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Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing compl

Auditory processing disorders may have detrimental consequences on a child's life, if undiagnosed and untreated. We review causes of auditory processing disorders in order to raise clinical awareness. Auditory processing disorders may present against a background of neurological disease or developmental disorders, as well as in isolation. Clinicians need to be aware of potential causes and implications of auditory processing disorders. [ABSTRACT FROM AUTHOR]

Objective: To determine the feasibility and effectiveness of a community-based universal infant hearing screening programme for detecting permanent congenital and early-onset hearing loss (PCEHL) in Lagos, Nigeria.Method: This is a cross-sectional study in which all infants aged 3 months or under attending four bacille Calmette-Guérin (BCG) immunization clinics accounting for over 75% of the BCG coverage in the study location were screened by community health workers between July 2005 and April 2006. Screening followed a two-stage protocol involving transient evoked otoacoustic emissions and automated auditory brainstem responses. The main outcome measures were screening coverage, referral rates, return rates for second-stage screening and evaluation, yield and age at PCEHL diagnosis.Findings: In total, 2003 (88%) of 2277 eligible infants attending the four BCG clinics were successfully screened between July 2005 and April 2006 at a mean age of 17.7 days, with no parent declining screening. The majority (55.2%) were born outside a hospital and, of such infants, 77% were born in traditional herbal maternity homes. The overall referral rate for diagnostic evaluation was 4.1%. Only 61% (50/82) of those referred returned for evaluation, and 45 of them were confirmed with PCEHL. Additionally, 11 infants who had previously passed the first screening stage were also found to have PCEHL, resulting in a yield of 28 per 1000 (56/2003). The mean age at diagnosis was 51 days. The sensitivity, specificity and positive predictive value of the first screening stage were 80.4%, 99.7% and 90.0%, respectively. The positive likelihood ratio was 268, while the negative likelihood ratio was 0.2.Conclusion: Routine hearing screening of infants attending BCG immunization clinics by community health workers was feasible and effective for the early detection of PCEHL in Lagos, Nigeria. However, an efficient tracking and follow-up system is needed to improve return rates for second-stage screening and diagnostic evaluation. Copyright © 2008 World Health Organization [ABSTRACT FROM AUTHOR]

X-linked adrenoleukodystrophy (X-ALD) is characterized by demyelination that is associated with a deficient beta-oxidation of very long chain fatty acids. We report the unusual case of a male adult with X-ALD who was diagnosed at the age of 26 by a brain MRI performed because his brother had been diagnosed with a rapidly deteriorating form of X-ALD. His sole symptom was hearing difficulties in the presence of a normal audiogram since childhood. He has remained stable for seven years. Central auditory testing in our patient revealed severe deficits in several auditory processes. These findings correlated with involvement of the auditory pathway at the level of the trapezoid body, and posterior corpus callosum in particular, on his brain MRI. This case highlights not only the need for thorough audiological investigation of the patient who complains of hearing difficulties in the presence of a normal audiogram, but also that audiological investigations could be of value in the phenotypic evaluation of cases with adrenoleukodystrophy. [ABSTRACT FROM AUTHOR]

Background: Dizziness and imbalance are common symptoms that are often inadequately diagnosed or managed, due to a lack of dedicated specialists. Decision Support Systems (DSS) may support first-line physicians to diagnose and manage these patients based on personalised data., Aim: To examine the diagnostic accuracy and application of the EMBalance DSS for diagnosis and management of common vestibular disorders in primary care., Methods: Patients with persistent dizziness were recruited from primary care in Germany, Greece, Belgium and the UK and randomised to primary care clinicians assessing the patients with (+ DSS) versus assessment without (- DSS) the EMBalance DSS. Subsequently, specialists in neuro-otology/audiovestibular medicine performed clinical evaluation of each patient in a blinded way to provide the "gold standard" against which the + DSS, - DSS and the DSS as a standalone tool (i.e. without the final decision made by the clinician) were validated., Results: One hundred ninety-four participants (age range 25-85, mean = 57.7, SD = 16.7 years) were assigned to the + DSS (N = 100) and to the - DSS group (N = 94). The diagnosis suggested by the + DSS primary care physician agreed with the expert diagnosis in 54%, compared to 41.5% of cases in the - DSS group (odds ratio 1.35). Similar positive trends were observed for management and further referral in the + DSS vs. the - DSS group. The standalone DSS had better diagnostic and management accuracy than the + DSS group., Conclusion: There were trends for improved vestibular diagnosis and management when using the EMBalance DSS. The tool requires further development to improve its diagnostic accuracy, but holds promise for timely and effective diagnosis and management of dizzy patients in primary care., Trial Registration Number: NCT02704819 (clinicaltrials.gov)., (© 2021. The Author(s).)

Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular disorder that is diagnosed based solely on clinical findings. Rarely, central lesions can present with positional vertigo and nystagmus, mimicking BPPV. Recognised red flags that may help distinguish central mimics from BPPV include the presence of additional neurological symptoms and signs, atypical nystagmus patterns, and the absence of a sustained response to repositioning manoeuvres. We present seven cases that illustrate how heuristic bias may affect the detection of these features in practice. Furthermore, our cases suggest that isolated downbeat positional nystagmus (simulating anterior canal BPPV) and apogeotropic horizontal nystagmus on the supine roll test (simulating horizontal canal BPPV) should be considered additional red flags.

Aims: To develop and validate the Pediatric Visually Induced Dizziness Questionnaire (PVID) and quantify the presence and severity of visually induced dizziness (ViD), i.e., symptoms induced by visual motion stimuli including crowds and scrolling computer screens in children., Methods: 169 healthy (female n  = 89; recruited from mainstream schools, London, UK) and 114 children with a primary migraine, concussion, or vestibular disorder diagnosis (female n  = 62), aged 6-17 years, were included. Children with primary migraine were recruited from mainstream schools while children with concussion or vestibular disorder were recruited from tertiary balance centers in London, UK, and Pittsburgh, PA, USA. Children completed the PVID, which assesses the frequency of dizziness and unsteadiness experienced in specific environmental situations, and Strength and Difficulties Questionnaire (SDQ), a brief behavioral screening instrument., Results: The PVID showed high internal consistency (11 items; α = 0.90). A significant between-group difference was noted with higher (i.e., worse) PVID scores for patients vs. healthy participants ( U  = 2,436.5, z  = -10.719, p  < 0.001); a significant difference was noted between individual patient groups [χ 2 (2) = 11.014, p  = 0.004] but post hoc analysis showed no significant pairwise comparisons. The optimal cut-off score for discriminating between individuals with and without abnormal ViD levels was 0.45 out of 3 (sensitivity 83%, specificity 75%). Self-rated emotional ( U  = 2,730.0, z  = -6.169) and hyperactivity ( U  = 3,445.0, z  = -4.506) SDQ subscale as well as informant ( U  = 188.5, z  = -3.916) and self-rated ( U  = 3,178.5, z  = -5.083) total scores were significantly worse for patients compared to healthy participants ( p  < 0.001)., Conclusion: ViD is common in children with a primary concussion, migraine, or vestibular diagnosis. The PVID is a valid measure for identifying the presence of ViD in children and should be used to identify and quantify these symptoms, which require specific management incorporating exposure to optokinetic stimuli.

Objective: To develop and validate the Pediatric Vestibular Symptom Questionnaire (PVSQ) and quantify subjective vestibular symptom (ie, dizziness, unsteadiness) severity in children., Study Design: One hundred sixty-eight healthy children (female, n = 91) and 56 children with postconcussion dizziness or a vestibular disorder (female, n = 32), between ages 6 and 17 years, were included. The PVSQ contains questions regarding vestibular symptom frequency during the previous month. The Strengths and Difficulties Questionnaire (SDQ), a brief behavioral screening instrument, was also completed., Results: The PVSQ showed high internal consistency (10 items; Cronbach α = 0.88). A significant between-group difference was noted with higher (ie, worse) PVSQ scores for children with vestibular symptoms (P < .001); no significant differences were noted between patient groups. The optimal cut-off score for discriminating between individuals with and without abnormal levels of vestibular symptoms was 0.68 out of 3 (sensitivity 95%, specificity 85%). Emotional and hyperactivity SDQ subscale scores were significantly worse for patients compared with healthy participants (P ≤ .01). A significant relationship was noted between mean PVSQ and SDQ (parent-rated version) hyperactivity and total scores for patients (P ≤ .01) and the SDQ (self-rated) emotional, hyperactivity, and total score (P ≤ .01) in healthy controls. However, mean SDQ subscale and total scores were within normal ranges for both groups., Conclusions: Self-reported vestibular symptoms, measured by the PVSQ, discriminated between children presenting with vestibular symptoms and healthy controls and should be used to identify and quantify vestibular symptoms that require additional assessment and management., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.

