Publications by authors named "Tsutomu Nakashima"

247 Publications

Relationship between cognitive impairment and olfactory function among older adults with olfactory impairment.

Auris Nasus Larynx 2020 Dec 5. Epub 2020 Dec 5.

Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, 65, Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.

Objective: Understanding the relationships among aging, cognitive function, and olfaction may be useful for diagnosing olfactory decline in older adults. Olfactory function declines in the early stage of neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. Aging and cognitive impairment are associated with olfactory decline. Moreover, the assessment of hyposmia and anosmia is paramount to the diagnosis of neurodegenerative diseases. We aimed to assess the relationships among aging, cognitive function, and olfaction in patients with olfactory impairment.

Methods: This observational study included 141 patients with olfactory deterioration who presented with dementia, mild cognitive impairment (MCI), age-related hyposmia, or postviral olfactory dysfunction (PVOD). The patients underwent T&T olfactometry, a self-administered odor questionnaire (SAOQ), a visual analog scale (VAS), and a Mini-Mental State Examination.

Results: T&T odor recognition thresholds decreased with aging (p < 0.01) and cognitive impairment (p < 0.08). The average T&T recognition thresholds were 5.1,4.6,4.2, and 3.7 in dementia, MCI, age-related hyposmia, and PVOD, respectively. Moreover, the average differences between the detection and recognition thresholds were 3.7, 2.8, 2.3, and 2.0 in dementia, MCI, age-related hyposmia, and PVOD, respectively. Hyposmia with dementia presented the highest recognition thresholds (p < 0.05) and the largest differences between the T&T detection and recognition thresholds, compared with age-related hyposmia and PVOD (p < 0.05). Hyposmia with dementia had the highest SAOQ and VAS scores compared with the other groups (p < 0.05).

Conclusion: The possibility of dementia should be investigated in patients with hyposmia, including those with high T&T recognition thresholds, a large difference between the T&T detection and recognition thresholds, and high SAOQ and VAS scores.
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http://dx.doi.org/10.1016/j.anl.2020.11.020DOI Listing
December 2020

Hearing impairment is associated with cognitive function in community-dwelling older adults: A cross-sectional study.

Arch Gerontol Geriatr 2021 Mar-Apr;93:104302. Epub 2020 Nov 27.

Department of Otorhinolaryngology, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan; Department of Rehabilitation, Ichinomiya Medical Treatment & Habilitation Center, Ichinomiya, Aichi, Japan.

Background: Hearing impairment (HI) is associated with dementia. However, the cognitive screening tasks effective in older community dwellers presenting with HI are unclear.

Methods: We retrospectively and cross-sectionally investigated the associations between HI and cognitive function assessed with screening tasks using data from two healthcare check-up programs for community dwellers ≥65 years old in 2018. We examined demographics, risk factors, cognitive function, hearing condition, lifestyles, and self-care levels. Cognitive function was assessed using the clock drawing task and the delayed three words recall task. Hearing condition was assessed using questionnaires on the use of hearing aids and HI during conversation situations. Multivariate analysis was used to identify independent associations between HI and cognitive assessment tasks.

Results: We analyzed 1602 eligible participants (61.9% women; 74.3 ± 6.5 years old). Hearing aid users (n = 90) were older (80 vs. 73 years, respectively; p < 0.001) and less likely to draw the clock correctly (71.1% vs. 80.1% years, respectively; p = 0.044) than non-hearing aid users. Multivariate logistic regression analysis showed that HI was associated with inability to draw the clock correctly (odds ratio 1.60, 95% confidence interval 1.12-2.26; p = 0.011), independent of age, living alone, memory impairment, and impaired self-care levels.

Conclusion: Hearing impairment is independently associated with cognitive decline assessed by the clock drawing task. The clock drawing task may be useful for identifying an increased risk of dementia in older subjects presenting with HI.
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http://dx.doi.org/10.1016/j.archger.2020.104302DOI Listing
February 2021

Sensory impairment: A preventable risk factor in older adults.

Arch Gerontol Geriatr 2021 Mar-Apr;93:104300. Epub 2020 Nov 19.

Department of Otorhinolaryngology, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan; Department of Rehabilitation, Ichinomiya Medical Treatment & Habilitation Center, Ichinomiya, Aichi, Japan.

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http://dx.doi.org/10.1016/j.archger.2020.104300DOI Listing
February 2021

Olfactory and gustatory dysfunction caused by SARS-CoV-2: Comparison with cases of infection with influenza and other viruses.

Infect Control Hosp Epidemiol 2021 01 5;42(1):113-114. Epub 2020 May 5.

Departmeny of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

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http://dx.doi.org/10.1017/ice.2020.196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298085PMC
January 2021

Gustatory function in persons with cerebral palsy.

J Oral Rehabil 2020 Apr 31;47(4):523-527. Epub 2020 Jan 31.

Kashinoki Welfare Association, Ichinomiya, Japan.

Gustatory function is closely related to chewing and swallowing; however, there are currently no reports regarding gustatory function in persons with cerebral palsy (CP). The aim of this study was to compare the gustatory function between persons with CP and healthy controls. We investigated sweet, salty, sour and bitter tastes using the whole-mouth method and measured the electrogustometric thresholds in the chorda tympani nerve area. Twelve participants with CP (6 women and 6 men) for whom gustatory testing was possible at our facilities, and 17 age-matched controls (9 women and 8 men) were included. The mean age ± standard deviation was 58.6 ± 8.1 years and 58.5 ± 8.7 years in subjects with CP and controls, respectively. Taste detection and identification were significantly worse in persons with CP compared with the controls. Taste identification was more impaired than taste detection. At the highest concentration, taste identification was impossible 11 times out of 48 (12 persons × 4 kinds of tastes) in persons with CP but such a deficit was not observed in 68 attempts (17 persons × 4 kinds of tastes) involving controls. The electrogustometric thresholds were not significantly different between the groups. Gustatory function associated with chewing and swallowing is worse in persons with CP compared to the controls.
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http://dx.doi.org/10.1111/joor.12933DOI Listing
April 2020

Nasal patency as a factor for successful transnasal endoscopy.

