Patients with m.3243A>G mutation of mitochondrial DNA develop bilaterally symmetric sensorineural hearing loss. However, it is unclear how fast their hearing loss progresses over time, and whether they experience rapid progression of hearing loss. In the present study, we conducted a long-term hearing evaluation in patients with MELAS or MIDD who harbored the m.3243A>G mutation of mitochondrial DNA. A retrospective chart review was performed on 15 patients with this mutation who underwent pure-tone audiometry at least once a year for more than two years. The mean follow-up period was 12.8 years. The mean progression rate of hearing loss was 5.5 dB per year. Hearing loss progressed rapidly to be profoundly deaf in seven patients during the observation period. Heteroplasmy and age-corrected heteroplasmy levels correlated with the age of onset of hearing loss. These results indicate that patients with m.3243A>G mutation have a gradual progression of hearing loss in the early stages and rapid decline in hearing to be profoundly deaf in approximately half of the patients. Although it is possible to predict the age of onset of hearing loss from heteroplasmy and age-corrected heteroplasmy levels, it is difficult to predict whether and when the rapid hearing loss will occur. Sensorineural hearing loss is frequently associated with mitochondrial disease; it is observed in approximately half of the patients with three main syndromes—chronic progressive external ophthalmoplegia (CPEO); myoclonus epilepsy associated with ragged-red fibers (MERRF); mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) . HearingMitochondrial diseases are categorized into two groups: those characterized by ragged-red fibers (RRF), including MELAS, MERRF, and CPEO, and those caused by mutations in protein-coding genes, such as pure encephalopathy without RRF. RRF is a characteristic microscopic appearance of the muscle stained with Gomori trichrome, which is due to the accumulation of abnormal mitochondria below the plasma membrane of the muscle fiber. Hearing loss is highly prevalent in the first group but rarely seen in the second group. Oxidative phosphorylation is impaired in both types of encephalopathy; however, mitochondrial protein synthesis is impaired only in the first group, suggesting that hearing loss is caused by impairment of protein synthesis similar to RRF.An A-to-g transition mutation at nucleotide pair (np) 3243 in mitochondrial DNA (mtDNA) has been documented in most patients with MELAS and a few patients with CPEO. This mutation has been identified in pedigrees with maternal transmission of diabetes and deafness among families of different racial backgrounds ,7,8,9,10In patients with MELAS and MIDD, hearing is generally normal at birth, and hearing loss occurs eventually, appearing as early as in the teens or twenties and as late as the fifties. Hearing loss, in general, is bilateral and symmetrical; a pure-tone audiogram shows a flat type or falling type of sensorineural loss bilaterally in most cases ,9. HeariWe previously reported that, when present for several years, patients with np3243 point mutation showed a slightly progressive decline in their hearing; the progression rate of hearing loss ranged from 1.5 to 7.9 dB per year [In total, 27 patients with hearing loss and an A-to-g transition at np 3243 in the mtDNA visited the Department of Otolaryngology and Head and Neck Surgery, at the University of Tokyo Hospital, between 1989 and 2021. Among them, 15 patients who underwent audiological examinations for more than two years or until they became completely deaf were enrolled. The patients consisted of four males and eleven females, and their ages ranged from 22 to 66 years (mean: 40 years) at their first visit to our clinic. All patients had hearing loss, with a pure-tone average (PTA) value being greater than 25 dB HL (hearing level) on the initial audiological examination. They were interviewed regarding the onset of hearing loss, balance–gait disorder, diabetes mellitus, and the presence of other signs and symptoms. The presence of diabetes mellitus was confirmed by doctors in the Department of Nutrition and Metabolism of our hospital or their affiliated hospital, and the blood glucose and HbA1c levels were periodically measured in all patients. All procedures were in accordance with the Helsinki declaration and were approved by the University of Tokyo Human Ethics Committee (No. 2487). All patients gave informed consent for the use of their clinical data.The patients were evaluated using pure-tone audiometry, in general, every three months, to assess the longitudinal changes in their hearing thresholds. The pure-tone average (PTA) values were calculated as the mean air conduction threshold at 0.5, 1, 2, and 3 kHz. The pure-tone threshold at 3 kHz was obtained from the mean of 2 and 4 kHz, as it is not routinely measured in Japan. For calculating the PTA values, the hearing thresholds at the frequencies showing off-scale were calculated as 5 dB over the maximum sound level generated by an audiometer. The patients were also evaluated using speech recognition test, tympanometry, acoustic reflex threshold test, auditory brainstem response, and distortion-product otoacoustic emissions (DPOAEs), when necessary.The patients also underwent a battery of neuro-otological evaluations consisting of a physical examination, neurological examination, and neuro-otological examinations, including caloric and cervical vestibular evoked myogenic potential (cVEMP) testing.Caloric testing was performed with 2 mL ice water irrigation of the external auditory canal for 20 s. This caloric stimulation method is easier to perform than bithermal irrigation and has high sensitivity and specificity for detecting canal paresis . When MSIn the role of a stimulus for cVEMP, short tone bursts of 500 Hz ; rise/fall time, 1 ms; plateau time, 2 ms) were presented through headphones . Surface electromyographic activity was recorded in supine patients from symmetrical sites over the upper half of each sternocleidomastoid muscle (SCM), with a reference electrode on the lateral end of the upper sternum. During recording, the patients were instructed to raise their heads slightly to continuously contract the SCM. Background EMG was monitored during recording to confirm that subjects maintained SCM activity at a sufficient level (150 μV). We analyzed the first biphasic wave p13-n23) from the ipsilateral SCM to the stimulated side. For the evaluation of amplitude. The percentage of cVEMP asymmetry ratio (cVEMP AR) was calculated as 100|(Ar − Al)/ (Ar + Al)|, where Ar is the amplitude of p13-n23 on the right side, and Al is the amplitude of the p13-n23 on the left side. On the basis of results from normal subjects, the upper limit of cVEMP AR was set to 34.0 [ from the(age+12). This correction was previously published by Grady et al. [The invader assay contract by BML  was applied for the screening of mitochondrial tRNA (Leu). Briefly, mtDNA isolated from the peripheral leukocytes of patients and 1.2 μL of primary probe/invader oligonucleotides mixture  propanesulfonic acid) were poured into each well of the plates. Fluorescent resonance energy transfer (FRET)/Cleavase mixture  was added to the probe/invader oligonucleotide-containing plates. Subsequently, 3 μL of 5–100 mol/L synthetic target oligonucleotides (positive control), 10 ug/mL yeast tRNA (no target control), and denatured genomic DNA samples (>15 ng/μL) were added. Next, 6 μL of mineral oil  was overlayed into all reaction wells and incubated at 63 °C for 4 h. After incubation, the fluorescence was measured using a Cyto Fluor 4000 fluorescent microplate reader. The heteroplasmy rate for mitochondrial mutations was quantified by the detection of fluorescently labeled and digested PCR products through a fluorescence imaging system ,25. The y et al. . The curp-value. p < 0.05 was considered statistically significant.The correlation coefficients were calculated to assess the relationship between the heteroplasmy and age-corrected heteroplasmy levels and the progression rate of hearing loss and between the heteroplasmy and age-corrected heteroplasmy levels and the onset of hearing loss, balance or gait disorder, and diabetes mellitus, using JMP 16 . The age of onset of hearing loss, diabetes, and balance disorder was compared against each other using the Tukey–Kramer test. We performed the Shapiro–Wilk W test to value the normality of the sample. The relationship between the two continuous