Low-level radiofrequency (RF) signals may produce disorientation and nausea. In experiment I, we assessed mobile phone effects on graviception in nine symptomatic subjects after mobile telephone use and 21 controls. The mobile handset was strapped to each ear for 30 min in pulsed emission, continuous RF emission, or no emission test mode, respectively. The subjective visual vertical and horizontal (SVV/SVH) were tested from min 25 of exposure. There was no exposure effect; however, there was an ear effect, with the SVV/SVH being shifted to the opposite direction of the ear exposed. This could be due to thermal or RF effects or handset weight. In experiment II, we assessed the handset weight effect on 18 normal controls. After baseline SVV/SVH, the switched off handset was strapped to either ear; the SVV/SVH was repeated 25 min later. A significant ear effect was found. We compared the observed ear effect SVV/SVH change in the experiment II group to the continuous exposure ear effect change in the experiment I group, and the difference was not significant. The ear effect was attributed to a minor head tilt due to the handset weight, or proprioceptive stimulation of neck muscle affecting the perception of verticality., (© 2014 Wiley Periodicals, Inc.)

Objective: This paper reviews the current literature on involvement of the vestibular division of the eighth cranial nerve in peripheral neuropathies. The literature abounds with references to auditory neuropathy, which is frequently related to more generalized neuropathies, but there is a marked paucity of work regarding vestibular neuropathy. A brief overview of neuropathies and the anatomy of the vestibulocochlear nerve provide the background for a review of the literature of vestibular nerve involvement in a range of neuropathies., Design: A literature search including textbooks, and peer-reviewed published journal articles in online bibliographic databases was conducted., Study Sample: Two databases for medical research were included in this review., Results: The review of the literature indicates that vestibular involvement is a common and consistent finding in many peripheral neuropathies of different aetiologies. Specifically, if patients present unsteadiness/ataxia out of proportion to objective signs of somatosensory loss or muscle weakness., Conclusion: This review concludes that vestibular neuropathy, is common in peripheral neuropathy and should be identified to optimize patient management and rehabilitation.

Purpose: To evaluate the phenotypic variability and natural history of ocular disease in a cohort of 28 individuals with MYO7A-related disease. Mutations in the MYO7A gene are the most common cause of Usher syndrome type 1, characterized by profound congenital deafness, vestibular arreflexia, and progressive retinal degeneration., Design: Retrospective case series., Participants: Twenty-eight patients from 26 families (age range, 3-65 years; median, 32) with 2 likely disease-causing variants in MYO7A., Methods: Clinical investigations included fundus photography, optical coherence tomography, fundus autofluorescence (FAF) imaging, and audiologic and vestibular assessments. Longitudinal visual acuity and FAF data (over a 3-year period) were available for 20 and 10 study subjects, respectively., Main Outcome Measures: Clinical, structural, and functional characteristics., Results: All patients with MYO7A mutations presented with features consistent with Usher type 1. The median visual acuity for the cohort was 0.39 logarithm of the minimum angle of resolution (logMAR; range, 0.0-2.7) and visual acuity in logMAR correlated with age (Spearman's rank correlation coefficient, r = 0.71; P<0.0001). Survival analysis revealed that acuity ≤ 0.22 logMAR was maintained in 50% of studied subjects until age 33.9; legal blindness based on loss of acuity (≥ 1.00 logMAR) or loss of field (≤ 20°) was reached at a median age of 40.6 years. Three distinct patterns were observed on FAF imaging: 13 of 22 patients tested had relatively preserved foveal autofluorescence surrounded by a ring of high density, 4 of 22 had increased signal in the fovea with no obvious hyperautofluorescent ring, and 5 of 22 had widespread hypoautofluorescence corresponding to retinal pigment epithelial atrophy. Despite a number of cases presenting with a milder phenotype, there seemed to be no obvious genotype-phenotype correlation., Conclusions: MYO7A-related ocular disease is variable. Central vision typically remains preserved at least until the third decade of life, with 50% of affected individuals reaching legal blindness by 40 years of age. Distinct phenotypic subsets were identified on FAF imaging. A specific allele, previously reported in nonsyndromic deafness, may be associated with a mild retinopathy., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Usher Syndrome is the leading cause of inherited deaf-blindness. It is divided into three subtypes, of which the most common is Usher type 2, and the USH2A gene accounts for 75-80% of cases. Despite recent sequencing strategies, in our cohort a significant proportion of individuals with Usher type 2 have just one heterozygous disease-causing mutation in USH2A, or no convincing disease-causing mutations across nine Usher genes. The purpose of this study was to improve the molecular diagnosis in these families by screening USH2A for duplications, heterozygous deletions and a common pathogenic deep intronic variant USH2A: c.7595-2144A>G., Methods: Forty-nine Usher type 2 or atypical Usher families who had missing mutations (mono-allelic USH2A or no mutations following Sanger sequencing of nine Usher genes) were screened for duplications/deletions using the USH2A SALSA MLPA reagent kit (MRC-Holland). Identification of USH2A: c.7595-2144A>G was achieved by Sanger sequencing. Mutations were confirmed by a combination of reverse transcription PCR using RNA extracted from nasal epithelial cells or fibroblasts, and by array comparative genomic hybridisation with sequencing across the genomic breakpoints., Results: Eight mutations were identified in 23 Usher type 2 families (35%) with one previously identified heterozygous disease-causing mutation in USH2A. These consisted of five heterozygous deletions, one duplication, and two heterozygous instances of the pathogenic variant USH2A: c.7595-2144A>G. No variants were found in the 15 Usher type 2 families with no previously identified disease-causing mutations. In 11 atypical families, none of whom had any previously identified convincing disease-causing mutations, the mutation USH2A: c.7595-2144A>G was identified in a heterozygous state in one family. All five deletions and the heterozygous duplication we report here are novel. This is the first time that a duplication in USH2A has been reported as a cause of Usher syndrome., Conclusions: We found that 8 of 23 (35%) of 'missing' mutations in Usher type 2 probands with only a single heterozygous USH2A mutation detected with Sanger sequencing could be attributed to deletions, duplications or a pathogenic deep intronic variant. Future mutation detection strategies and genetic counselling will need to take into account the prevalence of these types of mutations in order to provide a more comprehensive diagnostic service.