Nagoya J Med Sci 2019 Nov;81(4):587-595

Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan.

In recent years, transnasal endoscopy had been more widely accepted for its safety and convenience, and although it can lead to a weaker pharyngeal reflex, compared with the effects of transoral endoscopy, examinees often suffer intolerable pain and discomfort during passage of the endoscope through the nasal cavity. The aim of this study was to estimate the relationship between the uncomfortable factors during transnasal endoscopy and nasal patency. The subjects comprised 23 consecutive patients who underwent transnasal endoscopy from October 2007 to April 2009 at our Gastroenterology and Otorhinolaryngology Departments. Immediately prior to endoscopy, the left and right nasal resistance was measured with an active anterior rhinomanometer; a value of 100 Pa was determined as nasal resistance. The transnasal endoscope was inserted in the subjectively preferred side by the examinee. Thereafter, the subjects were asked to fill in a questionnaire on physical tolerance during the procedure, to quantify the sensations of nasal pain, nausea, and choking on a 10-point visual analogue scale. The mean scores were 3.0 ± 2.7 for nasal pain, 1.7 ± 2.0 for choking, and 1.6 ± 1.9 for nausea. The most intolerable factor among the complaints was pain (45%), which was followed by nausea (18%) and choking (9%). Unilateral nasal resistance was significantly related with nasal pain only (P = 0.0135). In conclusion, the most difficult problem during transnasal endoscopy was pain, which was related to nasal patency. We successfully demonstrated the clinical significance of nasal patency in determining the side of insertion for transnasal endoscopy.
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http://dx.doi.org/10.18999/nagjms.81.4.587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892663PMC
November 2019

Heart rate variability in a patient with alternating hemiplegia.

Intractable Rare Dis Res 2019 May;8(2):134-137

Department of Pediatrics and Central Research Institute for the Molecular Pathomechanisms of Epilepsy, Fukuoka University School of Medicine, Fukuoka, Japan.

Alternating hemiplegia of childhood (AHC) is a rare disorder characterized by repetitive episodes of transient hemiplegia. Although autonomic nervous system dysfunction is believed to be associated with AHC, there are no reports of heart rate variability (HRV) in patients with AHC. In the current study, we analyzed HRV in a 20-year-old female with this disorder. The frequency of paralytic attacks have decreased since the patient was a teenager, compared to when she was < ten years old; however, as a 20-year-old, she still experiences paralytic attacks several times per month to more than ten times per month. Thus far, she has only suffered paralytic attacks and no epileptic seizures. Using Sanger sequencing, Gly947Arg (2839G>A) in the sodium-potassium (Na/K)-ATPaseα3 subunit gene () was confirmed from her blood sample. An elevated heart rate lasting one to two minutes and sometimes longer, was primarily observed at night while the patient was sleeping. Large fluctuations in HRV, including low- and high- frequency components, were primarily observed while the patient was sleeping but suppressed during paralytic attacks. These results confirm the presence of an autonomic nervous system disorder in AHC. Because large variation of the autonomic nervous function was observed at night, the pathophysiological function should be investigated for 24 hours.
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http://dx.doi.org/10.5582/irdr.2019.01060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557234PMC
May 2019

Association between Uncoupling Protein 2 Gene Ala55val Polymorphism and Sudden Sensorineural Hearing Loss.

J Int Adv Otol 2018 Aug;14(2):166-169

Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Objectives: The pathology of sudden sensorineural hearing loss, which is known as sudden deafness (SD), remains unknown. The purpose of this study was to investigate the association between mitochondrial uncoupling protein 2 (UCP2) polymorphism and SD risk.

Materials And Methods: We compared 83 patients suffering from SD and 2048 controls who participated in the Longitudinal Study of Aging at the National Institute for Longevity Sciences. Multiple logistic regression was used to calculate the odds ratios (ORs) for SD with a polymorphism of the UCP2 (rs660339) gene.

Results: Under the additive model of inheritance, UCP2 polymorphisms showed significant association with a SD risk. The OR was 1.468 (95% confidence interval, 1.056-2.040) with an adjustment for any past history, such as diabetes, dyslipidemia, or hypertension, and for age and sex.

Conclusion: Our results imply that the UCP2 (rs660339) polymorphism has a significant association with the risk of developing SD.
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http://dx.doi.org/10.5152/iao.2018.5442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354460PMC
August 2018

Prevalence and Risk Factors of MRI Abnormality Which Was Suspected as Sinusitis in Japanese Middle-Aged and Elderly Community Dwellers.

Biomed Res Int 2018 12;2018:4096845. Epub 2018 Jun 12.

Section of NILS-LSA, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi 474-8511, Japan.

The aims of this study were to determine the prevalence of MRI abnormalities which were suspected as sinusitis in community-dwelling middle-aged and elderly Japanese and to identify risk factors for the MRI abnormality. Brain magnetic resonance imaging (MRI) data from the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA) were used for the analysis. Among the 2330 subjects in the NILS-LSA, 1933 participants were categorized as having no MRI abnormality or MRI abnormality using the Lund-Mackay (LM) score. The mean LM score of the participants was 0.88±1.92, and 144 (7.4%) participants had MRI abnormalities which were suspected as sinusitis when it was classified as an LM score greater than or equal to 4. The prevalence of MRI abnormality was significantly higher in participants of older age and the male sex, in participants with obesity, hypertension, bronchial asthma, chronic bronchitis, gout, or hyperuricemia and in ex- or current smokers. A multivariate logistic regression revealed that older age (odds ratio [OR] = 1.17), obesity (OR = 1.54), a smoking habit (OR = 1.71), history of asthma (OR = 3.77), and chronic bronchitis (OR = 2.66) were significant risk factors for MRI abnormality.
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http://dx.doi.org/10.1155/2018/4096845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020666PMC
January 2019

<Editors' Choice> Maxillary sinus carcinoma outcomes over 60 years: experience at a single institution.