variables was analyzed by single regression analysis. R2 represented the coefficient of determination, and the significance of the slope indicated the The patients’ demographic characteristics of the patients are shown in The observation period ranged from 2 to 22 years, with a mean of 12.8 years. Hearing loss progressed in all patients during the observation period . In seveThe mean rate of the progression of hearing loss in all 15 patients was 5.5 dB per year. In eight patients, who did not show rapid deterioration of hearing, the progression rate of hearing loss was 3.0 dB per year, while it was 1.9 dB per year before the rapid deterioration in seven patients. When the progression rate of hearing loss prior to the rapid deterioration in the latter was added to the calculation, the mean progression rate of hearing loss was 2.5 dB per year in all patients. When the progression rate of hearing loss prior to the rapid deterioration in the latter was added to the calculation, the mean progression rate of hearing loss was 2.5 dB per year in all 15 patients and did not differ significantly between the patients with and without rapid deterioration in hearing.Caloric and cVEMP tests were performed in 13 out of 15 patients. In the caloric test, 4 (30%) out of 13 patients showed unilaterally decreased response, and 6 (46%) showed bilaterally decreased response. In cVEMP, 6 (46%) out of 13 patients showed unilateral abnormalities, and 7 (54%) showed bilateral abnormalities.p-values for the age of onset of hearing loss, diabetes, and balance disorder were 0.269, 0.400, and 0.189. The onset of balance disorder was delayed, compared with hearing loss and diabetes, but the difference was not statistically significant. However, balance disorder did not manifest in five patients until the end of the observation period; if we assume that the balance disorder appeared in these five patients one year later than the end of the observation period, the difference would be statistically significant .The mean age of onset of hearing loss, diabetes, and balance disorder was 28.6, 27.5, and 36.9 years, respectively . Based op = 0.0095); hearing loss appeared at a younger age in patients with higher heteroplasmy levels. Such a trend was also observed in the relationship between the heteroplasmy levels and the onset of balance disorder. The heteroplasmy levels were not associated with the onset of diabetes or the progression rate of hearing loss.p = 0.0291) and the onset of balance disorder (p = 0.0334); balance disorder appeared at a younger age in patients with higher age-corrected heteroplasmy. Age-corrected heteroplasmy level was not associated with the onset of diabetes or the progression rate of hearing loss.The current study evaluated the hearing in 15 patients with m.3243A>G mutation of mtDNA in the long-term period from 2 to 26 years (mean: 12.8 years) after their first hearing test. The mean age of onset of hearing loss was 28.6 years; hearing loss occurred between 10 and 56 years old. The age of onset of hearing loss was correlated with the heteroplasmy and age-corrected heteroplasmy levels. Initially, from the start of their follow-up, their hearing loss progressed gradually, but the hearing loss progressed rapidly to deafness in seven patients during the observation period. The hearing level ranged from 56 to 80 dB HL before the rapid deterioration of hearing. The progression rate of hearing loss before the rapid deterioration in these patients did not significantly differ from that in the remaining eight patients who did not show rapid hearing deterioration. All these results indicate that it is difficult to predict the rapid hearing decline in patients with m.3243A>G mutation of mtDNA. Oral or systemic steroid treatment was not effective in improving hearing loss.Unlike m.1555A>G mutation, hearing loss caused by m.3243A>G mutation of mtDNA is progressive. When we first reported the audiological findings of five patients with this mutation in 1996, the progression rate of hearing loss ranged from 1.5 to 7.9 dB per year . Since oIn the current study, the rapid progression of hearing loss occurred in 7 out of 15 patients, in both ears almost simultaneously in 3 patients, at different times in 2 patients, and only on one ear in 2 patients. This finding is quite interesting since such a rapid decline in hearing has not been reported except in one study. Oshima et al. 1996) reported the case of a 35-year-old woman with a complaint of right hearing loss and tinnitus in whom the pure-tone audiogram demonstrated 40 dB flat-type sensorineural hearing loss on the left and 85 dB saucer-type sensorineural hearing loss on the right ear [96 reportIn our case series, the rapid decline in hearing occurred after the hearing loss exceeded 55 dB HL. Prior to the rapid progression of hearing loss, their hearing level ranged from 56 to 80 dB HL. It is unclear why such a rapid decrease in hearing occurred. Since the rapid decline in patients’ hearing was not associated with worsening of the pre-existing signs and symptoms or other signs and symptoms, it is unlikely that it was caused by a rapid decline in systemic mitochondrial function, at least in the four patients who had rapid hearing loss in both ears at different times or only in one ear. It is possible that the vascular supply to the cochlea was compromised due to diabetes mellitus or the stroke-like episode seen in MELAS. It is also possible that the endolymphatic potential was rapidly reduced due to the acute impairment of energy production in the stria vascularis.Human temporal bone histopathological studies in patients with MIDD and MELAS showed that the stria vascularis most severely degenerated ,28,29; iIn the present study, patients noted balance–gait disorder later, compared with hearing loss, and five patients were not aware of balance or gait disorder. Balance–gait disorder tended to appear later, compared with hearing loss and diabetes mellitus. The use of cVEMP is essential in the diagnosis of saccular dysfunction in patients with moderate-to-profound sensorineural hearing loss . The lowHuman temporal bone histopathological studies on MIDD and MELAS demonstrated conflicting findings in terms of the degeneration of the vestibular systems. In a patient with MIDD, the vestibular end-organs, including the utricle and semicircular canals, were well preserved , whereasIt has been reported that the disease severity and the expression pattern of the impairment across organs and tissues may vary in mitochondrial diseases, depending on the heteroplasmy levels. In general, patients with a higher heteroplasmy level exhibit more severe phenotypes, although the correlation may be weak ,36,37,38It is worthy to note that the heteroplasmy and age-corrected heteroplasmy levels did not correlate with the progression rate of hearing loss or the presence of a rapid decline in hearing in our cases. It is unclear whether such a trend is also observed in other organs or tissues. De Laat et al.  scored dNo medication is known to prevent or slow the progression of hearing loss associated with m.3243A>G mutation of mtDNA. Since the hearing loss involves mainly the cochlea, hearing aids are effective until the hearing loss becomes severe to profound. When hearing aids become ineffective for oral communication, cochlear implantation, which directly stimulates the auditory nerve, is recommended . In the This study evaluating the hearing in 15 patients with m.3243A>G mutation in mtDNA in the long-term period demonstrated that hearing loss occurred from 10 to 56 years of age, that the age of onset of hearing loss was correlated with heteroplasmy and age-corrected heteroplasmy levels, that the hearing loss progressed gradually initially, and that the rapid decline in hearing loss to profound deafness occurred in approximately half of the patients during the observation period. The hearing level prior to the rapid decline ranged from 56 to 80 dB HL, and the progression rate of hearing loss prior to the rapid decline was not significantly different from that in the remaining patients, who did not experience a rapid decline in hearing. Heteroplasmy and age-corrected heteroplasmy levels did not correlate with the presence of rapid progression of hearing loss or with the progression rate of hearing loss. These results indicate that it is difficult to predict the rapid decline in hearing in patients with m.3243A>G mutation of mtDNA. Neither oral nor systemic steroid treatment was effective in improving hearing loss.


