A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing.

The miR-96, miR-182 and miR-183 microRNA (miRNA) family is essential for differentiation and function of the vertebrate inner ear. Recently, point mutations within the seed region of miR-96 were reported in two Spanish families with autosomal dominant non-syndromic sensorineural hearing loss (NSHL) and in a mouse model of NSHL. We screened 882 NSHL patients and 836 normal-hearing Italian controls and identified one putative novel mutation within the miR-96 gene in a family with autosomal dominant NSHL. Although located outside the mature miR-96 sequence, the detected variant replaces a highly conserved nucleotide within the companion miR-96*, and is predicted to reduce the stability of the pre-miRNA hairpin. To evaluate the effect of the detected mutation on miR-96/mir-96* biogenesis, we investigated the maturation of miR-96 by transient expression in mammalian cells, followed by real-time reverse-transcription polymerase chain reaction (PCR). We found that both miR-96 and miR-96* levels were significantly reduced in the mutant, whereas the precursor levels were unaffected. Moreover, miR-96 and miR-96* expression levels could be restored by a compensatory mutation that reconstitutes the secondary structure of the pre-miR-96 hairpin, demonstrating that the mutation hinders precursor processing, probably interfering with Dicer cleavage. Finally, even though the mature miR-96 sequence is not altered, we demonstrated that the identified mutation significantly impacts on miR-96 regulation of selected targets. In conclusion, we provide further evidence of the involvement of miR-96 mutations in human deafness and demonstrate that a quantitative defect of this miRNA may contribute to NSHL.

Exacerbation of audiovestibular symptoms in a patient with Ménière's disease and choroidal melanoma.

We report the case of a man affected by a unilateral Ménière's disease who, after being free from vertigo spells and tinnitus for more than ten years, manifested an exacerbation of symptoms just before the diagnosis of a choroidal melanoma. Melanoma is an aggressive form of cancer derived from neuroectodermal melanocytes. Melanocytes are present in the inner ear where they contribute to the production of endolymphatic potentials and to the maintenance of normal volumes of the inner ear fluids. A possible autoimmune connection between the exacerbation of audiovestibular symptoms and melanoma is discussed.

Reliability of postural control measures in children and young adolescents.

Although many studies have been carried out regarding postural stability during pediatric age, reliable information and a complete analysis of all age groups are still lacking. The purpose of this study was to verify the test-retest reliability of posturographic parameters in four sensory conditions and provide normative values for children and young adolescents. 289 subjects, aged 6-14 years, were assessed by means of the static posturography system SVeP. 173 elementary school pupils (114 males and 59 females, aged 6-10 years; mean age 8.80 ± 1.53) and 116 middle school students (60 males and 56 females, aged 11-14 years; mean age 12.6 ± 0.9) underwent static posturography in two consecutive trials with four testing conditions: eyes open and eyes closed with and without foam pads. The participants were divided into nine age groups. Thirty healthy young adults were also recruited for comparison. The analysis of test-retest reliability demonstrated an excellent reliability of velocity measurement and a moderate reliability of area measurement. Velocity and area decreased significantly with age in all sensory conditions, indicating an improvement in postural control from childhood to adolescence. Postural stability had not reached the adult level by the age of 13-14 years. Reliable information regarding postural stability can be obtained in children and young adolescents by means of stabilometric parameters. These data can be used as a reference for early detection of atypical postural development and for the assessment of dizziness and balance disorders in children.

Ménière disease and gluten sensitivity: recovery after a gluten-free diet.

We report the case of a 63-year-old female with definite unilateral Ménière disease, osteoarthritis of the distal finger joints with mucous cysts and Heberden's nodes, and constipation with recurrent abdominal pain whose symptoms remitted after 6months of a restrictive gluten-free diet.

Public awareness of ear and hearing management as measured using a specific questionnaire.

