Published papers

Objective: We present a rare case of keratinic amyloidosis of the external auditory canal. This is only the seventh case reported of localized cutaneous amyloidosis of the external auditory canal with no systemic symptoms. Patient: A 62-year-old man, who had complained of an itchy external auditory canal and left-side hearing loss, was referred to our hospital because of a bilateral external auditory canal mass. Intervention: Biopsy of the external auditory canal mass suggested a diagnosis of amyloidosis. However, total systemic examination failed to identify any disease due to systemic amyloidosis. This led us to diagnose him with localized cutaneous amyloidosis of the external auditory canal. Main outcome measure: We follow up periodically with systemic examination and local observation. Results: Thirty months after the initial diagnosis, he remains in follow-up and has not shown any significant aggravation of the disease. Conclusion: In previous cases, the chief complaints were itching sensations and pain in the external auditory canal as well as a sense of discomfort when wearing a hearing aid. This suggests that chronic stimulation and inflammation of the skin lining the external auditory canal induced amyloidosis.

Dysphagia and hoarseness caused by laryngopharyngeal paralysis associated with internal carotid artery (ICA) dissection is rare. We reported a case which recovered spontaneously. A 57-year old man visited our hospital complaining of dysphagia and hoarseness lasting for two weeks. Paralysis of right vocal fold and rotational movement of the posterior pharyngeal wall toward the left side during swallowing were observed. Magnetic resonance imaging was performed under diagnosis of isolated right vagus nerve paralysis, and dissection of the right ICA was revealed. He was treated conservatively, and both of laryngopharyngeal movement and the ICA dissection were improved completely. There is a possibility that laryngeal paralysis caused by ICA dissection has been misdiagnosed as an idiopathic paralysis.

Objective: This study evaluated self-reported symptoms in patients with idiopathic sudden sensorineural hearing loss (ISSHL). Study Design: Cross-sectional study. Setting: Multicenter clinical investigation in 9 university hospitals. Patients: In total, 140 patients with ISSHL and 24 patients with unilateral sensorineural hearing loss (USHL; control) were included. Main Outcome Measures: A questionnaire on symptoms of ISSHL was distributed and the Short-Form Health Survey (Version 2) was used for assessing the quality of life. Results: In response to questions on hearing difficulty, many of patients in both groups experienced symptoms. In response to questions on hearing-related discomfort, a significantly higher number of patients with ISSHL experienced symptoms compared with those with USHL. Compared with a high incidence of tinnitus in patients with ISSHL, very low incidence of tinnitus was observed in those with USHL.In the multiple linear regression analysis, hearing-related discomfort was the sole significant factor on the Mental Component Summary scores of the Short-Form Health Survey (Version 2). Conclusion: Many patients with ISSHL experience several symptoms such as hearing difficulty, hearing-related discomfort, tinnitus, and anxiety. Hearing-related discomfort strongly affected the quality of life in patients with ISSHL.

Background: Because of its low incidence, the clinical characteristics of the salivary duct carcinoma (SDC) based on a statistical analysis with a large number of patients remain to be elucidated, and thus it has been impossible to standardize the optimal treatments of SDC including adjuvant systemic therapy. Aims: The present study aimed to determine the prognostic factors along with the clinical outcomes of patients with SDC and to evaluate the expression of several receptor molecules as treatment targets. Methods: We performed a statistical analysis and immunohistochemical examination of 16 patients with SDC who had undergone initial treatment in the Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine from 1996 to 2010. Results: The 3-year disease-free survival (DFS) and cause-specific survival (CSS) rates were 29.2% and 72.7%, respectively. At the time of the analysis, 6 patients are alive without the disease, 2 patients are alive with distant metastasis, whereas 7 patients had died of distant metastasis, and 1 patient had died of another cause (pulmonary embolism). We examined the prognostic value of the clinico-pathological factors such as age, sex, T classification, N classification, clinical stage, primary site, histological pre-existence of pleomorphic adenoma. A univariate analysis revealed that DFS was significantly correlated with age (p = 0.049), T classification (p = 0.018), and clinical stage (p = 0.029), whereas no factor was found to be correlated with CSS. A multivariate analysis demonstrated that age (≥61 vs. ≤60, risk ratio (RR) = 5.423, p = 0.042) and T classification (3, 4 vs. 1, 2, RR= 1.087, p = 0.020) were the independent prognostic factors for DFS. Positive expressions of HER2, ER (estrogen receptor), PR (progesterone receptor), AR (androgen receptor), and MIB-1 (index<20%) were found in 50%, 6%, 13%, 100%, and 69%, respectively. However, none of them showed significant correlation with survival. Conclusion: Frequent expressions of HER-2 and AR in SDC suggest that these receptors can be suitable molecular targets of systemic therapy for patients with SDC in which distant metastasis seems to be the largest obstacle to improving survival. In order to assess the efficacy of anti-HER-2 therapy and anti-androgen therapy for each receptor-positive SDC, a multi-institutional joint research system should be organized.