Manipulation of auditory stimuli affect the ABR evoked potentials and aid the diagnosis, particularly in auditory neuropathy patients. Some patients with auditory neuropathy lose evoked otoacoustic emissions over time; in these cases, comparing responses to rarefaction and condensation clicks, and decreasing the stimulus rate can show an extended cochlear microphonism or yield an improved electric potential record.To analyze the effect of these click manipulations on the records of potentials of patients with hearing loss as a form of improving the diagnosis.A clinical prospective study.59 patients with hearing loss underwent ABR recording using rarefaction and condensation clicks at a stimulus rate of 27.7/sec, and rarefaction clicks at a stimulus rate of 3.3/sec. The records were compared to the otoacoustic evoked emission.Eight (13.53%) patients showed changes in the recorded ABR potentials as a result of manipulating the characteristics of clicks, such as extended cochlear microphonism or an improved record of electric potentials. Five patients had no otoacoustic evoked emissions.Manipulation of click stimuli can improve the topographic diagnosis of hearing loss, particularly in the group of auditory neuropathy patients with no otoacoustic evoked emissions, where usually, the diagnosis is only possible through the method described above. ABR recording or auditory and brainstem audiometry is defined as a set of electric responses generated in a variety of anatomical sites as a result of an external auditory stimulus of any kind. Since Jewett et al. discovered them in 1970, these potentials - together with otoacoustic emissions - have supported the topographic diagnosis of a number of auditory alterations.However, in certain patients, among them very young children that do not respond or respond inconsistently to behavioral tests, and present no response to evoked otoacoustic emissions and ABR recordings, the diagnosis of cochlear hearing loss is not always aligned with the progression and improvement following treatment, suggesting that other anatomical sites might be involved besides the cochlea.Clicks are the most frequently used auditory stimuli to produce electrical responses and ABRs. Recently other stimuli have been introduced to improve the diagnosis, such as the tone burst, used to analyze auditory thresholds at lower frequencies not reached by the click. The stimuli facilitate the diagnosis of sloping loss and the adaptation of sound amplification devices in young children. The bone conduction click is particularly important for the diagnosis of hearing loss associated with malformation of the auricle and the middle ear.Changes in click characteristics may also add sensitivity to the diagnosis, adding extra information about the workings of the auditory system. Among these changes, two are often cited in literature: 1. polarity inversion of the stimulus, which facilitates visualization of cochlear microphonism ; 2. changes in the click presentation frequency, which is important for analysis of neural synchronism.Rarefaction clicks initiate cochlear potentials with different polarities and neural/brain stem potentials with lower latency and slightly higher amplitude, compared with those initiated by condensation clicks, while higher stimulus presentation frequencies reduce wave reproduction and clearness, particularly those generated in distal sites. None of these changes significantly affects the interpretation of results in individuals with no hearing loss.1 However, in subjects with hearing loss and especially individuals with auditory neuropathy (AN), where changes are found between the internal ciliated cells and the auditory nerve, these changes can markedly help the diagnosis.The aim of this study was to assess the effect of these two click parameter changes in patients with hearing loss, as a form of improving the topographic diagnosis.The project was approved by the Research Ethics Committee of Derdic and of the Sao Paulo Catholic University.We conducted a prospective clinical trial involving 59 hearing loss patients  that sought the medical unit of the DERDIC/PUCSP between August 2002 and February 2004.The inclusion criterion was the presence of severe hearing loss demonstrated by auditory tests done prior to the first consultation in our institution.Participants underwent a medical consultation, an audiometric exam (with the appropriate technique for each age group), the immitance test, recording of transient otoacoustic emissions HPT (TOAE) and distortion product (OAEDP), and ABR.1.Rarefaction clicks, presentation frequency of 27.7 stimuli/sec (standard)2.Condensation clicks, presentation frequency of 27.7 stimuli/sec3.Rarefaction clicks, presentation frequency of 3.3 stimuli/secClicks were presented through insertion phones with the following characteristics to record ABR results:Reference electrodes were placed over the right mastoid (A2) and the left mastoid (A1); the active (Fz) and the ground (Fpz) electrodes were placed over the forehead. The test recorded potentials from the ipsilateral mastoid to the stimulated ear during 12 msec after the beginning of each click until an average of 1024 accepted. Response reproducibility was observed for each parameter and for each intensity level until reaching the patient's electrophysiological threshold. The auditory stimulus conduction tube was occluded to differentiate between electrical artifacts and auditory responses for any image suggesting cochlear microphonism.Data was compared within each test and with TOAE and OAEDP responses.Of 59 patients with severe or deep hearing loss included in this study, 8 (13.56%) showed changes in ABR recordings compared to tracings obtained with the standard click when the stimulus polarity was inverted and/or when the presentation frequency was changed. Three of these patients presented TOAE and OAEDP. The remaining 51 patients (84.44%) presented electrical potentials within audiometric thresholds, regardless of the type of click, and no TOAE and OAEDP.There have been many discussions on the early diagnosis and treatment of patients with AN since the description of the first cases. Classically the presence of evoked otoacoustic emission and an absent or significantly altered ABR suggest the diagnosis. However, external ciliated cells may be compromised - leading to OEA loss - in 30% of AN4 individuals, mostly children. There is no consensus about the reasons for this situation, or whether this event is the cause or consequence of neural disorder.Altered auditory stimuli modify auditory potentials and may offer support in these situations. When there are changes in neural conduction and synchronism, such as in AN, faster stimulus presentation frequencies reduce wave reproduction and clarity. Slower presentation frequencies increase wave amplitude and significantly improve wave patterns.Stimulus polarity modifications allow visualization of cochlear microphonism, which usually is increased in AN, possibly due to external ciliated cell dysfunction.4 The presence of cochlear microphonism has supported our diagnosis of AN in cases where OEA are absent.OF the 59 patients in our study, 8 presented altered ABR recordings, showing what we consider a standard response of stimulus polarity and frequency changes as a response to clicks . Three of these patients had a clear diagnosis of AN , having OAEDP and TOAE, absent ABR, and widened cochlear microphonism. A reduction of stimulus frequency did not improve recordings in these patients, which did not change the diagnosis.On the other hand, patients 1, 2, 4, and 5 had no OAEDP or TOAE, and presented no electrophysiological response to the standard click, which suggests deep cochlear loss. However, polarity inversion yielded a mirror image typical of cochlear microphonism. the appearance of wave V following a stimulus frequency reduction in patients 2 and 4 reinforced the diagnosis of altered electrical conduction in distal regions of the auditory pathway. Our hypothesis is that these were AN cases that had lost OEA with the progression of the disease. This diagnosis would not have been possible without this protocol. In our view, this is the group of patients that stands to benefit most from the protocol suggested in our study.The importance of specific topographic diagnosis is its effect on the treatment strategy. Auditory abilities based on electroacoustic devices, the benefits of sound amplification devices and cochlear implants, and the type of language therapy, may all be conducted differently for those cases of cochlear hearing loss compared to those that have neural or central hearing loss.Although we believe that a topographic diagnosis results from the sum of clinical, psychoacoustic, acoustic, and electrophysiological and image findings, 8 (13.56%) patients benefited from the proposed ABR protocol.Polarity and frequency changes when presenting clicks during ABR add support to the topographic diagnosis of hearing loss, and should be done in all patients with this condition.


As audition also seems to contribute to balance control, additionally to visual, proprioceptive, and vestibular information, we hypothesize that hearing rehabilitation with active middle ear and bone conduction implants can influence postural control.In a prospective explorative study, the impact of hearing rehabilitation with active middle ear  and bone conduction implants  on postural control in adults was examined in three experiments. Vestibulospinal control was measured by cranio-corpography (CCG), trunk sway velocity (°/s) by the Standard Balance Deficit Test (SBDT), and postural stability with a force plate system, each time in best aided (BA) and unaided (UA) condition with frontal-noise presentation , followed by subjective evaluation, respectively.n = 15; bilateral VSB/BB: n = 3, bimodal (VSB/BB + hearing aid): n = 8], CCG-analysis showed no difference between BA and UA conditions for the means of distance, angle of displacement, and angle of rotation, respectively. Trunk sway measurements revealed a relevant increase of sway in standing on foam  and a relevant sway reduction in walking  in BA condition. Selective postural subsystem analysis revealed a relevant increase of the vestibular component in BA condition . As measured with the Interactive Balance System (IBS), 42% of the subjects improved stability (ST) in BA condition, 31% showed no difference, and 27% deteriorated, while no difference was seen in comparison of means. Subjectively, 4–7% of participants felt that noise improved their balance, 73–85% felt no difference, and 7–23% reported deterioration by noise. Furthermore, 46–50% reported a better task performance in BA condition; 35–46% felt no difference and 4–15% found the UA situation more helpful.In 26 subjects [age 55.0 ± 12.8 years; unilateral VSB/BB: Subjectively, approximately half of the participants reported a benefit in task performance in BA condition. Objectively, this could only be shown in one mobile SBDT-task. Subsystem analysis of trunk sway provided insights in multisensory reweighting mechanisms. There is increasing evidence that hearing deterioration seems to be associated with reduced balanced control , 2. ConsHowever, the exact mechanisms of interaction between auditory and vestibular, proprioceptive, and visual cues for maintaining postural control are still unknown. Although many studies with normal hearing and healthy subjects generally demonstrated a stabilizing effect , 10–14, In patients with hearing impairment, the impact of hearing on balance control was so far studied mainly in patients with conventional hearing aids or with CI. When hearing rehabilitation with conventional hearing aids is not possible or insufficient in patients with conductive or mixed hearing loss, implantable active middle ear or bone conduction hearing devices offer an alternative. Since the effect of hearing amplification on postural control has not been investigated in these