Public awareness of audiological issues has never been measured in the general public even if the World Health Organization (WHO) has detected a common urgent need for action to prevent and manage ear diseases and hearing loss. The aim of this study was to measure urban community citizens' awareness of managing and preventing ear disease and hearing loss using a specific questionnaire. A questionnaire was formulated on the basis of WHO material concerning the major specific audiological issues and attitudes, focusing in particular on four domains: (1) knowledge of infant hearing loss, (2) correct management of the ears including cleaning and treating, (3) focus on the effect of overexposure to loud sounds and noise, (4) underestimated ear symptoms leading to diagnostic delay. 254 volunteers were enrolled in this cross-sectional study by a team of medical doctors and audiologists stationed in a mobile unit that visited different areas of Milan, Italy. More than 80% of correct responses were given to almost all of the statements by the interviewees, although certain important knowledge was found to be lacking. The proposed audiological questionnaire seems to be a suitable tool to evaluate the public awareness of ear and hearing management. The results showed a need for continued development of comprehensive hearing conservation programs, focused on hearing aid management and early infant hearing loss identification as well as noise exposure.

The effect of a gluten-free diet on a patient complaining of severe tinnitus.

We report a case of a patient complaining of severe high pitched tinnitus, dizziness, joint/muscle pain and gastrointestinal symptoms. A mild high-frequency sensorineural hearing loss of cochlear origin was diagnosed in the ear where tinnitus was present. The patient reported a considerable decrease in tinnitus and other symptoms with a gluten-free diet. Gluten sensitivity may have contributed to the pathogenesis of tinnitus in our patient; further research is needed to determine the exact role of gluten in this condition.

Benign paroxysmal positional vertigo and tinnitus.

INTRODUCTION: In our clinical experience, some of the patients affected by benign paroxysmal positional vertigo (BPPV) reported the onset of tinnitus shortly before or in association with the positional vertigo. OBJECTIVES: The aim of this study was to describe the prevalence and the clinical patterns of tinnitus episodes which occurred in association with BPPV and to suggest possible interpretative hypotheses. METHODS: 171 normal hearing patients affected by BPPV (50 males and 122 females; age range: 25-77 years; mean age 60.3 years ± 14.9) underwent pure tone audiometry, immittance test and a clinical vestibular evaluation before and after repositioning manoeuvers. Those suffering from tinnitus were also assessed using visual analogue scales and tinnitus handicap inventory. RESULTS: 19.3% of the patients reported the appearance of tinnitus concurrently with the onset of the positional vertigo. It was mostly unilateral, localized on the same ear as the BPPV, slight in intensity and intermittent. Tinnitus disappeared or decreased in all patients except two, either spontaneously, before performing the therapeutic manoeuvers, or shortly after. CONCLUSIONS: A possible vestibular origin of tinnitus determined by the detachment of macular debris into the ductus reuniens and cochlear duct is discussed.

Audiological findings in Williams syndrome: a study of 69 patients.

The aim of this study was to investigate, in a clinical setting, the auditory function of a group of individuals affected by Williams syndrome (WS). Sixty-nine patients with WS, aged 2-30, underwent comprehensive audiological testing including air/bone conduction behavioral audiometry, speech audiometry, tympanometry and measurement of the acoustic reflex, transient evoked otoacoustic emissions and brainstem auditory evoked responses. Hearing loss, defined by a pure-tone average above 15 dB HL, affected 22.6% of the patients studied with traditional audiometry and was mostly slight in severity. Hearing loss was conductive in 9.4% of patients, mainly children with otitis media with effusion, and sensorineural in 13.2% of patients. However, 30% of the ears studied had a hearing impairment in the high frequency range (high-frequency pure-tone audiometry above 15 dB HL), higher in participants above 15 years (46.15%) than in the younger ones (23.45%). Contralateral stapedial reflexes were present in all patients with A-type tympanograms. Transient otoacoustic emissions were absent in 44% of the ears of patients with normal hearing. Brainstem auditory evoked responses fell within normal ranges thus confirming the absence of retrocochlear dysfunction. Although hearing loss does not seem to be frequent, a cochlear fragility, especially in the high frequency range, related to outer hair cells is characteristic of WS. Therefore we strongly recommend monitoring patients affected by WS using annual audiometric tests and performing otoacoustic emissions in order to identify a subclinical cochlear dysfunction which might benefit from an audiological follow up before the possible onset of hearing loss.