Nagoya J Med Sci 2018 02;80(1):91-98

Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Advances in the diagnosis and treatment of patients with maxillary sinus carcinoma have improved patient prognosis. This study investigated changes in demographic and clinical characteristics, treatment methods, and outcomes of patients with maxillary sinus carcinomas during three different 10-year periods spanning 60 years at our university hospital. Of the 233 patients with maxillary sinus carcinomas managed at Nagoya University Hospital, 135 were treated between 1951 and 1960 (first period), 35 between 1981 and 1990 (second period), and 63 between 2003 and 2012 (third period). Patient age, sex, TN classifications, treatment methods, and survival rates were compared among patients treated during these time periods. Of the 135, 35, and 63 patients with maxillary sinus carcinomas treated during these time periods, 86 (63.7%), 21 (51.4%), and 48 (76.2%), respectively, were men; 14 (10.4%), six (17.1%), and 14 (22.2%), respectively, were aged ≥70 years; and 135 (100%), 28 (80.0%), and 43 (68.3%), respectively, were treated surgically. The 5-year overall survival rates in patients treated during the first, second, and third periods were 29.7%, 44.3%, and 57.5%, respectively. These findings indicated that advances in the diagnosis and treatment of patients with maxillary sinus carcinoma, including computed tomography and craniofacial resection, have contributed to improvements in patient survival rates.
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http://dx.doi.org/10.18999/nagjms.80.1.91DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857505PMC
February 2018

Imaging of the endolymphatic space in patients with Ménière's disease.

Auris Nasus Larynx 2018 Feb 28;45(1):33-38. Epub 2017 Feb 28.

Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Objective: To examine endolymphatic hydrops (EH) using magnetic resonance imaging (MRI) in patients with definite Ménière's disease (MD) and those with nonotological diseases.

Methods: We studied 32 patients with unilateral MD, 10 patients with bilateral MD and 21 patients with control ears who had other benign diseases not associated with hearing or vestibular dysfunction. The mean age of the subjects was 54.0 years (range 27-74) in the MD group and 56.1 years (range 24-79) in the control group. Using MRI, the degree of EH was classified as none, mild and significant in the cochlea and vestibule separately. The ratio of the area of endolymphatic space to the vestibular fluid space was calculated for the vestibule. The duration of MD was defined as the months between the first attack of MD and the MRI study.

Results: EH was present in the cochlea of 45/52 affected ears of patients with MD (87%) and in 16/42 control ears (38%). Significant cochlear hydrops was present in 37/52 affected ears (71%) and in 4/42 control ears (10%). EH in the vestibule was present in 49/52 affected ears (94%) and in 3/42 control ears (7%). Significant vestibular hydrops was present in 40/52 affected ears (77%) and in none of the 42 control ears. There was no relationship between the degree of EH and its duration. Using a cut off value for the relative size of EH in the vestibule of 41.9%, the test had a sensitivity of 88.5% and a specificity of 100% to diagnose definite MD.

Conclusion: Cochlear EH was occasionally observed in control ears on MRI, as in normal temporal bone specimens. The presence or absence and degree of vestibular EH were significantly different between ears with MD and control ears. EH in the vestibule might be a specific predictor of definite MD.
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http://dx.doi.org/10.1016/j.anl.2017.02.002DOI Listing
February 2018

Magnetic resonance imaging evaluation of endolymphatic hydrops andpost-operative findings in cases with otosclerosis.

Acta Otolaryngol 2017 Mar 27;137(3):242-245. Epub 2016 Sep 27.

a Department of Otorhinolaryngology , Nagoya University Graduate School of Medicine , Nagoya , Japan.

Conclusions: The presence of endolymphatic hydrops (EH) in the vestibule on magnetic resonance imaging (MRI) might be a high-risk factor for complications in cases that are candidates for stapes surgery.

Objective: Pre-operative detection of EH could be valuable in cases that are candidates for stapes surgery to prevent unpredictable complications following surgery. Pre-operative MRI findings and post-operative findings following stapes surgery were compared to evaluate the efficacy of such MRI evaluation for the management of cases with otosclerosis.

Subjects And Methods: Sixteen cases who underwent pre-operative evaluation by 3T MRI performed 4 h after intravenous injection of gadolinium and stapes surgery for otosclerosis were recruited. Imaging data concerning the degree of EH in the vestibule and cochlea were compared with post-operative clinical findings for all cases.

Results: Mild EH in the cochlea or the vestibule was observed in eight ears and one ear, respectively, whereas one ear showed significant EH both in the cochlea and the vestibule. The post-operative course was uneventful in 12 of 14 cases with no EH in the vestibule, and the other two cases had a short period of dizziness, but two cases with EH in the vestibule had a long period of dizziness.
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http://dx.doi.org/10.1080/00016489.2016.1232862DOI Listing
March 2017

The Longitudinal Impact of Hearing Impairment on Cognition Differs According to Cognitive Domain.

Front Aging Neurosci 2016 22;8:201. Epub 2016 Aug 22.

Section of Longitudinal Study of Aging, National Institute for Longevity Sciences, National Center for Geriatrics and GerontologyObu, Aichi Prefecture, Japan; Graduate School of Nutritional Sciences, Nagoya University of Art and ScienceNisshin, Aichi Prefecture, Japan.