Objective: To assess auditory processing in noise-exposed subjects with normal audiograms and compare the findings with those of non-noise-exposed normal controls., Methods: Ten noise-exposed Royal Air Force aircrew pilots were compared with 10 Royal Air Force administrators who had no history of noise exposure. Participants were matched in terms of age and sex. The subjects were assessed in terms of: pure tone audiometry, transient evoked otoacoustic emissions, suppression of transient evoked otoacoustic emissions in contralateral noise and auditory processing task performance (i.e. masking, frequency discrimination, auditory attention and speech-in-noise)., Results: All subjects had normal pure tone audiometry and transient evoked otoacoustic emissions amplitudes in both ears. The noise-exposed aircrew had similar pure tone audiometry thresholds to controls, but right ear transient evoked otoacoustic emissions were larger and speech-in-noise thresholds were elevated in the noise-exposed subjects compared to controls., Conclusion: The finding of poorer speech-in-noise perception may reflect noise-related impairment of auditory processing in retrocochlear pathways. Audiometry may not detect early, significant noise-induced hearing impairment.

Objectives/hypothesis: To compare self-reported symptoms of difficulty hearing speech in noise and hyperacusis in adults with auditory processing disorders (APDs) and normal controls; and to compare self-reported symptoms to objective test results (speech in babble test, transient evoked otoacoustic emission [TEOAE] suppression test using contralateral noise)., Study Design: A prospective case-control pilot study., Methods: Twenty-two participants were recruited in the study: 10 patients with reported hearing difficulty, normal audiometry, and a clinical diagnosis of APD; and 12 normal age-matched controls with no reported hearing difficulty. All participants completed the validated Amsterdam Inventory for Auditory Disability questionnaire, a hyperacusis questionnaire, a speech in babble test, and a TEOAE suppression test using contralateral noise., Results: Patients had significantly worse scores than controls in all domains of the Amsterdam Inventory questionnaire (with the exception of sound detection) and the hyperacusis questionnaire (P < .005). Patients also had worse TEOAE suppression test results in both ears than controls; however, this result was not significant after Bonferroni correction. Strong correlations were observed between self-reported symptoms of difficulty hearing speech in noise and speech in babble test results in the right ear (ρ = 0.624, P = .002), and between self-reported symptoms of hyperacusis and TEOAE suppression test results in the right ear (ρ = -0.597 P = .003)., Conclusions: There was no significant correlation between the two tests. A strong correlation was observed between right ear speech in babble and patient-reported intelligibility of speech in noise, and right ear TEOAE suppression by contralateral noise and hyperacusis questionnaire., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Background and Purpose: Auditory functional limitations experienced by patients after stroke of the central auditory pathways remain underinvestigated. Purpose- To measure patient-reported hearing difficulties in everyday life in nonaphasic patients with stroke of the auditory brain versus normal control subjects. To examine how hearing difficulties correlate with auditory tests and site of lesion in individual cases., Methods: We recruited 21 individuals with auditory brain stroke (excluding those with aphasia) diagnosed on the basis of a brain MRI conducted 1 to 2 weeks after the stroke and assessed in the chronic stage of stroke. Twenty-three controls matched for age and hearing were also recruited. All subjects completed the Amsterdam Inventory for Auditory Disability (consisting of subscales of sound detection, recognition, localization, speech in quiet, speech in noise) and underwent baseline audiometry and central auditory processing tests (dichotic digits, frequency and duration patterns, gaps in noise)., Results: Sound recognition and localization subscores of the inventory were significantly worse in case subjects versus control subjects, with severe and significant functional limitation (z score >3) reported by 9 out of 21 case subjects. None of the inventory subscales correlated with audiometric thresholds, but localization and recognition subscales showed a moderate to strong correlation with dichotic digits (left ear) and pattern tests., Conclusions: A substantial proportion of patients may experience and report severe auditory functional limitations not limited to speech sounds after stroke of the auditory brain. A hearing questionnaire may help identify patients who require more extensive assessment to inform rehabilitation plans.