VTMR, a new speech audiometry test with verbal tasks and motor responses.

OBJECTIVES: The aim of this study was to design a complementary speech audiometry test using verbal tasks and motor responses (VTMR) to assess the ability of a subject to understand and perform simple motor tasks with 3-dimensional objects, to describe its construction, and to show the preliminary results of a pilot study on the Italian version of the test. METHODS: The items used in the test setting included 1 base, 1 hammer, 1 wooden structure with 4 sticks, and 5 rings of different colors and 20 lists with 5 verbal tasks per list. The VTMR test and bisyllabic speech audiometry were evaluated in normal-hearing subjects with and without cognitive impairment and in subjects with sensorineural hearing loss. RESULTS: All normal-hearing subjects without cognitive impairment performed the VTMR tasks (100%) correctly at 35 dB sound pressure level. In subjects with sensorineural hearing loss, the percentage of correct answers was significantly higher for the VTMR test than for bisyllabic speech audiometry above 50 dB sound pressure level. This percentage was higher for the VTMR also in normal-hearing subjects with poor cognitive skills. CONCLUSIONS: The VTMR might make it easier to check patients' ability to understand verbal commands than does traditional speech audiometry, in particular in those patients with poor test-taking skills.

Non-verbal visual reinforcement affects speech audiometry in the elderly.

The purpose of this study was to investigate how non-verbal visual reinforcement provided by the audiologist during speech testing influences performance in the elderly. Thirty-two volunteers with age-related hearing loss with or without dual sensory-impairment (DSI), were administered a speech audiometry test in which they repeated lists of ten disyllabic words in two different conditions, namely with and without visual reinforcement. In the conditions of "with visual reinforcement", the tester provided non-verbal cues to acknowledge the response of each participant. The "visual reinforcement" condition did not apparently provide any significant variation in the results. However, when we considered the group of patients without DSI, the non-verbal "visual reinforcement" resulted in better scores (p < 0.001). Non-verbal visual reinforcement may influence speech audiometry results in the elderly. During speech testing of elderly people with age-related hearing loss, audiologists should always remember to administer visual reinforcement to the patients in order to remove a possible confounding factor from audiological evaluation.

The use of rubber foam pads and "sensory ratios" to reduce variability in static posturography assessment.

UNLABELLED: Despite the numerous works published, static posturography has still a limited clinical use due to its intrinsic inter-individual high variability. For this reason, foam pads have been introduced but their use is still not standardized. Aim of the study was to define the variability of static posturography parameters in standard and foam standing. METHODS: 50 healthy subjects were studied with static posturography in four standing conditions: eyes open (EO) and eyes closed (EC), with and without foam pads. Unstable tests have been performed with two different types of rubber foam pads placed on the force platform. "Sensory ratios" have been calculated by the ratio of sway length among the four different conditions, adapted from dynamic posturography, in order to measure the relative contributions of vestibular, visual and somatosensory inputs. RESULTS: Static posturography in standard conditions showed unacceptable coefficients of variation (>than 15%) for all the parameters. The use of foam pads reduced the high intrinsic variability, in particular for LFS (12.6-15.4%). The use of "sensory ratios" led to decrease the inter-subject coefficient of variation of this measurement to about 9.47-14.42% using the bilayer foam pads. CONCLUSIONS: Further studies are needed to confirm these data by applying the ratio formulas in clinical practice.

Auditory brainstem responses (ABR) in normal hearing adult subjects with Down's syndrome.

