[A case of autoimmune hepatitis with tuberculosis caused by prednisolone from undeterminable enzyme-linked immunospot assay].

An 88-year-old woman was referred to our hospital for autoimmune hepatitis in 2016. She was treated with prednisolone. In 2018, she was rehospitalized owing to hepatitis relapse. Steroid pulse therapy was performed. She exhibited good recovery of hepatitis, but was transferred to a convalescent ward in a general hospital because of decreased activity of daily life. After a month later, she had high fever and cough. She was diagnosed as having tuberculosis because of positive Mycobacterium tuberculosis polymerase chain reaction. At our first medical examination in 2016, we performed enzyme-linked immunospot and the result was undeterminable. There is an increase in the opportunities to use immunosuppressant and biologic agents for elderly patients. Our case report should contribute to future medical care for elderly patients who are at risk of latent tuberculosis infection.

A Melanocytic Lesion Extending From the Right Ear to the Nasopharynx in a Pediatric Patient: A Case Report.

BACKGROUND: Blue nevus is a benign dermal melanocyte tumor that mainly arises from the skin. We report an extremely rare case of blue nevus in a pediatric patient with extensive progression from the middle ear and inner ear to the nasopharynx through the Eustachian tube. CASE REPORT: A 2-year-old girl with blue tympanum was referred to our department. Computed tomography scans and magnetic resonance imaging were performed, followed by a tissue biopsy and histopathologic evaluations. Radiologic examinations revealed that the lesion had progressed beyond the middle ear into the inner ear and the nasopharynx through the Eustachian tube. Subsequent histopathologic examinations indicated dermal dendritic melanocytic proliferations, but no evidence of malignancy. Based on the clinical and histopathologic findings, we concluded that the lesion was consistent with blue nevus. DISCUSSION: Blue nevus is a relatively common skin lesion. However, no prior reports have described the extension of blue nevus from the auditory organ to the nasopharynx in a pediatric patient. Despite the benign nature of the lesion, the patient experienced profound hearing loss in the affected ear, which necessitates continued monitoring as the lesion may expand with patient growth.

Splenectomy as an effective treatment for macrothrombocytopenia in Takenouchi-Kosaki syndrome.

Takenouchi-Kosaki syndrome (TKS) is a rare congenital disease caused by a de novo heterozygous mutation in the CDC42 gene. Its characteristic clinical features are macrothrombocytopenia, developmental delay, dysmorphic facial features, and deafness. Splenectomy has been contraindicated for inherited thrombocytopenia, and there is little information on treatment of macrothrombocytopenia in TKS. In a previously reported case of autoimmune hemolytic anemia (AIHA) with TKS, we observed that AIHA initially resolved with prednisolone, but gradually became refractory to drug therapy. After splenectomy, both anemia and macrothrombocytopenia improved. This is a novel positive effect of splenectomy for thrombocytopenia in TKS, although further studies are required to assess the effectiveness and safety of splenectomy.

[Problem and assignment for distinguishing the Usher syndrome type].

Usher syndrome is an autosomal-recessive disorder that causes bilateral sensorineural hearing loss, retinitis pigmentosa (RP), and occasionally vestibular dysfunction. Usher syndrome types 1, 2, and 3 can be distinguished by differences in audiovestibular features. The objectives of this retrospective study were to evaluate 26 patients with Usher syndrome clinically. The 26 patients (male: 12 cases, female: 14 cases) with Usher syndrome, with a clinical diagnosis based on symptoms of bilateral sensorineural hearing loss and RP, had been registered from 13 hospitals as a multicenter study. We assessed the clinical history and performed audiovestibular and ophthalmologic examinations, and genetic testing. Eleven of the patients were classified as having Usher type 1 (38.5%), 6 with Usher type 2 (23.1%), and 9 with Usher type 3 (38.5%). However, many patients with atypical Usher type 1 (70%) and type 2 (83.3%) were found compared with Usher type 3 (10%). The conductive rate of vestibular examinations including the caloric test (50%) was low. There were many variations in the clinical symptoms in Usher syndrome patients, therefore the classification of Usher types 1, 2, and 3 has been complicated. We have proposed a flowchart for the diagnosis of Usher types 1, 2, and 3.

