introduction, etc.   Publisher：Society of Oto-Rhino-Laryngology Tokyo  

DOI： 10.3950/jibiinkoka.123.1214

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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Language：Japanese   Publisher：新潟県医師会  

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Language：Japanese   Publisher：(一社)日本聴覚医学会  

CI2004の子音検査を用いて、人工内耳装用者の子音聴取の明瞭度と異聴傾向を調べた。対象は成人人工内耳装用者CI群22名(26〜86歳)、および健聴の対照N群10名(50〜69歳)とした。聞きとりを異聴マトリックスで示し明瞭度と誤りを分析した。CI群の明瞭度は、最小7%から最大88%(平均63%)と、症例によって違いがあった。N群の明瞭度は96〜100%であった。CI群の子音別の明瞭度は、/j/98%、/k/92%、/dz/83%、/w/82%、/s/77%、/b/と/h/68%、/d/64%、/g/53%、/n/51%、/p/48%、IPA番号124 47%、/m/43%、/t/3%、であった。多くみられた異聴傾向は、/p/→/t//k/、/t/→/k/、/g/→/d/、/m/→/n/、/n/→/m/、IPA番号124→/n/、/s/→/dz/、/h/→/s/、であった。特に、/t/を[k]と聞き取る誤りは90%と極めて高く、ごく短時間での高周波数成分が手がかりとなる/t/での人工内耳装用者の知覚困難があると推測された。(著者抄録)

DOI： 10.4295/audiology.61.65

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DOI： 10.3950/jibiinkoka.120.596

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Language：Japanese   Publisher：(一社)日本耳科学会  

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DOI： 10.4295/audiology.59.553

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DOI： 10.4295/audiology.59.369

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Language：Japanese   Publisher：(株)医学書院  

＜POINT＞Barany学会が作成した精神疾患が関与するめまいの新分類を紹介した。このなかでは不安症とうつを中心に9つの病態が定義されているが,精神疾患が引き起こすめまいだけでなく,逆に前庭疾患により2次的に精神疾患を発症した病態も区別して明記された。これは,器質的前庭疾患を治療する際には,2次的に生じた精神疾患にも十分配慮すべきであることを示唆している。めまい患者ではうつや不安の程度とめまいの自覚症状には相関があり,抗うつ・抗不安両作用のあるSSRI投与は精神症状のみならずめまいの自覚症状も改善させる。(著者抄録)

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DOI： 10.4295/audiology.58.417

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Other Link： http://search.jamas.or.jp/link/ui/2016019244

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DOI： 10.4295/audiology.58.397

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Other Link： http://search.jamas.or.jp/link/ui/2016019234

Language：Japanese   Publisher：日本口腔・咽頭科学会  

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Language：Japanese   Publisher：(株)自然科学社  

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

症例は68歳女性で、アーノルド・キアリ奇形の既往があった。頭位変換時の回転性めまいで近医にて難治性良性発作性頭位めまい症が疑われ紹介受診した。明所、暗所とも座位開眼でbow-tie眼振を認め、開発した240Hz高速画像サンプリングデジタルカメラに記録した。Dix-Hallpike法による頭位変換眼振検査で急速相の垂直成分は上眼瞼向き、回旋成分は患者から見て時計回りであり、右後半規管型良性発作性頭位めまい症と診断し、アナログカメラに記録した。2ヵ月後の再診時に頭位眼振を認めなかったが、暗所座位で頭部を左右振子様の回転で誘発された前庭動眼反射による眼球運動をアナログカメラに記録した。デジタル・アナログカメラの3画像を、開発したアルゴリズムにて三次元眼球運動解析を行った。Bow-tie眼振のgeneratorは存在せず、純垂直性の緩徐相に対する急速相が水平成分をもった場合、bow-tie眼振の形状を取ると考えられた。

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

J-GLOBAL

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Language：Japanese   Publisher：Japan Society for Equilibrium Research  

We have recently encountered two cases of intractable Meniere's disease with a history of head trauma. Both patients underwent surgical treatments because conservative medical treatment had failed. As we supposed that they had developed a secondary endolymphatic hydrops associated with perilymphatic fistula, we first performed a simple mastoidectomy and opened the facial recess to carry out an exploratory tympanotomy. Next, we performed endolymphatic sac drainage and closed both oval and round windows with connective tissue whether we found an obvious fistula or not. One year-follow-up results showed complete relief from vertigo after the operation in both cases. It is suggested that relative increase in the endolymph pressure can become a cause of endolymphatic hydrops due to the decline of the perilymph pressure. In patients with Meniere's disease who have a history of trauma, we propose that it should be better to keep in mind the possibility of fistula-induced secondary hydrops.

DOI： 10.3757/jser.73.16

CiNii Article

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

J-GLOBAL

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