BACKGROUND: Auditory brainstem responses (ABRs) have been previously investigated in subjects with Down's syndrome (DS), but the published data are generally from children with hearing loss. The aim of this study was to evaluate the hearing pathway in normal hearing adult DS patients. METHODS: We used ABRs to analyze absolute and interpeak latencies in 19 adult DS patients aged 18-45 years whose pure tone audiometry (PTA) test results indicated thresholds within normal limits, and 19 normal controls. RESULTS: The DS sample showed statistically significant gender-related differences in interpeak interval III-V (p = 0.015). The latencies of waves III and V, and interpeak intervals III-V and I-V, were significantly shortened in the DS patients than in the controls. CONCLUSIONS: Our findings may be due to the smaller brain sizes and simpler afferent auditory pathways of DS subjects.

[Prevalence of hearing loss in elderly individuals over 65 years of age: a pilot study in Lombardia (Italy)]. / Prevalenza della sordità in soggetti di età superiore ai 65 anni. Studio pilota in un campione di popolazione Lombarda.

A cross sectional study was performed to determine the prevalence of hearing loss in individuals over age 65 years presenting to a medical centre in Lombardia (Italy). The aim was to assess the feasibility of performing a survey to evaluate the prevalence of hearing loss in the entire region. Audiometric testing was performed in each enrolled subject, to reveal losses in hearing levels at 250 to 8000 Hz; hearing levels were measured in decibels. Prevalences of mild, moderate, severe, and profound hearing impairment were found to be 39%, 17.4%, 2.9% and 0.6% respectively when using the WHO classification, and 59.9%, 25.6%, 2.9%, and 0.6% respectively when using the classification of the Bureau International d'Audiophonologie (BIAP).This study has shown that a relevant part of the study population is affected by hearing impairment and has served as a pilot study for a larger-scale study to be performed in the Lombardia region.

A new de novo missense mutation in connexin 26 in a sporadic case of nonsyndromic deafness.

OBJECTIVES: Mutations in the GJB2 gene, encoding Connexin 26, can cause nonsyndromic recessive deafness or dominant hearing loss (HL) with or without keratoderma. The objective was to perform a molecular evaluation to establish the inherited pattern of deafness in the sporadic cases afferent to our center. METHODS: The subject was a 2-year-old Italian girl with nonsyndromic early onset HL. We performed DNA sequencing of the GJB2 gene and deletion analysis of the GJB6 gene in all family members. RESULTS: Direct sequencing of the gene showed a heterozygous C-->G transition at nucleotide 172 resulting in a proline to alanine amino acid substitution at codon 58 (P58A). The analyses indicate that the P58A mutation appeared de novo in the proband with a possible dominant effect. CONCLUSIONS: This mutation occurs in the first extracellular domain (EC1), which seems to be very important for connexon-connexon interaction and for the control of voltage gating of the channel. The de novo occurrence of an EC1 mutation in a sporadic case of deafness is consistent with the assumption that P58A can cause dominant HL.

Tinnitus school: an educational approach to tinnitus management based on a stress-reaction tinnitus model.

Stress is a significant factor influencing the clinical course of tinnitus. The auditory system is particularly sensitive to the effects of various stress factors (chemical, oxidative, emotional, etc.). Different stages of reaction (alarm, resistance, exhaustion) lead to different characteristics of tinnitus and to different therapeutic approaches. Individual characteristics of stress reaction may explain different aspects of tinnitus in various patients with different responses to treatment, despite similar audiological and etiological factors. A model based on individual reactions to stress factors (stress-reaction tinnitus model, or SRTM) could explain tinnitus as an alarm signal. In each patient, stressors have to be identified during the alarm phase to prevent an evolution toward the resistance and exhaustion phases. In the exhaustion phase, chronic tinnitus is due to the organization of a paradoxical auditory memory and a pathologically shifted attention to tinnitus. The aim of our study is to describe a therapeutic proposal based on the SRTM by taking an educational approach to management of chronic tinnitus. The educational aspect is emphasized; thus, we named our approach tinnitus school. Selection of appropriate patients and follow-up is based on psychometrics of tinnitus and stress questionnaires, including a tinnitus reaction questionnaire, a tinnitus cognitive questionnaire, and a 20-item perceived stress questionnaire. Tinnitus school is a three-phase program: counseling, training, and home training. Training is based on a tinnitus-fitted physiotherapeutic protocol.