[Cartilage palisade tympanoplasty for adhesive otitis media].

PURPOSE: We evaluated the clinical utility of cartilage palisade tympanoplasty (CRPT) in adhesive otitis media, a condition known to recur frequently with poor success in hearing gain. OBJECTIVE: Specimens were 9 ears having adhesive otitis media and undergoing CPT in January 2006 and December 2007. Cases of pars tensa cholesteatoma were excluded. Mean subject age was 35.2 years. Seven had total drum adhesion and 2 posterior half-adhesion. Preoperative pure-tone hearing averaged 20-102 dB (mean: 56 dB). METHODS: A small piece of cartilage harvested from the cymba was obliquely sectioned to yield wide, thin cartilage strips. Strips were overlapped slightly anteriorly to posteriorly parallel to the malleus handle when present. Tympanoplasty type 1 was conducted in 2 cases, type 3c in 6, and type 4c in 1. RESULTS: No ears undergoing CPT produced recurrent adhesion or perforation although 2 suffered transient partial erosion healed easily in topical management. An air-bone gap of <15 dB was achieved in 3 ears, a hearing gain exceeding 15 dB in 5, and a hearing level of less than 30 dB in 3. Conditions falling in at least 1 of the above categories are considered successful based on Japan Otological Society criteria. Seven of the 9 (78%) were regarded as audiologically successful. CONCLUSION: CPT conducted for adhesive otitis media appears worthwhile, given the present better-than-expected results in our cases, although further study is needed to confirm this conclusion.

[Community-based hearing screening project in Tochigi prefecture and results thorough audiometric test].

Community-based hearing screening projects have the objectives of screening hearing to identify early and intervene in cases of hearing-impaired infants and to consider how to implement mass screening, education, and support suitable. This project started in Tochigi prefecture in 2002. Of 6198 infants undergoing automatic auditory brainstem response (ABR), those rescreened accounted for 1.1% and those referred for diagnostic testing for 0.7%. After initial thorough audiometric testing, 20 infants were suggested to have bilateral hearing loss, although this was finally reduced to 17. Inconsistency between automatic and conventional ABR was found in 10 cases. Automatic ABR showed 7 false-positive and 3 false-negative cases, all of which finally proved to be within normal range hearing. Newborn-hearing screening enabled infants with hearing loss to be identified early. Japan has yet, however, to implement needed medical treatment and appropriate educational and support systems for hearing-impaired infants.

The Prevalence and Clinical Characteristics of TECTA-Associated Autosomal Dominant Hearing Loss.

TECTA is well known as a causative gene for autosomal dominant mid-frequency hearing loss observed in various populations. In this study, we performed next-generation sequencing analysis of a large Japanese hearing loss cohort, including eight hundred and twelve (812) subjects from unrelated autosomal dominant hearing loss families, to estimate the prevalence and phenotype-genotype correlations in patients with TECTA mutations. The prevalence of TECTA mutations in Japanese autosomal dominant sensorineural hearing loss families was found to be 3.2%. With regard to the type of hearing loss, the patients with mutations in the nidogen-like domain or ZA domain of TECTA showed varied audiograms. However, most of the patients with mutations in the ZP domain showed mid-frequency hearing loss. The rate of hearing deterioration in TECTA-associated hearing loss patients and in the normal hearing Japanese control population were the same and regression lines for each group were parallel. We carried out haplotype analysis for four families which had one recurring missense variant, c.5597C>T (p.Thr1866Met). Our results revealed four different haplotypes, suggesting that this mutation occurred independently in each family. In conclusion, TECTA variants represent the second largest cause of autosomal dominant sensorineural hearing loss in Japan. The hearing loss progression observed in the patients with TECTA mutations might reflect presbycusis. The c.5597C>T mutation occurred in a mutational hot spot and is observed in many ethnic populations.