Identification and modification of the risk factors for cognitive decline throughout the adult life span are priority subjects in a progressively aging society; however, much remains to be learned. The aim of this study was to understand whether changes in cognitive function can be affected by hearing impairment (HI) and whether the impact of HI differs depending on the cognitive domain. A total of 1109 individuals aged 60-79 years at baseline who participated in the Longitudinal Study of Aging at the National Institute for Longevity Sciences (NILS-LSA) was followed up for a maximum of 13.3 years. Cognitive function was evaluated using four subtests of the Japanese Wechsler Adult Intelligence Scale-Revised Short Forms (JWAIS-R-SF): namely, Information, Similarities, Picture Completion, and the Digit Symbol Substitution subtests. The HI was defined as a pure-tone average of the better ear >25 dB. A longitudinal analysis of 4437 observations obtained during a follow-up period of approximately 12 years was performed. We estimated linear changes in subtest scores by HI status, using the time-varying mixed-effects regression model, which included fixed terms for the intercept, HI status at baseline, time (years elapsed since baseline) and an HI × time interaction term adjusted for age at baseline, sex, education, and other possible confounders. There were significant main effects of HI on the scores of the four subtests after adjustment. The HI × time interaction was significant for the scores of the Information (p = 0.001) and Digit Symbol Substitution subtests (p = 0.001). The scores of the HI group declined faster in the Information and Digit Symbol Substitution subtests compared to those in the no-HI group. The model-predicted 12-year slope using a mean baseline age (68.7 years) indicated no significant decline in the individuals without HI at baseline for the Information and Similarities subtests, however, this tolerance was lost in the individuals with HI. In conclusion, the present observation showed that the impact of HI on cognition was longitudinally significant and implied that the effect differs according to cognitive domain.
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http://dx.doi.org/10.3389/fnagi.2016.00201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992677PMC
September 2016

Endolymphatic hydrops in patients with unilateral and bilateral Meniere's disease.

Acta Otolaryngol 2017 Jan 26;137(1):23-28. Epub 2016 Aug 26.

a Department of Otorhinolaryngology , Nagoya University Graduate School of Medicine , Nagoya , Japan.

Conclusion: All definite Meniere's disease (MD) had endolymphatic hydrops (EH) at least in the cochlea or the vestibule. Symptoms of MD may appear after formation of EH. It is assumed that the probability of immediate progression to bilateral MD from unilateral MD is very low in patients without EH on the non-affected side.

Objective: To evaluate the EH on both sides in patients with unilateral and bilateral MD, and to investigate factors with progression to bilateral MD including the degree of EH, hearing level, and the duration of MD.

Patients And Methods: The study included 29 patients with unilateral definite MD and 12 patients with bilateral definite MD. The endolymphatic space size was visualized by using 3-Tesla magnetic resonance imaging.

Results: All patients with unilateral and bilateral MD had significant or mild EH at least in the cochlea or the vestibule on the affected side. On the non-affected side, EH was not observed at all in eight patients, but asymptomatic EH was observed in the cochlea in 14 patients and in the vestibule in 16 patients. There was no relationship between the EH on the non-affected side and the duration of MD.
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http://dx.doi.org/10.1080/00016489.2016.1217042DOI Listing
January 2017

Meniere's disease.

Nat Rev Dis Primers 2016 05 12;2:16028. Epub 2016 May 12.

Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.

Meniere's disease (MD) is a disorder of the inner ear that causes vertigo attacks, fluctuating hearing loss, tinnitus and aural fullness. The aetiology of MD is multifactorial. A characteristic sign of MD is endolymphatic hydrops (EH), a disorder in which excessive endolymph accumulates in the inner ear and causes damage to the ganglion cells. In most patients, the clinical symptoms of MD present after considerable accumulation of endolymph has occurred. However, some patients develop symptoms in the early stages of EH. The reason for the variability in the symptomatology is unknown and the relationship between EH and the clinical symptoms of MD requires further study. The diagnosis of MD is based on clinical symptoms but can be complemented with functional inner ear tests, including audiometry, vestibular-evoked myogenic potential testing, caloric testing, electrocochleography or head impulse tests. MRI has been optimized to directly visualize EH in the cochlea, vestibule and semicircular canals, and its use is shifting from the research setting to the clinic. The management of MD is mainly aimed at the relief of acute attacks of vertigo and the prevention of recurrent attacks. Therapeutic options are based on empirical evidence and include the management of risk factors and a conservative approach as the first line of treatment. When medical treatment is unable to suppress vertigo attacks, intratympanic gentamicin therapy or endolymphatic sac decompression surgery is usually considered. This Primer covers the pathophysiology, symptomatology, diagnosis, management, quality of life and prevention of MD.
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http://dx.doi.org/10.1038/nrdp.2016.28DOI Listing
May 2016

A nationwide study on enlargement of the vestibular aqueduct in Japan.

Auris Nasus Larynx 2017 Feb 6;44(1):33-39. Epub 2016 May 6.

Department of Otolaryngology, Tokyo Medical and Dental University School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

Objective: To document the clinical features and associated pure-tone audiometry data in patients with enlargement of the vestibular aqueduct (EVA), and to identify risk factors for fluctuating hearing loss (HL) and vertigo/dizziness in EVA patients.

Methods: In this nationwide survey in Japan, a first survey sheet was mailed to 662 board-certified otolaryngology departments to identify the ones treating EVA patients. A second survey sheet, which contained solicited clinical information and the results of the hearing tests, was mailed to all facilities that reported treating EVA cases. We analyzed clinical information, including age at the time of the most recent evaluation, gender, EVA side, age at onset, initial symptoms, precipitating factors, and etiology from survey responses, and assessed 4-frequency (500, 1000, 2000, and 4000Hz) pure-tone average (PTA) from accompanying pure-tone audiometry data. A multivariate logistic regression analysis was utilized to identify the possible risk factors for fluctuating HL and vertigo/dizziness.

