Natural history of hearing and tumor growth in vestibular schwannoma in neurofibromatosis type 2-related schwannomatosis.

OBJECTIVES: To determine the natural history of hearing loss and tumor volume in patients with untreated neurofibromatosis type 2 (NF2)-related schwannomatosis. Moreover, we statistically examined the factors affecting hearing prognosis. METHODS: This retrospective cohort study was conducted on 37 ears of 24 patients with NF2-related vestibular schwannomatosis followed up without treatment for more than 1 year. We obtained detailed chronological changes in the PTA and tumor volume in each case over time, and the rate of change per year was obtained. Multivariate analysis was also conducted to investigate factors associated with changes in hearing. RESULTS: The average follow-up period was approximately 9 years, and hearing deteriorated at an average rate of approximately 4 dB/year. The rate of maintaining effective hearing decreased from 30 ears (81%) at the first visit to 19 ears (51%) at the final follow-up. The average rate of change in tumor growth for volume was approximately 686.0 mm3/year. This study revealed that most patients with NF2 experienced deterioration in hearing acuity and tumor growth during the natural course. A correlation was observed between an increase in tumor volume and hearing loss (r = 0.686; p < 0.001). CONCLUSIONS: Although the hearing preservation rate in NF2 cases is poor with the current treatment methods, many cases exist in which hearing acuity deteriorates, even during the natural course. Patients with an increased tumor volume during the follow-up period were more likely to experience hearing deterioration. Trial registration number 20140242 (date of registration: 27 October 2014).

[A case of intestinal myiasis in a bedridden elderly patient].

A 75-year-old man with type 2 diabetes and a history of previous empyema surgery was admitted to our hospital due to difficulty moving caused by chronic obstructive pulmonary disease and dehydration. During the first two days of hospitalization, intestinal myiasis was diagnosed after maggots were found in his diapers. After the maggots disappeared, he developed a fever, prompting antibiotic therapy for a suspected secondary infection, resulting in clinical improvement. Despite thorough home cleaning, no flies or maggots were found, and the source of infection and the fly species remained unknown. Recent reports suggest a higher prevalence of myiasis among the elderly, even with overall improvement in hygiene. While myiasis is typically mild, it is a condition that requires consideration in an aging society. Myiasis is a disease that should be considered in the differential diagnosis of the elderly, especially in people who are bedridden or frail.

Isolated Bone Recurrence of Medulloblastoma With MYCN Amplification and TP53 Loss: A Case Report.

Extraneural recurrence of a medulloblastoma is rare with dismal prognosis. A 9-year-old girl with medulloblastoma was treated with gross total resection followed by a combination of chemotherapy and radiotherapy. Fourteen months after treatment completion, she developed multifocal bone metastases. Despite chemotherapy combined with irradiation, she died 18 months after recurrence due to progressive disease. Fluorescence in situ hybridization on formalin-fixed paraffin-embedded tissue sections revealed MYCN amplification and TP53 loss, consistent with the genetic alterations of a rapidly progressive subgroup of recurrent medulloblastomas. In clinical practice, dismal biologic features can be determined using fluorescence in situ hybridization in defective materials.

Cut-off score of the Khalfa Hyperacusis Questionnaire with 10 selected items.

OBJECTIVE: In the management of hyperacusis, the hyperacusis questionnaire (HQ) is a frequently used measure. It is comprised of 14 items, with a total score of 42 points. We have developed the Japanese version of the HQ, but the validity of the factors has not been considered. This study was performed to re-evaluate the HQ to confirm its validity and reliability. DESIGN: Exploratory factor analysis was performed and we removed the problematic items with low factor loadings and re-evaluated the reliability and validity. STUDY SAMPLE: Patients with hyperacusis (n = 109) were included. Hyperacusis was confirmed based on the patients' complaint of "intolerance to sound". Patients without hyperacusis but with tinnitus and/or hearing loss (n = 103) were also included. RESULTS: Items 1, 5, 6, and 11 had low factor loadings; therefore, we removed these four items. The HQ with 10 items had high internal consistency reliability (Cronbach's α = 0.926). The mean total scores for the patients with and without hyperacusis were 16.3 and 4.0, respectively; the inter-group difference was statistically significant. We found the best score that maximised sensitivity and specificity was 8. CONCLUSIONS: The HQ with 10 items, up to 30 points and a cut-off score of 8 is appropriate for classifying hyperacusis.