implantable devices until now, this study focuses on patients with hearing rehabilitation with a semi-implantable active middle ear  or bone conduction  hearing device. Here, conductive hearing loss is “bypassed” and sound is transmitted to the inner ear by bone conduction –24 or byIn the current literature, the methods of assessing balance or postural performance are inhomogeneous, which also illustrates the complexity of postural regulation processes. Considering different (patho) physiological pathways of balance subsystem interaction, different measurement methods are established for quantification of postural control.The Unterberger (Fukuda) test, as an established assessment method for vestibulospinal control, is a frequently used method for clinical orientation of vestibular performance, offering objective measurement options as cranio-corpography (CCG) –31. For An additional approach is the IBS-System , 34, a fWe hypothesize that hearing rehabilitation with active middle ear and bone conduction implants can influence postural control in this study. As exact interaction mechanisms are still unclear, different approaches of postural control quantification were used in this explorative study to find out which approach might be more relevant in a wide variety of patients. Additionally, subjective evaluation was included in the analysis.A prospective explorative study was conducted to examine the objective and subjective impact of hearing rehabilitation with active middle ear  and bone conduction implants  on postural regulation in adults. Inclusion criteria were hearing rehabilitation for at least 6 months, BMI of <35, and age between 18 and 75 years.Before testing, microscopic otoscopy was conducted in all patients. For subjective balance evaluation, all patients were asked to answer the Dizziness Handicap Inventory (DHI) questionnaire. A video head impulse test (vHIT) of the horizontal semicircular canal was conducted. Additionally, directional hearing was tested in unaided (UA) and best aided (BA) condition. White noise was presented in random order at 65 dB SPL each from the angles 90, 45, 0, −45, and −90° with respect to the patient's position. Each angle was presented five times and the patients were asked to indicate the sound direction. The angle detection error was calculated as the mean square error.In three experimental series, that were conducted on the same day, different balance measurement approaches were considered: Vestibulospinal control was measured by cranio-corpography , trunk sway was measured in pitch and roll plane with the VertiGuard-System  performing the Standard Balance Deficit Test , and postural stability was evaluated with a footplate-measurement system .The experiments were all performed in a sound-insulated booth  with constant presentation of Fastl noise , d   was used. Testing for normality distribution was conducted by Kolmogorov-Smirnov test. Due to the descriptive character of this explorative study, there was no indication for multiple testing corrections. Depending on the respective experiment, the effect sizes t: ≥0.8) , or resp2 (≥0.1)  are indiThe study was approved by the responsible Ethics Committee  and conducted in accordance with the Declaration of Helsinki. All patients gave informed consent.The subjects were asked to extend their arms with the palms facing the ceiling and to perform 50 test steps in place (Unterberger (Fukuda) stepping test) while they were wearing a blindfold. Changes in the participant's position and displacement in relation to the starting position were continuously recorded by CCG. Markers were located on the subject's right and left shoulder and at two points on the vertex  and theiMeasurement parameters were the distance of displacement D (cm) (the distance from the starting position after 50 steps), the angle of displacement α (°) (the angle between the distance line and the 0°-line) and the angle of rotation β (angle between the anterior-posterior body axis and the 0°-line) . CompariThe VertiGuard-System, which consists of two orthogonally mounted gyroscopes, records body sway by measuring the angular velocity (°/s) at a sampling rate of 80 Hz and in pitch and roll dimensions. Patients wore the sensor close to the body's center of mass unit on their hips. Subjects performed 14 different tasks  of the SThe Interactive Balance System  consists of two force measurement plates with four sensors for forefoot and heel, respectively (sampling rate: 32 Hz). Subjects were standing without shoes on the plates while performing eight different tasks with changing sensory conditions . Two foaAfter each experiment, the participants were asked to answer two questions: (1) How did, subjectively, the noise influence your sense of balance? Answer options were: “improved,” “no influence,” “deteriorated.” (2) Under which condition did you feel to achieve a better testing result? Answer options were “best aided,” “no difference,” or “unaided.”n = 14, f: n = 12; age 55.0 ± 12.8 years). Out of these, fifteen patients had unilateral ; eight bimodal , and three bilateral  hearing rehabilitation (n = 15), most of participants showed normal or near normal hearing (n = 9) on the contralateral side, but there was also moderate (n = 4), or severe hearing loss (n = 2).Total 26 subjects were included in the study (m: litation . In the SD = 28.3) in BA and 46.2° (SD = 33.7) in UA condition (p = 0.46). The mean DHI-score was 17.1 (SD = 18.5). Testing of the vHIT  showed mean gain-values of 1.01 (SD = 0.13) for the right and 0.91 (SD = 0.17) for the left side. In total, 13.6% of subjects (n = 3) showed unilateral corrective saccades with pathological gain value (<0.8) on the respective side.In directional hearing testing, comparison of means showed an angle detection error of 42.0° , angle of displacement α  and angle of rotation β   .p = 0.01, r = 0.51) and a relevant sway reduction in BA condition in the task “walking 3 m forward with eyes open,” . No differences were seen in SBDT tasks in pitch plane , while visual and proprioceptive parts were not affected  revealed increased values for the vestibular component in BA condition (affected . No chann = 25).No clinically relevant differences were seen in the output parameters by comparison of means of the BA and UA test conditions . RegardiSubjectively, 85% (CCG) and 73% (VertiGuard and IBS), respectively, felt that noise had no influence on their testing performance, 8% (CCG) and 4% (VertiGuard and IBS) felt an improvement and 8% (CCG), and 23% (Vertiguard and IBS) reported a deterioration.Regarding the influence of hearing rehabilitation, 50% (CCG and VertiGuard) and 46% (IBS) felt to have achieved a better test result in the BA condition, 46% (CCG), 35% (VertiGuard), and 42% (IBS) felt no difference and 4% (CCG), 15% (VertiGuard), and 12% (IBS) found the UA situation more helpful for test performance .In the present study, the impact of hearing rehabilitation with active middle ear and bone conduction implants on postural control was evaluated considering different approaches of postural assessment.In vestibulospinal control measurement, CCG-testing revealed no relevant differences in the performance of the Unterberger (Fukuda) stepping test between the UA and BA conditions regarding the distance of displacement, angle of displacement, and angel of rotation. A previous study demonstrated a clear benefit in normal hearing people, where a significant reduction of distance of displacement and angle of rotation were described in the condition with auditory input . A similIn the present study, the results of angle of rotation and angle of displacement were in both conditions generally found to be within the physiological range . HoweverAlthough many studies analyzing the effect of audition on balance have used pressure plate measurements to assess postural control, a different, trunk sway-based approach was considered in the second experiment of our study: body sway was measured close to the center of body mass, including also mobile tasks, which is considered closer to daily-life conditions . As falln = 8) deviated laterally when their eyes were closed while sound presentation could induce an improvement of that abnormal deviation. No effects were seen in healthy people (n = 8). A further study analyzing the effect of bilateral hearing aid use on balance, where posturography was measured on a force plate in 22 adults, revealed no significant benefit of hearing aids on balance  and F2-4  was reported in sense of a reweighting of postural subsystems in the presence of sound . This efRegarding the subjective evaluation, there was a partially considerable discrepancy between the answers to the two questions as well as between the objective evaluation and the subjective estimation depending on the respective task. Only 4–7% of participants felt that noise improved their balance and 7–23% reported even deterioration by noise. On the other hand, nearly half of subjects reported to have better performed the task in the BA condition, while only 4–15% found the UA situation more helpful for test performance. In summary, hearing rehabilitation itself was seen subjectively as a benefit by a larger group of patients, while the presented sound itself seemed to be more a disturbing factor during the experiments. In this study, Fastl noise , a whiteThat uncomfortable noise can deteriorate balance was shown by Chen et al.  where inTo our knowledge, this is the first study analyzing the impact of hearing rehabilitation with active middle ear and bone conduction implants on postural control. While CI surgery can be associated with postoperative vertigo , 53, vesIn VSB surgery, even decreases of bone conduction hearing thresholds were reported as postoperative complications , vestibuSD = 18.5). As the focus of the present paper was on the effect of hearing rehabilitation with active middle ear and bone conduction implants across a wide variety of patients, subjects with possible sensory impairment were not excluded from the study. However, to answer the question how vestibular impairment is affected by auditory input, further specific work is necessary including more detailed vestibular diagnostic. Furthermore, the inhomogeneity of hearing rehabilitation in the study group , Germany.SP, TR, and LF are investigators in controlled post market entry studies or investigator-initiated research projects with implantable active middle ear and bone conduction hearing devices produced by MED-EL, Innsbruck, Austria. SP is investigator in research projects with grant support to the department of the corresponding author. SP received honorary for lectures from MED-EL Austria and MED-EL Germany. None of this was related to the research presented here. This study was not funded by MED-EL Austria or MED-EL Germany. There are not other commercial or financial relationships that could be construed as a potential conflict of interest. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Sudden sensorineural hearing loss (SSNHL) is a common otology emergency in the practice. Its severe hearing impairment and prognosis impair the quality of life. Given that cochlear hair cell vulnerability is not consistent across frequencies, this study aims to investigate the impact of frequency-specific hearing loss on prognosis in SSNHL.The study included 255 patients with full-frequency SSNHL. The baseline, clinical, and hearing characteristics, as well as possible cardiovascular predictors in blood, were collected for analysis.p = 0.008, p < 0.001), while the average hearing was not (p = 0.081). Logistic regression showed that only vertigo  and 8,000 Hz hearing level  were strongly associated with treatment outcome.The 4,000 and 8,000 Hz hearing levels in the responder group were significantly lower than those in the non-responder group (Compared with other frequencies, 8,000 Hz hearing level was closely related to prognosis in SSNHL. In an adjusted model, our study did not find an effect of mean hearing on prognosis in SSNHL. However, further multicenter prospective studies are needed for validation. Sudden sensorineural hearing loss (SSNHL) is characterized by rapid hearing loss of at least 30 dB on at least three consecutive frequencies on an audiogram within 3 days . SSNHL aGiven the anatomical specificity of the cochlea and the possible pathogenesis of SSNHL, in this study, we observed the clinical data of SSNHL patients to explore whether hearing thresholds at different frequencies were associated with the prognosis of SSNHL.We reviewed the clinical data of full-frequency SSNHL patients admitted to the head and neck surgery department of a university hospital between January 2018 and May 2022. Patients included in the study had their first visit within 14 days of the onset of SSNHL. All patients underwent a detailed physical examination, audiometry, computed tomography, and magnetic resonance imaging of the inner ear. Patients with conductive hearing loss, chronic otitis media, Meniere's disease, or retrocochlear lesions that might interfere with the diagnosis of SSNHL were excluded. At the same time, patients with recent fever and previous comorbidities such as malignant disease, mental illness, heart failure, stroke, and diabetes were excluded. To exclude the influence of the hearing level of the unaffected ear, patients with hearing loss in the unaffected ear were not included in the inclusion criteria of this study.Baseline characteristics , clinical characteristics , and pure-tone average (PTA) of impaired frequencies , 17–19. According to the Chinese SSNHL guidelines , all inct-tests were used for normally distributed quantitative data comparisons; Mann-Whitney U tests were used for non-normal quantitative data. Linear correlation to assess the association between different frequency hearing thresholds and hearing recovery. Receiver operating characteristic (ROC) curve analysis was used to assess the relationship between pre-treatment hearing thresholds at different frequencies and prognosis in SSNHL. Odds ratios (OR) and 95% confidence intervals (CI) for associations between admission hearing and SSNHL outcomes were calculated using logistic regression models. A variance inflation factor was used to check for collinearity among variables before performing multivariate logistic regression. p < 0.01 was considered significant for all tests. The figures were generated using GraphPad Prism 8.0.Statistical analysis was performed using SPSS 26.0. Continuous data are expressed as mean ± standard deviation, or median (interquartile range). Categorical data are presented as numbers (percentages), and statistical analysis used the chi-square test. Data were surveyed using the Kolmogorov-Smirnov test to determine distribution patterns. Two-sample After excluding 41 patients with hearing loss in the unaffected ear, a total of 255 patients with full-range SSNHL were included, as shown in n = 71) and Non-responder (n = 184), as shown in p > 0.05). There was no significant difference in the affected side, audiogram, accompanying tinnitus, aural fullness, and treatment time after the onset between the two groups . The number of vertigo patients in the responder was significantly lower than that in the non-responder (p < 0.05). In terms of hearing at various frequencies, the hearing loss levels of the non-responder at 4,000 and 8,000 Hz were 80.00 (58.50–100.00) and 87.50 (65.00–100.00) dB, which were significantly higher than those of the responder [70.00 (60.00–85.00) and 70.00 (50.00–80.00) dB] (p < 0.05). In the comparison of blood parameters between the two groups, the albumin level in the responder was significantly higher than that in the non-responder, while the level of fibrinogen was the opposite . There was no significant difference between the two groups in some other possible cardiovascular validation markers .Hearing recovery patients were divided into Responder , while other frequencies and PTA were not significantly correlated with hearing improvement . ROC curve analysis of SSNHL results showed that the areas under the curve at 4,000 and 8,000 Hz before treatment were 0.624  and 0.700 , respectively , and 0.943 , respectively. These results suggest that the presence of vertigo and higher hearing loss at 8,000 Hz are independent factors for poor prognosis in SSNHL.In univariate logistic regression analysis, the OR of SSNHL prognosis and parameters are shown in In this study, we found that vertigo and initial hearing at 8,000 Hz were associated with hearing recovery in patients with SSNHL. To assess the role of each frequency threshold in the prognosis of SSNHL, this study included SSNHL patients with full-frequency hearing impairment. Considering the roles of inflammation and hemodynamics in patients with full-frequency SSNHL, we included some possible blood predictors for analysis. Our results suggest that it's hearing at 8,000 Hz, but not other frequencies, that predicts full-frequency SSNHL.There are many hypotheses about the pathogenesis of SSNHL: infectious, vascular, inflammatory, immune, degenerative, etc., , 21. It The cochlea consists of three adjacent membranous tubes, shaped like a snail, surrounded by a bony shell , 36. FreAudiograms are thought to correlate with prognosis in SSNHL, with low-frequency decreased SSNHL having a favorable prognosis and full-frequency hearing decreased poor prognosis , 39. In To our knowledge, this is the first study that adjusted for multiple factors and used a single frequency as an influencing factor to predict SSNHL and prognosis. Based on the vulnerability characteristics of specific frequencies of the cochlea and the diagnostic criteria for SSNHL, it is logical to predict the prognosis of hearing loss by the vulnerable frequencies before treatment. This study has some limitations. First, as a preliminary study, the reproducibility of the results needs to be validated in a multicenter prospective study. Then, as an adjustment for confounders, we included only blood parameters known to have predictors in SSNHL into the analysis, and future studies should consider and incorporate other possible cardiovascular predictors. Finally, we have a short follow-up period. Although several current literatures suggest that the long-term follow-up hearing changes are 4–5 dB –49, whicIn this study, we explored the relationship of individual frequencies to SSNHL hearing improvement. Unlike previous studies, our study demonstrated that initial 8,000 Hz hearing and not other frequencies were independently associated with hearing improvement. The presence of vertigo and higher hearing at 8,000 Hz may be risk factors for poor prognosis in SSNHL, and these patients may require early combination therapy to increase the likelihood of hearing recovery.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of the Second Hospital of Anhui Medical University: YJ-YX2019-039. The patients/participants provided their written informed consent to participate in this study.CL and QF: built the models, analyzed the data, and drafted the manuscript. HC, ZW, CL, and LL: collect and filter data. HC, XQ, YL, and MC: participated in manuscript editing. JY: reviewed the manuscript and support for this assistance was funded. All authors contributed to the article and approved the submitted version.The study was supported by funding from the Incubation Program of National Natural Science Foundation of China (Grant No. 2019GMFY06).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


In the United Kingdom, atopic dermatitis (AD) affects 20% of children and topical corticosteroids (TCS) are a mainstay of AD treatment regimes. Many TCS have similar packaging despite significant differences in potency frequently leading to confusion, and along with misinformation and steroid phobia, potentially reducing treatment adherence. We aimed to evaluate parents' knowledge/concerns regarding TCS and explore benefits of/preference for a TCS‐labelling system.Hundred parents of children with AD attending paediatric dermatology and/or allergy appointments completed mixed‐methodology Survey 1 . Thirty parents, adolescents, and healthcare professionals completed Survey 2. Qualitative/quantitative data was thematically/statistically analysed (SPSS v25) respectively.n = 71/100) and reported significantly increased willingness and comfort in using TCS if a labelling system was used p ≤ 0.001). Knowledge regarding TCS potency was lacking: 62% (n = 46/74) of mild TCS‐users overestimated potency; 51% (n = 67/131) of potent TCS‐users underestimated potency. Common concerns were TCS‐related skin thinning, long‐term side effects and themes for improved AD‐care/support included: better information, written plans, access to advice, involvement of certain staff. Parents wanted accessible information in various formats: verbally, electronic resources, leaflets, and education sessions.Parents preferred the traffic light system (green = mild, yellow = moderate, red = potent; Parents of children with AD confirmed significant concerns and demonstrated poor knowledge regarding TCS use. Our findings suggest that a simple labelling system may improve TCS adherence. Future work to test refined label prototypes and evaluating their impact on adherence and correct use is needed. A recent UK qualitative study suggested several contributing factors were; confusion about topical application, limited use of written information, conflicting aetiology and management advice from healthcare professionals (HCPs), and lack of self‐management.Confusion may increase when treatment plans feature multiple TCS with differing potencies depending on disease severity and the intended body application site. This confusion is confounded by the absence of clear indication of TCS potency on packaging. A previously unexplored solution for this is a labelling system, denoting different potencies. A labelling system could provide an inexpensive, simple and quick reminder of the specific steroid potency and its appropriate/intended body site for use, whilst facilitating use in individuals who may not read or speak English fluently. Effective labelling enhances children and adolescents' understanding, for example of nutritional values in food, promoting healthier choices.Despite recommendations from the National Institute for Health and Care Excellence (NICE) that potency should be indicated on all TCS containers, parents rarely report experience with such labelling.Our study aims to explore the feasibility and potential benefits of a labelling system to help parents understand appropriate TCS use and improve adherence, with the aim of providing the basis for future interventional studies. As another major barrier to good adherence is steroid phobia, our study also explores parental concerns and understanding of safe TCS use.2Parents of children with a clinical diagnosis of AD attending paediatric allergy and dermatology clinics in a secondary/tertiary care setting were invited to participate in an anonymous survey (Survey 1) from January to February 2020. A mixed‐method approach was chosen to allow qualitative and quantitative investigation. Following this, due to COVID‐19 restrictions, a digital anonymous survey (Survey 2) was created and distributed via email to parents, adolescents, and HCPs, to gain feedback on the refined the labelling prototypes.2.1The surveys were devised by Erika Harnik and Claudia Gore, with the assistance of a clinical psychologist to avoid misleading questions. The surveys were piloted with several families and feedback was given. Adjustments were made before formal data collection commenced  with AD and have used at least one TCSExclusion criteria:Parents or carers who use TCS for other medical conditionsParents or carers of children with AD with no experience of TCSPatients with AD over 16 years old2.3All participants were informed the surveys were voluntary, and all data would be reported anonymously. No patient identifiable