Results: In total, 513 hospitals (response rate, 77.5%) responded to the first survey, and 113 reported treating patients with EVA. Seventy-nine out of the 113 hospitals (response rate 69.9%) responded to the second survey, and the data of 380 EVA patients were registered and analyzed. Of the 380 patients, 221 (58.2%) were female, suggesting female preponderance. The patient age ranged from 0 to 73 years (mean, 16.7 years; median, 13 years; interquartile range, 6-24 years). EVA was bilateral in 91.1% of the patients (346/380). The most prevalent initial symptom was HL (341/380), followed by vertigo/dizziness/imbalance (34/380). Sudden HL occurred secondary to head trauma in 5.3% of the patients and upper respiratory infection in 5.0%. Pure-tone audiometry showed profound HL (PTA >91dB) in 316 (52.0%) of the 608 ears in the 304 patients tested, and asymmetric HL, defined as >10dB, in 147 (48.4%) of the 304 patients. The mean PTA was 83.7dB (median, 91.3dB; interquartile range, 71.3-103.8dB), and the severity in PTA did not correlate with age. Multivariate logistic regression identified age ≥10 years (compared to age of 0-9 years), bilateral HL (compared to unilateral HL/normal hearing), a history of head trauma, and Pendred syndrome (compared to the other EVA-associated disorders) as significant risk factors for fluctuating HL and/or vertigo/dizziness.

Conclusion: The present nationwide survey of 380 EVA patients provided a more precise description of the clinical features, including risk factors for fluctuating HL and vertigo/dizziness.
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http://dx.doi.org/10.1016/j.anl.2016.04.012DOI Listing
February 2017

SOD1 gene polymorphisms in sudden sensorineural hearing loss.

Acta Otolaryngol 2016 16;136(5):465-9. Epub 2016 Feb 16.

a Department of Otorhinolaryngology , Shinshu University School of Medicine , Matsumoto , Nagano , Japan ;

Conclusion: The results suggest that SOD1 rs4998557 could be associated with susceptibility to SSNHL in the Japanese population.

Objectives: To assess the gene association with sudden sensorineural hearing loss (SSNHL).

Methods: A two-stage case control study was conducted to explore the relationship of the candidate genes to SSNHL. The 192 gene samples from SSNHL patients registered in the intractable inner ear disease gene bank were enrolled. As the candidate genes, 39 SNPs from 31 genes were selected for the first stage study. The second stage study examined whether the SOD1 gene polymorphisms, defined by significant differences between cases and controls in the first stage study, are associated with SSNHL.

Results: Significant differences were observed in four SNPs from three genes, Glutathione-S-transferase pai 1 (GSTP1), proteine kinase C heta (PRKCH), and superoxide dismutase 1 (SOD1), in terms of allele frequency between SSNHL patients and HapMap controls. In the SOD1 gene, a significant difference was observed in the dominant model study of the SNP rs4998557 in the second stage study. Furthermore, as a result of dividing SSNHL patients based on the clinical data, the difference was more apparent in the case of the over 60 dB group and the tinnitus-positive group.
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http://dx.doi.org/10.3109/00016489.2015.1116047DOI Listing
January 2017

Endolymphatic hydrops in superior canal dehiscence and large vestibular aqueduct syndromes.

Laryngoscope 2016 06 3;126(6):1446-50. Epub 2015 Nov 3.

Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Objectives/hypothesis: Pathologic third window lesions, such as superior semicircular canal dehiscence syndrome (SCDS) or large vestibular aqueduct syndrome (LVAS), cause several auditory and vestibular symptoms, which might affect perilymphatic pressure and induce endolymphatic hydrops (EH). In this study, the existence of EH in subjects with SCDS or LVAS was investigated using contrast-enhanced magnetic resonance imaging (MRI).

Study Design: Case series at university hospital.

Methods: Seventeen ears from nine subjects who were diagnosed as having SCDS (five ears from three cases) or LVAS (12 ears from six cases) were studied. Ears were evaluated by 3-T MRI performed 4 hours after intravenous injection of gadodiamide hydrate. Imaging data concerning the degree of EH in the cochlea and the vestibule were compared with clinical symptoms and hearing levels for all ears.

Results: All ears showed air-bone gaps at low frequencies on pure tone audiometry. None of the subjects with SCDS had episodes of acute sensorineural hearing loss (SNHL) or vestibular symptoms, except for one patient who complained of head vibration induced by loud noise. Conversely, five of six subjects with LVAS had episodes of acute SNHL or vestibular symptoms. Four of five ears with SCDS showed severe EH in the cochlea, and two ears showed mild EH in the vestibule. All ears with LVAS showed mild to severe EH in both the cochlea and vestibule.

Conclusions: The present study demonstrated the existence of EH in ears with pathologic third window lesions, which might affect patients' auditory or vestibular symptoms.

Level Of Evidence: 4 Laryngoscope, 126:1446-1450, 2016.
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http://dx.doi.org/10.1002/lary.25747DOI Listing
June 2016

Prevalence of Sinusitis Detected by Magnetic Resonance Imaging in Subjects with Dementia or Alzheimer's Disease.

Curr Alzheimer Res 2015 ;12(10):1006-11

Department of Otorhinolaryngology, National Center for Geriatrics and Gerontology, 7-430, Morioka- cho, Obu City, 474-0038, Japan.

Background: It has been reported that periodontitis is associated with Alzheimer's disease. However, the association between paranasal sinusitis and Alzheimer's disease has not been studied, although olfactory dysfunction frequently precedes the progress of dementia or Alzheimer's disease.