Background: Usher syndrome (USH) is an autosomal recessive disorder comprising retinitis pigmentosa, hearing loss and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous with three distinctive clinical types (I-III) and nine Usher genes identified. This study is a comprehensive clinical and genetic analysis of 172 Usher patients and evaluates the contribution of digenic inheritance., Methods: The genes MYO7A, USH1C, CDH23, PCDH15, USH1G, USH2A, GPR98, WHRN, CLRN1 and the candidate gene SLC4A7 were sequenced in 172 UK Usher patients, regardless of clinical type., Results: No subject had definite mutations (nonsense, frameshift or consensus splice site mutations) in two different USH genes. Novel missense variants were classified UV1-4 (unclassified variant): UV4 is 'probably pathogenic', based on control frequency <0.23%, identification in trans to a pathogenic/probably pathogenic mutation and segregation with USH in only one family; and UV3 ('likely pathogenic') as above, but no information on phase. Overall 79% of identified pathogenic/UV4/UV3 variants were truncating and 21% were missense changes. MYO7A accounted for 53.2%, and USH1C for 14.9% of USH1 families (USH1C:c.496+1G>A being the most common USH1 mutation in the cohort). USH2A was responsible for 79.3% of USH2 families and GPR98 for only 6.6%. No mutations were found in USH1G, WHRN or SLC4A7., Conclusions: One or two pathogenic/likely pathogenic variants were identified in 86% of cases. No convincing cases of digenic inheritance were found. It is concluded that digenic inheritance does not make a significant contribution to Usher syndrome; the observation of multiple variants in different genes is likely to reflect polymorphic variation, rather than digenic effects.

Unlabelled: Individuals with vestibular dysfunction may experience visual vertigo (VV), in which symptoms are provoked or exacerbated by excessive or disorientating visual stimuli (e.g. supermarkets). VV can significantly improve when customized vestibular rehabilitation exercises are combined with exposure to optokinetic stimuli. Virtual reality (VR), which immerses patients in realistic, visually challenging environments, has also been suggested as an adjunct to VR to improve VV symptoms. This pilot study compared the responses of sixteen patients with unilateral peripheral vestibular disorder randomly allocated to a VR regime incorporating exposure to a static (Group S) or dynamic (Group D) VR environment. Participants practiced vestibular exercises, twice weekly for four weeks, inside a static (Group S) or dynamic (Group D) virtual crowded square environment, presented in an immersive projection theatre (IPT), and received a vestibular exercise program to practice on days not attending clinic. A third Group D1 completed both the static and dynamic VR training. Treatment response was assessed with the Dynamic Gait Index and questionnaires concerning symptom triggers and psychological state. At final assessment, significant between-group differences were noted between Groups D (p=0.001) and D1 (p=0.03) compared to Group S for VV symptoms with the former two showing a significant 59.2% and 25.8% improvement respectively compared to 1.6% for the latter. Depression scores improved only for Group S (p=0.01) while a trend towards significance was noted for Group D regarding anxiety scores (p=0.07)., Conclusion: Exposure to dynamic VR environments should be considered as a useful adjunct to vestibular rehabilitation programs for patients with peripheral vestibular disorders and VV symptoms.

Purpose: To determine the molecular cause of sector retinitis pigmentosa and hearing loss in two affected siblings., Methods: Direct DNA sequencing of the USH1C gene was performed in two affected siblings. Putative pathogenic sequence changes were assayed in their parent's chromosomes and in control chromosomes. Clinical examination included visual acuity measurement, visual field measurement, electrophysiologic assessment, and fine matrix mapping. Retinal imaging with fundus photography, scanning laser ophthalmoscope (fundus autofluorescence), and optical coherence tomography was performed. Hearing and vestibular function was also assessed., Results: The siblings were aged 42 years and 40 years, and both were compound heterozygotes for the p.R103H missense change and the novel splice site change c.2227-1G>A in the USH1C gene. Both alleles were found to be in trans. Neither allele was identified in a panel of 866 control chromosomes, and both were considered pathogenic. Both siblings had sector retinitis pigmentosa restricted to the inferior and nasal retina. Fundus autofluorescence imaging showed a clear demarcation between normal and abnormal areas of retina, which corresponded to areas of reduced sensitivity on fine matrix mapping and loss of visual field. Both siblings had severe hearing loss but were able to develop language., Conclusion: We report a novel molecular cause of sector retinitis pigmentosa associated with hearing loss representing a new phenotype associated with mutations in the USH1C gene.