information was collected. The surveys were interviewer administered by FW, a student researcher, who did not have any involvement with the patient's clinical management. Permission for this service improvement study was granted by the Clinical Governance department of the Trust. Due to the nature of study, consent forms were not necessary.The study did not meet the criteria requiring NHS Research Ethics Committee review.2.4For Survey 1, the objectives of the study were explained, and participants were guided through the survey by FW to ensure queries were addressed and surveys were completed accurately. On completion, surveys were passed to participants to verify and complete the open‐text questions in their own words. For Survey 2, the information was sent via email and participants completed the survey electronically.2.5Survey data were populated into Excel by Florence Wilson. Original paper copies were destroyed once data was inputted to avoid any duplicates.2.6Data analysis were completed using SPSS v25. Quantitative data were analysed using descriptive statistics:t‐test would have been usedIf the data were normally distributed, a paired If the data were skewed, a Wilcoxon signed‐rank test would have been usedp‐value of <0.05 was deemed the cut off for rejecting the null hypothesis.A Qualitative data from the open‐text questions were coded by FW using NVivo, checked by Erika Harnik, and thematically analysed using Creswell's coding framework Figure .173Hundred surveys were completed for Survey 1, and 30 completed for Survey 2.3.1n = 71), 26 preferred numerical, and only 1 participant preferred alphabetical  to 5 (very comfortable/willing).Scores of willingness and comfort to use TCS for paediatric AD were recorded from 1  were higher than comfort levels ‘before’  with a statistical significance of Z = −7.365 and p < 0.001.As the data was skewed, a Wilcoxon signed‐rank test was calculated and indicated comfort levels ‘after’ the suggestion of a labelling system , general long‐term side effects (n = 24), dependence/tolerance (n = 10), and skin bleaching (n = 7) . The number of participants who correctly identified a TCS′ potency, additional effects and appropriate site of application varied between creams with some trends identified  The most commonly used cream was 1% Hydrocortosone with Miconazole .62% of users overestimated the potency of Daktacort® (n = 38).The appropriate body sites for use were identified ‘completely’ by 51% (Medium TCS:n = 26) and 0.05% Clobetasone butyrate‐Calcium oxytetracycline and nystatin (Trimovate®),  correctly identified their potency.The majority who had used 0.05% Clobetasone butyrate (Eumovate®), .Only around one third ‘completely’ identified the appropriate body sites for use , 88% (n = 7), 26% (n = 9), 62% (n = 24), 31% (n = 4), 48% (n = 12), respectively].The majority who had used 0.1% Betamethasone (Betnovate®), 0.05% Fluticasone propionate (Cutivate®), Mometasone furoate (Elocon®), Fusidic acid‐Betamethasone (Fucibet®), 0.025% Fluocinolone acetonide  and/or 0.05% Clobetasol propionate (Dermovate®) did not correctly identify their potency. Instead, most users underestimated the potency [71%  where similar misconceptions and fears exist would be beneficial but was delayed due to the COVID‐19 pandemic.5Parents of children with AD confirmed significant concerns and demonstrated poor knowledge regarding TCS use. Our findings suggest that a simple labelling system may help improve TCS adherence. Future work will test the refined labelling system prototypes and formally assess effectiveness in improving adherence and correct use.This research received no specific grant from any funding agency in the public, commercial, or not‐for‐profit sectors.No conflict of interests have been declared.Supporting InformationClick here for additional data file.


The Speech, Spatial, and Qualities of Hearing Scale (SSQ) and the Abbreviated Profile of Hearing Aid Benefit (APHAB) are two most commonly used questionnaires in the audiology clinic to assess an individual’s self-perception of their hearing ability. Here, we present the outcomes of these two questionnaires on a large group of self-reported normal hearing adult listeners. A total of 254 self-reported normal-hearing younger and older adults completed the SSQ and the APHAB questionnaire. The younger participants completed the questionnaires through Qualtrics, whereas the older participants completed the questionnaire through Qualtrics and a traditional pen-and-paper method. The younger listeners perceived a higher ability compared to the older adults in all the SSQ subscales  and reported a lesser frequency of the problems in three of the four APHAB subscales . There was no significant difference in the frequency of the problems reported in the Aversiveness subscale. Self-reported normal-hearing listeners do not rate their listening ability at the top of the ability scale. Additionally, the large dataset presented here has a potential normative value for the SSQ and the APHAB questionnaires for self-reported normal-hearing adult listeners. Questionnaires are frequently used in audiologic clinics worldwide to assess listeners’ subjective sense of their listening ability in everyday complex listening scenarios. The Speech, Spatial, and Qualities of Hearing Scale  and theThe Speech, Spatial, and Qualities of Hearing Scale  is a 50Investigators have been using the SSQ to obtain individuals’ self-perception of their hearing abilities in a variety of populations. Gatehouse and Noble  validateOver the last ten years, the SSQ has been translated and validated into several languages other than English with children and adults as participants, e.g., in Brazilian Portuguese with older adults , in DutcThe Abbreviated Profile of Hearing Aid Benefit  is a 24Even though the APHAB was initially developed to quantify the disability associated with hearing loss and the reduction in the abovementioned disability that happens with the uptake of a hearing aid, it has been used to obtain a self-perception of hearing abilities in individuals with normal hearing, cochlear implant users, and bone-anchored hearing aid users. Löhler et al.  used lisAlthough both the SSQ and the APHAB measure individuals’ self-reported hearing ability, there are few studies in the literature that compare the outcomes of these two questionnaires on the same group of listeners. Valente et al.  used theA total of 136 younger listeners  and 118 older listeners  participated in this study. All YLs received course credit for their participation and data were collected using Qualtrics software. The OLs data were collected using a combination of Qualtrics software and a traditional pen-and-paper method. All participants completed a series of intake questions, and those that responded “yes” to questions related to having hearing loss or being a hearing aid user were excluded from the study. All younger listeners were provided with course credit for one of their courses for participating in this research. The older listeners were not provided any compensation for their effort.Each participant completed a 49-item SSQ , and a 2Analyses were performed with SPSS 25.0 . A mixed ANOVA was used to investigate the effects of age on the various subscales for both questionnaires. Pearson’s correlations were computed to examine the relationships between the subscales.F = 77.5, p < 0.001, F = 16.32, p < 0.001, F = 5.79, p = 0.02, F = 18.56, p < 0.001, F values, degrees of freedom and the corresponding p values are reported in p = 0.06). A correlation analysis was conducted to investigate the relationship between the subscales of the two questionnaires used in this study. n = 21; mean age = 67 years, age range = 60–79 years), compared to this study, which has a much larger sample size. Additionally, this difference in the study sample could have led to the absence of age and subscale x age interaction effects in [The main purpose of this study was to investigate the effects of age on the self-perceived hearing abilities and to study the relationships between the subscales of the SSQ and APHAB questionnaires in a large sample of self-reported normal-hearing listeners. As expected, younger listeners (YL) reported higher abilities to communicate in complex listening environments compared to older listeners (OL) when questioned using the SSQ. However, it is interesting to note that both the groups still perceived some problems in such environments. Both YL and OL reported the highest ability in the qualities subscale. However, the YL reported the lowest ability in the spatial subscale, whereas the OL reported the lowest ability in the speech subscale. Additionally, the average subscale scores and the order of the scores  reported in this study for the YL group were similar to the scored reported in the literature with audiometrically screened normal-hearing (≤20 dB HL) listeners ,34 and tFor the APHAB questionnaire, YL had a significantly lower frequency of problems for the EC, BN, and RV subscales and there was no significant difference in the frequency of problems for the AV subscale. The mean frequency of problems reported for both the groups reported here were larger than the scores reported in . HoweverSignificant negative correlation between the three SSQ subscales and Ease of Communication, Reverberation, and Background Noise APHAB subscales indicated that individuals who perceived higher abilities in the SSQ subscales reported a lower frequency of problems in the three APHAB subscales. The fourth APHAB subscale, aversiveness, was not significantly correlated with any of the SSQ subscales. This was expected as the underlying construct of the aversiveness subscale was to assess negative reactions to environmental sound and how noisy situations were misperceived ,21,35 whEven though the SSQ subscales and three of the four APHAB subscales are correlated, the amount of variance accounted for by these comparisons ranged from 0.02 to 0.10. Given the fact that the variance accounted is small, it would be beneficial to use both the questionnaires in the evaluation of hearing-impaired subjects with any type of hearing aid. If the clinician wishes to factor in listener fatigue and the time taken to complete the questionnaires, the responses could be collected before the clinical appointment using a self-administered method (questionnaires mailed or creating a web-based system). Alternatively, a new questionnaire could be created incorporating the best aspects of both the SSQ and the APHAB questionnaires. However, the Aversiveness subscale of the APHAB should certainly be considered while developing this new questionnaire as it provides unique and very important information that is not provided by the SSQ questionnaire or the other three subscales of the APHAB questionnaire.Overall, the results presented here indicate that both the SSQ and APHAB probe self-perceived hearing abilities for similar circumstances, except for the fact that the aversiveness subscale of the APHAB probes an entirely different dimension which is not probed by any of the SSQ subscales. Additionally, self-reported normal-hearing younger listeners do not necessarily rate their listening abilities at the top of the ability scale in all three SSQ subscales. The big limitation of this study is that the data presented here are from a large cohort of self-reported normal-hearing participants and the audiometric thresholds are not measured. The absence of the audiometric thresholds from the participants should be taken into consideration while interpreting these results as the presence of high-frequency hearing loss or slight/mild hearing loss in the older listeners group could have impacted the scores in the two questionnaires. Together, the results presented here suggest that this dataset has a potential normative value, and more data need to be collected, especially from middle-aged participants, to develop normative data as a function of age group.