Methods: We studied 783 patients (283 men, 500 women; mean age 77.0 ± 7.9 years) who visited the Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, and 2139 control subjects who participated in a population-based study conducted by the National Institute for Longevity Sciences - Longitudinal Study of Aging (NILS-LSA) in Japan. Sinusitis was evaluated using magnetic resonance imaging (MRI) according to the Lund-Mackay scoring system. A sinusitis score of ≥ 4 was classified as positive and a score of ≤ 3 was classified as negative.

Results: The prevalence of positive sinusitis was 6.3% in patients with a mini-mental state examination (MMSE) score of < 24 (n = 507), and 5.7% in patients with Alzheimer's disease (n = 280). The rate of positive sinusitis was7.2% in the control group. The prevalence of sinusitis was not significantly different between normal controls and patients with dementia or Alzheimer's disease after adjustments for age and sex. The rate of positive sinusitis was higher in male than in female subjects in both groups.

Conclusion: The prevalence of sinusitis in patients with Alzheimer's disease or dementia was not higher than in the general population.
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http://dx.doi.org/10.2174/1567205012666150710105152DOI Listing
August 2016

Changes in endolymphatic hydrops in patients with Ménière's disease treated conservatively for more than 1 year.

Acta Otolaryngol 2015 Sep 20;135(9):866-70. Epub 2015 Jun 20.

Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine , Nagoya , Japan.

Conclusion: This study revealed that endolymphatic hydrops (EH) reduced in some cases with Ménière's disease (MD) treated conservatively. It appears that the EH reduction was associated with improvement of the clinical symptoms.

Objectives: The relationship between the degree of EH and clinical symptoms is not clear at present. The purpose of the present study was to investigate the time course of the relationship in patients with MD treated conservatively.

Patients: Twelve patients with MD treated conservatively for more than 1 year in a university hospital.

Methods: Twenty ears of 12 patients with MD treated conservatively were evaluated. The presence or absence of vertigo, tinnitus and ear fullness was confirmed when magnetic resonance imaging (MRI) was performed. Using a 3 T MRI scanner, three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) MRI was performed 2 or 3 times 24 hours after intra-tympanic gadolinium injection or 4 hours after intravenous gadolinium injection.

Results: In the three ears in which the symptoms alleviated, EH was reduced in two ears, but EH was reduced in only one of 17 ears in which the symptoms did not alleviate. The Fisher exact test revealed that EH reduction occurred more frequently in ears with alleviation of the symptoms (p < 0.05).
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http://dx.doi.org/10.3109/00016489.2015.1015607DOI Listing
September 2015

Craniofacial Resection for T4 Maxillary Sinus Carcinoma: Managing Cases with Involvement of the Skull Base.

Otolaryngol Head Neck Surg 2015 Aug 4;153(2):231-8. Epub 2015 Jun 4.

Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Objective: The objective of this study was to clarify the outcomes of craniofacial resection for locally advanced maxillary sinus carcinoma classified as T4 and to present methods for managing cases involving the skull base.

Study Design: Case series with chart review.

Setting: Tertiary university hospital.

Subjects And Methods: We performed anterolateral craniofacial resection in en bloc fashion for locally advanced maxillary sinus carcinoma at stage T4. Participants comprised 40 patients with T4 maxillary sinus carcinoma treated between 1992 and 2011. Surgical outcomes were analyzed retrospectively.

Results: Forty patients with stage T4a (n = 26) or stage T4b (n = 14) were included in this study. Five-year overall and disease-free survival rates for the 40 patients with T4 maxillary sinus carcinoma were 62.7% and 52.6%, respectively. Cavernous sinus involvement correlated significantly with worse prognosis (P = .012). In 35 cases without cavernous sinus involvement, previous treatment (P = .017) and positive margins (P = .019) correlated significantly with worse prognosis, and 5-year overall and disease-free survival rates were 72.4% and 55.3%, respectively.

Conclusion: This study only included cases of locally advanced maxillary sinus carcinoma classified as T4. Considering the advanced stage, our study suggests relatively favorable outcomes and the importance of managing the cavernous sinus in en bloc resections of malignant skull base tumors. Craniofacial resection in en bloc fashion achieved good survival rates.
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http://dx.doi.org/10.1177/0194599815586770DOI Listing
August 2015

Cerumen impaction shown by brain magnetic resonance imaging in patients with cognitive impairment.

Geriatr Gerontol Int 2016 Mar 28;16(3):392-5. Epub 2015 May 28.

Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, Obu, Japan.

Aim: Hearing loss is a risk factor for the progression of dementia. Cognitive improvement is occasionally found after removal of cerumen impaction. Because patients with dementia do not usually complain about cerumen impaction, detection methods are important. The present study aimed to investigate whether cerumen impaction is observable using brain magnetic resonance imaging.

Methods: Participants were six patients whose hearing level improved 15 dB or more unilaterally or bilaterally after the removal of cerumen impaction. A radiologist who was blind to the impaction side and whether magnetic resonance imaging scans were taken before or after impaction removal classified cerumen impaction as positive, negative or unclear.

Results: Three ears classified as impaction positive and five ears classified as impaction negative corresponded accurately to the presence or absence of cerumen impaction. Among four ears classified as unclear, two did and two did not have cerumen impaction.

Conclusion: Careful examination of the external ear canal on brain magnetic resonance imaging can be used to detect cerumen impaction.
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http://dx.doi.org/10.1111/ggi.12529DOI Listing
March 2016

Magnetic Resonance Imaging Evaluation of Endolymphatic Hydrops in Cases With Otosclerosis.

Otol Neurotol 2015 Aug;36(7):1146-50

*Department of Otorhinolaryngology, Toyota Memorial Hospital, Toyota, Japan; †Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan; ‡Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan; and §Department of Otorhinolaryngology, National Center for Geriatrics and Gerontology, Obu, Japan.

