Pre-registered controlled comparison of auditory function reveals no difference between hospitalised adults with and without COVID-19.

OBJECTIVE: Several viruses are known to have a negative impact on hearing health. The global prevalence of COVID-19 means that it is crucial to understand whether and how SARS-CoV2 affects hearing. Evidence to date is mixed, with studies frequently exhibiting limitations in the methodological approaches used or the populations sampled, leading to a substantial risk of bias. This study addressed many of these limitations. DESIGN: A comprehensive battery of measures was administered, including lab-based behavioural and physiological measures, as well as self-report instruments. Performance was thoroughly assessed across the auditory system, including measures of cochlear function, neural function and auditory perception. Hypotheses and analyses were pre-registered. STUDY SAMPLES: Participants who were hospitalised as a result of COVID-19 (n = 57) were compared with a well-matched control group (n = 40) who had also been hospitalised but had never had COVID-19. RESULTS: We find no evidence to support the hypothesis that COVID-19 is associated with deficits in auditory function on any auditory test measure. Of all the confirmatory analyses, only the self-report measure of hearing decline indicated any difference between groups. CONCLUSION: Results do not support the hypothesis that COVID-19 infection has a significant long-term impact on the auditory system.

Expanding the genotypic spectrum of Perrault syndrome.

Perrault syndrome is a rare autosomal recessive disorder characterized by sensorineural hearing loss (SNHL) in both sexes and primary ovarian insufficiency in 46, XX karyotype females. Biallelic variants in five genes are reported to be causative: HSD17B4, HARS2, LARS2, CLPP and C10orf2. Here we present eight families affected by Perrault syndrome. In five families we identified novel or previously reported variants in HSD17B4, LARS2, CLPP and C10orf2. The proband from each family was whole exome sequenced and variants confirmed by Sanger sequencing. A female was compound heterozygous for a known, p.(Gly16Ser) and novel, p.(Val82Phe) variant in D-bifunctional protein (HSD17B4). A family was homozygous for mitochondrial leucyl aminocyl tRNA synthetase (mtLeuRS) (LARS2) p.(Thr522Asn), previously associated with Perrault syndrome. A further family was compound heterozygous for mtLeuRS, p.(Thr522Asn) and a novel variant, p.(Met117Ile). Affected individuals with LARS2 variants had low frequency SNHL, a feature previously described in Perrault syndrome. A female with significant neurological disability was compound heterozygous for p.(Arg323Gln) and p.(Asn399Ser) variants in Twinkle (C10orf2). A male was homozygous for a novel variant in CLPP, p.(Cys144Arg). In three families there were no putative pathogenic variants in these genes confirming additional disease-causing genes remain unidentified. We have expanded the spectrum of disease-causing variants associated with Perrault syndrome.

Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness.

Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.

Stimulus level effects on speech-evoked obligatory cortical auditory evoked potentials in infants with normal hearing.

OBJECTIVE: To determine stimulus level effects on speech-evoked cortical auditory evoked potentials (CAEPs) in infants for a low (/m/) and high (/t/) frequency speech sound. METHODS: CAEPs were recorded for two natural speech tokens, /m/ and /t/. Participants were 16 infants aged 3-8months with no risk factors for hearing impairment, no parental concern regarding hearing or development, and normal tympanograms and otoacoustic emissions. Infants were either tested at levels of 30, 50, and 70dB SPL or at 40, 60, and 80dB SPL, in counterbalanced order. RESULTS: Input-output functions show different effects of increasing sound level between stimuli. There were minimal changes in latency with increase in level for /t/. For /m/, there were approximately 50-60ms latency increases at soft compared to loud levels. Amplitudes saturated at moderate-high levels (60-80dB SPL) for both stimuli. CONCLUSIONS: Infants' CAEP input-output functions differ for /t/ versus /m/ and differ from those previously reported for adults for other stimuli. Effects of stimulus and level on CAEPs should be considered when using CAEPs for hearing aid or cochlear implant evaluation in infants. SIGNIFICANCE: Speech-evoked CAEPs provide an objective measure of central auditory processing. Possible differences in CAEP growth between infants and adults suggest developmental effects on intensity coding by the auditory cortex.

Deriving the real-ear SPL of audiometric data using the "coupler to dial difference" and the "real ear to coupler difference".