Deficiency of large tumor suppressor kinase 1 causes congenital hearing loss associated with cochlear abnormalities in mice.

Mammalian auditory hair cells are not spontaneously replaced. Their number and coordinated polarization are fairly well-maintained and both these factors might be essential for the cochlear amplifier. Cell cycle regulation has critical roles in regulating appropriate cell size and cell number. However, little is known about the physiological roles of the Hippo pathway, which is one of the most important signaling cascades that regulates cell growth, differentiation, and regenerative capacity in the cochlear sensory epithelium. Herein, we investigated the in vivo role of the large tumor suppressor 1 (LATS1), an essential kinase in the Hippo/yes-associated protein pathway, in the cochlea using the LATS1 knockout mice. LATS1 was expressed in hair cells and supporting cells. It was strongly expressed on the surface of the cuticular plate of the organ of Corti. We found that LATS1 knockout caused congenital hearing loss due to the irregular orientation and slightly reduced number of hair cells, whereas the number of supporting cells remained unchanged. On the surface of the hair cells, the kinocilium and stereocilia were dispersed during and after morphogenesis. However, the expression of the receptor-independent polarity regulators, such as Par3 or Gαi, was not affected. We concluded that LATS1 has an indispensable role in the maturation of mammalian auditory hair cells, but not in the development of the supporting cells, and thus, has a role in the hearing acquisition.

Three cases of otitis media caused by Mycobacterium abscessus subsp. abscessus: Importance of medical treatment and efficacy of surgery.

This study aimed to assess the clinical presentation, antibiotic therapy, surgery, and outcomes in patients with otitis media caused by Mycobacterium abscessus subsp. abscessus and discuss the efficacy of surgery. This is a retrospective case review of three patients diagnosed with otomastoiditis caused by M. abscessus subsp. abscessus. All patients had refractory otorrhea. One patient had granulation tissue in the tympanic membrane. They received medical treatment and underwent surgery. Otorrhea was resolved several months after the initiation of long-term multiantibiotic therapy in all cases. The timing of surgery varied among patients. Before initiating antibiotic therapy, mastoidectomy was performed to achieve definitive diagnosis in two patients, and wound dehiscence developed in these patients. Two patients underwent debridement after the initiation of multiantibiotic therapy. After antibiotic administration, tympanoplasty was performed to improve hearing in one patient. All patients achieved culture negativity after treatment, and no recurrences have been noted. From three cases, it is suggested that the mainstay of treatment for M. abscessus subsp. abscessus is long-term multiantibiotic therapy, and surgery itself may have little effect on achieving ear dryness. Thus, in most patients, drug therapy should be prioritized. Considering postoperative complications, surgery before achieving ear dryness should be avoided, except in emergency cases. In addition, if the diagnosis is not confirmed by repeated bacteriological tests, mastoidectomy should be performed to collect specimens. Tympanoplasty for hearing loss or eardrum perforation is recommended after discontinuation of medications.

Who are good adult candidates for cartilage conduction hearing aids?

PURPOSE: Cartilage conduction hearing aids (CC-HAs) are novel hearing aids using the third hearing pathway of cartilage conduction. We assessed the efficacy of CC-HAs in adult hearing-loss patients who had various anatomical conditions of their ear canal(s) and determined who are good candidates for CC-HAs. METHODS: Patients (n = 37) were categorised into three groups of participants based on ear canal anatomy: (1) canal stenosis; (2) abnormal canal; (3) normal canal. After a 1-month free trial of normal usage, CC-HA-aided and unaided hearing thresholds (43 fitted ears) were determined using standard audiograms, after which participants could choose to purchase the device or not. Group and subgroup purchase rates were calculated along with the purchase reason (or not). Subgroup binary analysis of purchase rates was done according to hearing loss severity (< 70 dB and ≥ 70 dB) of unaided average air conduction (AC) hearing thresholds. RESULTS: CC-HA provided hearing improvements in all frequencies within each group. Overall, 60.47% of participants purchased a CC-HA after the trial. Over 70% participants with canal stenosis purchased CC-HAs, regardless of their AC hearing thresholds (severe vs. mild), and significantly more mild-loss participants in the abnormal canal group purchased their trial CC-HA compared to severe-loss participants (85.71% vs. 20%). CONCLUSION: Adult patients with ear canal stenosis or closure are the best candidates for CC-HAs, regardless of their hearing thresholds. Patients with more severe hearing loss accompanied by ear canal anomalies and patients with normal canal anatomy may not be good candidates.