Objective: Endolymphatic hydrops (EH) has been reported in cases with otosclerosis, and preoperative EH could be a risk factor for inner ear disturbances after stapes surgery. Visualization of EH has recently become possible using magnetic resonance imaging (MRI) with contrast agents. This study investigated the presence of EH on MRI in ears with clinical otosclerosis.

Study Design: Retrospective case series.

Setting: University hospital.

Patients: 27 ears of 15 cases diagnosed with otosclerosis.

Intervention: Ears were evaluated by 3-T MRI performed 4 hours after intravenous injection of gadolinium. The degree of EH in the vestibule and cochlea was classified into three grades (none, mild, and significant). Imaging data were compared with clinical findings for all ears.

Main Outcome Measures: Imaging and clinical findings.

Results: Varying degrees of cochlear EH and vestibular EH were observed in 20 and 15 ears, respectively. Episodes of acute sensorineural hearing loss with rotatory vertigo occurred in four ears that showed severe EH in the cochleae and vestibules. Severe EH, however, was also observed in ears without such symptoms.

Conclusions: The presence of EH in ears with otosclerosis was clearly visualized in the present patient series. Such MRI evaluation could provide useful information for managing symptoms related to EH.
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http://dx.doi.org/10.1097/MAO.0000000000000685DOI Listing
August 2015

Imaging of endolymphatic hydrops in 10 minutes: a new strategy to reduce scan time to one third.

Magn Reson Med Sci 2015 15;14(1):77-83. Epub 2014 Dec 15.

Department of Radiology, Nagoya University Graduate School of Medicine.

We measured the size of the endolymph using a newly proposed 10-min magnetic resonance (MR) imaging protocol and compared values with those of the previously reported 31- and 17-min protocols in 15 patients. Values for the 3 protocols did not differ significantly in either the cochlea or vestibule. Correlation among the 3 protocols was strong or relatively strong. Evaluation of endolymphatic hydrops is feasible using the newly proposed 10-min protocol.
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http://dx.doi.org/10.2463/mrms.2014-0065DOI Listing
December 2015

Role of induction chemotherapy for N3 head and neck squamous cell carcinoma.

Auris Nasus Larynx 2015 Apr 8;42(2):150-5. Epub 2014 Dec 8.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. Electronic address:

Objective: The treatment of head and neck squamous cell carcinoma (HNSCC) with N3 (>6cm) lymph nodes remains difficult, and the best treatment strategy has not been elucidated. The aim of this study was to evaluate the outcomes of various treatment modalities.

Methods: Sixty-nine patients with HNSCC and N3 neck disease treated with definitive therapy in our institute between 1987 and 2013 were included in the analysis. We compared the clinical outcomes of radiotherapy (RT) alone, chemoradiotherapy (CRT) and surgery with or without induction chemotherapy (ICT).

Results: The overall survival (OS) at three years for the patients with N3 neck disease was 41%. The three-year OS rates of patients treated with definitive surgery and definitive CRT were 41% and 48%, respectively. There were no significant differences between these two treatments (P=0.82). The OS of patients who received ICT followed by definitive therapy was significantly better than that of patients who did not (P<0.001). The most common recurrence pattern was distant metastases. The rate of distant metastases was 61% of all treatment failures (20/33).

Conclusion: The high rate of distant metastases in patients with N3 neck disease suggests that prevention of distant metastases can improve survival. Based on this study, we consider that ICT may play an important role in the treatment of N3 neck disease.
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http://dx.doi.org/10.1016/j.anl.2014.10.007DOI Listing
April 2015

The association between hearing impairment and polymorphisms of genes encoding inflammatory mediators in Japanese aged population.

Immun Ageing 2014 26;11(1):18. Epub 2014 Nov 26.

Department for Development of Preventive Medicine, National Center for Geriatrics and Gerontology, Obu City, Aichi prefecture Japan ; Graduate School of Nutritional Sciences, Nagoya University of Arts and Sciences, Nisshin, Japan.

Background: Aging process is accompanied by a chronic sub-clinical systemic inflammation. This study aimed to assess the association between hearing impairment and polymorphisms of genes encoding cytokines deeply-committed to the inflammatory response and immune homeostasis in an elderly Japanese population. Data were collected in the Longitudinal Study of Aging surveyed biennially between 1997 and 2010. The participants without any missing information at baseline were 1,957 individuals, and the gross accumulated number of 8,675 subjects (40-89 years of age) was analyzed. Two hearing impairment criteria were taken as the better ear pure-tone average (PTABE) greater than 25 dB and greater than 40 dB. We analyzed cumulative data using generalized estimating equations to investigate the effect of 9 polymorphisms, namely, tumor necrosis factor (TNF) α, rs1800630; TNF receptor super family (TNFRSF) 1B, rs1061624; interleukin (IL)-1A, rs1800587; IL-1B, rs16944; IL-4R, rs1801275; IL-6, rs1800796; IL-10, rs1800872; IL-1 receptor-associated kinase 1 (IRAK1), rs1059702; C reactive protein (CRP), rs1130864.

Results: The odds ratios for the hearing impairment (PTABE >25 dB) risk under additive genetic model were significant in TNF-α rs1800630 and TNFRSF1B rs1061624, which were respectively 1.172 (confidence interval [CI]: 1.005-1.367), 1.211 (CI: 1.053-1.392) in model after adjustment for possible confounders. Using the criterion of PTABE >40 dB as disabling hearing impairment, the association remains significant in TNFRSF1B rs1061624, but not in TNF-α rs1800630. No other polymorphisms showed a significant association.