This study investigates whether physiological variations in ovarian hormones during the ovarian cycle (OC) are associated with changes in auditory function. Sixteen women with normal hearing underwent auditory tests and simultaneous measurements of the hormone levels four times during OC. The auditory tests included recording of otoacoustic emissions (OAEs), the medial olivocochlear (MOC) suppression and auditory brainstem responses (ABRs). The OC was defined by oestradiol and progesterone serum levels and menstrual cycle dating. A significant spontaneous OAE frequency shift [F(3,114.6)=15.8, p<0.001], with the greatest shift in the late follicular phase (highest oestrogen levels), was observed. Transient evoked OAE levels showed a consistent tendency in an increase in all frequency bands in the late follicular/early luteal stage and a decrease in the late follicular stage; TEOAE inter-session comparison indicated very small statistical differences. The MOC suppression changed significantly during OC [F(3,33.8)=3.2, p=0.036], with significant inter-session difference, lower in session 2 than in session 1 (p=0.019) and lower in session 4 than in session 1 (p=0.007). The ABR wave V absolute latency changed significantly during OC [F(3,33)=3.3, p=0.03], longer in the late follicular phase. There was also a significant positive correlation of TEOAEs and ABR (wave V latency and III-V interval) and significant negative correlation of MOC suppression with oestradiol levels in the follicular phase. The results of this study reflect very small changes in auditory function during OC, and they are suggestive of an increased hearing sensitivity around the time of ovulation., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

This article reviews the evidence for computer-based auditory training (CBAT) in children with language, reading, and related learning difficulties, and evaluates the extent it can benefit children with auditory processing disorder (APD). Searches were confined to studies published between 2000 and 2008, and they are rated according to the level of evidence hierarchy proposed by the American Speech-Language Hearing Association (ASHA) in 2004. We identified 16 studies of two commercially available CBAT programs (13 studies of Fast ForWord (FFW) and three studies of Earobics) and five further outcome studies of other non-speech and simple speech sounds training, available for children with language, learning, and reading difficulties. The results suggest that, apart from the phonological awareness skills, the FFW and Earobics programs seem to have little effect on the language, spelling, and reading skills of children. Non-speech and simple speech sounds training may be effective in improving children's reading skills, but only if it is delivered by an audio-visual method. There is some initial evidence to suggest that CBAT may be of benefit for children with APD. Further research is necessary, however, to substantiate these preliminary findings.

Unlabelled: Impaired musical skills are reported in parental questionnaires to be present in children with an auditory processing disorder (APD)., Objectives: To formally assess musical skills in children with a diagnosis of APD., Methods: We used a validated musical test battery with extensive normative pediatric data, the Gordon's Musical Aptitude Profile and the tests of metre and melody in particular, in order to assess the musical skills of 8 children with a previously given diagnosis of APD (APD group) and 8 normal controls (control group) aged 7-15 years old. The two groups were well matched for age, sex, handedness, socio-economic factors and musical training., Results: The APD group had significantly lower metre percentile scores than normal children (mean difference 28.9, p=0.003). Melody scores tended to be lower in the APD group than in the controls, but this did not reach significance, possibly due to low power of the study., Conclusion: This is the first study that systematically assesses musical skills in children with a formal diagnosis of APD in the absence of other developmental disorders. The APD group did significantly worse than the control group in judging metre. Musical skills assessment in children with APD may help constrain our understanding of this heterogeneous condition and possibly inform the management plan for these children., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To define the phenotype and elucidate the molecular basis for an autosomal recessively inherited optic atrophy and auditory neuropathy in a consanguineous family with two affected children., Methods: Family members underwent detailed ophthalmologic, electrophysiological, and audiological assessments. An autozygosity mapping strategy using high-density single nucleotide polymorphism microarrays and microsatellite markers was used to detect regions of genome homozygosity that might contain the disease gene. Candidate genes were then screened for mutations by direct sequencing., Results: Both affected subjects had poor vision from birth and complained of progressive visual loss over time. Current visual acuity ranged from 6/60 to 6/120. Fundus examination revealed bilateral temporal optic nerve pallor in both patients with otherwise normal retinal findings. International-standard full-field electroretinograms were normal in both individuals, with no evidence of generalized retinal dysfunction. Pattern cortical visual evoked potentials were grossly abnormal bilaterally in both cases. The pattern electroretinogram N95:P50 ratio was subnormal, and the P50 was of shortened peak time bilaterally in both patients. The electrophysiological findings were consistent with bilateral retinal ganglion cell/optic nerve dysfunction. Audiological investigation in both siblings revealed abnormalities falling within the auditory neuropathy/dysynchrony spectrum. There were no auditory symptoms and good outer hair cell function (as demonstrated by transient evoked otoacoustic emissions) but impaired inner hair cell/neural function with abnormal stapedial reflex thresholds and abnormal or absent auditory brainstem-evoked responses. The single nucleotide polymorphism microarray data demonstrated a 24.17 Mb region of homozygosity at 11q14.1-11q22.3, which was confirmed by microsatellite marker analysis. The candidate target region contained the transmembrane protein 126A (TMEM126A) gene, and direct sequencing identified a previously described nonsense mutation (c.163C>T; p.Arg55X)., Conclusions: We describe the first detailed phenotyping of patients with autosomal recessive TMEM126A-associated optic atrophy and auditory neuropathy. These findings will facilitate the identification of individuals with this recently described disorder.