Management of tinnitus in patients with vestibular schwannoma who underwent surgical resection.

PURPOSE: To evaluate tinnitus and its management in patients with vestibular schwannoma (VS) who underwent surgery, we investigate the effect of surgical approach or residual hearing on tinnitus severity and the effects of intervention for tinnitus including educational counseling, sound therapy using hearing aids (HAs), and medication (selective serotonin reuptake inhibitors, and SSRIs). METHODS: Seventy-one subjects of VS patients who underwent surgery were included. Their tinnitus severity was evaluated using the Japanese version of the Tinnitus Handicap Inventory (THI). The relationships between postoperative THI scores and surgery types or residual hearing levels were examined. We also examined longitudinal changes in THI scores and the efficacy of the intervention. RESULTS: Surgery approach, hearing preservation or hearing loss surgery, and residual hearing levels were not significantly related to the postoperative tinnitus severity. In 71 cases, 45 cases did not require any management for tinnitus. On the contrary, 26 patients had at least one episode of tinnitus distress (THI score was greater than or equal to 18). Educational counseling alone was found to be effective in 17 cases out of the 26 cases, and the remaining 9 cases required more intervention than educational counseling alone. We selected sound therapy with HA for 7 cases and administration of SSRI for 2 cases, which was found to be highly effective in 8 cases. CONCLUSION: Based on the present study, we consider that appropriate management may be possible for tinnitus in the majority of VS patients who underwent surgery.

Early hearing improvement predicts the prognosis of idiopathic sudden sensorineural hearing loss.

PURPOSE: To determine pre- and post-treatment factors that are useful for predicting the prognosis of hearing improvement in idiopathic sudden sensorineural hearing loss (ISSHL). METHODS: This retrospective study included 332 patients with ISSHL. Patients received intravenous steroid treatment (prednisolone sodium succinate; 120 mg/day followed by dose tapering). Complete recovery of hearing levels was defined as a final pure-tone audiometry of ≤ 20 dB HL or the same level as the contralateral ear. Patients' age; sex; side of hearing loss; initial hearing level; days from onset to treatment; presence of vertigo, diabetes, and hypertension; and hearing improvement on days 3-4 and 6-7 after treatment initiation were analyzed as potential prognostic factors. RESULTS: Overall, 109 patients (32%) had complete recovery. Results of the multivariate logistic regression model identified age (odds ratio [OR] = 0.974), initial hearing level (OR = 0.949), vertigo (OR = 0.409), and hearing improvement on days 6-7 after treatment initiation (OR = 1.11) as significant independent predictors of complete recovery. Age ≥ 60 years, initial hearing level ≥ 72.5 dB HL, and vertigo contributed to poor prognosis. Patients without these three factors and a hearing improvement of ≥ 10 dB HL on days 6-7 post-treatment had a complete recovery rate of 80%. Only 1.5% of the patients with 2-3 of these factors and a hearing improvement of < 10 dB HL on days 6-7 after treatment initiation achieved complete recovery. CONCLUSION: Age, initial hearing level, vertigo, and hearing improvement on days 6-7 after treatment initiation were independent predictors of hearing recovery in ISSHL.

Endoscopic Endonasal Transinfraturbinate Approach With Nasoseptal Window for Removal of the Pterygopalatine Fossa Tumor.

ABSTRACT: Recent advances in endoscopic intranasal technology have allowed for a safe approach to the pterygopalatine fossa lesion. However, we consider that there is still scope of improvement to approach a broader area with better operability and minimal invasiveness. A 51-year-old man underwent endoscopic endonasal surgery due to the recurrence of chordoma at the left pterygopalatine fossa. To access the lower and lateral part of the pterygopalatine fossa, we performed endoscopic endonasal transmaxillary removal via an inferior turbinate incision. During surgery, a wide operative field and good operability could be secured by inserting an endoscope from the right nostril through a window of the nasal septum. Subtotal removal of the tumor was achieved without any complication during the surgery. Endoscopic endonasal transinfraturbinate approach with nasoseptal window was effective in the removal of the pterygopalatine fossa tumor because it is less invasive and provides a good surgical view with better operability.