OBJECTIVE: The purpose of the study was to compare the measured real-ear sound pressure level (SPL) of audiometer output with the derived real-ear SPL obtained by adding the coupler to dial difference (CDD) and real-ear to coupler difference (RECD) to the audiometer dial reading. DESIGN: The real-ear SPL and RECD were measured in one ear of 16 normally hearing subjects using a probe-tube microphone. The CDD transform and the RECD transfer function were measured in an HA1 and an HA2 2-cc coupler using an EAR-LINK foam ear-tip or a customized earmold. The RECD transfer function was measured using the EARTone ER 3A and the Audioscan RE770 insert earphone. RESULTS: The procedures were very reliable with mean differences on retest of less than 1 dB. The mean difference between the measured and derived real-ear SPL was generally less than 1 dB and rarely exceeded 3 dB in any subject. CONCLUSIONS: The CDD measured for an individual audiometer and the RECD measured for an individual ear can be used to derive a valid estimate of real-ear SPL when it has not been possible to measure this directly.

Perforation of the tympanic membrane and its effect on the real-ear-to-coupler difference acoustic transform function.

It is not always possible to undertake extensive real-ear measurements, especially in infants and young children. An alternative approach is to estimate the real-ear SPL by use of an acoustic transform function such as the real-ear-to-coupler difference (RECD). This may be used to estimate the real-ear sound pressure level (SPL) obtained from an insert transducer or a hearing instrument. The aim of the present study was to investigate the effects of tympanic membrane perforation on the RECD transform function. Subjects in the study comprised two groups of 12 individuals aged between nine and 65 years. One group of subjects had a tympanic membrane perforation and was recruited to the study before admission for myringoplasty. There was no evidence of middle ear pathology in the remaining subjects who comprised the control group. An RECD transform function for an insert transducer was measured on each subject using the standard clinical protocol on the Audioscan RM500 real-ear measurement system. There was a statistically significant difference between the two groups; mean RECD transform value of the perforation group was 9-12 dB lower than the corresponding value in the control group at audiometric frequencies below 1.5 kHz. This difference is probably due to the perforation acting as a vent and allowing low-frequency acoustic energy to escape into the middle ear cavity. Use of an average RECD transform function to estimate real-ear SPL in subjects with a perforation will overestimate the SPL reaching the tympanic membrane. As a result, the derived real-ear SPL obtained by use of either an insert transducer or a hearing instrument will be overestimated. This has implications for the selection and verification of a hearing instrument. The difference in the mean RECD transform function between the control group and subjects with a tympanic membrane perforation supports the use of individually measured RECD values wherever possible.

Use of the 'real-ear to dial difference' to derive real-ear SPL from hearing level obtained with insert earphones.

The electroacoustic characteristics of a hearing instrument are normally selected for individuals using data obtained during audiological assessment. The precise inter-relationship between the electroacoustic and audiometric variables is most readily appreciated when they have been measured at the same reference point, such as the tympanic membrane. However, it is not always possible to obtain the real-ear sound pressure level (SPL) directly if this is below the noise floor of the probe-tube microphone system or if the subject is unco-operative. The real-ear SPL may be derived by adding the subject's real-ear to dial difference (REDD) acoustic transform to the audiometer dial setting. The aim of the present study was to confirm the validity of the Audioscan RM500 to measure the REDD with the ER-3A insert earphone. A probe-tube microphone was used to measure the real-ear SPL and REDD from the right ears of 16 adult subjects ranging in age from 22 to 41 years (mean age 27 years). Measurements were made from 0.25 kHz to 6 kHz at a dial setting of 70 dB with an ER-3A insert earphone and two earmould configurations: the EAR-LINK foam ear-tip and the subjects' customized skeleton earmoulds. Mean REDD varied as a function of frequency but was typically approximately 12 dB with a standard deviation (SD) of +/- 1.7 dB and +/- 2.7 dB for the foam ear-tip and customized earmould, respectively. The mean test-retest difference of the REDD varied with frequency but was typically 0.5 dB (SD 1 dB). Over the frequency range 0.5-4 kHz, the derived values were found to be within 5 dB of the measured values in 95% of subjects when using the EAR-LINK foam ear-tip and within 4 dB when using the skeleton earmould. The individually measured REDD transform can be used in clinical practice to derive a valid estimate of real-ear SPL when it has not been possible to measure this directly.

Customized acoustic transform functions and their accuracy at predicting real-ear hearing aid performance.