Pharmacological and non-pharmacological approaches are the treatment options for dizzy patients. Vestibular exercises are a potential treatment option for intractable dizzy patients who do not respond to conventional drug therapy. The retention rate of exercises is quite important for a successful outcome. We organized vestibular exercise courses to improve the retention rate in the outpatient groups; these courses comprised introduction sessions with a clinical psychologist and rehabilitation sessions with a clinical technologist. It is unclear whether the effects of vestibular rehabilitation are based on the improvement of the psychological parameters of vestibular function. Therefore, we evaluated the functional mechanism of vestibular rehabilitation by using questionnaires and balance function tests. Our study comprised 16 patients with chronic dizziness. The patients performing the self-administered home-based vestibular exercise courses were supervised in small groups. The patients were taught that the exercises were to be performed 4 times a day at their respective homes. The symptoms of dizziness were evaluated using the Japanese version of the dizziness handicap inventory (DHI). Anxiety and depression levels were assessed using a set of psychological questionnaires. The static and dynamic balance function was assessed using static posturography and foam posturography and by measuring the time required for performing a certain series of eye-head movement protocols at the initial visit, before rehabilitation, and 2 and 3 months after rehabilitation. Of 16 patients, 15 could successfully complete the study (93.8%). The DHI score significantly improved 1 month after the rehabilitation, whereas anxiety and depression levels did not improve. The results of static and foam posturography as well as the time required for the eye-head movements also significantly improved. The improvement in the DHI scores was not associated with psychological changes, but with the improvement in the static and dynamic balance function.

Fibrocytes in the cochlear lateral wall and spiral limbus play an important role in transporting K+ and have the capacity of self-renewal. We showed that acute energy failure in the rat cochlea induced by local administration of the mitochondrial toxin 3-nitropropionic acid (3NP) caused hearing loss in a concentration-dependent manner, mainly due to degeneration of cochlear fibrocytes. We produced long-lasting profound cochlear damage in this model by modifying the 3NP administration protocol and observed morphological changes at 16 weeks after the administration. In the spiral ligament, severe degeneration of fibrocytes was observed in the basal turn, and the levels of the Na,K-ATPase alpha and beta1 subunits and of NKCC1 were decreased in these cells, whereas connexin 26 (Cx26) level increased in the type 1 fibrocytes adjacent to the stria vascularis. In the stria vascularis, levels of Kir4.1 and L-PGDS decreased. In the spiral limbus, severe degeneration of fibrocytes was observed in the middle and basal turns, but NKCC1 and Cx26 were still found in the center of the limbus in the middle turn. These results indicate long-lasting changes in the cochlear lateral wall and spiral limbus, which may compensate for damaged K+ recycling and protect cells from ATP shortage.