Endoscopic Endonasal Management of Pterygopalatine Fossa Tumors.

ABSTRACT: Surgical removal of pterygopalatine fossa (PPF) tumors with endoscopic endonasal approach is still challenging. The present study aimed to evaluate our endoscopic endonasal management of PPF tumors based on the tumor pathology and purpose of the surgery. This comprised both a single nostril approach for biopsy and a binostril approach for complete resection of benign and noninfiltrating tumors. Based on this strategy, 12 patients underwent endoscopic endonasal surgery for PPF tumors between 2013 and 2018. The patients' data were analyzed retrospectively to demonstrate the significance of our treatment scheme. The surgery was terminated only after taking a biopsy specimen in 6 patients. Other 6 patients underwent gross total resection or bulk tumor reduction. Final pathological diagnosis was malignant in 6 cases and benign in the remaining 6. Post-operative treatment was needed in 7 patients. Four operations for the 6 patients who underwent either debulking or radical surgery were performed by the binostril approach; while 5 surgeries for the 6 biopsy patients were performed by the single nostril approach. Postoperative complications were tolerable. Endoscopic resection should be adopted preferentially for benign tumors that can be removed in a piecemeal fashion. However, as most malignant tumors were impossible to resect with a negative margin, priority should be given to tumor biopsy using an endoscopic approach, which is less invasive than an open approach, and an appropriate treatment customized to the pathological diagnosis should be administered.

Pros and Cons of the Exoscope for Otologic Surgery.

Introduction. There are a few discussions regarding usefulness of an exoscope in otologic surgery compared to a traditional microscope. Objective. The pros and cons of using a newly developed exoscope (ORBEYE™) during microotologic surgery were evaluated. Methods. The usefulness of the ORBEYE™ exoscope was retrospectively assessed in 6 otologic surgeries by 8 surgeons postoperatively. A questionnaire comprising 20 questions was designed and used for evaluation. Results. All the otologic surgeons agreed that the exoscope is useful as an educational tool; the exoscope had the highest score in the questionnaire (average: 4.75). The question "Will the ORBEYETM exoscope replace the conventional tympanoplasty or stapes surgery?" had the lowest score (average: 3.13). Conclusions. The quality of the images and movies in the exoscope was considered to be high and improved; therefore, the exoscope was considered as a useful educational tool in otologic surgery. Similar to otologic endoscopic surgery, all the members such as the operator and assistants could head up and share 1 image.

Personality and Sleep Evaluation of Patients with Tinnitus in Japan.

In Japan, there have been no examinations of tinnitus with respect to personality traits, and only a few studies have investigated sleep disorders in tinnitus. Understanding the association between these can aid in selecting and developing effective treatment options for patients with tinnitus. This study aimed to clarify the relationship between tinnitus severity, personality, and sleep disorders, in patients with chronic tinnitus in Japan. We retrospectively evaluated the personality factors of 56 patients presenting with tinnitus using the NEO Five-Factor Inventory (NEO-FFI), which examines five personality characteristics, including Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness. We evaluated tinnitus severity, sleep disorders, depression, and anxiety using the Tinnitus Handicap Inventory, Pittsburgh Sleep Quality Index (PSQI), Self-Rating Depression Scale, and State-Trait Anxiety Inventory, respectively. Neuroticism and tinnitus severity were positively correlated (r = 0.548, p < 0.001). Sleep disorders were observed in 73.2% of patients; however, there was no correlation between the PSQI score and tinnitus severity or between PSQI score and scores of the five NEO-FFI items. Sleep disorders are frequently experienced by patients with chronic tinnitus, regardless of tinnitus severity or personality. Understanding the relationship between personality and tinnitus severity could lead to better management of tinnitus.

Systematic quantification of the anion transport function of pendrin (SLC26A4) and its disease-associated variants.