OBJECTIVE: The purpose of the study was to evaluate the validity of predicting the real-ear aided response by adding customized acoustic transform functions to the performance of a hearing aid in a 2-cc coupler. DESIGN: The real-ear hearing aid response, the real-ear-to-coupler difference (RECD/HA2), and field to behind-the-ear microphone transfer functions were measured in both ears of 24 normally hearing subjects using probe-tube microphone equipment. The RECD/HA2 transform function was obtained using both insert earphones and with the hearing aid/ pressure comparison method. An RECD/HA2 transfer function was also obtained with a customized earmold, ER-3A foam tip, and an oto-admittance tip. RESULTS: Validity estimates were calculated as the difference between the derived and measured real-ear response. The derived response was generally within 5 dB of the measured real-ear response when it incorporated an RECD/HA2 transform function obtained with a customized earmold for the specific ear in question. Discrepancies increased when the RECD/HA2 transfer function was obtained from the same subject but the opposite ear. There were significant differences between the RECD/HA2 transform function obtained with customized and temporary earmolds. As a result, the derived response incorporating these transforms differed significantly from the measured real-ear response obtained with the customized earmold. The insert earphone and the hearing aid RECD/HA2 transfer function were equally valid. CONCLUSIONS: The derived response may be used as a substitute for in situ hearing aid response procedures when it incorporates acoustic transform functions obtained with a customized earmold from the specific ear in question.

A comparison of inter-aural attenuation with the Etymotic ER-3A insert earphone and the Telephonics TDH-39 supra-aural earphone.

One of the many reported advantages of the insert earphone over the supra-aural earphone is increased inter-aural attenuation (IA). Minimum values of IA determine the need for masking of the non-test ear in air-conduction audiometry. The aim of the present study was to measure inter-aural attenuation for the Etymotic Research ER-3A insert earphone (with deep and shallow insertion of the ear plug within the ear canal) and compare this with the supra-aural Telephonics TDH-39/MX41-AR earphone/cushion combination. Subjects were 18 adults ranging in age from 38 to 68 years (mean 50 years). Each subject had no hearing in one ear following translabyrinthine surgery for removal of an acoustic neuroma. The opposite ear had hearing thresholds better than 40 dB HL and an air-bone gap of less than 10 dB at any audiometric frequency. Pure tone air-conduction thresholds were obtained in the range 0.25-8 kHz. Deep insertion of the insert earphone was deemed to occur when the outside edge of the ear plug was flush with the entrance of the ear canal. Shallow insertion was deemed to occur when half of the ear plug (6 mm) was inside the entrance of the ear canal. IA was defined operationally as the difference between the good-ear and poor-ear not-masked air conduction threshold for a given audiometric frequency and earphone. The results show that the TDH-39/MX41-AR combination provides a median IA of approximately 60 dB with a lower limit of approximately 45 dB. Greater IA was obtained with the ER-3A insert earphone but this depended on the depth of insertion. With a deep insertion, the 1A values were some 15-20 dB greater than with the supra-aural earphone. Although frequency-specific IA values are provided, a simple rule of thumb is to apply masking to the non-test ear when the pure tone airconduction signal from the ER-3A insert earphone exceeds the bone conduction threshold of the non-test ear by 55 dB HL or more. If it is not possible to obtain a deep insertion depth this value should be reduced by 5 dB.

Sonotubometry findings in children at high risk from middle ear effusion.

The functioning of the eustachian tube has an important role to play in the development of middle ear disease. It would be useful if a clinical test could assist in the identification of eustachian tube dysfunction, particularly if this is shown to be an indicator of persistent middle ear effusion. The aim of this study was to compare the results of sonotubometry using the MMS-10 instrument in children at high risk from middle ear effusion with a group of normal subjects. Forty-one subjects (age range 5-6 years) were allocated to one of two groups (experimental group, 21 subjects; control group 20 subjects) based on a questionnaire designed to identify subjects at high risk from middle ear effusion. The test protocol allowed each subject to swallow three times for each of two pure-tones (7 and 8 kHz) delivered by the nasal probe. Sonotubometry indicated opening of the eustachian tube on swallowing in around 80% of subjects. The incidence of positive findings varied greatly amongst subjects across both groups. In the control group, the mean increase in sound pressure level on swallowing was 11.5 dB (+/- 4.3) and 9.8 dB (+/- 2.5) for 7 and 8 kHz, respectively. The corresponding means for duration were 118 ms (+/- 47.9) and 137 ms (+/- 61.8). Sonotubometry failed to demonstrate a difference between the two groups of subjects. Hence, the clinical application of sonotubometry to identify subjects at high risk from middle ear effusion is not supported.

Are clinical measurements of uncomfortable loudness levels a valid indicator of real-world auditory discomfort?