While hearing aids are recommended for people with age-related hearing loss, many with impaired hearing do not use them. In this study, we investigated how many elderly people in the study area needed hearing aids, and the factors that determined continued wearing of the devices. The study area was Kurabuchi Town, Japan, where 1,437 residents (those aged 65 years or over) were eligible for participation in the study; 1,414 participated, of whom, 103 (7.3%) were already using hearing aids at the start of the study. After the primary screening, hearing aids were lent to 68 participants (4.8%) who did not already have one, 38 of whom (60.3% of the borrowers, representing 2.7% of the total aged population) went on to wear the hearing aid continuously. The Hearing Handicap Inventory for the Elderly (HHIE) score was significantly elevated among these 38 participants. This study indicated that hearing aids are of potential benefit to many local residents. Multivariate logistic regression revealed that HHIE scores were associated with the extent of HA usage. The adjusted odds ratio for a 1-unit increase in HHIE score was 1.08 (95% confidence interval: 1.02-1.14). Programs like this, in which people with impaired hearing are identified at the local level and given appropriate assistance, are useful models for future use in societies with aging populations.

Migraine-associated vertigo (MAV) is proposed as a new clinical entity on the basis of the assumption that the typical migraine and vertigo or dizziness have a common pathophysiology. Some of the patients with recurrent vertigo syndromes with unknown pathology may have MAV. We performed a retrospective study to clarify the clinical characteristics of MAV in the Japanese population. The following were considered as diagnostic criteria: (1) recurrent vestibular symptoms, (2) migraine headache as defined by the International Headache Society (IHS) criteria, (3) at least one instance of synchronization of a vertiginous attack with a migraine headache, (4) no associated unilateral hearing loss, and (5) absence of other diseases that may have caused vertiginous attacks. Of 552 patients with dizziness or vertigo, 46 (8.3%) were diagnosed as having MAV. A typical feature of this clinical entity is that migraine occurs before the onset of vertigo in women aged 30-40 years. Usually the attacks occur once in a year for 1 to 10 years. An attack lasts for 1-24 h and presents as vertigo and unsteadiness with simultaneous headache. The presence of hearing loss presents an important clinical dilemma. Whether the condition in patients experiencing hearing loss should be defined as MAV or not is still a matter for discussion.

Objective: To assess the perception of hearing handicap in adult patients with unilateral sudden sensorineural hearing loss (SNHL) compared with those with bilateral SNHL or unilateral congenital SNHL. Study Design: Retrospective chart review. Setting: Multicenter department of otolaryngology referrals. Patients: Seventy-one subjects in the unilateral severe-profound (>70 dB) sudden SNHL group (Group 1), 17 subjects in the unilateral prelingual or congenital SNHL group (Group 2), and 121 subjects in the bilateral SNHL group (Group 3). Interventions: Questionnaire. Main Outcome Measures: Hearing Handicap Inventory for Adults (HHIA) and visual analogue scale (VAS) measurements of hearing handicap. Results: Average levels of hearing loss were 92 dB in Group 1, 109 dB in Group 2, and 67 dB in Group 3. The relative percentage scores ofHHIA andVAS compared with Group 3 were 72.6%and 81.0%in Group 1 and 25.4%and 50.3%in Group 2, respectively. A mild correlation between the HHIA subscale or VAS scores and degree of hearing loss could be found in Group 3. No significant correlation was found between the HHIA subscale or VAS scores and duration of hearing loss in Group 1 or Group 3. Higher scores were obtained in male subjects than in female subjects. Patients in Group 1 who were troubled by tinnitus scored significantly higher in the HHIA. In multiple logistic regression analysis, presence of tinnitus, older age, higher average hearing loss level, and group (bilateral SNHL>unilateral sudden SNHL>unilateral precongenital SNHL) revealed a significant positive association with high score (>42) of HHIA (odds ratio, 3.171, 1.021, 1.031, and 6.690, respectively). Conclusion: The results of HHIA and VAS suggest that not only patients with bilateral SNHL but also those with unilateral sudden SNHL, particularly those who have tinnitus, experience a hearing handicap.