Thanks to the advent of rapid DNA sequencing technology and its prevalence, many disease-associated genetic variants are rapidly identified in many genes from patient samples. However, the subsequent effort to experimentally validate and define their pathological roles is extremely slow. Consequently, the pathogenicity of most disease-associated genetic variants is solely speculated in silico, which is no longer deemed compelling. We developed an experimental approach to efficiently quantify the pathogenic effects of disease-associated genetic variants with a focus on SLC26A4, which is essential for normal inner ear function. Alterations of this gene are associated with both syndromic and nonsyndromic hereditary hearing loss with various degrees of severity. We established HEK293T-based stable cell lines that express pendrin missense variants in a doxycycline-dependent manner, and systematically determined their anion transport activities with high accuracy in a 96-well plate format using a high throughput plate reader. Our doxycycline dosage-dependent transport assay objectively distinguishes missense variants that indeed impair the function of pendrin from those that do not (functional variants). We also found that some of these putative missense variants disrupt normal messenger RNA splicing. Our comprehensive experimental approach helps determine the pathogenicity of each pendrin variant, which should guide future efforts to benefit patients.

Application of Mesenchymal Stem Cell Therapy and Inner Ear Regeneration for Hearing Loss: A Review.

Inner and middle ear disorders are the leading cause of hearing loss, and are said to be among the greatest risk factors of dementia. The use of regenerative medicine for the treatment of inner ear disorders may offer a potential alternative to cochlear implants for hearing recovery. In this paper, we reviewed recent research and clinical applications in middle and inner ear regeneration and cell therapy. Recently, the mechanism of inner ear regeneration has gradually been elucidated. "Inner ear stem cells," which may be considered the precursors of various cells in the inner ear, have been discovered in the cochlea and vestibule. Research indicates that cells such as hair cells, neurons, and spiral ligaments may form promising targets for inner ear regenerative therapies by the transplantation of stem cells, including mesenchymal stem cells. In addition, it is necessary to develop tests for the clinical monitoring of cell transplantation. Real-time imaging techniques and hearing rehabilitation techniques are also being investigated, and cell therapy has found clinical application in cochlear implant techniques.

Descending musculospinal branch of the ascending pharyngeal artery as a feeder of carotid body tumors: Angio-architecture and embryological consideration.

INTRODUCTION: Although the ascending pharyngeal artery (APhA) is known as a main feeder of carotid body tumors (CBTs), its detailed architecture and embryological consideration have not been described. The objective of this study was to describe the architecture of a descending feeder of the APhA and to consider its origin embryologically through a review of our CBT embolizations. METHODS: We retrospectively analyzed data from patients with CBTs who underwent transarterial embolization or angiographic examination-only between July 2010 and February 2017. The arterial supply of the tumors, the number of feeder pedicles, the mean tumor size, embolization materials, complication of embolization, and extent of tumor removal were assessed. The embryological origin of feeding artery was considered based on the literature. RESULTS: Eighteen patients with 20 CBTs underwent preoperative embolization or angiographic examination. The number of feeder pedicles was significantly related to the size of the CBT (P = 0.0002). The main feeding artery was the descending branch of APhA, which was hypertrophied and tortuous (18/20, 90%). Embryologically, this artery originated from the musculospinal branch and is termed the "descending musculospinal branch". CONCLUSION: The main feeder of the CBTs was the "descending musculospinal branch" of the APhA and needs special consideration such as dangerous anastomosis for embolization.

Two-Point Method for Measuring the Temporal Modulation Transfer Function.

OBJECTIVE: The temporal modulation transfer function (TMTF) has been proposed to estimate the temporal resolution abilities of listeners with normal hearing and listeners with hearing loss. The TMTF data of patients would be useful for clinical diagnosis and for adjusting the hearing instruments at clinical and fitting sites. However, practical application is precluded by the long measurement time of the conventional method, which requires several measurement points. This article presents a new method to measure the TMTF that requires only two measurement points. DESIGN: Experiments were performed to estimate the TMTF of normal listeners and listeners with hearing loss to demonstrate that the two-point method can estimate the TMTF parameter and the conventional method. Sixteen normal hearing and 21 subjects with hearing loss participated, and the difference between the estimated TMTF parameters and measurement time were compared. RESULTS: The TMTF parameters (the peak sensitivity Lps and cutoff frequency fcutoff) estimated by the conventional and two-point methods showed significantly high correlations: the correlation coefficient for Lps was 0.91 (t(45) = 14.3; p < 10) and that for fcutoff was 0.89 (t(45) = 13.2; p < 10). There were no fixed and proportional biases. Therefore, the estimated values were in good agreement. Moreover, there was no systematic bias depending on the subject's profile. The measurement time of the two-point method was approximately 10 min, which is approximately one-third that of the conventional method. CONCLUSION: The two-point method enables the introduction of TMTF measurement in clinical diagnosis.