Sudden sensorineural hearing loss is usually unilateral and can be associated with tinnitus and vertigo. In most cases the cause is not identified, although various infective, vascular, and immune causes have been proposed. A careful examination is needed to exclude life threatening or treatable causes such as vascular events and malignant diseases, and patients should be referred urgently for further assessment. About half of patients completely recover, usually in about 2 weeks. Many treatments are used, including corticosteroids, antiviral drugs, and vasoactive and oxygen-based treatments. Although no treatment is proven, we recommend a short course of oral high-dose corticosteroids. There is much to learn about pathogenesis of sudden sensorineural hearing loss, and more clinical trials are needed to establish evidence-based management., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Objective: The objective of this study was to determine the role of non-hospital delivery and other risk factors for permanent congenital and early-onset hearing loss (PCEHL) in a developing country., Design: Matched case-control study., Setting: Four primary healthcare centres in inner-city Lagos, Nigeria., Population: Fifty-six infants with PCEHL and 280 normal hearing controls matched for age and sex from a population of infants not older than 3 months attending Bacille de Calmette-Guérin immunisation clinics., Methods: Conditional logistic regression analyses of infant and maternal characteristics associated with PCEHL, and the evaluation of population exposure to each risk factor., Main Outcome Measures: Adjusted matched odds ratios and population attributable risk percent (PAR%)., Results: Children with PCEHL were significantly more likely to be first born (OR 1.9, 95% CI 1.1-3.6) without skilled attendants at birth (OR 2.4, 95% CI 1.3-4.5) and have a history of neonatal jaundice requiring exchange blood transfusion (NNJ/EBT) (OR 9.6, 95% CI 2.4-38.2) but less likely to be small for gestational age (SGA) (OR 0.1, 95% CI 0.0-0.5). After controlling for other covariates, the absence of skilled attendants at birth (OR 4.2, 95% CI 2.0-8.6) and NNJ/EBT (OR 19.1, 95% CI 4.3-85.5) emerged as predictors of PCEHL, while SGA (OR 0.1, 95% CI 0.0-0.2) retained its inverse relationship with PCEHL. The PAR% was 35.9% for the lack of skilled attendants at birth and 10.6% for having NNJ/EBT. About 23% of children with PCEHL did not exhibit any risk factors., Conclusions: NNJ/EBT and the absence of skilled attendant at birth rather than the place of delivery are significant predictors of PCEHL in this study population. Targeted hearing screening using these risk factors would facilitate the detection of about 77% of children with PCEHL.

Paediatric vestibular assessment is necessary in various situations, yielding invaluable information relating to diagnoses and allowing for the formulation of appropriate rehabilitative strategies when considering the management of children with vestibular and balance problems, alone or in association with hearing impairment or other developmental disorders. The development and assessment of the vestibular system is considered in this article.