Seventeen infants presented auditory improvement, with a mean maturation time of 6.17 months. A significant difference emerged between patients with stable SNHL and those who improved only in the case of hyperbilirubinemia (p = 0.005). The initial hearing threshold was a predictor of auditory improvement and moderately correlated to the time of auditory maturation (p = 0.02). Conclusions: Our study supports the trend toward recognizing worse prognoses and slower maturation processes among NICU children who suffer from severe to profound SNHL. Caution must be taken when deciding on earlier cochlear implantation.Background: Newborns admitted to neonatal intensive care units (NICUs) are at higher risk of developing sensorineural hearing loss (SNHL), which may improve over time. The aim of this study was to describe the prevalence of the main risk factors for SNHL in a NICU cohort, focusing on children who underwent auditory maturation. Methods: An observational study of 378 children admitted to NICUs, who were followed for at least 18 months, with periodic audiologic assessments. Results: Out of 378 patients, 338 had normal hearing and 40 were hearing-impaired; we found a higher percentage of extremely preterm (EPT) and extremely low-birthweight (ELBW) infants in SNHL children ( It has been estimated that permanent bilateral sensorineural hearing loss (SNHL) involves 1–3/1000 live births in wellborn infants, increasing up to 50-fold in children who are at risk ; in partMany perinatal problems may require NICU admission, including hyperbilirubinemia, ototoxic drug use, TORCH infections, meningitis, mechanical ventilation, and periventricular hemorrhage, making the immature brain more sensitive to damage . In addiThe maturation of the auditory system is characterized by two different stages: the first lasts until the sixth month of gestation and involves the complete development of the peripheral part of the auditory system; the second includes synaptogenesis and the continued refinement of the central part of the auditory system, which continues until the second year of life ,10. The In the first year of life, the hearing threshold is not always stable ,11. ModiEarly rehabilitative treatment is essential to providing adequate access to the sound environment; however, prompt audiological diagnoses are not always reliable ,18. EvenPrevious investigations have attempted to identify predictive factors for auditory maturation among at-risk infants, though with contradictory results. Hof et al. 2013) hypothesized that hearing improvement in cases of initially identified SNHL is more frequent among infants with a gestational age of <28 weeks  hypothes. In addiThe purpose of our investigtion was to describe the prevalence of the main risk factors for SNHL in a NICU cohort and to understand whether there are differences in their distribution between normal-hearing babies and infants with stable and unstable hearing loss; in addition, we focused on identifying the main characteristics of children who experienced hearing threshold improvement.From January 2017 to February 2021, 436 children who were admitted to the NICU for more than 5 days were enrolled at the Department of Audiology of the Policlinico “P. Giaccone” University Hospital of Palermo, Italy. All patients included were referred to our service for audiological evaluation because of the presence of risk factors for SNHL according to the American Joint Committee on Infant Hearing (JCIH) guidelines [Out of these 436 patients, 394 (90.36%) participated in this study from the start, but we lost touch with 16 infants during follow-up monitoring. The final response rate was 86.69%, corresponding to 378 infants. The mean age at the time of the first appointment was 4 weeks’ corrected age (CA).After approval by the Hospital Ethics Committee , the study protocol was fully explained to the children’s parents and informed consent was obtained for each patient.Parents of the children were informed about the importance of their children’s participation in the audiological follow-up and were invited to complete a questionnaire administered by a trained staff member to assess the following risk factors for SNHL: prematurity , very low birthweight , respiratory distress , hyperbilirubinemia (serum bilirubin > 10 mg/dL), pregnant maternal infection (TORCH), perinatal infections , and exposure to ototoxic drugs . Exclusion criteria were: family history of hearing impairment, GJB2 gene mutation, neurological disorders , cranio-facial abnormalities, and syndromes associated with hearing impairment or permanent conductive hearing loss.An experienced audiologist and otorhinolaryngologist examined the condition of the external auditory canal and tympanic membrane with otoscopy, along with the nose, throat, head, and face to rule out any ear anomalies or syndromic features related to hearing impairment.The same qualified biomedical staff member assessed all children using auditory brainstem responses (ABR), transient-evoked otoacoustic emissions (TEOAEs), and tympanometry. In addition, depending on the child’s age and whether the child could be conditioned, patients were evaluated with either behavioral observation audiometry (BOA) or visual reinforcement audiometry (VRA).ABR recording was performed through an AMPLAID mk22 auditory-evoked potentials device in a soundproof room; all children were in natural sleep or in calm conditions throughout the evaluation. After adequate preparation of the skin, silver recording electrodes were attached to the upper forehead (recording electrode), the ipsilateral mastoid process (reference electrode), and contralateral mastoid process (ground electrode). Thus, the Fpz–M1–M2 electrode montage was used for recording ABR. Unfiltered full square-wave pulses of 100 ms duration were used, with alternating polarity. The clicks were delivered monaurally by a handheld TDH-49 headphone at a rate of 21/s. The analysis time was 15 ms. The recording bandwidth for click threshold determination was 100–2500 Hz. Electrode and interelectrode impedance were ensured to be below 5 kHz and 2 kHz, respectively. Each run consisted of summing the responses to 2000 clicks. Click stimuli were presented starting at a level of 100 dB HL. With step sizes of 10 dB, the level was decreased until no response was found. The response threshold was estimated by the lowest level at which a response was recorded. An infant was considered to have passed the ABR test if a replicable wave V response was recordable at 30 dB HL in both ears, whereas SNHL was defined as elevated ABR response thresholds (≥40 dB) in one or both ears. ABR thresholds at 20 dB HL or lower were considered normal, thresholds between 30 db HL and 40 dB HL were considered as indicative of mild hearing loss, thresholds between 50 db HL and 60 dB HL as moderate hearing loss, thresholds between 70 db HL and 80 dB HL as severe hearing loss, and thresholds higher than 90 dB HL as profound hearing loss [Experienced clinical audiologists interpreted the ABR response waves. The response latencies (in milliseconds) were obtained by establishing the peak of the wave and reading out the digitally displayed time.TEOAEs were recorded using the Otodynamics ILO 288 USB II device with standard settings; the stimulus was a nonlinear click at an intensity of 84 dB SPL, and a number of 260 averages was used. TEOAEs were considered ‘‘PASS’ only when the reproducibility of the recorded emissions exceeded 70% in at least three octave bands and the stimulus stability exceeded 80%. A second TEOAEs test was also performed in re-examined infants if the middle ear was free from disease .Tympanometry was performed with an Inventis Flute Diagnostic Middle Ear Analyzer system using the standard settings and a 226/1000 Hz probe tone (depending on the age) and an air pressure range of −400 to +200 daPa with automatic recording.BOA and VRA were performed with a pediatric audiometer (Interacoustics PA5) at 500, 1000, 2000, and 4000 Hz, with 20 and 80 dB being the minimum and maximum levels assessed by the device. To obtain responses, stimuli were presented in decreasing order in the right and left lateral planes, with or without visual conditioning.All patients included in the study had a minimum follow-up of 18 months from the time of the first appointment. The frequency of audiological examinations depended on the age and hearing status of the child. Evaluations of patients diagnosed with hearing loss were performed 3–4 times a year for children under 2 years of age and 2–3 times a year for children from 2 to 5 years of age; infants without any hearing impairment were assessed 2–3 times a year during their first year of life, followed by annual examinations as they got older .Each child was recommended to wear hearing aids (HAs) if their ABR thresholds were 40 dB nHL or worse (up to 95 nHL) in