Comprehensive analysis of syndromic hearing loss patients in Japan.

More than 400 syndromes associated with hearing loss and other symptoms have been described, corresponding to 30% of cases of hereditary hearing loss. In this study we aimed to clarify the mutation spectrum of syndromic hearing loss patients in Japan by using next-generation sequencing analysis with a multiple syndromic targeted resequencing panel (36 target genes). We analyzed single nucleotide variants, small insertions, deletions and copy number variations in the target genes. We enrolled 140 patients with any of 14 syndromes (BOR syndrome, Waardenburg syndrome, osteogenesis imperfecta, spondyloepiphyseal dysplasia congenita, Stickler syndrome, CHARGE syndrome, Jervell and Lange-Nielsen syndrome, Pendred syndrome, Klippel-Feil syndrome, Alport syndrome, Norrie disease, Treacher-Collins syndrome, Perrault syndrome and auditory neuropathy with optic atrophy) and identified the causative variants in 56% of the patients. This analysis could identify the causative variants in syndromic hearing loss patients in a short time with a high diagnostic rate. In addition, it was useful for the analysis of the cases who only partially fulfilled the diagnostic criteria.

Anxiety and otovestibular disorders: linking behavioral phenotypes in men and mice.

Human anxiety and vestibular disorders have long been known to co-occur. Paralleling human clinical and non-clinical data, mounting genetic, pharmacological and behavioral evidence confirms that animal anxiety interplays and co-exists with vestibular/balance deficits. However, relatively few animal models have addressed the nature of this relationship. This paper examines side-by-side human psychiatric and otovestibular phenotypes with animal experimentation data, and outlines future directions of translational research in this field. Discussed here are recently developed specific animal models targeting this interplay, other traditional animal tests sensitive to altered anxiety and vestibular domains, and the existing problems with translation of animal data into human phenotypes. The role of hearing deficits and their contribution to anxiety and vestibular phenotypes are also outlined. Overall, the overlap between anxiety and balance disorders emerges as an important phenomenon in both animal and clinical studies, and may contribute markedly to the complexity of behavioral and physiological phenotypes. Animal experimental models that focus on the interplay between anxiety and vestibular disorders are needed to improve our understanding of this important biomedical problem.

WFS1 mutation screening in a large series of Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis.

A heterozygous mutation in the Wolfram syndrome type 1 gene (WFS1) causes autosomal dominant nonsyndromic hereditary hearing loss, DFNA6/14/38, or Wolfram-like syndrome. To date, more than 40 different mutations have been reported to be responsible for DFNA6/14/38. In the present study, WFS1 variants were screened in a large series of Japanese hearing loss (HL) patients to clarify the prevalence and clinical characteristics of DFNA6/14/38 and Wolfram-like syndrome. Massively parallel DNA sequencing of 68 target genes was performed in 2,549 unrelated Japanese HL patients to identify genomic variations responsible for HL. The detailed clinical features in patients with WFS1 variants were collected from medical charts and analyzed. We successfully identified 13 WFS1 variants in 19 probands: eight of the 13 variants were previously reported mutations, including three mutations (p.A684V, p.K836N, and p.E864K) known to cause Wolfram-like syndrome, and five were novel mutations. Variants were detected in 15 probands (2.5%) in 602 families with presumably autosomal dominant or mitochondrial HL, and in four probands (0.7%) in 559 sporadic cases; however, no variants were detected in the other 1,388 probands with autosomal recessive or unknown family history. Among the 30 individuals possessing variants, marked variations were observed in the onset of HL as well as in the presence of progressive HL and tinnitus. Vestibular symptoms, which had been rarely reported, were present in 7 out of 30 (23%) of the affected individuals. The most prevalent audiometric configuration was low-frequency type; however, some individuals had high-frequency HL. Haplotype analysis in three mutations (p.A716T, p.K836T, and p.E864K) suggested that the mutations occurred at these mutation hot spots. The present study provided new insights into the audiovestibular phenotypes in patients with WFS1 mutations.