The clinical features of Ménière's disease and migraine-associated vertigo are quite similar. Both disorders are characterized by repeated vertigo spells. Several diagnostic criteria are used to diagnose migraine-associated vertigo. None of these criteria has been internationally defined,although the criteria proposed by Neuhauser are wieldy accepted. Hearing impairment is believed to be a key factor for diagnosing Meniere's disease. We report herein on a case of repeated vertigo spells with sensorineural hearing loss in the right ear. Initially,the condition was diagnosed as Meniere's disease. Treatment for improving endolymphatic hydrops did not have an effect on the vertigo spells. On careful questioning, we noted the coexistence of migraines without any aura. Treatment with Ca antagonists to prevent the migraine attacks successfully stopped the patient's vertigo spells. On the basis of this clinical course, it is safe to assume that the patient had migraine-associated vertigo with sensorineural hearing loss rather than Meniere's disease. For a patient experiencing migraines together with sensorineural hearing loss, an accurate diagnosis requires careful evaluation. The coexistence of migraines should be carefully ruled out, even if Meniere's disease with hearing loss is strongly suspected.

Conclusion: The Japanese version of the Tinnitus Handicap Inventory-12 (THI-12), Tinnitus Rating Scale (TRS), TRS 1-week version (TRSw), Tinnitus Severity Scale (TSS), and TSS 1-week version (TSSw), which were developed in this study, showed high reliability and validity, suggesting their usefulness in clinical practice. Based on the THI severity grades, we propose that the severity grades of THI-12 (draft) are categorized into four groups: 0-4 points, 5-9 points, 10-14 points, and 15-24 points. Objectives: We developed Japanese versions of new questionnaires for evaluating the level of psychological distress and difficulty in activities of daily living due to tinnitus, and performed their psychometric validation to determine the reliability and validity. The THI-12 is an assessment consisting of 12 items, each of which is rated on a 3-point scale that was created by reducing the number of questions from the 25 items of the THI. The TRS, TRSw, TSS, and TSSw, which were self-evaluation questionnaires of tinnitus on an 11-grade integer Likert scale from 0 to10 points, were used as additional instruments to assess tinnitus severity and distress. Methods: The subjects were healthy adults, and patients with subjective tinnitus who were examined at the Otolaryngology Department of Keio University Hospital, Osaka City University Hospital, or Nagoya City University Hospital with a chief complaint of tinnitus between September 2010 and January 2011. In all, 38 healthy adult subjects and 113 patients with subjective tinnitus were included. We examined the reproducibility and the internal consistency for reliability. We also examined the relationship with the available scales (THI and Hospital Anxiety and Depression Scale, HADS) and group divergence for validity. Results: The psychometric validation showed high reliability and validity of the THI-12, TRS, TRSw, TSS, and TSSw.

Objective: To verify whether the severity of globus sensation would be affected by the results of investigations on possible underlying serious pathology in the head, neck and esophagus. Methods: Thirty-six patients with globus sensation were enrolled in this study. All the patients suffered relatively persistent globus sensation which remained after conventional laryngoscopy at their family doctors. These patients were investigated for possible underlying oropharyngeal and esophageal lesions using fiberoptic endoscopy. The severity of globus was evaluated by the visual analog scales (VAS), and the degree of anxiety was evaluated by the state section of State Trait Anxiety Inventory (STAI-s). The questionnaires were administered at their first visits, and 9.6. ±. 3.2 months after endoscopy. The follow-up data obtained from 22 patients were incorporated in the further evaluations. Multiple regression analysis was used to evaluate the relationship between the improvement of VAS scores and that of STAI-s scores. Afterwards, Pearson product-moment correlation coefficient was measured. The recorded images of fiberoptic endoscopy were retrospectively verified by an expert of upper gastrointestinal endoscopy. Results: No malignancies were observed in the endoscopic examination. Despite no treatment administered during the follow-up period, significant improvement of VAS scores was observed from the initial scores (40. ±. 21) to follow-up scores (27. ±. 27, p= 0.014) in the patients examined in this study. The multiple linear regression analysis proved that the improvement of STAI-s scores was the only factor significantly affected the improvement of VAS scores (p= 0.029) among the dependent valuables. The retrospective evaluation of the recorded images revealed comorbid esophagitis in 10 out of the 22 patients. When patients were stratified with the presence of comorbid esophagitis, significant improvement of VAS scores was observed only in the group without comorbid esophagitis at their follow up (17. ±. 20, p= 0.026) compared with their initial scores (36. ±. 17). The multiple linear regression analysis proved that the improvement of VAS scores was significantly affected by the improvement of STAI-s scores (p= 0.047) in this group. Moreover, significant positive relationship between the improvement of VAS scores and that of STAI-s scores was observed only in the group without comorbid esophagitis (r= 0.61, p= 0.047). Conclusion: Proper investigation to prove no underlying serious pathology may lead to the improvement of globus sensation in the patients without comorbid esophagitis through the reduction of their anxiety even when their symptoms are relatively persistent. Our results also indicated that some treatments against esophagitis may be helpful for the improvement of globus sensation in the patients with this comorbid disease.