A recent study revealed that most patients were wearing National Health Service hearing aids that were capable of exceeding their uncomfortable loudness level (ULL) measured clinically (Munro et al., 1996). However, there is little evidence to show that these clinical measurements are a valid indicator of real-world auditory discomfort. The aim of this study was to investigate the relationship between ULL and real-world discomfort. The study involved 20 adult subjects, aged 41-92 years, who had been fitted monaurally with an NHS hearing aid. ULLs were measured using a probe-tube microphone situated close to the eardrum. Individual real ear to coupler differences were added to the SSPL90 in order to predict the maximum power output (MPO) of the hearing aid at the eardrum. Subjects completed a questionnaire designed to rate the loudness of different environmental sounds. The results show that the more the MPO value exceeded the ULL value, the more likely it was that the subjects reported loudness tolerance problems to environmental sounds of long duration. There was a statistically significant correlation between the ULL and discomfort ratings for sounds of longer duration, such as traffic and wind noise; but not for shorter-duration sounds, such as door banging. Subjects did not express real-world auditory discomfort when the MPO value matched the ULL value. These findings support the argument for setting hearing-aid MPO close to ULL.

Balancing the caloric-induced nystagmus velocity with cold air and water.

A useful alternative to the traditional water caloric is to use an air stimulus. However, the caloric test has not been standardized and a range of parameters are being used in different audiology clinics. The aim of this study was to determine cold air parameters that resulted in a similar slow-component eye velocity to that for water irrigation. Twelve normal subjects underwent caloric testing using air temperatures in the range 18-33 degrees C. The duration and air-flow rate were held constant at 60 s and 5 l/min. A water irrigation at 30 degrees C for 30 s and delivering 150 ml resulted in a mean slow-component eye velocity of 17 degrees/s. An equal response was obtained with an air temperature of 21.0 degrees C. Further work is required to find equivalent air and water responses for other combinations of parameters.

The effect of head size on the auditory brainstem response for two breeds of dog.

Many studies have shown that the auditory brainstem response (ABR) is influenced by the sex of the subject. The explanation offered most often for this sex difference is the smaller head size and brain dimensions in the female. Since breeds of dog have different head sizes, this makes them useful subjects to test the hypothesis that ABR latency covaries with head size. Subjects comprised 20 Dalmatians and 20 Jack Russell terriers. The maximum width of the head was 123 +/- 8 mm in the Dalmatian and 88 +/- 5 mm in the Jack Russell. An auditory brainstem response was carried out using a click stimulus at 75 dB nHL. The latency of wave V and the I-V interval was longer (0.3 and 0.17 ms respectively) in the Dalmatian, although the correlation of these measurements with head size (which ranged from -0.2 to +0.3) was not statistically significant. These findings do not support the theory that differences in ABR latency are due to differences in head size per se. Correlation of latency with body temperature and with age was also weak and not statistically significant.

Normative auditory brainstem response data for bone conduction in the dog.

Auditory brainstem response (ABR) is a valuable tool for the diagnosis of hearing disorders in dogs, but is hampered by the lack of published normative data. The aim of the present study was to obtain normative data for bone conduction, without masking, under clearly defined conditions. Subjects comprised 20 Dalmatians and 20 Jack Russell terriers. Two methods were investigated: holding the bone vibrator against the head by hand or by applying a 500 g weight. The results revealed no difference in hearing threshold between the two breeds or for the two methods of applying the bone vibrator to the head. The mean hearing threshold was close to 0 decibels re normal hearing level (dB nHL), which is the biological norm for humans. Hence, bone conduction thresholds can be used for confirmation of conductive hearing impairment in the dog, in the same way as in humans.

Normative auditory brainstem response data for hearing threshold and neuro-otological diagnosis in the dog.

There is growing interest in the application of auditory brainstem response (ABR) audiometry for hearing assessment in dogs. The technique is far from standardised, however, resulting in large discrepancies between studies. This study aimed to obtain normative data, under clearly defined conditions, for two breeds of significantly different size; head size being a potential factor determining ABR latency values. The subjects, 20 dalmatians and 20 Jack Russell terriers, were sedated prior to ABR testing, and subcutaneous scalp electrodes used to detect the evoked potential elicited by a click stimulus presented via insert earphones. The mean ABR thresholds for the two breeds, 0 and -5 decibels re normal hearing level (dB nHL), respectively, were very similar to those for humans. The latency values of the main ABR waves and the interval between them were statistically significantly smaller for the smaller breed, but there was no correlation with head size within either breed. The results provide a baseline to assist with confirmation of hearing impairment and neuro-otological diagnosis in the dog.

Real-ear to coupler differences in children with grommets.