Conclusions: The present population-based cohort study demonstrated that TNF-α rs1800630 and TNFRSF1B rs1061624 contributed to the incremental risk of hearing impairment in the elderly. TNF-α and TNF receptor interactions play a pivotal role in the pathogenesis of the inflammatory response, and also cause programmed cell death and cell proliferation. The present observation implied the signalling cascades of TNF were involved in ear aging.
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http://dx.doi.org/10.1186/s12979-014-0018-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252019PMC
December 2014

Idiopathic sudden sensorineural hearing loss in Japan.

Acta Otolaryngol 2014 Nov;134(11):1158-63

Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine , Nagoya.

Conclusion: An epidemiological survey of hospitals and private clinics in Japan regarding idiopathic sudden sensorineural hearing loss (SSNHL) revealed that the incidence of SSNHL was 60.9 per 100 000 population. There were more females than males in the younger generation.

Objective: The incidence of SSNHL varies largely by country. Because the Japanese criteria for diagnosing SSNHL have changed in accordance with those widely used in other parts of the world, a clinicoepidemiological study was undertaken using the new criteria.

Methods: Ehime, Aichi, and Iwate Prefectures were selected from the western, central, and northeastern regions of Japan, respectively. The subjects for this study were patients who suffered SSNHL between April 1, 2012 and March 31, 2013. Questionnaires were mailed to all hospitals and private clinics in which ENT doctors were working. Initial and final audiograms were requested for 10% of the patients.

Results: In all, 78 of 90 hospitals (87%) and 303 of 407 private clinics (74%) responded. It was reported that 1663 patients visited hospitals and 3090 patients visited only private clinics. It was estimated that 6205 SSNHL patients visited hospitals or private clinics in 1 year from a population of 10 145 000. Also, 23% of patients suffered acute low-tone SNHL (female to male ratio; 3:1 in definite cases).
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http://dx.doi.org/10.3109/00016489.2014.919406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266072PMC
November 2014

[Decline of speech understanding in the hearing impaired elderly listeners who visited our hearing aid clinic].

Nihon Jibiinkoka Gakkai Kaiho 2014 Aug;117(8):1080-6

The aim of this study was to investigate distinctive change in the hearing impaired elderly listeners, especially about speech recognition. Subjects were 525 patients (235 males, 290 females), from 60 to 98 years of age who had visited the Hearing Aid Clinic of Otorhinolaryngology, National Center for Geriatrics and Gerontology Hospital, between June 2001 and December 2012. Pure-tone air conduction threshold determination was administered to each subject. The speech audiometry materials used to define speech discrimination ability were Japanese monosyllabic word lists, 67S word lists. Sex- and age-specific trends in maximum discrimination score (MDS) and rollover index (RI) were shown in this study. RI was computed by the formula (PBmax-PBmin)/PBmax. PBmax has almost the same meaning as MDS in Japan. PBmin represented the lowest PB score above the test intensity level of PBmax. Mean MDSs were 80.8% in their sixties, 75.3% in their seventies, 60.7% in their eighties, and 45.5% in their nineties. The rate of decrease in mean MDS per decade accelerated in the older generation. Mean RIs were 0.18 in patients in their sixties, 0.24 in their seventies, 0.30 in their eighties, and 0.30 in their nineties. It increased until the age of eighties. In the model 1, multiple logistic analyses were performed to examine the effect of age (in 10-year increments), sex and mean hearing levels in pure tone average of values at 500, 1000, 2000, 4000 Hz (in 10 dB increments) on the MDS < 60%. Significant associations were observed between MDS < 60% and age (odds ratio, 3.03; 95% confidence interval, 2.38 to 3.85), and mean hearing levels in pure tone average of values at 500, 1000, 2000, 4000 Hz (2.33; 2.03 to 2.68). Sex was not associated with MDS < 60%. In the model 2, multiple logistic analyses adjusted for age and sex were performed to examine the effect of hearing level at test frequencies of 125, 250, 500, 1000, 2000, 4000, and 8000 Hz (in 10 dB increments)on the MDS < 60%. Significant associations were observed between MDS < 60% and hearing level at 250 Hz (2.04; 1.44 to 2.89), and 2000 Hz (1.46; 1.16 to 1.83), and 4000 Hz(1.24; 1.02 to 1.50). These outcomes suggest that the important point in qualifying the fitting of hearing aid is to present the list words at an adequate sound pressure level for evaluation of speech understanding especially in the hearing impaired elderly listeners.
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http://dx.doi.org/10.3950/jibiinkoka.117.1080DOI Listing
August 2014

Progress and prospects in human genetic research into age-related hearing impairment.

Biomed Res Int 2014 22;2014:390601. Epub 2014 Jul 22.

Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.

Age-related hearing impairment (ARHI) is a complex, multifactorial disorder that is attributable to confounding intrinsic and extrinsic factors. The degree of impairment shows substantial variation between individuals, as is also observed in the senescence of other functions. This individual variation would seem to refute the stereotypical view that hearing deterioration with age is inevitable and may indicate that there is ample scope for preventive intervention. Genetic predisposition could account for a sizable proportion of interindividual variation. Over the past decade or so, tremendous progress has been made through research into the genetics of various forms of hearing impairment, including ARHI and our knowledge of the complex mechanisms of auditory function has increased substantially. Here, we give an overview of recent investigations aimed at identifying the genetic risk factors involved in ARHI and of what we currently know about its pathophysiology. This review is divided into the following sections: (i) genes causing monogenic hearing impairment with phenotypic similarities to ARHI; (ii) genes involved in oxidative stress, biologic stress responses, and mitochondrial dysfunction; and (iii) candidate genes for senescence, other geriatric diseases, and neurodegeneration. Progress and prospects in genetic research are discussed.
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http://dx.doi.org/10.1155/2014/390601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4130297PMC
May 2015