Validation of the Japanese version of the tinnitus functional index (TFI).

OBJECTIVE: The tinnitus functional index (TFI), a new self-report questionnaire, was developed for the measurement of tinnitus severity and treatment-related changes. The original English version has been translated into several languages. The aim of this study was to evaluate the reliability and validity of the Japanese version of the TFI. DESIGN: The English version of the TFI was translated into Japanese using a translation-back translation method. Participants completed a series of questionnaires including the TFI, Tinnitus Handicap Inventory (THI), Self-rating Depression Scale, State-Trait Anxiety Inventory, Visual Analogue Scale, and the questionnaire of subjective symptom improvement. We examined internal consistency, reproducibility, convergent and discriminant validity, and effect sizes. STUDY SAMPLE: One hundred and forty-three patients with subjective tinnitus were included. RESULTS: The Japanese version of the TFI had high internal consistency and reproducibility, and good convergent and discriminant validity. At six months after the start of treatment, the effect sizes for the TFI were somewhat larger than those for the THI. CONCLUSIONS: The Japanese version of the TFI is appropriate for measuring tinnitus severity and treatment-related changes. The reliability and validity of this version are comparable to those of the original English version of the TFI.

Mechanism of Action of the Anti-Influenza Virus Active Kampo (Traditional Japanese Herbal) Medicine, Hochuekkito.

When the Kampo medicine, Hochuekkito (Hochu), was administered to normal mice for 2 weeks, influenza virus titer was reduced. The mechanism of action of Hochu was examined using the plaque assay method. It was suggested that Hochu may either obstruct the first stage of the infection process (adsorption and entry) or may directly target viral particles. Using the plaque assay method, these 2 modes of action could not be differentiated. Virus RNA in the infected cell was verified by quantitative real-time polymerase chain reaction. An equal inhibition effect was obtained when Hochu was preprocessed for normal cells and when they were made to act simultaneously with virus adsorption. The viral load at the cell surface following UV irradiation was higher in the Hochu-administered group as compared with that of the control. Moreover, the affinity of Hochu for the influenza virus was hundred times higher than its affinity for the host cell. The effect of entry obstruction by Hochu was observed via image analysis, where the amount of virus nucleocapsid protein (NP) invading the cell was visualized with FITC-labeled NP antibody. Hochu does not seem to have an effect on nucleic acid synthesis, viral release from infected cells, and on the subsequent second round of infection. In conclusion, Hochu binds to viral particles and forms complexes that can obstruct the entry of influenza virus into cells.

Effects of tinnitus treatments on sleep disorders in patients with tinnitus.

OBJECTIVE: To assess the effects of tinnitus treatments on sleep disorders in patients with tinnitus. DESIGN: Subjects completed the Pittsburg Sleep Quality Index (PSQI), Tinnitus Handicap Inventory (THI), Self-rating Depression Scale (SDS), and State Trait Anxiety Inventory (STAI). The questionnaire results and the patients' sex, age, time since the onset of tinnitus, and mean hearing level were examined, and differences between a sleep disorder group and a normal sleep group were examined. Patients completed the questionnaires again after initiating tinnitus treatments (counselling and use of sound generators), and the change in questionnaire scores at follow-up was evaluated. STUDY SAMPLE: Patients (N = 100) with tinnitus who visited Keio University Hospital and started treatment without medication between 2005 and 2008. RESULTS: Sixty-six percent of the patients had sleep disorders. Compared with patients without sleep disorders, patients with sleep disorders had significantly higher SDS and STAI scores at the first visit. The mean PSQI scores showed significant improvement at follow-up. CONCLUSIONS: Sleep disorders in patients with tinnitus improved after tinnitus treatments. Complex interactions between depressive symptoms and anxiety may occur in these patients. The improvement in sleep disorders at follow-up was correlated with improvements in tinnitus severity and state anxiety.