[Fiberscopic reduction under local anesthesia for anterior arytenoid cartilage dislocation].

Arytenoid cartilage dislocation is a known complication of tracheal intubation and is also a type of laryngeal injury. Although spontaneous recovery has been reported, most patients require reduction via pharyngoscopy under general or neuroleptic anesthesia, and some must be treated by open reduction such as laryngoplasty. We report 8 cases of arytenoid cartilage dislocation between August 2003 and August 2004. Excluding 3 patients who recovered spontaneously, we conducted reduction under local anesthesia as an ambulatory procedure in the other 5 with anterior dislocation, i.e., 2 men and 3 women aged 53 to 75 years old. Of these 5, dislocation occurred after tracheal intubation in 4, and in 1 after wearing a laryngeal mask. The outcome was favorable in all 5. Surgery was conducteded after a fiberscope was inserted nasally and a urethral balloon catheter was inserted via the other nasal cavity under topical anesthesia with 4% lidocaine for both nasal cavities and the larynx. While monitoring the larynx, we expanded the balloon and pulled it away from the glottis. The expanded balloon was then placed at the arytenoid region for a few seconds. This procedure was repeated several times to achieve reduction. Three patients recovered well within 1 to 2 weeks of the first reduction, while 2 requierd a second reduction because of insufficient improvement after the first. These two both showed improved vocal cord movement and recovery from hoarseness within 1 to 2 weeks after the second reduction. We conducted 7 reductions without complications in any patient. Our approach is usable in the ambulatory setting, and is simple, minimally invasive, and effective. We consider it to be useful treatment for anterior arytenoid cartilage dislocation.

Epidemiological survey of acute low-tone sensorineural hearing loss.

OBJECTIVES: A nationwide epidemiological survey involving 23 hospitals in Japan was conducted and the predictive values of demographic data were examined statistically. METHODS: A total of 642 patients from 23 hospitals, including 20 university hospitals, in Japan were enrolled in the study. Age ranged from 8 to 87 years, and all were diagnosed with acute low-tone sensorineural hearing loss (ALHL) between 1994 and 2016. Demographic data for the patients, such as symptoms, gender, mean age, and distribution of ALHL grading, were collected and analyzed in relation to prognosis using Student's t-test, χ2 test and logistic regression. RESULTS: Female gender (p < .013), younger age (p < .001), low-grade hearing loss (p < .001), and shorter interval between onset and initial visit (p < .004) were significantly predictive of a good prognosis. The prognosis for definite ALHL was significantly better than that for probable ALHL (p < .007). CONCLUSIONS: The severity of initial hearing loss, interval between onset and initial visit and age were important prognostic indicators for ALHL, while female gender was an important prognostic indicator peculiar to ALHL.

Relationships among drinking and smoking habits, history of diseases, body mass index and idiopathic sudden sensorineural hearing loss in Japanese patients.

OBJECTIVES: To present the cardiovascular risk factors in idiopathic sudden sensorineural hearing loss (SSNHL) patients enrolled in a nationwide epidemiological survey of hearing disorders in Japan. MATERIALS AND METHODS: We compiled the cardiovascular risk factors in 3073 idiopathic SSNHL subjects (1621 men and 1452 women) and compared their proportions with controls as part of the National Health and Nutrition Survey in Japan, 2014. The cardiovascular risk factors consisted of drinking and smoking habits, a history of five conditions related to cardiovascular disease and body mass index. RESULTS: The proportion of current smokers was significantly higher among men aged 50-59, 60-69 and 70+ and among women aged 30-39, 40-49 and 60-69. The proportion of patients with a history of diabetes mellitus was significantly higher among men aged 50-59, 60-69 and 70+, but not in women. In addition, male and female SSNHL subjects aged 60-69 showed lower proportions of current drinking; and female SSNHL subjects aged 60-69 showed higher proportions of overweight (BMI ≥25 kg/m2). CONCLUSIONS: The present cross-sectional study revealed showed significantly higher proportions of current smokers among both men and women as well as those with a history of diabetes mellitus among men across many age groups in patients with idiopathic SSNHL compared with the controls.