Objective: To determine the feasibility and effectiveness of hospital-based universal newborn hearing screening programme for the early detection of permanent congenital or early-onset hearing loss (PCEHL) in Lagos, Nigeria., Methods: A cross-sectional pilot study based on a two-stage universal newborn hearing screening by non-specialist health workers using transient evoked otoacoustic emissions (TEOAE) and automated auditory brainstem-response (AABR) in an inner-city maternity hospital over a consecutive period of 40 weeks. The main outcome measures were the practicality of screening by non-specialist staff with minimal training, functionality of screening instruments in an inner-city environment, screening coverage, referral rate, return rate for diagnosis, yield of PCEHL and average age of PCEHL confirmation., Results: Universal hearing screening of newborns by non-specialist staff without prior audiological experience is feasible in an inner-city environment in Lagos after a training period of two-weeks. Notwithstanding excessive ambient noise within and outside the wards, it was possible to identify a test site for TEOAE screening within the hospital. The screening coverage was 98.7% (1330/1347) of all eligible newborns and the mean age of screening was 2.6 days. Forty-four babies out of the 1274 who completed the two-stage screening were referred yielding a referral rate of 3.5%. Only 16% (7/44) of babies scheduled for diagnostic evaluation returned and all were confirmed with hearing loss resulting in an incidence of 5.5 (7/1274) per 1000 live births or a programme yield of 5.3 (7/1330) per 1000. Six infants had bilateral hearing loss and the degree was severe (> or =70 dB nHL) in three infants, moderate (40 dB nHL) in one infant and mild (<40 dB nHL) in two infants. The age at diagnosis ranged from 46 days to 360 days and only two infants were diagnosed within 90 days., Conclusions: Hospital-based universal hearing screening of newborns before discharge is feasible in Nigeria. Non-specialist staff are valuable in achieving a satisfactory referral rate with a two-stage screening protocol. However, a more efficient tracking and follow-up system is needed to improve the return rate for diagnosis and age of confirmation of hearing loss.

This review explores the potential role of hormones in modulating the auditory function. The review describes four groups of hormones (the hormones of the circadian cycle, reproduction, stress response and the fluid and electrolyte balance), their physiological variations, interactions, as well as the physiological basis for their effect on the auditory system. Possible contribution of hormones to pathophysiology of auditory dysfunctions, including hyperacusis, tinnitus, Menière's disease and pre-menstrual auditory dysfunction, has also been discussed.

Low level radio-frequency (RF) signals may produce disorientation, headache and nausea. This double blind study tested nine case-subjects, who complained of various symptoms after prolonged mobile telephone use and 21 control subjects. Each subject underwent a series of trials, in which a dummy mobile telephone exposure system was held to each ear for 30 min in (a) pulsed, (b) continuous RF emission or, (c) no emission test modes. In the active pulsed and continuous modes the same mean power as the output of a typical handset was delivered at a carrier frequency of 882 MHz and at a maximum specific absorption rate (SAR) value of 1.3 W kg(-1) (+/- 30%). In Experiment I (auditory), transient evoked otoacoustic emissions (TEOAE), which assess the outer hair cells in the inner ear, were conducted. In Experiment II (vestibular) the vestibulo-ocular reflex was recorded by video-oculography (VOG), at baseline and immediately post exposure. There were no significant TEOAE changes from baseline to post-exposure recording for any of the exposures and no significant differences in the TEOAEs' change from baseline to post exposure between cases and controls. The VOG did not identify any effect of the exposure on the vestibular end organ in either cases or controls. In conclusion, 30 min exposure to mobile phone RF did not show any immediate effects on vestibulocochlear function as measured by TEOAE and the VOR., ((c) 2007 Wiley-Liss, Inc.)

Saccadic eye movements can be used to evaluate different aspects of brain function, and in this article we are concerned with possible applications in relation to anti-epileptic drug treatment. Recent improvements in the technology of measurement have improved the sensitivity and objectivity of the measures. Here we review the neurophysiology of saccades, their classification, their anatomical basis and cortical control, and then published research articles concerned with the influence of anti-epileptic drugs on saccades and their parameters. It seems likely that certain anti-epileptic drugs (especially those acting on ion channels) exert their effect on saccades through ion channels, and this may have relevance to clinical and pharmacogenetic studies.

The corpus callosum consists of heavily myelinated fibres connecting the two hemispheres. Its caudal portion and splenium contain fibres that originate from the primary and second auditory cortices, and from other auditory responsive areas. The anterior commissure in humans is much smaller than the corpus callosum, and it also contains interhemispheric fibres from auditory responsive cortical areas. The corpus callosum is exclusively present in placental mammals, while in acallosal mammals, most of the corpus callosum-related functions are carried out by the anterior commissure. The exact contribution of these two structures and of interhemispheric transfer in hearing in humans is still a matter of debate. In more recent years, human behavioural studies which employ psychoacoustic tasks designed to tap into interhemispheric transfer, combined with sophisticated neuroimaging paradigms, have helped to interpret information from animal experiments and post-mortem studies. This review will summarize and discuss the available information of the contributions of the human interhemispheric pathway in hearing in humans from behavioural, neuroimaging and histopathological studies in humans.