their best ear. HAs were provided at a mean age of 3.4 ± 0.6 months. Subjects who did not benefit from hearing aid amplification and who met criteria for cochlear implant (CI) candidacy were referred for CI surgery.A ‘maturated’ ABR was hypothesized when the following conditions were satisfied: (1) a unilateral or bilateral wave V identifiable over 30 dB nHL during the first clinical ABR; (2) the psychoacoustic threshold improved by 20 dB nHL or more with respect to the previous ABR threshold.p < 0.05 was considered significant.Continuous variables were represented as mean ± standard deviation (SD) and categorical variables as number and percentage. Comparisons between categorical variables were performed using the chi-square test and Fisher’s exact test. The Mann–Whitney U test was used to analyze continuous variables without normal distribution. Spearman’s correlation coefficients were calculated. Simple logistic regression (SLR) analysis was performed, considering hearing threshold amelioration as the dependent variable and prematurity, VLBW, and ABR initial threshold as independent variables. A two-tailed p < 0.05). Hearing-impaired children also showed a higher prevalence of prenatal (4.49%) and perinatal infections (9.52%) compared to normal-hearing infants (p < 0.0001). No significant differences between the groups were found in terms of respiratory distress, hyperbilirubinemia, and ototoxic drug exposure (p > 0.05).We found a higher percentage of EPT and ELBW infants in the SNHL group with respect to normal-hearing children, with a statistically significant difference  among children with stable hearing loss . Seventep < 0.05) in the final evaluation. When focusing on patients with maturation of auditory pathways, we recognized an initial mean hearing threshold of 63.82 db HL in the right ear and 62.35 db HL in the left ear, and a final mean hearing threshold of 33.52 db HL in the right ear and 26.47 db HL in the left ear (p < 0.001); a mean improvement of more than 30 db HL was evidenced in both ears.The study of auditory threshold in the SNHL group evidenced a mean hearing threshold of 74.87 db HL in the right ear and 70.75 db HL in the left ear at the first evaluation, and a mean hearing threshold of 61 db HL in the right ear and 55.25 db HL in the left ear (p = 0.014).Initial hearing threshold was shown to be weakly correlated to gestational age, with a higher hearing threshold as gestational age decreased . The analysis of SNHL risk factors evidenced a significant difference only in the case of hyperbilirubinemia between patients with stable hearing loss and individuals who improved (p = 0.005), with the former showing a higher prevalence (47.82%) of abnormal bilirubin serum levels. No significant correlation was observed between hearing improvement and time of maturation , while a moderate positive correlation between initial ABR threshold and time of maturation was recognized .We found a lower (35.29%) percentage of infants with severe SNHL in the better ear among patients who underwent hearing threshold improvement with respect to those who did not (56.52%), whether or not significant (p = 0.001).Out of 17 patients who exhibited an improvement in their hearing threshold, 4 cases presented an association between recordable TEOAEs and abnormal ABR, with a suspected pattern of auditory neuropathy spectrum disorder (ANSD); all infants with stable SNHL had absent TEOAEs. In particular, only 10 ears were PASS at the initial TEOAEs screening, while 27 were PASS at the final examination , while the least frequent was hyperbilirubinemia (5.88%). All cases of prenatal infection were caused by cytomegalovirus (CMV) infection.p = 0.33), VLBW , and improvement in hearing threshold. However, initial ABR hearing threshold was found to be a predictor of auditory improvement: children who showed worse hearing thresholds were less likely to experience maturation of the auditory pathways .Simple logistic regression analysis did not show any statistically significant association between prematurity . It may be supposed that the severity of the interacting factors affecting NICU infants might play a crucial role in the development of SNHL. With the exception of hyperbilirubinemia (p = 0.005), we did not find any significant difference in the prevalence of risk factors between children with stable SNHL and infants with auditory maturation; due to their immature brain barrier, NICU preterm children are less likely to recover from hearing loss induced by hyperbilirubinemia [Children who experienced SNHL tended to suffer from a higher degree of prematurity and lower birthweight than normal-hearing infants, as well as a higher rate of pre- and postnatal infections (ubinemia . Howeverubinemia .p = 0.02) and a slower process of maturation of auditory pathways, regardless of when it occurred (p = 0.02). These results may be read in light of the numerous mechanisms interfering with auditory plasticity in NICU infants; in fact, different and heterogenous conditions may transitorily or permanently injure a susceptible auditory brainstem, negatively influencing the pathway’s maturation or regeneration [Interestingly, it seems that those showing worse initial hearing thresholds had a reduced chance of experiencing hearing improvement , our cohort could be compared to the study by Hof et al., with a similar percentage of respiratory distress syndrome but a lower number of infants exposed to ototoxic drugs. Even if we observed a lower number of cases with hearing improvement (only three among preterm babies), we recognized the same number of complete recoveries from hearing impairment. Differently from these authors, though, no significant relationship between auditory maturation and gestational age was found; we should underline that the results may be influenced by the different timing of initial ABR , which could have led to the overestimation of the frequency of transitory auditory dysfunction .p = 0.02). In addition, it was clear that patients with severe-to-profound hearing loss had a worse prognosis, corroborating the possible role of hearing threshold as a predictive factor (p = 0.02). This result is further supported by Yang et al., who longitudinally assessed 64 infants who failed the TEOAEs screening test, concluding that patients with a lower initial auditory steady-state response (ASSR) threshold were more likely to show improved hearing over time [Similarly to Frezza et al., we observed a significant difference in terms of gestational age and birthweight between normal-hearing and SNHL infants. When comparing data regarding patients with hearing threshold change, it also emerged that, in their study, children with a higher degree of hearing loss needed a longer time to reach a normalization of their hearing threshold; this finding supports the evidence of a positive correlation between ABR threshold and time of improvement  because they may increase the number of cases of stable hearing loss due to their rare tendency to transform into a normal hearing threshold. In addition, we did not include the length of NICU stay, thus excluding some intrinsic NICU risk factors  that may affect our results.In summary, it is clear that audiological follow-up of NICU children is a challenging diagnostic process in which the clinician needs to promptly recognize any sign of auditory improvement/deterioration in order to implement the best rehabilitative strategy according to the hearing status and age of the patient; apart from the initial hearing threshold, it is difficult to find strong predictors of hearing improvement because children who are admitted to the NICU often present numerous risk factors whose interaction might partially explain the evolution of hearing threshold over time. It should be kept in mind that even cases of profound SNHL can transform into normal hearing, and, for this reason, waiting until 80–85 weeks of gestational age before deciding on cochlear implantation is still a good cut-off time, especially in preterm infants ,14,29,30Our study supports the trend toward recognizing a worse prognosis and a slower process of maturation among NICU children who suffer from severe-to-profound hearing impairment. Of course, being premature and having a VLBW means being at a higher risk of incomplete maturation of the auditory brainstem; nevertheless, the multiple interacting factors that characterize NICU newborns, acting on a susceptible auditory nervous system, may further influence the chance of auditory improvement. Caution must be taken when deciding on earlier cochlear implantation because auditory maturation after birth is still an unpredictable and dynamic process; future research is needed to better clarify the prognostic factors that may further assist audiologists in the management of NICU hearing-impaired children and better address parental concerns.