Idiopathic sudden sensorineural hearing loss and acute low-tone sensorineural hearing loss: a comparison of the results of a nationwide epidemiological survey in Japan.

OBJECTIVES: The aim of this study was to investigate the differences between idiopathic sudden sensorineural hearing loss (SSNHL), and acute low-tone sensorineural hearing loss (ALHL) using the results of a nationwide survey database in Japan and to analyze the variables associated with their clinical features and the severity of hearing impairment, treatment, and prognosis. METHODS: Participants were patients registered between April 2014 and March 2016 in a multicenter epidemiological survey database involving 30 university hospitals and medical centers across Japan. Statistical analysis was performed to clarify the factors associated with their clinical characteristics and the severity of hearing impairment, treatment, and prognosis. RESULTS: Idiopathic SSNHL and ALHL differed significantly in terms of male-to-female ratio, age distribution, and time from onset to start of treatment. The treatment methods and hearing prognosis also differed markedly between the two diseases. A majority (92%) of idiopathic SSNHL patients were administered some type of corticosteroid, while half of the ALHL patients received corticosteroids and a diuretic agent. CONCLUSION: The results suggested that idiopathic SSNHL and ALHL belonged to different categories of inner ear disease.

The effect of initial treatment on hearing prognosis in idiopathic sudden sensorineural hearing loss: a nationwide survey in Japan.

OBJECTIVE: To investigate the hearing prognosis of idiopathic sudden sensorineural hearing loss (SSNHL) treated with different initial therapies. METHODS: Subjects consisted of patients diagnosed with idiopathic SSNHL within 7 days from onset and showing severe hearing loss (≥60 dB), who were registered in a Japanese multicenter database between April 2014 and March 2016. Subjects were divided into four groups according to initial therapy: (1) steroids, (2) steroids + Prostaglandins (PGs), (3) intratympanic steroids (ITS), and (4) no steroids. Hearing outcomes were compared among the groups. RESULTS: In total, 1305 patients were enrolled. The final hearing level and hearing gain of patients treated with steroids + PGs were significantly higher than those of patients treated with steroids alone or no steroids. The ratio of good prognosis (complete recovery or marked improvement) in patients treated with steroids + PGs was higher than that in patients treated with steroids alone or no steroids. There was no difference in the prognosis of patients treated with steroids alone or no steroids. CONCLUSION: A large number of patients with idiopathic SSNHL were registered in a multicenter database. PG use in combination with steroid administration was associated with a good hearing prognosis in patients with severe hearing loss.

The clinical features and prognosis of mumps-associated hearing loss: a retrospective, multi-institutional investigation in Japan.

CONCLUSIONS: The majority of hearing loss due to mumps presents as unilateral profound sensorineural hearing loss, which is refractory to treatment. In rare cases of bilateral total deafness, cochlear implants were beneficial for speech perception. Vaccination against mumps is recommended to prevent mumps-associated hearing loss. OBJECTIVE: The objective of this study is to investigate the clinical characteristics of hearing loss due to mumps and to evaluate hearing outcomes. SUBJECTS AND METHODS: The clinical parameters were analyzed under a retrospective multi-institutional study design in patients diagnosed with hearing loss due to mumps at the Otolaryngology departments of 19 hospitals between 1987 and 2016. RESULTS: Sixty-seven patients with hearing loss due to mumps were enrolled. The study population consisted of 35 males and 32 females, ranging in age from 1 to 54, with a median age of 9.5 years. Sixty-three patients presented with unilateral, and 4 with bilateral hearing loss. Profound hearing loss was observed in 65 ears. Only one ear with severe hearing loss showed complete recovery. Four patients with bilateral hearing loss received cochlear implant surgery. Most of the patients with hearing loss due to mumps had no history of vaccination.

Nationwide epidemiological survey of idiopathic sudden sensorineural hearing loss in Japan.