Viral infection and serum antibodies to heat shock protein 70 in the acute phase of Ménière's disease.

Ménière's disease (MD) is an idiopathic inner-ear disorder characterized by fluctuating hearing loss, episodic vertigo, and tinnitus. Though MD's etiology is unknown, growing evidence suggests that autoimmunity may be involved in its development. The aim of this prospective study was to investigate the presence of anti-heat shock protein 70 (anti-HSP70) antibodies during the acute phase of MD and to relate its presence to the antibody pattern. We examined the sera of 13 patients by Western blot immunoassays for reactivity to bovine inner-ear antigen (anti-HSP70) antibodies. The presence of viral antibodies and autoantibodies (herpes simplex, types 1, 2; herpes zoster; cytomegalovirus; Epstein-Barr; IgM; IgG; cardiolipin; thyroglobulin and thyroperoxidase; and antinuclear, antimitochondrial, and anti-smooth-cell antibodies) were also tested. We found reactivity to HSP70 in only 1 of the 13 MD patients (7.7%), and it occurred during herpes zoster reactivation. We found no relationship between the presence of antibodies to HSP70 and immunological or viral testing.

A comparison between oculomotor rehabilitation and vestibular electrical stimulation in unilateral peripheral vestibular deficit.

Rehabilitation therapy is proved to be effective in reducing disability in patients with persistent symptoms of disequilibrium after acute unilateral peripheral vestibular deficit. The aim of this study was to evaluate the effects of oculomotor rehabilitation (group 2) on static balance and a dizziness handicap and to compare those with the effects to vestibular electrical stimulation (group 1). Before and after therapy, we tested 28 patients, using static posturography and.the dizziness handicap inventory short form. After therapy, all subjects reported a reduction of symptoms (p = .00019). In group 1, the reductions seen in eyes-opened length of the oscillations and eyes-opened and eyes-closed surface of the body sway were statistically significant, respectively (p = .04; p = .02; p = .02). Group 2 patients revealed better stability on all parameters, and the reductions of eyes-opened length and of eyes-opened correlation function between length and surface were statistically significant (p = .01 and p = .01, respectively). Analysis of the equilibrium system subcomponents did not show any variation. Oculomotor exercises,employed in most rehabilitative protocols and including head movements to improve vestibular adaptation, have proved to reduce the perceived overall impairment and postural sway in patients with recent unilateral vestibular disorders, even though the disorders are not associated with head movements. Comparison of our two study groups did not show any significant difference, revealing that both forms of therapy are effective.

The occlusal imaging and analysis system by T-scan III in tinnitus patients.

BACKGROUND: Several studies have demonstrated that the prevalence of temporomandibular disorders (TMDs) in tinnitus patients ranges from 7% to 95%, and it is reported in literature that idiopathic tinnitus patients should be referred to a dentist to define whether or not the tinnitus is associated with TMD. However, the possible pathophysiological relation between TMDs and tinnitus is not generally investigated in clinical practice. METHODS: The patterns and forces of occlusal contacts have been studied by means of T-scan III in 47 tinnitus patients (23 suffering from idiopathic tinnitus and 24 affected by Ménière disease [MD]) and 13 healthy subjects. RESULTS: The center of force target was offset in the opposite direction in 15/23 idiopathic tinnitus and in 7/24 MD patients (p = 0.026). No significant variation was found in the occlusal force. CONCLUSIONS: Our data suggest that a diagnostic screening method for occlusal stability in the intercuspidal position might be clinically useful in idiopathic tinnitus patients.