Conclusions: Patients with migraine-associated vertigo (MAV) may have a higher incidence of photic-driven electroencephalography (EEG) response. The occurrence of photic-driven responses for stimulation at frequencies of 10, 12, and 15 Hz can be considered a positive indicator for MAV. Although photic driving is not specific to migraine, patients with MAV have a higher incidence of photic driving. The distinction between Ménière's disease and MAV by means of EEG would be another interesting topic of research. Objective: The objective of this study was to distinguish between patients with MAV and patients with other vestibulopathies (VPs) using EEG. Methods: EEG with intermittent photic stimulation (PS) at frequencies between 3 and 24 Hz was recorded to quantify photic driving in patients with MAV (n = 21) and VPs (n = 15). The presence or absence of photic driving was determined; a score of 1 was counted for response to a particular frequency. Results: Total scores were calculated for each patient for statistical comparison. There was a significant difference in the average total score between MAV and VP patients (p < 0.05), and photic-driven responses were observed for 10, 12, and 15 Hz stimulation.

Genetic mutation is one of the causative factors for idiopathic progressive hearing loss. A patient with late-onset, moderate, and high-frequency hearing loss was found to have a novel, heterozygous KCNQ4 mutation, c.806_808delCCT, which led to a p.Ser260del located between S5 and the pore helix (PH). Molecular modeling analysis suggested that the p.Ser269del mutation could cause structural distortion and change in the electrostatic surface potential of the KCNQ4 channel protein, which may impede K+ transport. The present study supports the idea that a non-truncating mutation around the N-terminus of PH may be related to moderate hearing loss.

The aim of this study was to assess how tinnitus retraining therapy (TRT) employing monaural noise generators (NGs) affects tinnitus patients. Ninety-five patients with chronic tinnitus were included in this study. All received directive counseling and monaural NGs without any other combination treatment. Effects were evaluated with the Tinnitus Handicap Inventory (THI) 6, 12, and 24 months after the start of treatment. Multiple regression analysis was used to evaluate factors associated with improvement of THI scores. We observed a significant improvement in the average THI scores, which ranged from 59 at baseline to 36 after 6 months and were stable up to 24 months. Severely distressed (SD) patients experienced more benefits from the therapy than moderately distressed (MD) patients. Multiple regression analysis revealed that the presence of transient anxiety symptoms, measured by the state section of the State Trait Anxiety Inventory at the beginning of treatment, were associated the most to a decline in THI scores in SD patients. Pure-tone average at three mid frequencies was a negatively contributing factor. Analysis of MD patients did not provide a good model. In conclusion, TRT employing monaural NGs was an effective intervention especially for SD patients, although plateau of the effects after 6 months may be indicative of limitation of applying NGs monoaurally. Reducing the patients' hearing handicap may reinforce the effects of TRT in SD patients. Additional evaluation and interventions for both SD and MD patients might be needed.