OBJECTIVES: Using a large-scale nationwide survey database, we investigated the epidemiological characteristics for idiopathic SSNHL in Japan. METHODS: The subjects for this analysis were patients registered in a Japanese multicentre database between April 2014 and March 2016. A total of 3419 idiopathic SSNHL patients were registered in the database, and the clinical characteristics of the idiopathic SSNHL patients were obtained. Several factors associated with the severity of hearing impairment and prognosis were then investigated. Statistical analysis was performed to clarify the factors associated with the severity of hearing impairment and prognosis. RESULTS: There were significant correlations between the severity of hearing loss and diabetes mellitus, kidney disease, past history of brain infarction, heart disease, age (under 16 years/elderly), and symptoms of vertigo/dizziness. We also analyzed the prognostic factors for idiopathic SSNHL, and found that the severity of hearing loss (Grade 3 or 4), heart disease, aged 65 years or over, time from onset to treatment (over 7 days), and symptoms of vertigo/dizziness were all significantly related to poor prognosis. CONCLUSION: The present large-scale clinical survey revealed current epidemiological trends for idiopathic sudden sensorineural hearing loss (SSNHL) and various factors associated with the severity of hearing impairment and prognosis.

Temporal bone histopathologic abnormalities associated with mitochondrial mutation T7511C.

OBJECTIVES: We previously reported a mitochondrial T7511C mutation in the tRNA gene in a Japanese family with nonsyndromic hearing loss (HL). However, the temporal bone histopathology associated with T7511C has not been reported. The aim of the present study is to report histopathologic findings of a temporal bone from a patient in the Japanese family with this mutation. STUDY DESIGN: Single case study. METHODS: A temporal bone was obtained from the right ear of a male subject with progressive HL from 5 years of age and who died at 60 years of age from cerebral infarction. The bone was embedded, sectioned, and stained with hematoxylin-eosin for light microscopic study. Graphic reconstruction of the cochlea was performed using the method described by Schuknecht to determine loss of the stria vascularis and neurosensory elements including hair cells and spiral ganglion neurons. RESULTS: The most significant histopathologic finding was severe loss of spiral ganglion cells in all turns of the cochlea. Severe loss of neuronal filaments in Rosenthal's canal was also observed. The organ of Corti showed scattered loss of inner and outer hair cells in the basal turn. Partial atrophy of the stria vascularis was observed in all turns of the cochlea. CONCLUSION: Our results suggest that severe loss of spiral ganglion cells was the main cause of sensorineural HL associated with the T7511C mutation.

Guidelines for the evaluation of hearing aid fitting (2010).

OBJECTIVE: The methods to evaluate the efficacy of the adjusted hearing aid for a hearing-impaired person are fitting tests. The tests include those presently carried out for evaluating hearing aid fitting, and the methods of testing and evaluation have been published as "Guidelines for the evaluation of hearing aid fitting (2010)" by the Japan Audiological Society. METHODS: Guidelines for the following 8 test methods are presented. (1) Measurements of speech performance-intensity functions and speech recognition scores; (2) Assessment of hearing aid fitting from the aspect of tolerance of environmental noise; (3) Measurement of real-ear insertion gain (measurement of sound pressure levels at the eardrum); (4) Measurement of the hearing threshold level and the uncomfortable loudness level (UCL) in sound pressure level (SPL) with an inserted earphone; (5) Aided threshold test in a sound field (functional gain measurement); (6) Prediction of insertion gain and aided threshold from hearing aid characteristics and the pure tone audiogram; (7) Measurement of speech recognition in noise; (8) Assessment of hearing aid fitting using questionnaires. In the above tests, (1) and (2) are mandatory tests, and (3) to (8) are informative tests. RESULTS: By performing test combinations properly selected from the above 8 tests, the benefits of a hearing aid could be determined. CONCLUSION: The above test methods were useful and valuable in determining the efficacy of the adjusted hearing aid for a hearing-impaired person during clinical practice.