Real-ear to coupler differences (RECDs) are important for the selection of appropriate amplification characteristics for hearing impaired children. The aim of this study was to investigate the effects of patent grommets on RECDs in children. Subjects were 32 children aged between 4 and 7 years, 16 had a patent grommet in one or both ears as confirmed by otoscopy and large equivalent ear canal volumes on tympanometry. There was no evidence of middle ear pathology in the remaining 16 who comprised the control group. All real-ear and coupler measures showed good test-retest repeatability across the whole frequency range. The mean difference in RECDs between the two groups in the frequency range 0.125-0.75 kHz was 15 dB. The differences in RECDs were statistically significant (P < 0.01) for all frequencies below 0.75 kHz. There was a strong correlation between the mean RECD and equivalent ear canal volume at all frequencies between 0.125 and 0.5 kHz, and a moderate correlation at 0.75 kHz. Large inter-subject variability was found, with a maximum standard deviation of 6.6 dB at 4.0 kHz. Therefore, this study supports the need for individual RECD measures to be made, particularly for subjects with grommets, rather than using averaged transformation figures. It suggests that more low frequency gain should be given to hearing aid users with patent grommets to overcome the reduced SPL in the ear canal, due to leakage through the vented tympanic membrane.

Investigation of hearing impairment in Cavalier King Charles spaniels using auditory brainstem response audiometry.

Auditory brainstem response audiometry was used to investigate nine Cavalier King Charles spaniels with a history of hearing impairment. Successful recordings were made in all cases. In eight of the dogs, the hearing impairment was between 40 and 85 decibels re normal hearing level. In addition to confirming the degree of impairment in each ear, information was obtained concerning the site of the lesion. The auditory brainstem technique may have an important role to play in assessing treatment outcome. Other applications include screening animals used in breeding programmes as well as working dogs requiring good binaural hearing.

Audiological findings after multichannel cochlear implantation in patients with Mondini dysplasia.

Mondini dysplasia is a congenital malformation of the inner ear. To date, five individuals with this malformation have received cochlear implants at the South of England Cochlear Implant Centre. The aim of this study was to review the audiological findings of these individuals after implantation. The soundfield thresholds after implantation are in the region of 30-40 dB (A). The results of suprathreshold speech recognition tasks show substantial variability in performance but this is no greater than that obtained from implant users with no malformation. All individuals were able to detect and recognize a variety of environmental sounds that would previously have been inaudible. These findings, along with the reported improvement in quality of life, mean that Mondini dysplasia is not a contra-indication for multichannel cochlear implantation. This information will be useful to other centres when considering implantation in similar patients.

The test-retest variability of the caloric test: a comparison of a modified air irrigation with the conventional water technique.

The bithermal caloric test has traditionally been carried out using water but air may also be used. One of the reported disadvantages of air is the high test-retest variability (Coats et al., 1976). A recent study by Moon and Munro (1996) demonstrated that the variability could be reduced by modifying the air irrigator probe to allow greater control of probe placement and direction of air flow within the ear canal. The aim of the present study was to compare the test-retest variability of the modified air technique and the conventional water technique. Twelve normal subjects underwent four full caloric tests: twice with water and twice with air. The results show that it is possible to obtain a similar test-retest variability with the two techniques. The range for canal paresis and directional preponderance are also similar. While further research is required, the modified air technique appears to provide a reliable alternative to the traditional water technique.

The relationship between uncomfortable loudness level and maximum power output in subjects recently fitted with NHS hearing aids.

It is generally agreed that the maximum output from a hearing aid should not exceed the subject's uncomfortable loudness level (ULL). However, this relationship is not easily defined as electroacoustic data are usually measured in a 2 cc coupler and auditory measurements are usually obtained from supra-aural transducers calibrated in a 6 cc coupler. The aim of the study was to investigate this relationship in 21 adults who were being fitted with a hearing aid for the first time. A probe-tube microphone system was used to measure the sound pressure level of both variables in the ear canal. The measurement of ULL was determined using the method recommended by the British Society of Audiology (1987). The ULL values were around 110 dB SPL (+/-10) when measured in the ear canal. The maximum output of the hearing aid was obtained by correcting the SSPL90 with the subject's own real ear to coupler difference. The results revealed that the real ear saturation response (RESR) of the newly fitted hearing aid was typically 115-120 dB SPL (+/-8). The RESR exceeded the ULL for 19 (90%) subjects on average at five of the seven frequencies and by 12 dB. While further research is needed to determine whether discomfort occurred in real life situations, the implications are that the subject may use the hearing aid at less than optimum settings to prevent loudness discomfort or may ultimately reject the hearing aid altogether.