OBJECTIVE: This study evaluated quality of life (QOL) in the patients with idiopathic sudden sensorineural hearing loss (ISSHL). STUDY DESIGN: Cross-sectional study. SETTING: Multicenter clinical investigation in ten university hospitals. PATIENTS: In total, 167 patients with ISSHL and 134 patients with bilateral sensorineural hearing loss (BSHL; control) were included. MAIN OUTCOME MEASURES: The Short Form Health Survey Version 2 was used to assess the health-related QOL. RESULTS: The average scores of 8 domains and 2 summary components were similar between the 2 groups. All scores except those for bodily pain (BP) in ISSHL patients and BP and vitality in BSHL patients were significantly lower than the Japanese average. Scores for the mental component summary (MCS) were especially low in ISSHL patients. MCS scores of ISSHL patients aged 40 to 49, 50 to 59, 60 to 69, and 70 years or older were significantly lower than the Japanese average for each age group. MCS scores of BSHL patients 70 years or older were significantly lower than the Japanese average. Two-way analysis of variance revealed no significant association of disease (ISSHL and BSHL) and age with MCS score. Interactions were also not significant. The effects of sex, age, hearing level, and time interval from the onset on MCS scores of ISSHL patients were evaluated using multiple regression analysis. Age and time interval from the onset were observed to be significant confounders. CONCLUSION: The QOL of patients with ISSHL deteriorated especially in terms of mental functioning. Similar deterioration was observed in BSHL patients.

Objective: No conventional pharmacotherapy is available for the treatment of psychogenic dizziness in pediatric patients. Adults with psychogenic dizziness are treated with psychiatric medicines as the standard treatment. In children, this treatment is not widely accepted because of the potential for adverse reactions. Instead, Kampo, an alternative medicine, is probably the best choice of treatment. Design: We report herein three of four cases of pediatric psychogenic dizziness successfully treated with Yoku-kan-san-ka-chimpi-hange (YKCH), a traditional Japanese Kampo medicine known to ameliorate psychiatric symptoms. Subjects: YKCH was prescribed to four patients (two boys and two girls) with psychiatric dizziness whose ages ranged from 11 to 15 years. Four weeks after the initiation of treatment, clinical improvement was assessed by the Clinical Global impression-Improvement scale. Results: In three of the four patients, the drug showed some significant effects. The remaining patient could not continue the medication. It is reasonable to assume that YKCH was effective because of its serotonergic mechanism and the improvement of sleep in our patients. Conclusions: This report is the first to describe the beneficial effects of YKCH in the treatment of pediatric psychogenic dizziness. We conclude that administration of YKCH may be a suitable complementary therapy for pediatric psychogenic dizziness.

Background and Aims: Allergic rhinitis annually reaches epidemic proportions in Japan, and represents a major problem. The application of the CO2 laser in the treatment of allergic rhinitis was first successfully reported in 1982, but CO2 laser ablation is associated with side effects. The Ohshiro Clinic started using the conventional Nd: YAG laser for the treatment of allergic rhinitis in 1993, and from 2005 we started using a diode laser-pumped Nd: YAG laser with efficacy and safety at least equal to the others. Even more recently, we have adopted a novel 808 nm diode laser, and the present retrospective study examined the difference in of the efficacy rate between the preseasonal and intra-seasonal treatment of allergic rhinitis with this system. Subjects and methods: One thousand, two hundred and ten patients primarily presented to the Ohshiro Clinic with allergic rhinitis during the period from December 2010 to April 2011, of whom 531 were selected for blood tests to identify 13 kinds of Japanese allergens including cedar pollen. In the 2010-2011 season, huge clouds of cedar pollen appeared from February 26 th. The subjects were therefore divided into two groups depending on the treatment period, namely the preseasonal and intra-seasonal groups, December 1 st, 2010 to February 25 th, 2011 and February 26 th to April 6 th 2011, respectively. All patients were treated with the new 808 nm diode laser system. Results: A high success rate was achieved in both groups, with no significant difference seen regarding the symptoms of rhinorrhea, obstruction, sneezing, quality of life (QOL) or severity. Conclusions: The 808 nm diode laser offers an excellent solution for the uncomfortable symptoms of allergic rhinitis, and could be equally well applied before or during the Japanese cedar pollen dispersed season.